==================================CMR05================================== 5. Phototherapy of tumors. Photodynamic therapy of tumors. Hematoporphyrin derivative treatment of tumors using a laser. Fluorescence of tumors. Detection and treatment of tumors by light and/or dyes. 1 UI - 87119115 AU - Berns MW ; Wile AG TI - Hematoporphyrin phototherapy of cancer. AB - Hematoporphyrin phototherapy of cancer is a new modality for cancer diagnosis and treatment that is currently undergoing clinical trials worldwide. A variety of tumors have been studied, e.g., breast (mostly recurrent skin), lung, bladder, eye, head and neck, gynecological and brain. The most success to date has been with lung and the gynecological tract. Cell and animal studies are being conducted to elucidate the basic photobiological mechanisms involved, as well as the histopathological events associated with tumor destruction. Although major questions remain to be resolved, hematoporphyrin phototherapy is an exciting new therapeutic modality for the treatment of cancer, especially in sites where the unique features of lasers and fiber optics are advantageous. MH - Breast Neoplasms/DRUG THERAPY ; Cell Survival/DRUG EFFECTS ; Head and Neck Neoplasms/DRUG THERAPY ; *Hematoporphyrin Photoradiation ; Human ; Lung Neoplasms/DRUG THERAPY ; Neoplasm Recurrence, Local/DRUG THERAPY ; Neoplasms/*DRUG THERAPY ; *Photochemotherapy ; Prognosis ; Support, U.S. Gov't, P.H.S. SO - Radiother Oncol 1986 Nov;7(3):233-40 2 UI - 87114801 AU - Grossweiner LI TI - Optical dosimetry in photodynamic therapy. AB - The diffusion approximation for the radiant flux distribution in a tissue layer has been applied to optical dosimetry in photodynamic therapy of malignant tumors. The model assumes that tumor eradication requires a minimum absorbed energy by the localized photosensitizer, taken as 0.19 J/cm3 for hematoporphyrin derivative (HPD) at 630 nm. The analysis leads to the required incident irradiance for front surface illumination as a function of the tumor depth, the optical penetration depth of the tumor, and the concentration of localized sensitizer. The effect of HPD photobleaching on the required light dose and drug dose levels is considered. The results are given in tabular form for typical clinical applications. MH - Hematoporphyrins/*THERAPEUTIC USE ; Human ; Models, Biological ; Neoplasms/*DRUG THERAPY ; *Photochemotherapy ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Lasers Surg Med 1986;6(5):462-6 3 UI - 87113803 AU - Panucci A ; Angonese C ; Del Favero G ; Fabris C ; Marchioro L ; Basso D ; Di Mario F ; Naccarato R TI - Pancreolauryl test in chronic pancreatitis. AB - The pancreolauryl test was performed in 30 subjects with chronic pancreatitis, in order to evaluate its behavior in relation to the duration of the clinical history and the presence of pancreatic calcifications, diabetes mellitus, jaundice, and pancreatic pseudocysts. A significant inverse linear correlation was found between the onset of symptoms and FDL test values. While calcifications and diabetes were present in patients with both normal and abnormal test results, those with pseudocysts or jaundice always had pathological results. MH - Adult ; Aged ; Calcinosis/DIAGNOSIS ; Chronic Disease ; Diabetes Mellitus/DIAGNOSIS ; Female ; Fluoresceins/*DIAGNOSTIC USE ; Human ; Male ; Middle Age ; Pancreatic Pseudocyst/DIAGNOSIS ; Pancreatitis/*DIAGNOSIS ; Support, Non-U.S. Gov't SO - Klin Wochenschr 1986 Dec 1;64(23):1222-3 4 UI - 87106747 AU - Ja:skowski J ; Witkowski J ; My:sliwski A ; Zawadzki H TI - Effect of air ions on L 1210 cells: changes in fluorescence of membrane-bound 1,8-aniline-naphthalene-sulfonate (ANS) after in vitro exposure of cells to air ions. AB - The ability of air ions to produce changes in the electrical properties of L 1210 mouse leukemia cells was tested. The fluorescence of ANS incorporated into a membrane lipid bilayer (measured microphotometrically) was used as a probe. It was shown that the action of air ions of both signs could change (negative ions by increasing and the positive ones by decreasing) the fluorescence intensity of ANS in the cell surface structures or to an imbalance of ions inside and outside the cell. Both possibilities are discussed in the light of the results of experiments using ouabain or biguanide as factors diminishing the intensity of ANS fluorescence. MH - *Air Ionization ; Anilino Naphthalenesulfonates/*PHARMACODYNAMICS ; Animal ; Biguanides/PHARMACODYNAMICS ; Cell Membrane/DRUG EFFECTS/METABOLISM ; *Fluorescence ; Leukemia L1210/*METABOLISM ; Membrane Potentials/DRUG EFFECTS ; Ouabain/PHARMACODYNAMICS SO - Gen Physiol Biophys 1986 Oct;5(5):511-5 5 UI - 87100733 AU - Berenbaum MC ; Akande SL ; Bonnett R ; Kaur H ; Ioannou S ; White RD ; Winfield UJ TI - meso-Tetra(hydroxyphenyl)porphyrins, a new class of potent tumour photosensitisers with favourable selectivity. AB - We compared para-, meta- and ortho-isomers of meso-tetra(hydroxyphenyl)porphyrin (p-, m- and o-THPP) and the potassium salt of the para compound (K-p-THPP) with haematoporphyrin derivative (HpD) and Photofrin II in their ability to sensitise tumours, skin and brain to light. HpD and Photofrin II induced modest tumour photosensitisation at the cost of substantial skin and brain sensitisation. At doses low enough to keep sensitisation of these normal tissues within acceptable limits, tumour sensitisation was sufficient to give necrosis only approximately 2 mm deep after exposure to 10 J cm-2 light. In contrast, doses of p-THPP, K-p-THPP and m-THPP that produced skin and brain sensitivity within acceptable limits sensitised tumours enough to give 4-9 mm necrosis after 10 J cm-2 light. m-THPP was, on a molar basis, about 25-30 times as potent as HpD and Photofrin II in sensitising tumours. o-THPP was also a potent tumour photosensitiser, but induced a prohibitive degree of skin photosensitivity even at low doses. It is unlikely that these differences in relative selectivity are due to differences in such photophysical parameters as optimum activating wavelength (which would affect tissue penetration by light), or light absorption, and physicochemical factors that determine tissue localisation may be involved. The high tumour sensitising potency and favourable tissue selectivity of m-THPP, p-THPP and K-p-THPP make them promising candidates for clinical tumour phototherapy. MH - Animal ; Antineoplastic Agents/*THERAPEUTIC USE ; Brain/DRUG EFFECTS/RADIATION EFFECTS ; Comparative Study ; Female ; Hematoporphyrins/ADVERSE EFFECTS/THERAPEUTIC USE ; Male ; Mice ; Mice, Inbred BALB C ; Photochemotherapy ; Photosensitivity Disorders/CHEMICALLY INDUCED ; Plasmacytoma/DRUG THERAPY ; Porphyrins/ADVERSE EFFECTS/*THERAPEUTIC USE ; Skin/DRUG EFFECTS/ RADIATION EFFECTS ; Support, Non-U.S. Gov't SO - Br J Cancer 1986 Nov;54(5):717-25 6 UI - 87092321 AU - Oseroff AR ; Ohuoha D ; Ara G ; McAuliffe D ; Foley J ; Cincotta L TI - Intramitochondrial dyes allow selective in vitro photolysis of carcinoma cells. AB - Carcinoma cell mitochondria preferentially accumulate and retain certain cationic dyes to a much greater extent than most normal cells. Thus, they can potentially serve as targets for highly selective photochemotherapy. We evaluated 10 rhodamine and cyanine dyes as carcinoma-specific mitochondrial photosensitizers in vitro. The most effective, N,N'-bis(2-ethyl-1,3-dioxolane)kryptocyanine (EDKC), caused marked, light-dependent killing of human bladder, squamous, and colon carcinoma cell lines after 30-min incubations at 1-0.01 microM but was minimally toxic to human keratinocytes and to normal monkey kidney epithelial cells (CV-1). Carcinoma cell phototoxicity was proportional to the amount of dye incorporated by the different cell lines. Selective killing ratios were 70-1000 for 0.1 microM dye and light doses of 100-175 J/cm2 between 680 and 720 nm. MH - Biological Transport ; Carbocyanines/*METABOLISM ; Carcinoma/ *THERAPY ; Cell Line ; Dose-Response Relationship, Radiation ; Dyes/METABOLISM/*THERAPEUTIC USE ; Human ; In Vitro ; Mitochondria/*DRUG EFFECTS/METABOLISM ; Photochemotherapy/ *METHODS ; Quinolines/*METABOLISM ; Rhodamines/METABOLISM/ THERAPEUTIC USE ; Spectrum Analysis ; Support, Non-U.S. Gov't SO - Proc Natl Acad Sci USA 1986 Dec;83(24):9729-33 7 UI - 87075461 AU - Gluckman JL TI - Photodynamic therapy for early squamous cell cancer of the upper aerodigestive tract. AB - Photodynamic therapy (PDT) is a treatment modality that results in selective destruction of malignant cells by combining a photosensitizing agent (hematoporphyrin derivative), which is taken up by the cells, and a laser light. This therapeutic modality has been effectively used in managing cancers of the skin, bronchi and bladder. In the head and neck area, however, its use has been confined to the palliation of advanced lesions which have proved refractory to conventional therapy. While this is unquestionably a valid role, its true value, therapeutically, may be in the management of early cancers arising in the upper aerodigestive tract. At the University of Cincinnati, PDT has been used on a variety of such early cancers where, for a variety of reasons, conventional therapy was not possible. A preliminary experience with this modality in managing lesions of the larynx, oral cavity and oropharynx has demonstrated that this is a viable alternative. MH - Aged ; Carcinoma, Squamous Cell/*DRUG THERAPY ; Case Report ; Female ; Head and Neck Neoplasms/*DRUG THERAPY ; Human ; Male ; Middle Age ; *Photochemotherapy SO - Aust NZ J Surg 1986 Nov;56(11):853-7 8 UI - 87071645 AU - Romagnoli P ; Nardi F ; Tonelli F ; Bechi P TI - Histochemistry of small intestinal dysplasia in familial polyposis coli. AB - Biopsies of duodenal and ileal mucosa from patients with familial polyposis coli were studied. Areas of atypia were identified in the duodenum of six patients and in the ileum of three patients. Grade I atypia was characterized by crowding and elongation of cells and nuclei, a slight reduction in the number of goblet cells and the presence of a brush border; grade II atypia was further characterized by pseudo- or pluristratification of cells, a marked reduction in the number of goblet cells and the absence of a brush border. In areas of atypia, columnar cells often contained PAS-positive apical granules, which were diastase-resistant and unstained by alcian blue at any pH; the brush border, even where recognizable in haematoxylin-eosin and PAS-stained sections, was unreactive histochemically for alkaline phosphatase. Goblet cells were few in areas of atypia, but those present were regularly stained by PAS and alcian blue pH 2.6. Apical granules, similar in their histochemical characteristics to those observed in columnar cells in areas of atypia, were also found in otherwise normal mucosal areas, even in some patients with no overt areas of atypia in the biopsies studied. These granules have been interpreted as an abnormality, possibly preceding the onset of atypia. Hyperplasia of goblet cells, secreting mucins with the same staining pattern as in normal intestine, was found in some patients, either adjacent to areas of atypia or independent of them. Intervening columnar cells had a normal morphology, alkaline phosphatase-reactive brush borders and no sign of mucus secretion. This goblet cell hyperplasia has been interpreted as a reactive, nonspecific alteration of the mucosa. MH - Adolescence ; Adult ; Aged ; Alcian Blue/DIAGNOSTIC USE ; Biopsy ; Duodenum/*PATHOLOGY ; Histocytochemistry ; Human ; Hyperplasia ; Ileum/*PATHOLOGY ; Intestinal Mucosa/*PATHOLOGY ; Middle Age ; Periodic Acid-Schiff Reaction ; Polyposis Syndrome, Familial/ *PATHOLOGY ; Support, Non-U.S. Gov't SO - Virchows Arch [B] 1986;52(2):117-28 9 UI - 87065509 AU - Wharen RE Jr ; So S ; Anderson RE ; Laws ER Jr TI - Hematoporphyrin derivative photocytotoxicity of human glioblastoma in cell culture. AB - The parameters of hematoporphyrin-derivative (HpD) photocytotoxicity of human glioma cells in cell culture were studied to determine the optimum wavelength and power density of light, to investigate the influence of tissue oxygenation, and to evaluate the role of singlet oxygen and free radicals in producing cell death. Cell survival curves demonstrated a relative killing efficiency of 12:1 for violet compared to red light. Eighty joules of red light were required to produce 100% cell kill at an HpD concentration of 10 micrograms/ml, a level of HpD that has been quantitated in biopsies from patients receiving HpD photoradiation therapy. No difference in cellular killing efficiency was observed for power densities of red light varying from 10 to 100 mW/cm2. Cytotoxicity was directly related to O2 tension from 12 to 490 torr with a slight but consistent increase in cell kill at O2 tensions from 7 to 12 torr. Cytotoxicity was effectively quenched by beta-carotene, whereas mannitol had no effect, indicating that cytotoxicity is probably mediated via a mechanism involving singlet oxygen. This information may serve as a basis for more effective application of HpD photoradiation therapy and for designing protocols to study the efficacy of such therapy. MH - Cell Line ; Cell Survival/DRUG EFFECTS/RADIATION EFFECTS ; Glioma/ METABOLISM/*PATHOLOGY ; *Hematoporphyrin Photoradiation ; Human ; Light ; Oxygen/METABOLISM ; *Photochemotherapy SO - Neurosurgery 1986 Oct;19(4):495-501 10 UI - 87063198 AU - Gavil:an J ; Gavil:an C ; Tom:as MD TI - Methylene blue infusion for intraoperative identification of the parathyroid glands. AB - Identifying the parathyroid glands is of fundamental importance in thyroid and parathyroid surgery. We found that intravenous infusion of methylene blue was beneficial in intraoperative identification of the parathyroid glands in patients undergoing surgery for hyperparathyroidism as well as total and bilateral subtotal thyroidectomy. The technique is safe and easy to use, and it clearly reduces the operative time. We suggest that it be used routinely in thyroid and parathyroid surgery. MH - Adult ; Aged ; Female ; Graves' Disease/SURGERY ; Human ; Hyperparathyroidism/*SURGERY ; Intraoperative Period ; Male ; Methylene Blue/*DIAGNOSTIC USE ; Middle Age ; Thyroid Neoplasms/ SURGERY ; Thyroidectomy SO - Laryngoscope 1986 Dec;96(12):1389-90 11 UI - 87060278 AU - Sun D ; Aydelotte MB ; Maldonado B ; Kuettner KE ; Kimura JH TI - Clonal analysis of the population of chondrocytes from the Swarm rat chondrosarcoma in agarose culture. AB - Chondrocytes from the Swarm chondrosarcoma, a transplantable rat tumor, have been difficult to maintain in tissue culture for extended periods due to a time-dependent alteration of the culture to a more fibroblastic phenotype. This feature precluded the use of these cultures to examine chronic conditions that may affect cell metabolism, and the homogeneity or heterogeneity of the tumor cells within the culture population could not be examined. Use of suspension culture in agarose stabilized the chondrocyte phenotype, permitting long-term culture. Clones of tumor chondrocytes were established in agarose and were examined over 2-3 weeks for evidence that the cells were accumulating a proteoglycan-rich extracellular matrix, as determined by positive staining by Alcian blue, and were undergoing cell division. Nearly 90% of the cloned cells exhibited a prominent extracellular matrix by day 7 of culture and greater than 99% did so by day 14. Cell division did not occur to any great extent until days 6-7 of culture. After this lag, the cells appeared to undergo logarithmic growth, with a cell generation time of about 12 days. By 20 days of culture, between 80 and 90% of the initial clones contained multiple cells, indicating that nearly all the cells were in, or had entered, the cell cycle. These results suggest that the chondrocytes from the rat chondrosarcoma form a homogeneous cell population with respect to their ability to synthesize an extra-cellular matrix and divide. MH - Alcian Blue/DIAGNOSTIC USE ; Animal ; Cartilage/METABOLISM/ *PATHOLOGY/ULTRASTRUCTURE ; Cell Count ; Cell Separation ; Cells, Cultured ; Chondrosarcoma/METABOLISM/*PATHOLOGY/ULTRASTRUCTURE ; Clone Cells ; Culture Media ; Extracellular Matrix/METABOLISM ; Microscopy, Electron ; Rats ; Rats, Inbred Strains ; Sepharose ; Stains and Staining ; Support, U.S. Gov't, P.H.S. SO - J Orthop Res 1986;4(4):427-36 12 UI - 87058267 AU - Tanew A ; H:onigsmann H ; Ortel B ; Zussner C ; Wolff K TI - Nonmelanoma skin tumors in long-term photochemotherapy treatment of psoriasis. An 8-year follow-up study. AB - Two hundred ninety-seven long-term photochemotherapy (PUVA)-treated patients from an original cohort of 418 subjects reported in 1980 were reevaluated in a second follow-up in order to determine the risk of tumor development under long-term PUVA. Within an observation period of up to 8 years (mean, 63.1 months) six patients with squamous cell carcinomas and three with basal cell carcinomas were observed. Eight of the nine tumor patients had been exposed to potential carcinogens such as arsenic and/or ionizing radiation prior to PUVA treatment. Five with squamous cell carcinomas were skin type I or II; in four of the six patients with squamous cell carcinomas the tumors were located on unexposed skin areas. The mean cumulative ultraviolet A (UVA) dose in three of the six squamous cell carcinoma patients was three times as high as that in the group of nontumor patients. The other three squamous cell carcinoma patients had lower mean doses than nontumor patients, as did the three patients with basal cell carcinomas. Although the cumulative UVA dose may eventually turn out to be relevant for PUVA carcinogenesis, our present data do not sufficiently substantiate a correlation between cumulative UVA dose and squamous cell carcinoma formation in PUVA-treated patients. This report confirms that previous exposure to carcinogens appears to be the most important factor for nonmelanoma skin tumor formation in long-term PUVA patients. MH - Adult ; Aged ; Aging/PHYSIOLOGY ; Arsenic/PHARMACODYNAMICS ; Carcinoma, Basal Cell/PATHOLOGY ; Carcinoma, Squamous Cell/ CHEMICALLY INDUCED/PATHOLOGY ; Combined Modality Therapy ; Dose-Response Relationship, Radiation ; Etretinate/THERAPEUTIC USE ; Follow-Up Studies ; Human ; Melanoma/*CHEMICALLY INDUCED/ OCCURRENCE ; Methotrexate/PHARMACODYNAMICS ; Middle Age ; Psoriasis/COMPLICATIONS/*DRUG THERAPY ; *PUVA Therapy/ADVERSE EFFECTS ; Skin Neoplasms/*CHEMICALLY INDUCED/OCCURRENCE SO - J Am Acad Dermatol 1986 Nov;15(5 Pt 1):960-5 13 UI - 87056400 AU - Bickers DR TI - Photoradiation diagnosis and therapy. Dermatologic and photobiologic aspects. AB - Photoradiation with photosensitizing porphyrins offers a potentially useful approach to the diagnosis and treatment of certain human cancers. The mechanism of porphyrin photosensitivity as studied in cultured cells or in the skin has been studied thoroughly. Possible targets that have been identified include membranous cellular organelles, DNA, and the plasma membrane. Mediators of the reaction include reactive oxygen species, particularly singlet oxygen, that may elicit lipid peroxidation and the activation of complement. Further research is needed to identify photosensitizers with greater selectivity for malignant cells and to develop even better sources of radiant energy. MH - Animal ; Human ; Light/*DIAGNOSTIC USE ; *Phototherapy ; Porphyrins/*DIAGNOSTIC USE/TOXICITY ; Review ; *Skin Neoplasms/ DIAGNOSIS/THERAPY SO - Invest Radiol 1986 Nov;21(11):885-90 14 UI - 87051302 AU - Davies CD ; Western A ; Lindmo T ; Moan J TI - Changes in antigen expression on human FME melanoma cells after exposure to photoactivated hematoporphyrin derivative. AB - Exponentially growing melanoma cells of the line FME were incubated with hematoporphyrin derivative (HpD) for 1 and 18 h and subsequently exposed to light in the presence of HpD. Quantitative changes in the expression of the melanoma-associated surface antigen p250 recognized by the monoclonal antibody 9.2.27 were studied by flow cytometry. Treatment with HpD and light resulted in no immediate changes in the antigen expression. However, a few hours after light exposure a significant reduction in antigen expression was observed. For cells incubated with HpD for 1 h, the minimum expression of the antigen was observed 6 h after the irradiation, and the duration of the reduced expression was almost dose independent. On the other hand, the duration of the reduced antigen expression increased strongly with light dose for cells incubated with HpD for 18 h. In both cases antigen expression decreased exponentially with the product of drug concentration and light dose, indicating that there is no rapid mechanism by which the cells can repair the damage which leads to reduced antigen expression. Days were needed before the cells expressed a normal level of the antigen. A slight overshoot of the level of antigen expression above that for untreated cells was observed 2-5 days after light exposure depending on the incubation conditions with HpD and the light dose. At a given cell survival level (greater than 0.1), the decrease in antigen expression was more pronounced on cells incubated with HpD for 1 h than on cells incubated with the drug for 18 h. MH - Antigens, Neoplasm/*ANALYSIS ; Antigens, Surface/*ANALYSIS ; Cell Line ; Hematoporphyrins/*PHARMACODYNAMICS ; Human ; Melanoma/DRUG THERAPY/*IMMUNOLOGY ; Neoplasm Proteins/*ANALYSIS ; Photochemotherapy ; Proteins/BIOSYNTHESIS ; Support, Non-U.S. Gov't SO - Cancer Res 1986 Dec;46(12 Pt 1):6068-72 15 UI - 87048756 AU - Ceckler TL ; Bryant RG ; Penney DP ; Gibson SL ; Hilf R TI - 31P-NMR spectroscopy demonstrates decreased ATP levels in vivo as an early response to photodynamic therapy. AB - 31P-Nuclear magnetic resonance was used to monitor in situ phosphorus containing compounds in mammary tumors after photodynamic therapy, consisting of administration of hematoporphyrin derivative followed by photoradiation of the lesion. A rapid decrease in ATP along with an increase in Pi resonance intensities was observed. The beta-ATP/Pi ratio decreased by 1 hour, dropping in 2 to 8 hours to 0 to 20 percent of that found prior to photoradiation. Disrupted cells and pycnotic nuclei were observed 48 to 72 hours after photoradiation to a depth of approximately 5 mm. Together with previous studies in vitro, reduction in tumor ATP levels appears to be an early biochemical response to photodynamic therapy. MH - Adenosine Triphosphate/*ANALYSIS ; Animal ; Female ; Mammary Neoplasms, Experimental/ANALYSIS/*DRUG THERAPY/PATHOLOGY ; Nuclear Magnetic Resonance/*DIAGNOSTIC USE ; Phosphates/ANALYSIS ; *Photochemotherapy ; Rats ; Rats, Inbred F344 ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Biochem Biophys Res Commun 1986 Oct 15;140(1):273-9 16 UI - 87045937 AU - Caldwell CW ; Taylor HM TI - A rapid, no-wash technic for immunophenotypic analysis by flow cytometry. AB - With the advent of fluorochrome-labeled monoclonal antibodies, it has now become possible to eliminate the removal of unbound antibodies during immunophenotypic analysis of lymphoid cells by flow cytometry. Suspensions of mononuclear cells from healthy controls and fluoresceinated monoclonal antibodies may be introduced directly into the flow cytometer. The percentage of nonwashed antibody-positive cells from healthy controls as compared with the conventional technic of cell washing shows a good correlation. However, the correlation is not as good when the lymphocytes from certain classes of diseased patients are analyzed. It appears that excessive washing in fact produces erroneous results for certain markers with cells from diseased patients. The no-wash technic is also applicable to various combinations of dual-fluorescence monoclonal antibody staining. This technic substantially reduces the processing time and, more importantly, eliminates some of the cell losses and artifacts induced during the process of cell washing. The shortened processing time has allowed rapid responsiveness in certain urgent clinical situations. MH - Acquired Immunodeficiency Syndrome/BLOOD ; Adult ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Autoimmune Diseases/BLOOD ; Female ; Flow Cytometry ; Fluoresceins/DIAGNOSTIC USE ; Human ; Infection/ BLOOD ; Leukemia/BLOOD ; Lymphocytes/*IMMUNOLOGY ; Male SO - Am J Clin Pathol 1986 Nov;86(5):600-7 17 UI - 87042329 AU - Dougherty TJ TI - Photosensitization of malignant tumors. AB - Photodynamic therapy is a new, experimental method of treating malignant tumors by utilizing the relatively selective retention of the photosensitizer (hematoporphyrin derivative or dihematoporphyrin ether) and its ability to elicit an efficient photodynamic reaction upon activation with penetrating viable light. Application of this therapy to tumors in the bronchus, bladder, skin, and several other sites has demonstrated both safety and efficacy, even in advanced cases. Eradication of early stage tumors in the bronchus and bladder has been demonstrated. Selective retention of the photosensitizers in tumors is apparently related to the relatively large size of the aggregates of these materials causing phagocytosis by reticuloendothelial cells as well as preventing rapid clearance from tumor interstitial fluid and subsequent uptake in lipophylic components of cells. Upon light activation, generally delivered from lasers via fiber optics, the sensitizers generate singlet oxygen, the apparent cytotoxic agent, causing both vascular damage and injury to tumor cells. MH - Animal ; Female ; Hematoporphyrin Photoradiation/ADVERSE EFFECTS ; Hematoporphyrins/ADVERSE EFFECTS/PHARMACODYNAMICS/THERAPEUTIC USE ; Human ; Male ; Neoplasms/*DRUG THERAPY ; Neoplasms, Experimental/*DRUG THERAPY ; *Photochemotherapy/ADVERSE EFFECTS ; Review ; Thermoluminescent Dosimetry SO - Semin Surg Oncol 1986;2(1):24-37 18 UI - 87035932 AU - Hemstreet GP 3d ; West SS ; Cook MS TI - Improved nuclear fluorescence screening technique. AB - Three separate screening studies have tested the sensitivity and specificity of quantitative fluorescence image analysis for detecting bladder cancer. Nuclear intensity (NI) measurements of fluorescent dye-stained epithelial cells from voided urine and bladder washings were compared with routine Papanicolaou (Pap) cytology results, and findings were verified against pathological biopsy diagnoses. The NI cytology method detected the pathologically confirmed tumors earlier and with greater specificity than did conventional cytology. In the study of 140 clinically symptomatic patients in Oklahoma, the NI method detected 91.1% (31 of 34) of the pathologically confirmed grades 1 and 2 tumors and 100% of 18 grades 3 and 4 tumors. Pap cytology detected only 47% (16 of 34) of low-grade and 78% (14 of 18) of high-grade tumors. Comparable results were obtained in a study of symptomatic patients in Mississippi and the method has been employed in the screening of a high-risk occupationally exposed cohort in Georgia. MH - Acridine Orange ; Bladder Neoplasms/CHEMICALLY INDUCED/*DIAGNOSIS ; Cell Separation ; Flow Cytometry ; Fluorescence ; Human ; Occupational Diseases/CHEMICALLY INDUCED/*DIAGNOSIS ; Risk ; Support, U.S. Gov't, P.H.S. ; United States ; 2-Naphthylamine/ TOXICITY SO - J Occup Med 1986 Oct;28(10):1004-10 19 UI - 87033893 AU - Wiskemann A ; Sturm E ; Klehr NW TI - Fluorescent lighting enhances chemically induced papilloma formation and increases susceptibility to tumor challenge in mice. AB - To study whether fluorescent lighting at work might increase carcinogenesis, hairless mice were exposed to a bank of six 36 W standard fluorescent lamps (neutral-white) every workday for 8 h at an illuminance level of 1,000 lx. For comparison, other mice were exposed to UVB radiation or to simulated solar radiation. In experiment A the animals were irradiated for 6 weeks prior to the application of 7,12-dimethyl-benzanthracene once and--following an interval of 2 days--for 10 weeks after DMBA application. The number of blue nevi and papillomas was enhanced by exposure to all spectra 10 weeks after chemical tumor induction. In experiment B the animals were irradiated for 6 weeks prior to the transplantation of UV-induced fibrosarcoma cells from syngeneic mice into the dorsal and ventral skin. Within the following 4 months fibrosarcoma developed in the dorsal skin exposed to the fluorescent lighting and to the UVB radiation, as well as in the non-irradiated ventral skin of 10-20% of the mice. The results suggest that fluorescent lighting as used in certain work environments may increase carcinogenesis caused by other factors. MH - Animal ; Female ; Fibrosarcoma/IMMUNOLOGY ; *Fluorescence ; Immune Tolerance ; Mice ; Mice, Inbred HRS ; Neoplasm Transplantation ; Neoplasms, Radiation-Induced/IMMUNOLOGY ; Papilloma/*ETIOLOGY ; Skin Neoplasms/*ETIOLOGY/IMMUNOLOGY ; Ultraviolet Rays/ADVERSE EFFECTS ; 9,10-Dimethyl-1,2-Benzanthracene SO - J Cancer Res Clin Oncol 1986;112(2):141-3 20 UI - 87031150 AU - Baran R ; Brun P TI - Photoonycholysis induced by the fluoroquinolones pefloxacine and ofloxacine. Report on 2 cases. AB - Pefloxacine and ofloxacine are 2 new synthetic fluoroquinolones which should be added to the list of drugs inducing photoonycholysis. Two cases are reported. MH - Aged ; Aged, 80 and over ; Case Report ; Dermatitis Medicamentosa/ *ETIOLOGY ; Human ; Male ; Mycosis Fungoides/COMPLICATIONS/DRUG THERAPY ; Nail Diseases/*CHEMICALLY INDUCED ; Norfloxacin/ *ANALOGS & DERIVATIVES/ADVERSE EFFECTS ; Oxazines/*ADVERSE EFFECTS ; Photosensitivity Disorders/*CHEMICALLY INDUCED ; PUVA Therapy/ADVERSE EFFECTS SO - Dermatologica 1986;173(4):185-8 21 UI - 87031143 AU - Nakagawa T ; Nishimoto M ; Takaiwa T TI - Disseminated epidermolytic acanthoma revealed by PUVA. AB - Disseminated epidermolytic acanthoma was observed during PUVA therapy in a patient with S:ezary syndrome. The majority of the lesions resolved within 5 months after the cessation of therapy. This circumstantial evidence together with our knowledge of the effects of PUVA suggest that the skin lesions were revealed by topical photochemotherapy. MH - Case Report ; Human ; Male ; Middle Age ; Papilloma/*ETIOLOGY ; PUVA Therapy/*ADVERSE EFFECTS ; Sezary Syndrome/*COMPLICATIONS/ THERAPY ; Skin Neoplasms/*ETIOLOGY SO - Dermatologica 1986;173(3):150-3 22 UI - 87030953 AU - Pandiella-Alonso A ; Malgaroli A ; Vicentini LM ; Meldolesi J TI - Early rise of cytosolic Ca2+ induced by NGF in PC12 and chromaffin cells. AB - A rise of cytosolic Ca2+ is induced by NGF in rat pheochromocytoma PC12 and bovine chromaffin cells investigated (both in suspension and while attached to polyornithine-coated glass slides) by fluorescence techniques (with quin-2 and fura-2). The effect of NGF on [Ca2+]i is delayed (30-40 s of lag phase), slow (t1/2 = 40 s), relatively small (+50-75%) and persistent (over 10 min). It is due to Ca2+ influx (requires extracellular Ca2+ greater than 10 microM) through a pathway different from the voltage-gated Ca2+ channel, possibly accompanied by intracellular Ca2+ redistribution, and might play a messenger role in NGF action. MH - Adrenal Gland Neoplasms/METABOLISM ; Aminoquinolines/DIAGNOSTIC USE ; Animal ; Benzofurans/DIAGNOSTIC USE ; Calcium/*METABOLISM ; Cattle ; Chromaffin System/*METABOLISM ; Cytosol/*METABOLISM ; Epidermal Growth Factor-Urogastrone/PHARMACODYNAMICS ; Fluorescent Dyes/DIAGNOSTIC USE ; Nerve Growth Factors/ *PHARMACODYNAMICS ; Pheochromocytoma/METABOLISM ; Rats ; Support, Non-U.S. Gov't SO - FEBS Lett 1986 Nov 10;208(1):48-51 23 UI - 87030444 AU - Benson RC Jr TI - Integral photoradiation therapy of multifocal bladder tumors. AB - Focal and diffuse hematoporphyrin derivative (HpD) photodynamic therapy was used for the treatment of resistant transitional cell carcinoma in situ (Tis) in 30 patients. Patients were given HpD intravenously followed by either focal light irradiation (630 nm) or diffuse bladder irradiation via a light bulb fiber. The light source was an argon ion pumped dye laser circulating rhodamine B dye. All patients were followed with periodic cystoscopic examinations, bladder biopsies, and urine cytologic examinations. All of the 15 patients who underwent focal therapy had biopsy and cytologic evidence of disappearance of the lesion in the treated area at the 3-month follow-up cystoscopic examination. Eight patients have experienced one or more recurrent lesions either in the treated area or in distant areas, and in each the recurrence was successfully treated with HpD photodynamic therapy. Eight of the 11 patients with diffuse Tis have returned for their 3-month follow-up evaluation, and all demonstrated disappearance of tumor (3 of these 8 patients have subsequently developed focal recurrent Tis). Four patients had diffuse Tis plus Ta lesions (2 patients) or T2 lesions (2 patients), and all had disappearance of the Tis, but persistence of the Ta or T2 disease. We conclude that HpD photodynamic therapy appears effective in the treatment of resistant Tis. MH - Aged ; Bladder Neoplasms/SURGERY/*THERAPY ; Carcinoma, Transitional Cell/SURGERY/THERAPY ; Cystoscopy ; Female ; Hematoporphyrins/*THERAPEUTIC USE ; Human ; Laser Surgery ; Male ; Middle Age ; *Phototherapy SO - Eur Urol 1986;12 Suppl 1:47-53 24 UI - 87029540 AU - Kato H ; Konaka C ; Kawate N ; Shinohara H ; Kinoshita K ; Noguchi M ; Ootomo S ; Hayata Y TI - Five-year disease-free survival of a lung cancer patient treated only by photodynamic therapy. AB - A 59-year-old woman had suffered cough and sputum production for several months. Chest x-ray film findings were negative, but sputum cytology yielded a diagnosis of squamous cell carcinoma. This stage Ia lung cancer in the right upper lobe bronchus was deemed inoperable due to poor cardiopulmonary function. She was treated by photodynamic therapy in February 1981, involving intravenous injection of hematoporphyrin derivative and fiberoptic endoscopically delivered argon dye laser light. She responded well to the treatment and the lesion disappeared within a week. At present, she is apparently disease-free more than five years after treatment. This is the first known report of five-year disease-free survival following treatment of a malignant lesion by PDT only. MH - Carcinoma, Squamous Cell/*DRUG THERAPY ; Case Report ; Female ; Follow-Up Studies ; Human ; Lung Neoplasms/*DRUG THERAPY ; Middle Age ; *Photochemotherapy ; Prognosis ; Support, Non-U.S. Gov't SO - Chest 1986 Nov;90(5):768-70 25 UI - 87025944 AU - Teicher BA ; Holden SA ; Jacobs JL ; Abrams MJ ; Jones AG TI - Intracellular distribution of a platinum-rhodamine 123 complex in cis-platinum sensitive and resistant human squamous carcinoma cell lines. AB - The platinum(II) tetrachlorodianion and two molecules of rhodamine-123 associate to form a neutral tight ion pair. To examine the intracellular fate of this ionic complex, the levels of uptake after a 1-hr exposure to a 100 microM concentration of each component of the complex, the complex itself and cis-diamminedichloroplatinum(II) (CDDP) were measured in SCC-25 cells. The uptake of Pt(Rh-123)2 was measured by two independent methods: fluorescence and 195mPt gamma-counting. There was excellent agreement between these two methods as to the amount of Pt(Rh-123)2 which was taken up by the cells, indicating that the Pt(Rh-123)2 is probably entering cell intact. Association with Rh-123 increased the amount of platinum which entered the cells by about 70-fold compared to CDDP and increased by about 700-fold the amount of platinum which entered the cells compared to K2PtCl4. The subcellular distributions of Pt(Rh-123)2, Rh-123, CDDP and K2PtCl4 were also examined. When measured by fluorescence or 195mPt gamma-counting, 40-54% of the Pt(Rh-123)2 was in the nuclei of the SCC-25 or SCC-25/CP cells and 27-35% was in the cytosol of the cells. There was excellent agreement between the findings of fluorescence and 195mPt gamma-counting regarding the amount of Pt(Rh-123)2 in each of the subcellular fractions immediately after incubation with the drug and over the time course of observation after drug removal, indicating that the Pt(Rh-123)2 is probably remaining largely intact intracellularly. On a per mg protein basis, there was about a 55-fold greater amount of platinum in the nuclei of the SCC-25 cells exposed to Pt(Rh-123)2 compared to cells exposed to CDDP. In the SCC-25/CP cells, there was about 258-fold greater platinum in the nuclei of cells exposed to Pt(Rh-123)2 than those exposed to CDDP because CDDP was taken up to a much lesser extent by the SCC-25/CP cells. Association of Rh-123 with potassium tetrachlorodianion forms a tight ion pair, which enters cells in relatively high amounts and is selectively concentrated in the nuclei of the cells. MH - Antineoplastic Agents/*METABOLISM ; Carcinoma, Squamous Cell/DRUG THERAPY/*METABOLISM ; Cell Line ; Cisplatin/*PHARMACODYNAMICS ; Drug Resistance ; Fluorescence ; Human ; Platinum/*METABOLISM ; Radiation-Sensitizing Agents/*METABOLISM ; Rhodamines/*METABOLISM ; Xanthenes/*METABOLISM SO - Biochem Pharmacol 1986 Oct 1;35(19):3365-9 26 UI - 87022053 AU - Nennesmo I ; Kristensson K TI - Effects of retrograde axonal transport of Ricinus communis agglutinin I on neuroma formation. AB - The lectin Ricinus communis agglutinin I (RCAI) was topically applied to transected mouse sciatic nerve or to neuromas formed 2 months after a nerve transection. Fluorochrome-labelled ricin was transferred to the corresponding dorsal root ganglia where it accumulated selectively in the nerve cells, apparently as a consequence of retrograde axonal transport. The ricin caused an almost total loss of the dorsal root ganglionic neurons and, consequently, could prevent formation of neuromas or eliminate an already existing neuroma. The hybrid toxin wheat germ agglutinin (WGA)-ricin-A chain caused no apparent increased sensitivity for neuronal destruction. The drugs doxorubicin and ethidium bromide, similarly applied, labelled satellite and other cells in addition to neurons in the ganglia, and caused only a moderate neuronal loss. The presented method to eliminate neuromas by selectively destroying sensory neurons may provide a means to study pain mechanisms in neuromas. MH - Animal ; *Axoplasmic Flow ; Doxorubicin/PHARMACODYNAMICS ; Ethidium/PHARMACODYNAMICS ; Fluoresceins/DIAGNOSTIC USE ; Ganglia, Spinal/DRUG EFFECTS/METABOLISM ; Lectins/*METABOLISM/ PHARMACODYNAMICS ; Male ; Mice ; Mice, Inbred Strains ; Neuroma/ *DRUG THERAPY/ETIOLOGY ; Ricin/PHARMACODYNAMICS ; Sciatic Nerve/ DRUG EFFECTS/METABOLISM ; Support, Non-U.S. Gov't ; Thiocyanates/ DIAGNOSTIC USE ; Wheat Germ Agglutinins/PHARMACODYNAMICS SO - Acta Neuropathol (Berl) 1986;70(3-4):279-83 27 UI - 87013763 AU - Carruth JA TI - Photodynamic therapy: the state of the art. AB - Photodynamic therapy is a new and exciting treatment modality for many forms of localised malignant disease. A considerable amount of laboratory and clinical research has been carried out using the tumour sensitiser haematoporphyrin derivative activated by red light at a wavelength of 630 n commonly produced by either an argon/dye laser or a pulsed gold vapour laser. It appears certain that continuing research will produce better tumour sensitisers activated by different wavelengths of light, but it will be several years before any new drug/light combination is ready for clinical trials. This paper presents an overview of the current situation and a summary of some of the exciting results that are being obtained in clinical trials throughout the world. MH - Clinical Trials ; *Hematoporphyrin Photoradiation ; Human ; Lasers/*THERAPEUTIC USE ; Neoplasms/DIAGNOSIS/*DRUG THERAPY/ METABOLISM ; *Photochemotherapy SO - Lasers Surg Med 1986;6(4):404-7 28 UI - 87013735 AU - Werkhaven J ; Harris DM ; Krol G ; Hill JH TI - Light dosimetry in animal models: application to photodynamic therapy in otolaryngology. AB - Photodynamic therapy (PDT) for treatment of head and neck cancer uses a photoactive compound that is illuminated with 630 nm (red) light. The effectiveness of PDT depends on the penetration of light into tissue that is both tissue and wavelength dependent. The characterization of the optical properties of an animal oral mucosa and skin has been done to determine the amount of light below these tissues available to be used for photodynamic therapy. The tissue absorbance of visible light from 400 nm to 700 nm has been determined in vitro for hamster check pouch mucosa and for athymic mouse skin. The pattern of absorbance is similar for both tissues and demonstrates greater transmission at the longer wavelengths. The diffuse transmittance of light in vivo for these animal models was measured with an interstitial fiberoptic probe. At 630 nm the diffuse transmittance for nude mouse skin averages 10% of the incident light energy, and that for the hamster mucosa almost 50% of the incident light energy. MH - Animal ; Hamsters ; Head and Neck Neoplasms/DRUG THERAPY ; In Vitro ; *Light ; Mesocricetus ; Mice ; Mouth Mucosa/*RADIATION EFFECTS ; Optics ; Photochemotherapy ; Radiation Dosage ; Skin/ *RADIATION EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. SO - Laryngoscope 1986 Oct;96(10):1058-61 29 UI - 87013399 AU - Benson RC Jr TI - Laser photodynamic therapy for bladder cancer. AB - The lack of a tumor-localization aid for transitional cell carcinoma of the bladder and the known cytotoxic effect of light-activated intracellular hematoporphyrin derivative (HpD) prompted the initiation of a trial of HpD photodynamic therapy in patients with focal and diffuse bladder cancer. An argon-ion, pumped-dye laser was used as a source of red light. In 15 patients with focal disease and circumscribed treatment, 3-month follow-up cystoscopic examination showed disappearance of the lesions, but the subsequent recurrence rate seemed high. Therefore, whole-bladder HpD photodynamic therapy was administered to 14 patients with diffuse resistant carcinoma in situ. Three of these patients had focal recurrent disease. The only adverse effects of therapy were cutaneous photosensitivity and bladder irritability. HpD seems to be a good tumor-localizing aid for transitional cell carcinoma of the bladder, and HpD photodynamic therapy effectively destroys this type of carcinoma. MH - Antineoplastic Agents/*THERAPEUTIC USE ; Argon ; Bladder Neoplasms/*DRUG THERAPY ; Carcinoma in Situ/DRUG THERAPY ; Carcinoma, Transitional Cell/*DRUG THERAPY ; Cystoscopy ; Fiber Optics ; Hematoporphyrins/*THERAPEUTIC USE ; Human ; Lasers ; Neoplasm Recurrence, Local ; Photochemotherapy/INSTRUMENTATION/ *METHODS ; Physics SO - Mayo Clin Proc 1986 Nov;61(11):859-64 30 UI - 87003001 AU - Leiner MJ ; Schaur RJ ; Desoye G ; Wolfbeis OS TI - Fluorescence topography in biology. III: Characteristic deviations of tryptophan fluorescence in sera of patients with gynecological tumors. AB - The near-ultraviolet region of the total fluorescence (excitation-emission matrix) of human serum reflects essentially the fluorescence of protein-bound tryptophan. We examined topographically the tryptophan fluorescence of human serum. In comparison with fluorescence topograms from sera of healthy donors, sera of patients with gynecological malignancies showed significantly different patterns of tryptophan fluorescence, the major deviations being at 325 and 365 nm. In healthy donors, the tryptophan fluorescence intensity at 365 nm, expressed as percent of the maximum fluorescence intensity (i.e., at 337 nm) varied little, but was markedly lower for sera from patients with malignancies. We found no clear correlation between the extent of the fluorescence deviations and the relative concentration of the protein fractions as determined by electrophoresis. Furthermore, we could rule out inflammation in tumor patients as an explanation for this effect. MH - Blood Proteins/METABOLISM ; Cervix Neoplasms/BLOOD ; Female ; *Fluorescence ; Genital Neoplasms, Female/*BLOOD ; Human ; Spectrometry, Fluorescence ; Support, Non-U.S. Gov't ; Tryptophan/ *BLOOD ; Uterine Neoplasms/BLOOD SO - Clin Chem 1986 Oct;32(10):1974-8 31 UI - 87002166 AU - Kessel D ; Thompson P TI - Photosensitization of leukemia L1210 cells with diaziquone. AB - Exposure of leukemia L1210 cells in culture to the drug diaziquone resulted in inhibition of incorporation of labeled thymidine into nucleic acid and loss of cell viability. These effects were markedly potentiated by irradiation of cells previously exposed to diaziquone in culture. This result shows that diaziquone can catalyze phototoxicity; the action spectrum of the drug may limit clinical applications of this phenomenon. MH - Animal ; Aziridines/*PHARMACODYNAMICS ; Azirines/ *PHARMACODYNAMICS ; Cell Cycle/DRUG EFFECTS ; Cell Survival/DRUG EFFECTS ; Cell-Free System ; Dose-Response Relationship, Radiation ; Leukemia L1210/*DRUG THERAPY ; Mice ; Phototherapy/ *METHODS ; Spectrum Analysis ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Nov;46(11):5587-8 32 UI - 87002106 AU - Larsen AK ; Paoletti J ; Belehradek J Jr ; Paoletti C TI - Uptake, cytofluorescence, and cytotoxicity of oxazolopyridocarbazoles (amino acid-ellipticine conjugates) in murine sarcoma cells. AB - The uptake, cytofluorescence, and cytotoxicity of elliptinium (NMHE) and a series of fluorescent oxazolopyridocarbazoles [amino acid-ellipticine conjugates (AA-NMHE)] were studied in murine sarcoma cells. For all these drugs, the uptake was rapid, directly proportional to the drug concentration, and unaffected by metabolic inhibitors which is consistent with a diffusion mechanism. By 4 h, the intracellular concentration of NMHE exceeded the external drug concentration by about 100 times; this suggests that the toxicity of NMHE is not, as previously assumed, limited by its transport across tumor cell membranes. Conjugation of NMHE with aliphatic amino acids increased the cellular uptake 5- to 7-fold. Cellular exposure to AA-NMHE conjugates resulted in the appearance of granular cytoplasmic fluorescence which was readily translocated to the nucleus upon continued exposure to fluorescent light. The cytotoxicity of the AA-NMHE conjugates (drug concentration required to reduce colony formation by 63% on the exponential part of the survival curve = 3-14 microM) was less than of NMHE (drug concentration required to reduce colony formation by 63% on the exponential part of the survival curve = 0.7 microM) as shown by colony formation following 4 h drug exposure. In contrast, the isoleucine-NMHE conjugate was the most cytotoxic compound (drug concentration required to reduce colony formation by 63% on the exponential part of the survival curve = 0.045 microM) when the drug exposure period was extended to 8 days. The general lower toxicity of the AA-NMHE conjugates is likely due to loss of the phenolic character of the NMHE moiety; therefore, attempts to link NMHE to amino acids remain attractive but will have to be done without affecting the 9-hydroxy group of NMHE. MH - Alkaloids/*METABOLISM ; Amino Acids/*METABOLISM ; Animal ; Antineoplastic Agents/*METABOLISM ; Cell Line ; Cell Survival/ DRUG EFFECTS ; Dose-Response Relationship, Drug ; Ellipticines/ *METABOLISM/PHARMACODYNAMICS ; Fluorescence ; Sarcoma, Experimental/*METABOLISM ; Structure-Activity Relationship ; Support, Non-U.S. Gov't ; Time Factors SO - Cancer Res 1986 Oct;46(10):5236-40 33 UI - 87002056 AU - Trimpe KL ; Zwilling BS TI - Modulation of B16 melanoma antigen expression by lymphokines and dimethyl sulfoxide. AB - We have developed two monoclonal antibodies, designated 152 E12 D7 and 153 C7 A6, which have reactivity with cell surface antigens expressed on the B16 mouse melanoma. These monoclonal antibodies are produced by hybridomas resulting from the fusion of splenocytes taken from C57BL/6 mice bearing the B16-F10 tumor. The monoclonal antibodies are of the immunoglobulin M class and have been shown to react with three variants of the B16 and another mouse melanoma but no normal murine tissues. Exposure of B16 melanoma cells to a concanavalin A stimulated spleen cell mixed lymphokine preparation (LK) and to dimethyl sulfoxide (DMSO) enhanced the expression of the cell surface antigens recognized by these monoclonal antibodies. The cultures stimulated with LK or DMSO contained a greater proportion of cells expressing the antigens recognized by monoclonal antibodies 152 E12 D7 and 153 C7 A6 than did unstimulated controls. In addition to increasing the proportion of antigen-positive cells, the antigen expression per cell, as measured by fluorescence intensity, was substantially increased following exposure to LK and DMSO. The effects of treatment with LK or DMSO were apparent after 24 h exposure but did not persist after the agent was removed from the cultures, suggesting that the enhancement of antigen expression was a transient event rather than a permanent differentiation of the melanoma cells. MH - Animal ; Antibodies, Monoclonal/IMMUNOLOGY ; Antigens, Neoplasm/ *ANALYSIS ; Antigens, Surface/*ANALYSIS ; Cell Line ; Dimethyl Sulfoxide/*PHARMACODYNAMICS ; Fluorescence ; Lymphokines/ *PHARMACODYNAMICS ; Male ; Melanoma/*IMMUNOLOGY ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Proteins/*ANALYSIS/ BIOSYNTHESIS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Oct;46(10):4953-9 34 UI - 87001898 AU - Lam S ; M:uller NL ; Miller RR ; Kostashuk EC ; Szasz IJ ; LeRiche JC ; Lee-Chuy E TI - Predicting the response of obstructive endobronchial tumors to photodynamic therapy. AB - To investigate the usefulness of bronchoscopic examination, computerized tomography (CT), and radionuclide quantitative ventilation-perfusion lung scan to determine the response of patients with obstructive endobronchial tumors to photodynamic therapy (PDT), the findings in 24 patients treated with PDT were analyzed. PDT was found to be most effective when the tumor was bronchoscopically polypoid in appearance, with little or no submucosal invasion or peribronchial extension seen on CT scans. With increasing submucosal and/or peribronchial extension, the immediate response to treatment was poorer. Patients who had 50% or more of the airway obstruction due to mucosal tumor had no evidence of local tumor recurrence for a median interval of 22 weeks after treatment. In patients with predominant submucosal and/or peribronchial tumor, the duration of response was 7 weeks. Response to treatment did not correlate with the degree of airway obstruction. CT provided valuable information regarding the extent of the peribronchial involvement and airway distortion, which was often underestimated by bronchoscopy alone. Absent perfusion or reduction of regional perfusion out of proportion to ventilation on scintigraphy in the involved lung zone was found to be associated with extensive peribronchial involvement and a poor outcome. The authors conclude that the addition of CT and radionuclide quantitative ventilation-perfusion lung scan to bronchoscopic examination is useful in predicting the response of patients with obstructive endobronchial tumors to PDT. MH - Adult ; Aged ; Airway Obstruction/*DRUG THERAPY ; Bronchial Neoplasms/DIAGNOSIS/*DRUG THERAPY ; Bronchoscopy ; Case Report ; Female ; *Hematoporphyrin Photoradiation ; Human ; Male ; Middle Age ; *Photochemotherapy ; Support, Non-U.S. Gov't ; Time Factors ; Tomography, X-Ray Computed SO - Cancer 1986 Nov 15;58(10):2298-306 35 UI - 87000776 AU - Patrice T ; Praloran V ; Le Bodic MF ; Le Bodic L TI - Experimental aspects of in vitro and in vivo photochemotherapy. AB - The selectivity of in vitro photodynamic reactions and the in vivo effects induced by PRT, whether the irradiation is applied interstitially or externally, still remains unclear. In vitro studies were performed using leukemic cell lines and syngeneic normal hemopoietic progenitors. For these, cells incubated with hematoporphyrin derivative (HPD) and non-incubated cells were irradiated with an argon laser. Data were obtained as the count of cell colonies found after a 7-day incubation period on semi-solid collagen gel medium. In vivo studies employed the HT 29 tumor model grafted into nude mice. Both animals injected with HPD and non-infected controls were irradiated with a dye laser pumped by an argon laser (Coherent) using a 400 micron optic fiber located either at a distance of 65 mm from the skin or inserted into the tumor. The temperature increase occurring during PRT was measured using non-absorbing thermocouples. In vitro, after HPD treatment and argon irradiation leukemic cells showed a greater phototoxicity (greater than 2 log10) than did the normal cells (0.25 log10). In vivo, when the heat rise is very similar (less than 4 degrees C) in both the tissues irradiated externally and those irradiated interstitially after HPD injection, histological examination of these did not reveal any quantitative differences (90% of tumor mass). These results are discussed. MH - Animal ; Body Temperature ; Cell Line ; Colonic Neoplasms/DRUG THERAPY ; *Hematoporphyrin Photoradiation/ADVERSE EFFECTS ; Hematoporphyrins/THERAPEUTIC USE ; Human ; Lasers/THERAPEUTIC USE ; Leukemia L1210/DRUG THERAPY ; Mice ; Mice, Inbred DBA ; Necrosis ; Neoplasm Transplantation ; Neoplasms, Experimental/ *DRUG THERAPY/PATHOLOGY ; *Photochemotherapy/ADVERSE EFFECTS ; Support, Non-U.S. Gov't SO - Biochimie 1986 Jun;68(6):923-6 36 UI - 87000775 AU - Brault D ; Vever-Bizet C ; Dellinger M TI - Fundamental aspects in tumor photochemotherapy: interactions of porphyrins with membrane model systems and cells. AB - Some molecular aspects underlying photochemotherapy and photodiagnosis of tumors with porphyrins are reviewed. The nature of the clinically used photosensitizer HpD is first presented along with structures of molecules found to be efficient in vitro. The possible role of pH in the preferential retention of dicarboxylic porphyrins by tumors is discussed in light of results obtained with membrane models. The uptake of dicarboxylic porphyrins by cells most likely involves passive mechanisms. Cell photoinactivation using a purified porphyrin does not depend upon the incubation time but only on the intracellular concentration of the dye. This likely reflects a poor specificity of the photoinactivation processes with regard to the cellular localization of the dye. The properties which should be presented by more efficient photosensitizers are discussed. MH - Blood Proteins/METABOLISM ; Cell Membrane/*METABOLISM ; Cells, Cultured ; Chemistry ; Comparative Study ; Cytoplasm/METABOLISM ; Dyes/THERAPEUTIC USE ; Hematoporphyrins/DIAGNOSTIC USE/ISOLATION & PURIFICATION/METABOLISM/THERAPEUTIC USE ; Human ; Hydrogen-Ion Concentration ; Kinetics ; Lipid Bilayers/METABOLISM ; Liposomes/ METABOLISM ; Macromolecular Systems ; Neoplasms/DIAGNOSIS/*DRUG THERAPY/METABOLISM ; *Photochemotherapy ; Porphyrins/DIAGNOSTIC USE/*METABOLISM/THERAPEUTIC USE ; Review ; Structure-Activity Relationship ; Support, Non-U.S. Gov't SO - Biochimie 1986 Jun;68(6):913-21 37 UI - 87000771 AU - Young AR TI - Aspects of psoralen phototumorigenesis with emphasis on the possible role of tumour promotion. AB - 8-Methoxypsoralen in combination with UVA radiation (PUVA) is carcinogenic in mice and probably so in man. PUVA is genotoxic and so has tumour initiation potential. Some evidence suggests that PUVA has other biological effects which may be equated with tumour promotion. Thus, the use of a two-stage model, similar to that of chemical carcinogenesis, may be a useful experimental approach for the further understanding of PUVA carcinogenesis. MH - Animal ; Cross-Linking Reagents ; DNA/METABOLISM ; Methoxsalen/ ADVERSE EFFECTS ; Neoplasms, Experimental/*CHEMICALLY INDUCED/ METABOLISM ; Ornithine Decarboxylase/METABOLISM ; Oxygen/ METABOLISM ; Photochemistry ; Psoralens/*ADVERSE EFFECTS ; PUVA Therapy/ADVERSE EFFECTS ; Review ; Skin Neoplasms/CHEMICALLY INDUCED ; Superoxide/METABOLISM ; Tetradecanoylphorbol Acetate ; *Ultraviolet Rays SO - Biochimie 1986 Jun;68(6):885-9 38 UI - 87000769 AU - Moreno G TI - Photosensitization of mammalian cells by psoralens and porphyrins. AB - Because of the ability of photosensitizers to induce specific photochemical reactions in vivo, leading to cell injury and death, many such molecules have been considered as therapeutic agents. Among them two classes of sensitizers, i.e. furocoumarins (psoralens) and porphyrins, are currently used for the photochemotherapy of various skin diseases and malignant lesions. Different types of cell responses can result according to the intracellular localization of the photosensitizer and to the nature of the photochemistry induced by the chromophore which absorbs photons. In this review, the cytological aspects of photosensitization by psoralens and porphyrins will be discussed. MH - Animal ; Cell Membrane/METABOLISM ; Cell Nucleus/METABOLISM ; Comparative Study ; DNA/RADIATION EFFECTS ; Ficusin/ PHARMACODYNAMICS ; Hematoporphyrins/PHARMACODYNAMICS ; *Light ; Liposomes/METABOLISM ; Microscopy, Fluorescence ; Mitochondria, Liver/DRUG EFFECTS/METABOLISM ; Neoplasms, Experimental/DRUG THERAPY/METABOLISM ; Oxidative Phosphorylation/DRUG EFFECTS ; Oxygen Consumption/DRUG EFFECTS ; Oxygen ; Photochemistry ; Porphyrins/METABOLISM/*PHARMACODYNAMICS ; Psoralens/METABOLISM/ *PHARMACODYNAMICS ; Psoriasis/DRUG THERAPY ; PUVA Therapy ; Review ; Spectrometry, Fluorescence ; Trioxsalen/PHARMACODYNAMICS SO - Biochimie 1986 Jun;68(6):869-73 39 UI - 87000768 AU - Salet C TI - Hematoporphyrin and hematoporphyrin-derivative photosensitization of mitochondria. AB - Laser micro-irradiation experiments show that mitochondria are profoundly affected when cells are irradiated with Hp as the photosensitizer. Functional as well as enzymatic studies on isolated mitochondria show that coupling between respiration and oxidative phosphorylation, Ca2+ transport and respiration are successively lost under irradiation in the presence of either Hp or HpD. ATP-driven Ca2+ uptake, which is not impaired under anoxic conditions with HpD alone, is impaired in the absence of oxygen by the synergistic action of HpD and nitroimidazoles. MH - Adenosine Triphosphatase/ANTAGONISTS & INHIBITORS ; Animal ; Biological Transport, Active/DRUG EFFECTS ; Calcium/METABOLISM ; Cell Line ; Cytochrome Oxidase/ANTAGONISTS & INHIBITORS ; *Hematoporphyrins/*PHARMACODYNAMICS ; Lasers ; *Light ; Mitochondria/*DRUG EFFECTS/PHYSIOLOGY/RADIATION EFFECTS ; Mitochondria, Liver/DRUG EFFECTS/METABOLISM/RADIATION EFFECTS ; Neoplasms, Experimental ; Nitroimidazoles/PHARMACODYNAMICS ; Oxidative Phosphorylation/DRUG EFFECTS ; Oxygen Consumption/DRUG EFFECTS ; Oxygen/PHARMACODYNAMICS ; Photochemistry ; Rats ; Review ; Succinate Dehydrogenase/ANTAGONISTS & INHIBITORS SO - Biochimie 1986 Jun;68(6):865-8 40 UI - 87000220 AU - Harris DM ; Hill JH ; Werkhaven JA ; Applebaum EL ; Lobraico RV ; Waldow SM TI - Porphyrin fluorescence and photosensitization in head and neck cancer. AB - Indistinct margin demarcation and autofluorescence are problems in fluorescence delineation of porphyrin-containing head and neck squamous cell cancer (HNSCC). We studied the time course and in vivo localization of porphyrin fluorescence in a squamous cell cancer hamster model and in human HNSCC. After intravenous injection, a gradient in fluorescence intensity developed rapidly until tumors fluoresced above a lower-intensity mucosal background. Hamster tumor and ulcerated HNSCC without porphyrin injection demonstrated autofluorescence grossly indistinguishable from fluorescence in porphyrin-injected tumors. However, fluorescence microscopy revealed autofluorescence to be a surface phenomenon and showed injected porphyrin localized in tumor stroma. We conclude that autofluorescence must be considered when interpreting porphyrin fluorescence. In addition, empirically designed photodynamic therapy can be effective in selected HNSCC. Data from animal experiments provide useful guidelines for the delivery of this therapy. MH - Aged ; Animal ; Carcinoma, Squamous Cell/*DIAGNOSIS/DRUG THERAPY ; Case Report ; Female ; Fluorescence ; Hamsters ; Head and Neck Neoplasms/*DIAGNOSIS/DRUG THERAPY ; Hematoporphyrins/*DIAGNOSTIC USE ; Human ; Male ; Mesocricetus ; Microscopy, Fluorescence ; Middle Age ; *Photochemotherapy ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Arch Otolaryngol Head Neck Surg 1986 Nov;112(11):1194-9 41 UI - 86300777 AU - Larussa FM ; Larocca LM ; Rusciani L ; Pagano L ; Leone G ; Venier A ; Serri F TI - OKT4/OKT8 ratio and serum beta 2-microglobulin in mycosis fungoides and chronic benign dermatitis. AB - Pre-treatment Serum Beta 2-microglobulin (S B2-m) and OKT4/OKT8 Ratio (T4/T8 R) were studied in 15 patients with Mycosis Fungoides (MF) and in 10 subjects with Chronic Superficial Benign Dermatitis (CSBD) in order to verify whether these parameters may lend support to an earlier differential diagnosis. S B2-m levels and T4/T8 R showed no significant difference in CSBD as compared to normal controls. MF patients displayed elevated S B2-m and T4/T8 R values in comparison to healthy controls and subjects suffering from CSBD (P less than 0.001). After photochemotherapy (PUVA), markedly decreased S B2-m and T4/T8 R values were observed in all patients but two who proved to be unresponsive to PUVA treatment. On the basis of reported data, S B2-m and T4/T8 R can be regarded as an additional tool to discriminate CSBD and MF when clinical and histological features are not significantly diagnostic. Finally, these parameters seem to provide reliable information in monitoring response to treatment. MH - Adult ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Beta 2 Microglobulin/*METABOLISM ; Dermatitis/*BLOOD/DIAGNOSIS ; Diagnosis, Differential ; Female ; Helper Cells ; Human ; Leukocyte Count ; Male ; Middle Age ; Mycosis Fungoides/*BLOOD/ DIAGNOSIS/THERAPY ; PUVA Therapy ; Support, Non-U.S. Gov't ; Suppressor Cells SO - Eur J Cancer Clin Oncol 1986 Jun;22(6):663-9 42 UI - 86283971 AU - Marchesini R ; Melloni E ; Pezzoni G ; Savi G ; Zunino F ; Docchio F ; Fava G TI - A study on the possible involvement of nonlinear mechanism of light absorption by HpD with Nd:YAG laser. AB - The purpose of this study was to investigate whether excitation of porphyrin could be related to nonlinear mechanisms of absorption of porphyrin itself or of the medium in which porphyrin is embedded. This possibility was proposed as an explanation for results of previous experiments where a Nd:YAG laser was used. An MS-2 sarcoma transplanted into the hind pad of BALB/c mice was used as the experimental tumor model. Mice were given HpD i.v. (25 mg/kg) 24 h before exposure to light delivered from an IR laser (1,060 nm). Since at dose-rates ranging between 600 and 1,200 mW/cm2 the thermal effect tended to mask the nonlinear effect, the temperature of the limb of mice was kept cold by running water. Irradiation performed under cooling conditions did not show any tumor growth inhibition. Experiments in vitro performed on HT-29 cells by a continuous wave (CW) or pulsed (Q-switch) Nd:YAG laser indicated no appreciable difference in DNA synthesis between irradiated and nonirradiated cells. Our results did not evidence nonlinear mechanisms of absorption by HpD with Nd:YAG laser both in CW and pulsed (nanosecond range) modes. Whether this effect should occur, in any case it is unlikely to be suitable to induce a photodynamic effect due to its low efficiency. Nd:YAG laser could induce a heating related effect, which can improve the therapeutic efficacy of PDT. MH - Aluminum Silicates ; Animal ; Hematoporphyrins/*THERAPEUTIC USE ; Hindlimb ; Light ; Mice ; Mice, Inbred BALB C ; Neodymium ; *Photochemotherapy ; Radiation-Sensitizing Agents/*THERAPEUTIC USE ; Sarcoma, Experimental/*DRUG THERAPY ; Support, Non-U.S. Gov't ; Yttrium SO - Lasers Surg Med 1986;6(3):323-7 43 UI - 86268306 AU - Sobrinho-Sim:oes M ; Damjanov I TI - Lectin histochemistry of papillary and follicular carcinoma of the thyroid gland. AB - The lectin-binding properties of human follicular and papillary carcinoma were studied histochemically and compared with lectin binding to normal or goitrous thyroid tissue. Well-differentiated minimally invasive follicular carcinoma showed a lectin-binding pattern essentially identical to those of the normal thyroid gland and benign adenomatous lesions. Overtly invasive follicular carcinoma showed focal reactivity with some lectins that were nonreactive with normal follicular thyroid cells (Solanum tuberosum and soybean in three of three cases; Ulex europaeus in two of three cases; and Dolichos biflorus, Laburnum alpinum, and peanut in one of three cases). In papillary carcinomas, the cells lining the papillary structures reacted focally with some lectins that did not bind to normal thyroid cells (S tuberosum and U europeaus in seven of seven cases; Helix pomatia, Helix aspersa, and soybean in four of seven cases; and peanut, Griffonia simplicifolia, D biflorus, and Vicia villosa in one of seven cases). All these lectins, as well as those reacting with normal thyroid cells, reacted more strongly with cells of papillary structures than with those forming solid nests and follicles. Despite these lectin-defined differences in the composition of glycoconjugates of benign and malignant thyroid cells, the inconsistent and focal nature of the changes precludes the use of lectins in diagnostic histopathology. MH - Adenocarcinoma/DIAGNOSIS/*METABOLISM/PATHOLOGY ; Carcinoma, Papillary/DIAGNOSIS/*METABOLISM/PATHOLOGY ; Comparative Study ; Diagnosis, Differential ; Fluoresceins/DIAGNOSTIC USE ; Goiter/ DIAGNOSIS/METABOLISM ; Human ; Lectins/DIAGNOSTIC USE/*METABOLISM ; Support, Non-U.S. Gov't ; Thiocyanates/DIAGNOSTIC USE ; Thyroid Gland/*METABOLISM ; Thyroid Neoplasms/DIAGNOSIS/*METABOLISM/ PATHOLOGY SO - Arch Pathol Lab Med 1986 Aug;110(8):722-9 44 UI - 86263038 AU - Stein BS TI - Laser physics and tissue interaction. AB - An understanding of basic laser physics and tissue interaction is required to select and utilize the appropriate laser for a given indication. Biophysical principles demonstrate how in-vivo use differs from bench-top physics. Dosimetry studies help to point out the effects of lasers. MH - Aluminum Silicates ; Animal ; Argon ; Bladder/SURGERY ; Carbon Dioxide ; Dogs ; Heat ; Hematoporphyrin Photoradiation ; Human ; *Lasers/THERAPEUTIC USE ; Liver/SURGERY ; Neodymium ; Neoplasms/ DRUG THERAPY/SURGERY ; Quantum Theory ; Yttrium SO - Urol Clin North Am 1986 Aug;13(3):365-80 45 UI - 86108687 AU - Falkenburg JH ; Fibbe WE ; Veenhof WF ; Koning F ; van Eeden G ; Voogt PJ ; Jansen J TI - Selective removal of clonogenic neoplastic B cells from human bone marrow using anti-HLA-DQ antibodies and complement. AB - Polymorphic HLA-DQ (DC/MB) determinants appeared to be not expressed on human hematopoietic progenitor cells (HPC), using several murine monoclonal and human polyclonal antibodies in a complement-dependent cytotoxicity (CDC) assay. Since mature HLA-DR-positive malignant lymphoma cells prove to be HLA-DQ positive, an attempt was made to remove clonogenic neoplastic DQwl-positive B cells selectively from DQwl-positive marrow samples without affecting hematopoietic progenitor cells. Using a combination of a clonogenic tumor cell assay, an HPC culture assay, and a mixed-tumor-cell-HPC culture assay, selective elimination of more than 98% of clonogenic neoplastic cells from tumor-cell-contaminated bone marrow suspensions was achieved with monoclonal anti-DQ antibodies and complement without depletion of HPC. These results indicate that anti-HLA-DQ antibodies can be used in autologous bone marrow transplantation to deplete the bone marrow cell suspension of DQ-positive malignant cells. MH - Antibodies, Monoclonal/DIAGNOSTIC USE ; Antigenic Determinants/ IMMUNOLOGY ; Antigens, Immune Response/*IMMUNOLOGY ; B Lymphocytes/IMMUNOLOGY ; Bone Marrow/*CYTOLOGY/TRANSPLANTATION ; Cell Line ; Complement/DIAGNOSTIC USE ; Cytotoxicity Tests, Immunologic ; Fluorescence ; Granulocytes/CYTOLOGY ; Hematopoietic Stem Cells/IMMUNOLOGY ; Human ; Monocytes/CYTOLOGY ; Neoplasms, Experimental/PATHOLOGY ; Support, Non-U.S. Gov't ; Tumor Stem Cell Assay SO - Exp Hematol 1986 Feb;14(2):101-7 46 UI - 86322076 AU - Hannuksela M ; Stenb:ack F ; Lahti A TI - The carcinogenic properties of topical PUVA. A lifelong study in mice. AB - The tumorigenic properties of topical methoxsalen (8-MOP) and trioxsalen (TMP) plus ultraviolet light A (UVA) were studied in NMRI female mice. The animals were treated three times weekly for 9 months, and followed up for 18 months. Acetonic solutions of TMP (0.1 mg in 0.2 ml) and 8-MOP (0.6 mg in 0.2 ml) were applied to the shaved back skin of the mice and irradiated with UVA. The doses needed to elicit equivalent phototoxic effects were 0.29 J/cm2 in the TMP group and 1.09 J/cm2 in the 8-MOP group. Papillomas, keratoacanthomas, and squamous cell carcinomas developed in the 8-MOP group only, and the first tumor was seen at 10 months after the beginning of the study. The results suggest that the carcinogenicity of these two modes of photochemotherapy may differ. MH - Animal ; *Carcinogens ; Dose-Response Relationship, Radiation ; Female ; *Methoxsalen ; Mice ; Mice, Inbred Strains ; *Psoralens ; PUVA Therapy/*ADVERSE EFFECTS ; Skin Neoplasms/*CHEMICALLY INDUCED/PATHOLOGY ; Time Factors ; *Trioxsalen ; Ultraviolet Rays SO - Arch Dermatol Res 1986;278(5):347-51 47 UI - 86319180 AU - Kellokumpu I ; Karhi K ; Andersson LC TI - Lectin-binding sites in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa. AB - The carbohydrate structures of cellular glycoconjugates in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa were analysed with six fluorescein isothiocyanate-conjugated lectins. In normal, hyperplastic and adenomatous colorectal mucosa showing mild or moderate dysplasia Concanavalin A (Con A), Lens culinaris (LCA), and wheat germ (WGA) agglutinins stained goblet cell glycoconjugates (actual mucin goblet itself) while peanut (PNA), Vicia villosa (VVA), and Griffonia simplicifolia-II (GSA-II) agglutinins showed a supranuclear staining of goblet cell glycoconjugates. After neuraminidase treatment of tissue sections PNA and VVA stained mucin goblets of mature cells in normal mucosa, while less differentiated cells in the lower crypt displayed a supranuclear staining with VVA. The mucin goblets in adenomatous mucosa with mild or moderate dysplasia did not stain with PNA and VVA, neither before nor after neuraminidase treatment. Areas of in situ cancer in adenomas and carcinomas displayed a strong and direct binding of Con A, LCA, WGA and PNA in an apical linear distribution, while the binding of VVA and GSA-II was heterogeneous. We conclude that there are alterations in the carbohydrate structures of cellular glycoconjugates, which can be related to goblet cell differentiation in normal colorectal mucosa and to the degree of dysplasia in adenomas. Heterogeneous and incompletely glycosylated glycoconjugates appear to be synthesized by the majority of colorectal carcinomas. MH - Adenoma/METABOLISM ; Carbohydrates/METABOLISM ; Colonic Neoplasms/ *METABOLISM ; Fluoresceins/DIAGNOSTIC USE ; Human ; Hyperplasia/ METABOLISM ; Intestinal Mucosa/*METABOLISM ; Lectins/*METABOLISM ; Receptors, Mitogen/*METABOLISM ; Rectal Neoplasms/*METABOLISM ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Thiocyanates/DIAGNOSTIC USE SO - Acta Pathol Microbiol Immunol Scand [A] 1986 Jul;94(4):271-80 48 UI - 86309946 AU - Berg LF ; Harris DM TI - Microscopic fluorescence in photodynamic therapy. AB - The use of hematoporphyrin derivative (HPD) as a photosensitizer has been studied in malignant tumor detection via fluorescence and in tumor destruction via a toxic photochemical reaction. Squamous cell carcinoma has been induced in hamster buccal mucosa utilizing the known carcinogen dimethyl-benzanthracene. HPD was injected intraperitoneally, then at 24 and 48 hours following injection, unstained frozen section specimens were studied with fluorescent microscopy and photographed. The same specimens were then stained with hematoxylin and eosin and the microscopy correlated. HPD fluorescence was documented in the fibrous stroma of the tumor and in the keratin layer. Essentially no fluorescence was noted in the malignant squamous cells themselves. No consistent differences between the two postinjection times were noted. These qualitative observations support the postulated mechanism of HPD accumulation in tumors. MH - Animal ; Carcinoma, Squamous Cell/*DRUG THERAPY/PATHOLOGY ; Cheek ; Fluorescence ; Hamsters ; *Hematoporphyrin Photoradiation ; Mesocricetus ; Microscopy, Fluorescence ; Mouth Mucosa/PATHOLOGY ; Neoplasms, Experimental/*DRUG THERAPY/PATHOLOGY ; *Photochemotherapy ; Support, Non-U.S. Gov't SO - Laryngoscope 1986 Sep;96(9 Pt 1):986-9 49 UI - 86306649 AU - Bolsover SR TI - Two components of voltage-dependent calcium influx in mouse neuroblastoma cells. Measurement with arsenazo III. AB - N1E-115 mouse neuroblastoma cells were injected with the calcium indicator dye arsenazo III. Optical absorbance changes during voltage-clamp depolarization were used to examine the properties of the two calcium currents present in these cells. The rapidly inactivating calcium current (Moolenar and Spector, 1979b, Journal of Physiology, 292:307-323) inactivates by a voltage-dependent mechanism. The slowly inactivating calcium current is dominant in raising intracellular calcium during depolarizations to greater than -20 mV. Lowering the extracellular calcium concentration affects the two calcium currents unequally, with the slowly inactivating current being reduced more. Intracellular calcium falls very slowly (tau greater than 1 min) after a depolarization. The rapidly inactivating calcium current is responsible for a calcium action potential under physiological conditions. In contrast, it is unlikely that the slowly inactivating calcium current has an important electrical role. Rather, its function may be to add a further increment of calcium influx over and above the calcium influx through the rapidly inactivating calcium channels. MH - Animal ; Arsenazo III/*DIAGNOSTIC USE ; Azo Compounds/*DIAGNOSTIC USE ; Calcium/*METABOLISM/PHARMACODYNAMICS ; Cobalt/METABOLISM/ PHARMACODYNAMICS ; Electrophysiology ; Extracellular Space/ METABOLISM ; Mice ; Neuroblastoma/*METABOLISM/PHYSIOPATHOLOGY ; Support, U.S. Gov't, P.H.S. ; Tetraethylammonium Compounds/ METABOLISM/PHARMACODYNAMICS SO - J Gen Physiol 1986 Aug;88(2):149-65 50 UI - 86304357 AU - Bodaness RS ; Heller DF ; Krasinski J ; King DS TI - The two-photon laser-induced fluorescence of the tumor-localizing photosensitizer hematoporphyrin derivative. Resonance-enhanced 750 nm two-photon excitation into the near-UV Soret band. AB - The tumor-localizing photosensitizer hematoporphyrin derivative (HPD) is shown to undergo a simultaneous two-photon excitation into the near-ultraviolet Soret band system upon intense laser irradiation at 750 nm, a spectral region where there is no significant HPD one-photon absorbance in aqueous solution. Subsequent to this excitation, internal conversion and vibrational relaxation occur, resulting in the population of the vibrationless level of the first electronically excited singlet state. This state relaxes by two channels, the emission of fluorescence in the spectral region 600-700 nm and intersystem crossing into the triplet manifold, followed by near-resonant electronic energy transfer with surrounding oxygen to result in the generation of highly reactive singlet molecular oxygen (1 delta g). Evidence for the two-photon excitation consists in the observation both of the HPD fluorescence spectrum in the region of 615 nm as a result of 750 nm excitation and the quadratic dependence of this fluorescence emission intensity upon the excitation laser intensity. Since, in general, the penetration depth of ultraviolet and visible light into tissue varies directly with wavelength (red penetrating more deeply than blue), these studies suggest the possibility that two-photon-induced localization of tumor-bound HPD might facilitate the detection of deeper lying tumors than allowed by the current one-photon photolocalization method. MH - *Hematoporphyrins ; Human ; *Lasers ; Mathematics ; Neoplasms/ *DIAGNOSIS ; Radiation ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet SO - J Biol Chem 1986 Sep 15;261(26):12098-101 51 UI - 86303810 AU - Franko AJ TI - Misonidazole and other hypoxia markers: metabolism and applications. AB - A substantial effort is being devoted to developing markers for hypoxia in tumors. Most of the work to date has been performed on misonidazole (MISO), which is selectively metabolized by hypoxic cells to reactive products that bind covalently to cellular constituents. This paper attempts to review the metabolism of MISO as it relates to binding, to summarize several of the properties of the binding of MISO to cells and tissues which appear to be directly relevant to the characteristics of the reactive species involved, and to evaluate the potential of MISO and other nitroheterocycles as markers for hypoxia. Four roles for a hypoxic marker are considered. MISO labeled with 3H or 14C is a good marker for local radiobiological hypoxia in autoradiograms of tumor sections, but more work is required to investigate factors other than oxygen concentration that conceivably might affect the binding process. In quantitating hypoxic fraction in tumors using non-destructive techniques, which has been modelled by correlating surviving fraction with 14C-misonidazole uptake, non-specific binding to aerobic and necrotic tissue limits the accuracy of the estimate, but useful clinical applications can still be envisaged. For quantitation of a change in the hypoxic fraction of an individual tumor using serial assays, preliminary data suggest that MISO binding should be a sensitive assay. Fluorescent nitroheterocycles have a great deal of potential as markers to enable the sorting of tumor cell suspensions into portions derived from the hypoxic and aerobic regions, but better compounds are needed. MH - Animal ; Fluorescent Dyes/DIAGNOSTIC USE/METABOLISM ; Human ; Misonidazole/DIAGNOSTIC USE/*METABOLISM ; Neoplasms/METABOLISM/ *RADIOTHERAPY ; Neoplasms, Experimental/METABOLISM/RADIOTHERAPY ; Oxygen/*PHYSIOLOGY ; Review ; Support, Non-U.S. Gov't SO - Int J Radiat Oncol Biol Phys 1986 Jul;12(7):1195-202 52 UI - 86303215 AU - Keye WR Jr TI - The present and future application of lasers to the treatment of endometriosis and infertility. AB - Conventional approaches to the treatment of endometriosis usually require major surgery, prolonged use of medications or both. The laser has provided an opportunity to treat mild and moderate endometriosis at the time of diagnosis at laparoscopy, thus avoiding delays in attempts to conceive. This review describes the current use of the CO2, argon and Nd:YAG lasers in the treatment of endometriosis. Potential and future uses of the free-electron laser (FEL) are also described. MH - Aluminum Silicates ; Argon ; Carbon Dioxide ; Comparative Study ; Electrons ; Endometriosis/DRUG THERAPY/*SURGERY ; Female ; Human ; Infertility, Female/*THERAPY ; Lasers/*THERAPEUTIC USE ; Neodymium ; Peritoneal Neoplasms/DRUG THERAPY/*SURGERY ; Peritoneoscopy ; Photochemotherapy ; Potassium ; Review ; Rhodamines/THERAPEUTIC USE ; Titanium ; Yttrium SO - Int J Fertil 1986 May-Jun;31(2):160-4 53 UI - 86296236 AU - Gluckman JL ; Waner M ; Shumrick K ; Peerless S TI - Photodynamic therapy. A viable alternative to conventional therapy for early lesion of the upper aerodigestive tract? AB - Photodynamic therapy (PDT) is a treatment modality that results in selective destruction of malignant cells by combining a photosensitizing agent (hematoporphyrin derivative), which is taken up by the cells, and a laser light. This therapeutic modality has been effectively used in managing cancers of the skin, bronchi, and bladder. In the head and neck area, however, its use has been confined to the palliation of advanced lesions that have proved refractory to conventional therapy. While this is unquestionably a valid role, its true therapeutic value may be in the management of early cancers arising in the upper aerodigestive tract. At the University of Cincinnati, PDT has been used on a variety of such early cancers where, for multiple reasons, conventional therapy was not possible. While no attempt will be made to comment on long-term survival or to compare PDT with more conventional therapeutic regimens, a preliminary experience with this modality in managing lesions of the larynx, oral cavity, and oropharynx will be presented. Apparent advantages, disadvantages, and pitfalls will be presented. MH - Aged ; Case Report ; Female ; *Hematoporphyrin Photoradiation ; Human ; Laryngeal Neoplasms/*DRUG THERAPY ; Male ; Middle Age ; Mouth Neoplasms/*DRUG THERAPY ; Oropharyngeal Neoplasms/*DRUG THERAPY ; Pharyngeal Neoplasms/*DRUG THERAPY ; *Photochemotherapy ; Skin Neoplasms/DRUG THERAPY SO - Arch Otolaryngol Head Neck Surg 1986 Sep;112(9):949-52 54 UI - 86295456 AU - Riccardi A ; Montecucco CM ; Danova M ; Ucci G ; Mazzini G ; Giordano PA ; Pasquali F TI - Flow cytometric evaluation of proliferative activity and ploidy in myelodysplastic syndromes and acute leukemias. AB - Propidium iodide (PI) DNA distribution of bone marrow (BM) cells was studied by flow cytometry (FCM) in 36 patients without hematologic or malignant disease (normal BM) and in 172 patients with anemias (36 pts), myelodysplastic syndromes (MDS) (33 pts) and acute leukemia (AL) at diagnosis (60 pts), remission (24 pts) and relapse (19 pts). White blood cells from normal male subjects were used as an external diploid reference standard (median CV = 3.8). Patients with normal BM, anemias, MDS and acute leukemia at diagnosis had tritiated thymidine labeling index (LI) and most with MDS and AL had also evaluable cytogenetics performed on the same BM sample used for FCM. In normal BM, median aliquot of cells with PI-DNA content intermediate between the diploid and the tetraploid value (2n-4n cells %) was 15.7. The ratio between the fluorescence intensity of the G0/1 peak of normal BM cells and the fluorescence intensity of the G0/1 peak of the reference standard (FI ratio) ranged from 93 to 1.05 (mean +/- 2SD). The 2n-4n cell % was higher than normal in anemias (p less than .001), lower in leukemias (p less than .001) and widely scattered in MDS. A linear correlation was found between 2n-4n cell % and LI, with 2n-4n cell % value higher than LI. The FI ratio was lower than normal in anemias (p less than .05), higher in AL with normal cytogenetics (p less than .02) and broadly scattered in MDS with normal cytogenetics. From our experience, PI-DNA-FCM is a simple and adequate method to evaluate proliferative activity in hematologic diseases. Nevertheless, caution must be taken in attributing small changes in FI ratio to aneuploidy, since they are found in anemias and in MDS and AL with normal cytogenetics, possibly due to differences in PI uptake by different cell types. MH - Acute Disease ; Cell Division ; DNA, Neoplasm/ANALYSIS ; *Flow Cytometry ; Fluorescent Dyes/DIAGNOSTIC USE ; Human ; Karyotyping ; Leukemia/FAMILIAL & GENETIC/*PATHOLOGY ; Male ; Myelodysplastic Syndromes/FAMILIAL & GENETIC/*PATHOLOGY ; *Ploidies ; Propidium ; Stains and Staining ; Support, Non-U.S. Gov't SO - Basic Appl Histochem 1986;30(2):181-92 55 UI - 86290820 AU - Kaisary AV TI - Assessment of radiotherapy in invasive bladder carcinoma using in vivo methylene blue staining technique. AB - In vivo methylene blue staining of the bladder urothelium is a useful method as an adjunct to cystoscopy in detection of recurrent tumors or new ones after radical radiotherapy. The depth of staining correlates well with the grade of bladder tumor differentiation. It is a simple, safe, and acceptable procedure. MH - Bladder Neoplasms/*PATHOLOGY/RADIOTHERAPY ; Carcinoma/*PATHOLOGY/ RADIOTHERAPY ; Human ; Methylene Blue/DIAGNOSTIC USE SO - Urology 1986 Aug;28(2):100-2 56 UI - 86288021 AU - Naruse S ; Horikawa Y ; Tanaka C ; Higuchi T ; Sekimoto H ; Ueda S ; Hirakawa K TI - Evaluation of the effects of photoradiation therapy on brain tumors with in vivo P-31 MR spectroscopy. AB - In vivo phosphorus-31 magnetic resonance (MR) spectra were obtained by a surface coil method from rat glioma tissue inoculated subcutaneously in CD Fisher rats, and the effects of photoradiation therapy on tumors were evaluated by sequentially observing spectral changes. In the control group, the nucleoside triphosphate (NTP) and phosphomonoester peaks were large, the phosphocreatine peak was small, and the inorganic phosphate (Pi) peak was intermediate. In all eight cases in the group in which a dose of 10 mg/kg of hematoporphyrin derivatives (HpD) was given before photoirradiation, NTP peaks decreased, and the Pi peak increased remarkably within 1 hour after the 60-minute white-light irradiation. Spectral changes were observed before histologic changes were apparent. Histologic examinations 3 days after irradiation showed extensive necrosis in the tumor tissue. With preinjection of 5 mg/kg HpD, three of the eight cases showed spectrum changes after the irradiation. No spectrum changes were observed in the group with preinjection of 2.5 mg/kg. In vivo P-31 MR spectra measurements are useful not only to investigate the energy metabolism of tumor tissue in vivo but also to evaluate the effects of photoradiation therapy on tumors. MH - Animal ; Brain Neoplasms/*DRUG THERAPY/METABOLISM/PATHOLOGY ; Energy Metabolism ; Evaluation Studies ; Glioma/*DRUG THERAPY/ METABOLISM/PATHOLOGY ; *Hematoporphyrin Photoradiation ; Necrosis/ PATHOLOGY ; Nuclear Magnetic Resonance/*DIAGNOSTIC USE ; Phosphates/ANALYSIS ; Phosphocreatine/ANALYSIS ; *Photochemotherapy ; Purine Nucleotides/ANALYSIS ; Rats ; Support, Non-U.S. Gov't SO - Radiology 1986 Sep;160(3):827-30 57 UI - 86283973 AU - McCaughan JS Jr ; Williams TE Jr ; Bethel BH TI - Photodynamic therapy of endobronchial tumors. AB - After presensitization with IV hematoporphyrin derivative (HpD), neoplasms in the tracheobronchial tree of 18 patients were treated by photodynamic therapy (PDT) with 630-nm light from a tunable dye argon laser system delivered through quartz fibers passed through the biopsy channel of a flexible bronchoscope under local anesthesia. Tumor effect was measured by complete response (CR)--no visible tumor in area treated, partial response (PR)--tumor size or degree of obstruction reduced by more than 50% and some response (SR)--tumor or degree of obstruction reduced by more than 20% but less than 50%. One month or less after 30 treatments to 26 areas in 18 patients, there was 40% CR, 57% PR, and 3% SR. All tumors showed at least some response. Since many of these patients had end-stage disease, the effect on the clinical condition and symptoms were evaluated using the Karnofsky Performance Status (KPS), oxygen requirements, and the presence or absence of respiratory symptoms. One month after treatment, 61% were clinically improved, with an increase of the average KPS from 48 to 61. Three patients with stage III primary lung cancer improved from being severely disabled requiring hospitalization to normal activity with effort and lived an average of 3.5 months. One patient with metastatic colon cancer was palliated from bedrest with continuous oxygen to normal activity with no oxygen for 12 months. A patient with hemoptysis and carcinoma in situ remains biopsy- and symptom-free for 34 months. A patient with hemoptysis and cough from breast cancer metastases maintained CR, biopsy- and symptom-free for 7 months. A patient with hemoptysis from recurrence at the bronchial stump maintained CR, biopsy- and symptom-free for 13 months. Six patients with Stage III primary lung cancer with average KPS of 27 (severe) died in the hospital and lived an average of 5 weeks (two CR, two PR, two SR). One patient with atelectasis of the right lower lobe re-expanded 14 days after treatments began. MH - Bronchial Neoplasms/*DRUG THERAPY ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/THERAPEUTIC USE ; Human ; Lung Neoplasms/*DRUG THERAPY ; *Photochemotherapy ; Radiation-Sensitizing Agents/THERAPEUTIC USE ; Time Factors SO - Lasers Surg Med 1986;6(3):336-45 58 UI - 86283972 AU - Lanzafame RJ ; Blackman JR ; Rogers DW ; Naim JO ; Pennino RP ; Hinshaw JR TI - Hematoporphyrin derivative fluorescence: photographic techniques for the localization of malignant tissue. AB - Three simple methods for the detection of malignancy by the photography of hematoporphyrin derivative (HPD) fluorescence are presented. Two methods employ a single lens reflex camera with macrolens and Kodak high-speed Ektachrome (EL 400) film. Both employ a Corning Glass #3482 filter as a barrier on the lens. In method I, a single Kodak Wratten #39 filter is placed over a fluorescent "black light: source (two General Electric F20T12BL 20-W bulbs). In method II, twin electronic flash units (5,500 BCPS unfiltered) with a double thickness of Kodak Wratten #39 filter over them provide the light of excitation. Method III employs an adapted Polaroid SLR 680E Sun camera with two electronic flash units (5,500 BCPS, total unfiltered) rigged with a slave trigger. A Corning Glass #3482 filter is placed on the lens to act as a barrier, and two filters of Kodak Wratten #39 glass are placed on each flash unit. Photographs are taken in a darkened room. MH - Animal ; Female ; Fluorescence ; Hematoporphyrins/*DIAGNOSTIC USE ; Mammary Neoplasms, Experimental/*DIAGNOSIS ; Photography/ *METHODS ; Radiation-Sensitizing Agents/*DIAGNOSTIC USE ; Rats ; Rats, Inbred F344 ; Support, Non-U.S. Gov't SO - Lasers Surg Med 1986;6(3):328-35 59 UI - 86281953 AU - Haas GP ; Shumaker BP ; Hetzel FW ; Bobrowski R ; Lutz MD ; Tilley B ; Cerny JC TI - Phototherapy of bladder cancer: dose/effect relationships. AB - Hematoporphyrin derivative photodynamic therapy has very important clinical applicability in the diagnosis and treatment of transitional cell carcinoma of the bladder, but many aspects of the photodynamic process are yet to be elucidated. This paper investigates the role of dihematoporphyrin ether (DHE) concentration, the duration of light exposure, and the initial size of the tumors in the treatment of a transplantable murine transitional cell tumor system. The best results were noted in tumors less than six mm. in diameter when treated with 15 mg./kg. DHE and exposed to 100 to 180 minutes of visible light. Animals with small initial tumor size combined with higher DHE concentration and longer light exposure time were most likely to show tumor response. MH - Animal ; Antineoplastic Agents/*ADMINISTRATION & DOSAGE/ THERAPEUTIC USE ; Bladder Neoplasms/CHEMICALLY INDUCED/*DRUG THERAPY ; Carcinoma, Transitional Cell/CHEMICALLY INDUCED/*DRUG THERAPY ; Dose-Response Relationship, Drug ; Female ; FANFT ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/ *ADMINISTRATION & DOSAGE/THERAPEUTIC USE ; Mice ; Mice, Inbred C3H ; *Photochemotherapy ; Time Factors SO - J Urol 1986 Aug;136(2):525-8 60 UI - 86276402 AU - Ooms EC ; Blomjous CE ; Zwartendijk J ; Veldhuizen RW ; Blok AP ; Heinhuis RJ ; Boon ME TI - Connective tissue stroma in bladder papillary transitional cell carcinoma, carcinoma in situ and benign cystitis. AB - The stromal characteristics in papillary and non-papillary tumours of the urinary bladder were investigated in an attempt to improve the accuracy of histopathological diagnosis. It appeared to be possible to differentiate true papillary tumours from pseudopapillary structures lined by carcinoma in situ. Stromal differences were not found in cases of carcinoma in situ accompanied by denuding cystitis and cystitis due to other aetiological factors. It is concluded that histopathological examination of the stroma of bladder tumours improves diagnostic accuracy. MH - Alcian Blue/DIAGNOSTIC USE ; Bladder Neoplasms/*PATHOLOGY ; Carcinoma in Situ/*PATHOLOGY ; Carcinoma, Transitional Cell/ *PATHOLOGY ; Connective Tissue/*PATHOLOGY ; Cystitis/*PATHOLOGY ; Human ; Stains and Staining SO - Histopathology 1986 Jun;10(6):613-9 61 UI - 86276015 AU - Shelley ED ; Swaminathan R TI - Psoriasis: how to relieve symptoms in older patients. AB - Topical steroid creams and ointments, applied once or twice daily, can help control psoriatic lesions and reduce itching. Intermediate-strength compounds are preferable for use in the elderly. Skin biopsy interpreted as psoriasiform dermatitis or nonspecific dermatitis, rather than psoriasis, should be considered a possible result of malignancy. MH - Administration, Topical ; Aged ; Carcinoma, Basal Cell/ COMPLICATIONS ; Human ; Middle Age ; Psoriasis/*DRUG THERAPY/ ETIOLOGY/MICROBIOLOGY ; PUVA Therapy ; Steroids/*THERAPEUTIC USE SO - Geriatrics 1986 Aug;41(8):71-4, 77-80 62 UI - 86275540 AU - Aalto ML TI - Mucosubstances in classification of serous and mucinous ovarian tumors: a morphometrical study. AB - 108 serous and 106 mucinous ovarian cystadenomas of varying malignancy were studied with the saliva-periodic acid-Schiff (SPAS) reaction and with the Alcian blue (AB) pH 2.7 method, which stain neutral and acid mucosubstances, respectively. Positively stained mucin was quantitated morphometrically and the measured parameters were tested by discriminant analysis. As expected, the mucinous tumors were more positive for mucin than the serous ones. Also the borderline tumors contained more mucin than their benign or malignant counterparts. The best discriminating capacity for mucin was obtained in serous tumors with the AB stain and in mucinous tumors with the SPAS reaction. The ratio of neutral to acid mucosubstances decreased in mucinous cystadenomas with increasing malignancy. MH - Alcian Blue/DIAGNOSTIC USE ; Cystadenoma/*CLASSIFICATION/ PATHOLOGY ; Female ; Human ; Mucins/*ANALYSIS ; Orosomucoid/ *ANALYSIS ; Ovarian Neoplasms/*CLASSIFICATION/PATHOLOGY ; Periodic Acid-Schiff Reaction/METHODS ; Support, Non-U.S. Gov't SO - Eur J Obstet Gynecol Reprod Biol 1986 Jul;22(3):139-44 63 UI - 86274516 AU - Varoli F ; Mariani C ; Fascianella A ; Cosentino F ; Roviaro GC TI - Vital staining in fiberoptic bronchoscopy. AB - The authors report on the results obtained using vital staining in fiberoptic bronchoscopic investigations. Vital staining is performed during normal fiberoptic bronchoscopic investigations under local anesthesia. The method has proved very sensitive for cancerous and precancerous lesions of the bronchial mucosa. MH - Bronchi/PATHOLOGY ; Bronchial Neoplasms/*DIAGNOSIS ; *Bronchoscopy ; Carcinoma, Squamous Cell/DIAGNOSIS ; Human ; Metaplasia ; Methylene Blue/DIAGNOSTIC USE ; Precancerous Conditions/*DIAGNOSIS ; Stains and Staining/*METHODS ; Tolonium Chloride/DIAGNOSTIC USE SO - Endoscopy 1986 Jul;18(4):142-3 64 UI - 86271604 AU - Svanberg K ; Kjell:en E ; Ankerst J ; Mont:an S ; Sj:oholm E ; Svanberg S TI - Fluorescence studies of hematoporphyrin derivative in normal and malignant rat tissue. AB - Laser-induced fluorescence in rat tissue was studied during the uptake and clearing period of i.v.-injected hematoporphyrin derivative. A malignant rat tumor and normal tissue of 20 different kinds from the tumor-bearing animals were investigated. A pulsed nitrogen laser (337 nm) was used in conjunction with an optical multichannel analyzer system, in which the whole fluorescence light distribution was captured for each laser pulse. Several of the organs exhibited an initial and a delayed intensity peak in the characteristic hematoporphyrin derivative laser-induced fluorescence intensity (630 nm) that might be interpreted as due to intracellular transformations of different chemical components of the hematoporphyrin derivative preparation. By dividing the background-free 630-nm signal by the blue fluorescence intensity, a dimensionless quantity is obtained that could have many advantages in practical endoscopic laser-induced fluorescence work. This ratio was also shown to exhibit a larger contrast between tumor and surrounding tissue. The ratio between the two red fluorescence peaks was also found to be useful for discriminating tumor from normal tissue. A combination of the two ratios was shown to be particularly valuable for tumor discrimination. MH - Animal ; Female ; Fluorescence ; Hematoporphyrins/*METABOLISM ; Lasers ; Neoplasms, Experimental/*METABOLISM ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't SO - Cancer Res 1986 Aug;46(8):3803-8 65 UI - 86263043 AU - Rosenberg SJ ; Williams RD TI - Photodynamic therapy of bladder carcinoma. AB - Photodynamic therapy for bladder cancer is an intriguing modality with theoretical potential for successful treatment of visible tumor and areas of carcinoma in situ and dysplasia throughout the bladder mucosa. There remain many unanswered determinations about photodynamic therapy, including the most effective photosensitizer, the dose of laser that should be used, and the optimum timing for laser therapy following the injection of photosensitizer. Nonetheless, clinical studies thus far have shown photodynamic therapy to have efficacy in eradicating superficial noninvasive tumors. Treatment of diffuse carcinoma in situ at present appears the most impressive. Prospective studies designed to examine photodynamic therapy in a standardized protocol in comparison with other conventional methods for treatment and prophylaxis of noninvasive bladder cancer are most needed and are currently in progress. In the future, development of alternate photosensitizers or methods of direct intravesical uptake of DHE, perhaps limiting cutaneous phototoxicity, are expected. MH - Bladder Neoplasms/DIAGNOSIS/*DRUG THERAPY ; Fluorescence ; Hematoporphyrin Photoradiation ; Hematoporphyrins/DIAGNOSTIC USE ; Human ; *Photochemotherapy/ADVERSE EFFECTS SO - Urol Clin North Am 1986 Aug;13(3):435-44 66 UI - 86256105 AU - Arnfield M ; Gonzalez S ; Lea P ; Tulip J ; McPhee M TI - Cylindrical irradiator fiber tip for photodynamic therapy. AB - In photodynamic therapy (PDT) the uniform distribution of intratumor or externally applied light is desirable but often difficult to achieve. An optical fiber tip producing cylindrical or lateral light emission can facilitate the application of laser energy by direct implantation of the tip into solid tumors or within tubular cavities of the body such as the bronchus or esophagus. A procedure is described for fabricating such a fiber tip, the main component of which is a hollow glass cylinder containing a light-scattering material. Light distributions emitted from the tip in air are documented. Useful properties of the tip include good light distribution, durability, heat resistance, and simplicity of construction. MH - Adenocarcinoma/*DRUG THERAPY ; Animal ; Photochemotherapy/ *INSTRUMENTATION ; Rats SO - Lasers Surg Med 1986;6(2):150-4 67 UI - 86256101 AU - Nelson JS ; Sun CH ; Berns MW TI - Study of the in vivo and in vitro photosensitizing capabilities of uroporphyrin I compared to photofrin II. AB - The in vivo biological activity of uroporphyrin I has been studied by determining the amount of necrosis produced in murine tumors exposed to various total doses of light at 615 nm. Similarly, the in vitro photosensitizing activity of uroporphyrin I was examined by measuring the percentage of cells killed in a cell culture system. Light doses used were 25-400 J/cm2. Mice that received uroporphyrin I at 40 mg/kg had only minimal superficial necrosis upon histological examination at doses of 400 J/cm2 (615 nm). Those tumors that received 300 J/cm2 or less showed no histological evidence of necrosis. Mice that received hematoporphyrin derivative (Photofrin II) at 10 mg/kg were completely necrotic at total doses of 100 J/cm2 (630 nm). PTK2 epithelial cells incubated with uroporphyrin I at either 40 micrograms/ml or 80 mu/ml and 10 J/cm2 (615 nm) showed no apparent damage and had 100% cell survival. By contrast, those cells treated with hematoporphyrin derivative (Photofrin II) at 25 micrograms/ml and 10 J/cm2 (630 nm) exhibited 100% cell kill. It is concluded that uroporphyrin I is a poor photosensitizer in both in vivo and in vitro systems compared to hematoporphyrin derivative (Photofrin II). MH - Animal ; Antineoplastic Agents/*THERAPEUTIC USE ; Cells, Cultured ; Comparative Study ; Female ; Hematoporphyrins/*THERAPEUTIC USE ; Lasers/*THERAPEUTIC USE ; Mammary Neoplasms, Experimental/*DRUG THERAPY/PATHOLOGY ; Mice ; Mice, Inbred BALB C ; *Photochemotherapy ; Porphyrins/*THERAPEUTIC USE ; Radiation-Sensitizing Agents/*THERAPEUTIC USE ; Sarcoma, Experimental/*DRUG THERAPY/PATHOLOGY ; Support, U.S. Gov't, P.H.S. ; Uroporphyrins/*THERAPEUTIC USE SO - Lasers Surg Med 1986;6(2):131-6 68 UI - 86256100 AU - Brackett KA ; Sankar MY ; Joffe SN TI - Effects of Nd:YAG laser photoradiation on intra-abdominal tissues: a histological study of tissue damage versus power density applied. AB - Liver, spleen, and pancreas were subjected to laser photoradiation of 50- to 100-Watt power levels. Samples were evaluated by light microscopy at 0 hours and 7, 14, and 21 days. Four zones of cellular damage were visible in liver and pancreas: coagulum, cavitation, acidophilia, and transition. Only the first three zones were clearly visible in the spleen. Mean lateral tissue penetration was 3.1 mm in liver, 3.3 mm in spleen, and 1.0 mm in pancreas. No significant increase in lateral penetration occurred with increasing power. Normal healing was observed in liver and spleen. Pancreatitis was found in all samples at 7 days postoperatively. At power levels of 80 W or less, recovery was observed. Above 80 W, pancreatic pseudocysts and necrosis led to death of the animals. MH - Abdomen/*RADIATION EFFECTS ; Animal ; Lasers/*ADVERSE EFFECTS ; Liver/PATHOLOGY/RADIATION EFFECTS/SURGERY ; Male ; Necrosis/ ETIOLOGY ; Pancreas/PATHOLOGY/RADIATION EFFECTS/SURGERY ; Pancreatic Pseudocyst/ETIOLOGY/PATHOLOGY ; Pancreatitis/ETIOLOGY/ PATHOLOGY ; Phototherapy/*ADVERSE EFFECTS ; Rabbits ; Rats ; Rats, Inbred Strains ; Spleen/PATHOLOGY/RADIATION EFFECTS/SURGERY SO - Lasers Surg Med 1986;6(2):123-30 69 UI - 86251527 AU - Abel EA ; Sendagorta E ; Hoppe RT TI - Cutaneous malignancies and metastatic squamous cell carcinoma following topical therapies for mycosis fungoides. AB - Specific treatments for mycosis fungoides, including electron beam irradiation, topical mechlorethamine, and psoralen plus ultraviolet A (PUVA) may be associated with the development of skin cancers after a variable latency period. Because these treatments are often not curative, topical therapies for mycosis fungoides, administered sequentially or concomitantly, are being used increasingly in order to control recurrent disease. This report documents the development of multiple cutaneous tumors, including squamous cell carcinoma, basal cell carcinoma, actinic keratoses, keratoacanthomas, and one case of lentigo maligna, in seven patients who received topical therapies for mycosis fungoides. In contrast to the usual latency period between ionizing radiation therapy and the development of skin cancer, two of our patients who had received prior PUVA therapy developed multiple skin tumors upon completion of electron beam irradiation. The development of metastatic squamous cell carcinoma in two of the other seven patients with multiple cutaneous neoplasms suggests that this potential hazard must be considered in the evaluation and treatment of patients with mycosis fungoides. MH - Administration, Topical ; Aged ; Biopsy ; Carcinoma, Squamous Cell/*ETIOLOGY/SECONDARY ; Case Report ; Female ; Human ; Male ; Mechlorethamine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS ; Middle Age ; Mycosis Fungoides/PATHOLOGY/*THERAPY ; Neoplasm Staging ; PUVA Therapy/ADVERSE EFFECTS ; Skin/PATHOLOGY ; Skin Neoplasms/ *ETIOLOGY/PATHOLOGY SO - J Am Acad Dermatol 1986 Jun;14(6):1029-38 70 UI - 86250949 AU - Ayala AG ; Murray JA ; Erling MA ; Raymond AK TI - Osteoid-osteoma: intraoperative tetracycline-fluorescence demonstration of the nidus. AB - Nine patients with a clinical and radiographic diagnosis of osteoid-osteoma received 750 to 4,000 milligrams of tetracycline preoperatively. Immediate examination of the surgically removed specimens under ultraviolet light demonstrated fluorescence of the nidus in all nine patients. Reactive and normal bone did not fluoresce. This simple technique permits quick, easy, economical, and sure verification that the nidus has been excised. MH - Adolescence ; Adult ; Bone Neoplasms/*PATHOLOGY/SURGERY ; Child ; Female ; Fluorescence ; Human ; Intraoperative Care/*METHODS ; Male ; Osteoma, Osteoid/*PATHOLOGY/SURGERY ; Preoperative Care ; Tetracycline/*DIAGNOSTIC USE ; Ultraviolet Rays SO - J Bone Joint Surg [Am] 1986 Jun;68(5):747-51 71 UI - 86250194 AU - Fukuda M ; Miyoshi N ; Hattori T ; Sugihara H ; Hosokawa Y ; Nakanishi K TI - Different instability of nuclear DNA at acid hydrolysis in cancerous and noncancerous cells as revealed by fluorescent staining with acridine orange. AB - Ehrlich cancer cells and inflammatory cells in mouse ascitic fluid were hydrolyzed and stained with acridine orange (AO). The AO hydrolysis curves for G1/G2 + M phase cancer cells and inflammatory cells were differentially determined using flow cytometry by monitoring the metachromatic red-shifted fluorescence of the fluorochrome bound to the single-stranded DNA produced by acid hydrolysis. By computer fitting of the Bateman function to the hydrolysis curves, the kinetic parameters k1 (rate constant for the production of single-stranded DNA), k2 (rate constant for the degradation of the produced single-stranded DNA), and y0 (theoretical value of the single-stranded DNA present initially) were determined. It was found that the k2 value, which reflects the degree of DNA instability, was much higher for cancer cells in both the G1 and G2 + M phases than for inflammatory cells. This finding led us to develop a method for the differential AO staining of cancer cells and non-cancerous cells utilizing the different degree of DNA instability at acid hydrolysis. AO staining after hydrolysis with 2N HCl at 30 degrees C for 8.5 min was found to be the optimal method. In the 60 cases of human malignant epithelial and nonepithelial tumors tested, all of the malignant tumor cells emitted metachromatic red fluorescence, while all of the nonmalignant tumor cells (5 cases of benign tumor) and normal cells emitted orthochromatic green fluorescence when observed with a violet excitation light under a fluorescence microscope. This new technique can be a useful tool for the screening of malignancy in exfoliative cytology and also for basic cancer research. MH - Acridine Orange/*DIAGNOSTIC USE ; Animal ; Cell Cycle ; DNA/ *ANALYSIS ; DNA, Neoplasm/*ANALYSIS ; Human ; Hydrolysis ; Male ; Mice ; Microscopy, Fluorescence ; Neoplasms/*DIAGNOSIS ; Stains and Staining SO - Histochemistry 1986;84(4-6):556-60 72 UI - 86250193 AU - Ploem JS ; van Driel-Kulker AM ; Goyarts-Veldstra L ; Ploem-Zaaijer JJ ; Verwoerd NP ; van der Zwan M TI - Image analysis combined with quantitative cytochemistry. Results and instrumental developments for cancer diagnosis. AB - This paper describes the application of image analysis combined with a quantitative staining method for the analysis of cervical specimens. The image analysis is carried out with the Leyden Television Analysis System, LEYTAS, of which two versions are described. LEYTAS-1 as well as LEYTAS-2 have both been designed with a high degree of flexibility and interaction facilities. A much wider range of image analysis programs is however, possible with LEYTAS-2, enabling many applications. LEYTAS-1, the earlier version, consists of a Leitz microscope with automated functions, a TV camera, the Texture Analysis System (TAS, Leitz), a four-bit grey value memory and a minicomputer (PDP 11/23). Using this instrumentation 1,500 cervical smears prepared from cell suspensions and stained with acriflavin-Feulgen-Sits have been analysed in a completely automated procedure. Image transformations working in parallel on entire fields, have been used for cell selection and artefact rejection. Resulting alarms, consisting of selected single cells and non-rejected artefacts are stored in the grey value memory, which is displayed on a TV monitor. This option allows visual interaction after the machine diagnosis has been made. The machine diagnosis was correct in 320 out 321 specimens with a severe dysplasia or more serious lesion. The false positive rate in 561 morphologically negative specimens (normal and inflammation) was 16% (machine diagnosis). Visual interaction by subtracting the visually recognized false alarms from the total number of alarms reduces the false positive rate to 11%.(ABSTRACT TRUNCATED AT 250 WORDS) MH - Acriflavine/DIAGNOSTIC USE ; Cervix Neoplasms/*DIAGNOSIS/ PATHOLOGY ; Computers ; Dyes/DIAGNOSTIC USE ; Female ; Human ; Inflammation/PATHOLOGY ; Precancerous Conditions/*DIAGNOSIS/ PATHOLOGY ; Stains and Staining ; Support, Non-U.S. Gov't ; SITS/ DIAGNOSTIC USE SO - Histochemistry 1986;84(4-6):549-55 73 UI - 86243029 AU - Tochner Z ; Mitchell JB ; Smith P ; Harrington F ; Glatstein E ; Russo D ; Russo A TI - Photodynamic therapy of ascites tumours within the peritoneal cavity. AB - A murine ascites tumour was treated with intraperitoneal haematoporphyrin derivative (HPD) and laser light (10mW, 514nm, Argon laser). HPD was given intraperitoneally 2 hours before 16 minute laser treatment. Uptake studies 2 hours after HPD injection showed 5-12 fold greater concentration of HPD in tumour cells than in 4 different normal tissues. A total of four HPD/laser treatments, given at 2 day intervals, resulted in 100% complete response; the cure rate was 85%. This study illustrates the effective use of intraperitoneal photodynamic therapy and opens the possibility of exploring different sensitizers, excitation wavelengths, and delivery systems in the treatment of human ascites tumours. MH - Animal ; Ascites/DRUG THERAPY ; Female ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/METABOLISM/THERAPEUTIC USE ; Lasers/THERAPEUTIC USE ; Mice ; Mice, Inbred C3H ; Peritoneal Neoplasms/*DRUG THERAPY ; *Photochemotherapy ; Teratoma/*DRUG THERAPY/METABOLISM ; Tissue Distribution SO - Br J Cancer 1986 Jun;53(6):733-6 74 UI - 86239547 AU - Tsokos M ; Kyritsis AP ; Chader GJ ; Triche TJ TI - Differentiation of human retinoblastoma in vitro into cell types with characteristics observed in embryonal or mature retina. AB - The capacity of a primitive human retinoblastoma cell line (Y-79) to differentiate into several cell types of normal human retina was investigated. Cells were studied in suspension and monolayer cultures, in serum-free or serum-supplemented medium, and in the presence or absence of differentiating agents such as N6O12-dibutyryl adenosine 3',5'-cyclic monophosphate (dbc-AMP) and sodium butyrate (Nabut). Electron microscopy, immunohistochemistry for detection of myelin basic protein (MBP), and formaldehyde-induced fluorescence (FIF) for catecholamines were performed. Treated cells exhibited morphologic characteristics supportive of differentiation toward photoreceptors, conventional neurons and glial cells, increased FIF reactivity, and MBP expression. Growth in serum-free medium without differentiating agents led to a similar but less enhanced morphologic differentiation. These results confirm the concept that human retinoblastoma originates from a primitive neuroectodermal multipotential cell. MH - Butyric Acids/PHARMACODYNAMICS ; Cell Differentiation ; Cells/ CLASSIFICATION ; Cells, Cultured ; Cytological Technics ; Cytoplasm/ULTRASTRUCTURE ; Dibutyryl Cyclic AMP/PHARMACODYNAMICS ; Eye Neoplasms/*PATHOLOGY/ULTRASTRUCTURE ; Fluorescence ; Formaldehyde/DIAGNOSTIC USE ; Histocytochemistry ; Human ; Immunochemistry ; Microscopy, Electron ; Microvilli/ ULTRASTRUCTURE ; Neuroglia/PATHOLOGY ; Neurons/PATHOLOGY ; Retina/ *CYTOLOGY/EMBRYOLOGY/GROWTH & DEVELOPMENT ; Retinoblastoma/ *PATHOLOGY/ULTRASTRUCTURE ; Rosette Formation SO - Am J Pathol 1986 Jun;123(3):542-52 75 UI - 86237069 AU - Roberts DH ; Lucas MH ; Wibberley G TI - To compare the incubation period following intratracheal and subcutaneous inoculation of bovine leukosis virus infected lymphocytes and to study their clearance from the circulation. AB - The migration of fluorescein isothiocyanate labelled lymphocytes through the tracheobronchial mucosa has been studied in cattle. Following intratracheal inoculation of labelled non-infected autologous lymphocytes and bovine leukosis virus (BLV) infected heterologous (presumed allogeneic) lymphocytes, the labelled lymphocytes appeared in the blood circulation between 4 and 7 days post inoculation. Following intravenous inoculation of labelled autologous lymphocytes, the cells could be detected in the circulation for 10 days post inoculation whereas BLV infected and non-infected heterologous lymphocytes could be detected for only 2 days. The migration of BLV-infected heterologous lymphocytes through the tracheobronchial mucosa caused a delay in the appearance of labelled lymphocytes in the circulation and a corresponding delay in the appearance of BLV antibodies. Comparison was made of the effect of two different routes of inoculation, subcutaneous and intratracheal on the incubation period as indicated by the detection of antibody. Subcutaneous inoculation of 1 X 10(4), 5 X 10(3), 1 X 10(3) of lymphocytes from a BLV infected cow caused seroconversion whereas 5 X 10(2) cells did not. Intratracheal inoculation of 5 X 10(3) cells caused sero-conversion. One animal did not develop BLV antibody until 30 weeks after inoculation although BLV could be isolated from the blood at 24 and 26 weeks post inoculation. MH - Animal ; Antibodies, Viral/ANALYSIS ; Bovine Leukemia Virus/ *IMMUNOLOGY/METABOLISM ; Cattle ; Comparative Study ; Fluoresceins/DIAGNOSTIC USE ; Injections ; Injections, Subcutaneous ; Leukemia, Experimental/*BLOOD/IMMUNOLOGY ; Lymphocytes/IMMUNOLOGY/METABOLISM/*TRANSPLANTATION ; Male ; Retroviridae/*IMMUNOLOGY ; Thiocyanates/DIAGNOSTIC USE ; Time Factors ; Trachea ; Transplantation, Autologous ; Transplantation, Heterologous SO - Vet Immunol Immunopathol 1986 Apr;11(4):351-9 76 UI - 86235599 AU - Thomas JA TI - Intracellularly trapped pH indicators. AB - The trapped indicator technique has several advantages for monitoring intracellular pH. It can be performed with equipment available in most laboratories, using either fluorescence or absorbance measurements. It is nondestructive to cells, and fluorescein dyes seem to have little effect on cell metabolism (however, see Spray et al., 1984). Continuous real-time monitoring of intracellular pH is possible, and the method can detect changes of 0.01 pH. It is sensitive enough for studies with monolayers (Thomas et al., 1982) or individual cells (Slavik and Kotyk, 1984; Udkoff and Norman, 1979). In addition, pH changes in the cytoplasmic and mitochondrial compartments can be distinguished by judicious use of CF and F. On the negative side, one of the main problems encountered is that of leakage, especially for F. Spectral measurements must be corrected for leakage in order to assess pH accurately. Three ways of minimizing leakage are as follows: (1) Use a less leaky indicator, such as BCECF (Rink et al., 1982); (2) lower the incubation temperature; (3) continuously remove external indicator by perfusion technique (Boron, 1982). Although CFA2 specifically monitors cytoplasmic pH in several different cell types, this may not necessarily be a general phenomenon. As shown in this chapter, it can report mitochondrial pH transitions if it is first hydrolyzed by mitochondrial esterases. Thus, this specificity for the cytoplasm should be established for any new cell type studied. As a final note, Spray et al. (1984) have recently reported that the intracellular hydrolysis of certain membrane-permeant esters causes an acidification of the cytoplasm in several cell types. The acidification was considerably in excess of that expected from the small amount of acid generation caused by the esterase reaction. How general this phenomenon is remains to be established. MH - Animal ; Body Fluids/*ANALYSIS ; Calibration ; Carcinoma, Ehrlich Tumor/ANALYSIS ; Cytosol/ANALYSIS ; Fluoresceins/DIAGNOSTIC USE ; Fluorescent Dyes/*DIAGNOSTIC USE ; *Hydrogen-Ion Concentration ; *Indicators and Reagents ; Intracellular Fluid/*ANALYSIS ; Liver/ CYTOLOGY ; Mice ; Mitochondria, Liver/ANALYSIS ; Review ; Spectrometry, Fluorescence/METHODS SO - Soc Gen Physiol Ser 1986;40:311-25 77 UI - 86234316 AU - Lindenberger J ; Hermeking H ; Kummermehr J ; Denekamp J TI - Response of human tumour xenografts to fractionated X-irradiation. AB - The response of two human tumour xenografts to single dose and fractionated X-rays has been tested using regrowth delay as the assay. The tumours were line transplanted cells from a moderately well-differentiated squamous carcinoma of the tonsillar fossa (XJ) and an undifferentiated carcinoma of the floor of the mouth (XR). Comparison of the dose response curves for single doses in air, clamped, or after misonidazole administration, led to estimates of the hypoxic fraction (approximately 15%) and the sensitizer enhancement ratio (less than or equal to 1.6). When 5 daily fractions were used, the effect of misonidazole (miso) was lost and reoxygenation appeared to be effective in both tumours. Comparison of single doses and 5 fractions in clamped tumours, and in those sensitized by miso, allowed the sparing effect of fractionation to be estimated. When analysed by the linear quadratic model the alpha/beta ratios were found to be in the range of 6.4-9.2 Gy and 6.8-16.0 Gy for the two tumours. These values are in good agreement with murine tumours (assayed in vivo or in vitro), with human tumour cells assayed in vitro, and with analyses of fractionated clinical data for skin cancer. MH - Animal ; Carcinoma/DRUG THERAPY/*RADIOTHERAPY ; Carcinoma, Squamous Cell/DRUG THERAPY/*RADIOTHERAPY ; Combined Modality Therapy ; Disease Models, Animal ; Dose-Response Relationship, Radiation ; Female ; Human ; Male ; Mice ; Mice, Nude ; Misonidazole/THERAPEUTIC USE ; Mouth Neoplasms/DRUG THERAPY/ *RADIOTHERAPY ; *Neoplasm Transplantation ; Photochemotherapy ; Radiotherapy Dosage ; Support, Non-U.S. Gov't ; Tonsillar Neoplasms/DRUG THERAPY/*RADIOTHERAPY ; *Transplantation, Heterologous SO - Radiother Oncol 1986 May;6(1):15-27 78 UI - 86230164 AU - Gerlowski LE ; Jain RK TI - Microvascular permeability of normal and neoplastic tissues. AB - A novel, noninvasive method was developed for microvascular permeability measurements in non-malignant (mature granulation) and neoplastic (VX2 carcinoma) tissues grown in the rabbit ear chamber. Dextran of 150,000 molecular weight, tagged with fluorescein isothiocyanate (FITC), was used as a representative tracer molecule. In vivo plasma concentration of dextran was measured by photometric analysis of the plasma layer of microvessels in the ear chamber. The plasma concentration in both normal and tumor preparations rose rapidly to a steady state with a time constant of 4.06 +/- 0.2 sec, and remained relatively constant at that level for the next 2 hr (elimination time constant = 1.77 +/- 0.9 X 10(5) sec). Extravasation of macromolecules from individual microvessels into the extravascular space was measured with the same photometric technique. Interstitial diffusion coefficients and microvascular permeability coefficients were determined by fitting a one-dimensional permeability-diffusion model to the extravasation data. The diffusivity of dextran in tumor interstitium was 2.2 +/- 1.4 X 10(-8) cm2/sec (n = 6) and in granulation tissue interstitium was 6.7 +/- 4.4 X 10(-10) cm2/sec (n = 6). Microvascular permeability in tumors was 7.26 +/- 3.29 X 10(-8) cm/sec (n = 11) and in granulation tissue was 57.24 +/- 39.24 X 10(-8) cm/sec (n = 10). These results on increased permeability (8-fold; P less than 0.002) and increased diffusivity (33-fold; P less than 0.001) in tumors provide a rational basis for the use of large-molecular-weight agents in the detection and treatment of solid tumors. MH - Animal ; Antineoplastic Agents/METABOLISM ; *Capillary Permeability ; Dextrans/DIAGNOSTIC USE ; Diffusion ; Fluoresceins/ DIAGNOSTIC USE ; Granulation Tissue/METABOLISM ; Male ; Models, Molecular ; Molecular Weight ; Neoplasms, Experimental/ *METABOLISM ; Rabbits ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Microvasc Res 1986 May;31(3):288-305 79 UI - 86224080 AU - Ronning SA ; Martin TF TI - Characterization of Ca2+-stimulated secretion in permeable GH3 pituitary cells. AB - In this report, the secretory response to Ca2+ in GH3 rat pituitary cells permeabilized by electric field discharge has been compared in both magnitude and Ca2+ sensitivity to prolactin (PRL) release from intact GH3 cells. The half-maximally effective [Ca2+] for stimulating PRL release in permeable cells was approximately 0.5 microM, and maximal stimulation was obtained at 3-10 microM Ca2+. The magnitude of Ca2+ stimulation in permeable cells was in the same range as that obtained from an equal number of intact cells stimulated by depolarizing K+. Moreover, the Ca2+ sensitivity of PRL release in intact GH3 cells (measured by Quin 2 fluorescence) closely resembled the Ca2+ sensitivity determined in permeable cells. Release of a sulfated proteoglycan whose release is stimulated by secretagogues in intact cells was stimulated by Ca2+ in permeable cells with the same Ca2+ sensitivity as for PRL release. Maximal Ca2+ stimulation of PRL release in permeable cells required the addition of MgATP. Other energy sources (ADP, GTP, and inorganic phosphate) also supported Ca2+-stimulated secretion but were less effective. The above results indicated that PRL release from permeable cells resembles the physiological process in intact cells. The permeable cell system should prove useful in investigating the mechanism mediating the effect of Ca2+ on secretion, although our studies with pharmacological agents have so far proved inconclusive. Among calmodulin antagonists tested, only trifluoroperazine inhibited Ca2+-stimulated secretion, whereas pimozide and calmidazolium did not. MH - Adenosine Triphosphate/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Aminoquinolines ; Animal ; Calcium/*PHARMACODYNAMICS ; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/PHARMACODYNAMICS ; Cell Line ; Cell Membrane Permeability ; Dyes ; Fluorescence ; Kinetics ; Pituitary Neoplasms/*SECRETION ; Prolactin/*SECRETION ; Rats ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - J Biol Chem 1986 Jun 15;261(17):7834-9 80 UI - 86222961 AU - Kessel D TI - Photosensitization with derivatives of haematoporphyrin. AB - This review describes recent progress in delineation of the structure of the active component(s) in the tumour-localizing photosensitizer HPD (haematoporphyrin derivative), along with suggestions concerning the likely determinants of accumulation of this product by different tissues. MH - *Hematoporphyrin Photoradiation ; Hematoporphyrins/DIAGNOSTIC USE ; Human ; Neoplasms/DIAGNOSIS/*DRUG THERAPY ; *Photochemotherapy ; Review ; Support, U.S. Gov't, P.H.S. SO - Int J Radiat Biol 1986 Jun;49(6):901-7 81 UI - 86213771 AU - Kiss R ; Lenglet G ; Danguy A TI - Binding of fluorescein isothiocyanate conjugated lectins to MXT mouse mammary neoplasm and their relation to steroid receptor status. AB - As previous studies have suggested a hormone dependence of binding sites for peanut agglutinin in mammary neoplasm, this feature has been thought to be correlated to steroid receptor status. The present investigation was undertaken on a well-established ovarian-dependent cancer model in order to check this hypothesis. Sections of primitive tumor transplants as well as of tumors induced in vivo by injection of cell clones were analyzed with the use of three fluorescent lectins. The lectin binding sites were evaluated semi-quantitatively and compared with estrogen and progesterone receptor levels. Using non-parametric statistical tests, the results revealed a strong correlation between the expression of peanut agglutinin (PNA) binding sites and steroid receptor status, but only in primitive tumor transplants. No such correlation was observed in tumors induced in vivo, by injection of cell clones. No correlation between the steroid receptor status and the two other lectins (Concanavalin A and Dolichos biflorus) was observed. These data suggest that PNA can be used as a valuable histochemical tool in steroid hormone dependence study. MH - Animal ; Concanavalin A/METABOLISM ; Female ; Fluoresceins/ *DIAGNOSTIC USE ; Histocytochemistry ; Lectins/METABOLISM ; Mammary Neoplasms, Experimental/*ANALYSIS/PATHOLOGY ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Neoplasm Transplantation ; Receptors, Estrogen/*ANALYSIS ; Receptors, Mitogen/*ANALYSIS ; Receptors, Progesterone/*ANALYSIS ; Support, Non-U.S. Gov't ; Thiocyanates/*DIAGNOSTIC USE SO - Anticancer Res 1986 Mar-Apr;6(2):209-13 82 UI - 86211804 AU - Dunn JF Jr TI - Vitiligo. AB - Vitiligo is characterized by depigmentation in large or small areas of the skin. There is a complete lack of melanin production in the hypopigmented areas, due to the destruction of previously active melanocytes. This is in contrast to albinism, in which melanocytes are present but there is little or no pigmentation because of defective or absent tyrosinase. Although the etiology of vitiligo remains unknown, an autoimmune theory is gaining acceptance. MH - Adolescence ; Adult ; Autoimmune Diseases/COMPLICATIONS ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Fluorouracil/THERAPEUTIC USE ; Human ; Hydroquinones/THERAPEUTIC USE ; Male ; Melanoma/COMPLICATIONS ; Photochemotherapy ; Skin Neoplasms/COMPLICATIONS ; Vitiligo/*DIAGNOSIS/DRUG THERAPY/ ETIOLOGY SO - Am Fam Physician 1986 May;33(5):137-43 83 UI - 86204847 AU - Burns RA ; Klaunig JE ; Shulok JR ; Davis WJ ; Goldblatt PJ TI - Tumor-localizing and photosensitizing properties of hematoporphyrin derivative in hamster buccal pouch carcinoma. AB - The tumor-localizing and photochemotherapeutic properties of hematoporphyrin derivative (HPD) were examined in 7, 12 dimethylbenzanthracene (DMBA)-induced oral cancers in the Syrian hamster. Oral tumors in hamsters injected with HPD (50 micrograms per gram of body weight) exhibited bright salmon pink fluorescence when exposed to long-wave ultraviolet light 24 hours after intraperitoneal HPD injection. Adjacent tumor-free mucosa did not fluoresce. Similarly, tumors not treated with HPD, normal mucosa treated with HPD, and normal mucosa not treated with HPD did not fluoresce. Tumors in animals that received HPD and photochemotherapy (PCT) were examined for gross and microscopic pathologic changes following the phototreatment. Tumors displayed edema, hemorrhage, and cellular necrosis that progressed with the time of sampling after photochemotherapy. Complete tumor necrosis was evident in the majority of oral tumors 24 hours after HPD PCT. MH - Animal ; Antineoplastic Agents/*THERAPEUTIC USE ; Carcinoma, Squamous Cell/*DRUG THERAPY/METABOLISM/PATHOLOGY ; Cheek ; Hamsters ; Hematoporphyrins/METABOLISM/*THERAPEUTIC USE ; Male ; Mesocricetus ; Mouth Mucosa/DRUG EFFECTS/METABOLISM/PATHOLOGY ; Mouth Neoplasms/*DRUG THERAPY/METABOLISM/PATHOLOGY ; Necrosis ; *Photochemotherapy ; Support, U.S. Gov't, P.H.S. SO - Oral Surg Oral Med Oral Pathol 1986 Apr;61(4):368-72 84 UI - 86201680 AU - Daxenbichler G ; D:urken M ; Marth C ; B:ock G ; Dapunt O TI - Influence of steroids and retinoic acid on peanut-lectin binding of human breast cancer cells. AB - Membrane binding sites for peanut lectin or peanut agglutinin (PNA) were investigated in the established mammary carcinoma cell lines MCF-7, 734-B, ZR-75.1 and BT-20. The determination of PNA binding sites was performed in a flow cytometer after staining with fluorescein(FITC)-labeled PNA. It appeared that only the estrogen-sensitive cell lines exhibited PNA binding sites, whereas the hormone-insensitive cell line BT-20 was clearly negative. Steroid hormones, when administered singly to the cells in physiological concentrations (10(-9)-10(-8) M) had no effect on PNA binding expression. Only the combination of estradiol and progesterone together increased PNA binding sites. Pharmacological doses (10(-6) M) of medroxyprogesteroneacetate (MPA) and dexamethasone increased the number of binding sites, whereas retinoic acid decreased them. A preliminary characterization of the binding sites revealed that they have high capacity and moderate affinity for PNA (KD greater than 10(-7) M). FITC-PNA binding could be inhibited selectively by fetuin (greater than 10(-5) M) and by galactose (greater than 10(-2) M). Cytosol from MCF-7 cells and from some primary breast cancer specimens were able to decrease PNA binding to the surface of 734-B cells. MH - Breast Neoplasms/*ANALYSIS ; Cell Line ; Dexamethasone/ PHARMACODYNAMICS ; Female ; Fluoresceins/DIAGNOSTIC USE ; Human ; Medroxyprogesterone/ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Receptors, Mitogen/*ANALYSIS/DRUG EFFECTS ; Steroids/ *PHARMACODYNAMICS ; Thiocyanates/DIAGNOSTIC USE ; Tretinoin/ *PHARMACODYNAMICS SO - J Steroid Biochem 1986 Jan;24(1):119-24 85 UI - 86198918 AU - Hamilton D ; McKean JD ; Tulip J ; Boisvert D ; Cummins J TI - In vitro photoradiation therapy of the rat 9L gliosarcoma. AB - The authors have investigated various factors involved in the photoradiation treatment of 9L glioma cells. The cells were grown in tissue culture and exposed to light from a laser source that allowed accurate quantitation of the light energy. Cell death was determined following treatment using the trypan blue exclusion test. It was shown that the treatment is very wavelength-dependent following the absorption spectrum of hematoporphyrin derivative (HPD). The absorption peaks in the lower part of the spectrum are more efficient than those of higher wavelengths. Photoradiation therapy is more effective the higher the concentration of HPD. Intensity of light is a very important factor in calculating the total dose of light necessary for this treatment. MH - Animal ; Brain Neoplasms/*DRUG THERAPY/SURGERY ; Cells, Cultured ; Glioma/*DRUG THERAPY/SURGERY ; Hematoporphyrin Photoradiation ; Hematoporphyrins/*THERAPEUTIC USE ; In Vitro ; Lasers/THERAPEUTIC USE ; Rodentia ; Support, Non-U.S. Gov't SO - J Neurosurg 1986 May;64(5):775-9 86 UI - 86198917 AU - Kostron H ; Bellnier DA ; Lin CW ; Swartz MR ; Martuza RL TI - Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma. Intraneoplastic versus intraperitoneal injection. AB - The distribution, retention, and phototoxicity of the sensitizer hematoporphyrin derivative (HPD) were studied following intraperitoneal and direct intraneoplastic injections of the agent into subcutaneous or intracerebral gliosarcomas in rats. Forty-eight hours after intraperitoneal injection, the ratio of tritiated (3H) HPD in subcutaneous tumor: adjacent normal skin was about 1.4:1 and the ratio in tumor: normal brain was 3:1. In contrast, direct injection of 3H-HPD into subcutaneous tumors resulted in tumor: adjacent normal skin concentration ratios of approximately 44:1 and tumor: normal brain ratios of about 61:1. For rats bearing intracerebral gliosarcomas, intraperitoneal administration of 3H-HPD resulted in approximately 1.3-fold sensitization in tumor tissue relative to adjacent edematous brain. In contrast, after direct injection into intracerebral tumors, the tumor: adjacent edematous brain and tumor: skin 3H-HPD ratios were 3:1 and 32:1, respectively. In all cases, 3H-HPD was found in every portion of the tumor, even at a distance from the injection site. For the 3H-HPD doses used in this study, after direct injection both subcutaneous and intracerebral tumor tissue contained about three to four times more 3H-HPD than tumors in rats receiving intraperitoneal 3H-HPD. Both in vitro and in vivo clonogenic assays demonstrated that the photodynamic inactivation of the tumors was significantly greater after direct injection than after intraperitoneal injection. MH - Animal ; Brain Edema/METABOLISM ; Brain Neoplasms/*DRUG THERAPY/ METABOLISM ; Comparative Study ; Glioma/*DRUG THERAPY/METABOLISM ; Hematoporphyrin Photoradiation ; Hematoporphyrins/ ADMINISTRATION & DOSAGE/METABOLISM/TOXICITY/*THERAPEUTIC USE ; Male ; Rats ; Rats, Inbred F344 ; Tritium SO - J Neurosurg 1986 May;64(5):768-74 87 UI - 86195526 AU - Hattori T ; Sugihara H ; Fukuda M ; Hamada S ; Fujita S TI - DNA ploidy patterns of minute carcinomas in the stomach. AB - DNA ploidy patterns of minute carcinomas in the stomach were determined by cytofluorometric measurement, using paraffin sections which had been prepared for histological examination. The examples studied were 19 minute carcinomas less than 5 mm in diameter, of which 12 were adenocarcinomas, and 7 were signet ring cell carcinomas. By measuring the fluorescence intensity of more than 30 mitotic nuclei, the DNA ploidy pattern of each tumor was determined. The control diploid DNA content was obtained by measuring the fluorescence intensity of non-cancerous mitoses in the gastric mucosa. In the present study, heteroploidy was seen in 5 carcinomas; 4 adenocarcinomas and one signet ring cell carcinoma. The remaining 14 carcinomas were composed of a diploid stem cell line. In 3 adenocarcinomas, polyploid cells were seen. The occurrence of heteroploidy in the minute cancers was similar to that found in advanced cancers, whereas polyploid cells appeared to occur less frequently in the minute cancers than in the advanced cancers. MH - Aged ; Carcinoma/*FAMILIAL & GENETIC/PATHOLOGY ; DNA, Neoplasm/ *ANALYSIS ; Female ; Fluorescence ; Human ; Male ; Middle Age ; *Ploidies ; Stomach Neoplasms/*FAMILIAL & GENETIC/PATHOLOGY ; Support, Non-U.S. Gov't SO - Jpn J Cancer Res 1986 Mar;77(3):276-81 88 UI - 86194991 AU - Rabbiosi G ; Carcaterra A ; Bellosta M TI - Treatment of cutaneous T cell lymphomas with PUVA. AB - A series of 39 patients with CTCL was treated with PUVA over a period of 5 years, comprising 6 patients in stage IA, 13 in stage IB, 15 in stage IIA and 5 in stage IIB. PUVA treatments were administered four times weekly until clearing; a maintenance therapy employed 2 to 1 exposures per week for 2 months. Complete clinical and histological examinations were taken. We obtained a complete remission in all stage IA patients, and a partial remission in stage IB and IIA patients, who required longer treatment schedules and more frequent maintenance therapy. Stage IIB patients required additional local and/or systemic therapy to achieve a partial remission. Recurrences were observed in 33% stage IA patients, in 84% stage IB patients and in all stage IIA and IIB patients. They responded to new induction phases only in early-stage CTCL. PUVA is well accepted by patients, and compares well with other treatments. MH - Follow-Up Studies ; Human ; Lymphoma/*DRUG THERAPY/PATHOLOGY ; Neoplasm Staging ; *PUVA Therapy ; Recurrence ; Skin Neoplasms/ *DRUG THERAPY/PATHOLOGY ; T Lymphocytes SO - Int J Tissue React 1986;8(2):141-3 89 UI - 86189666 AU - Sas DF ; McCarthy JB ; Furcht LT TI - Clearing and release of basement membrane proteins from substrates by metastatic tumor cell variants. AB - A variety of normal cells and tumor cell lines of differing metastatic potential were evaluated for their effect on various substrates consisting of purified preparations of the basement membrane-associated proteins fibronectin, laminin, and type IV collagen, which were labeled with tritium and/or rhodamine isothiocyanate. Different degrees of clearing or release of material from the substrate were observed, depending on the cell-protein combination. Normal fibroblasts as well as transformed cells and cells of low metastatic potential showed extensive clearing of surfaces coated with fibronectin, laminin, and type IV collagen. This clearing of protein began at sites of initial cell adhesion and was restricted to areas beneath and/or along the apparent paths of cell migration and beneath cellular processes. Covalent attachment of adhesion proteins to glass coverslips nearly eliminated clearing and release. Studies showed that a substantial amount of the fibronectin released from the substrate by HT-1080 fibrosarcoma cells is due to proteolysis. Release and clearing of substratum-attached protein is reduced by approximately 50% by antibodies specific for the protein on the substrate. Tumor cells with low metastatic potential were found to produce higher levels of clearing and release of protein adsorbed to the substrate than tumor cells with high metastatic potential. This was true for variants of the murine K-1735 melanoma and the UV-2237 fibrosarcoma with high and low metastatic capability on all three basement membrane-associated protein substrates. The differences in clearing and release between high and low metastatic cells were not due to differences in initial cell adhesion to the substrates but may be associated with differences in the affinity, type of cell-substrate interactions, proteases, or other variables. MH - Animal ; Antibodies/IMMUNOLOGY ; Basement Membrane/IMMUNOLOGY/ *METABOLISM ; Cell Adhesion ; Cell Communication ; Collagen/ METABOLISM ; Fibronectins/METABOLISM ; Fibrosarcoma/METABOLISM ; Human ; Laminin/METABOLISM ; Melanoma/METABOLISM ; Membrane Proteins/*METABOLISM ; Mice ; *Neoplasm Metastasis ; Plasminogen Activators/PHYSIOLOGY ; Rhodamines/DIAGNOSTIC USE ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Tritium/DIAGNOSTIC USE SO - Cancer Res 1986 Jun;46(6):3082-9 90 UI - 86189644 AU - Chaudhuri K ; Goldblatt PJ ; Kreimer-Birnbaum M ; Keck RW ; Selman SH TI - Histological study of the effect of hematoporphyrin derivative photodynamic therapy on the rat jejunum. AB - Hematoporphyrin derivative photodynamic therapy is evolving as a local treatment for neoplastic disease. The emphasis of previous research has been on the determination of mechanisms of tumoricidal activity and defining the tumoricidal porphyrin component in hematoporphyrin derivative. The effect of hematoporphyrin derivative photodynamic therapy on normal tissue has received little attention. In the following study we examined the morphological changes of normal rat intestine exposed to hematoporphyrin derivative and light. In this model a segment of rat jejunum was exposed to red light (greater than 590 nm; 360 J/cm2) 24 or 72 h after the i.v. administration of hematoporphyrin derivative (5 or 10 micrograms/g body weight). Control groups received either no treatment, hematoporphyrin derivative only, or light only. Four h after treatment, intestinal segments were removed and examined by light microscopy. Segments treated with hematoporphyrin derivative and light showed extensive sloughing of the mucosa and submucosa with sparing of the muscular and serosal layers. It appears that hematoporphyrin derivative photodynamic therapy is capable of causing mucosal and submucosal damage to normal rat jejunum at these doses of light and hematoporphyrin derivative. MH - Animal ; Hematoporphyrin Photoradiation/*ADVERSE EFFECTS ; Intestines/BLOOD SUPPLY ; Jejunum/*DRUG EFFECTS/PATHOLOGY ; Male ; Neoplasms/DRUG THERAPY ; Photochemotherapy/*ADVERSE EFFECTS ; Rats ; Rats, Inbred F344 ; Regional Blood Flow/DRUG EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Jun;46(6):2950-3 91 UI - 86189628 AU - Gonzalez S ; Arnfield MR ; Meeker BE ; Tulip J ; Lakey WH ; Chapman JD ; McPhee MS TI - Treatment of Dunning R3327-AT rat prostate tumors with photodynamic therapy in combination with misonidazole. AB - Fischer X Copenhagen rats bearing Dunning R3327-AT tumors were treated with hematoporphyrin derivative and red light (630 nm from an argon-driven dye laser) alone or in combination with the hypoxic cell radiosensitizer, misonidazole (MISO). In vitro studies had suggested that hypoxia might significantly decrease the cytotoxicity of photodynamic therapy (PDT) and labeling with [14C]MISO had revealed a significant fraction of viable hypoxic cells in this tumor. PDT alone resulted in a growth delay of 8.8 days but no tumor cures were observed. The administration of MISO (i.p. at 0.5 mg/g) 33 min prior to PDT resulted in an average growth delay of 15.2 days and tumor cures (local control at 33 days) in 20% of animals treated. If MISO at a similar dosage was administered 30 min after PDT an average growth delay of 16.3 days was measured and tumor cure was observed in 70% of the animals treated. These results suggest that the hypoxic cell fraction in R3327-AT tumors might be a limitation to their curability by PDT. The addition of MISO and/or other hypoxic cell cytotoxic agents to PDT procedures may provide an effective means of treating PDT-resistant hypoxic cells in solid tumors. MH - Animal ; Combined Modality Therapy ; Female ; Male ; Misonidazole/ *THERAPEUTIC USE ; Oxygen ; *Photochemotherapy ; Prostatic Neoplasms/*DRUG THERAPY/PATHOLOGY ; Rats ; Rats, Inbred Strains ; Support, Non-U.S. Gov't ; Temperature SO - Cancer Res 1986 Jun;46(6):2858-62 92 UI - 86189571 AU - Star WM ; Marijnissen HP ; van den Berg-Blok AE ; Versteeg JA ; Franken KA ; Reinhold HS TI - Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers. AB - The effect of hematoporphyrin derivative photoradiation on tumor and normal tissue microcirculation was studied microscopically in vivo on rats with mammary carcinomas transplanted into subcutis in transparent observation chambers. One day after i.p. injection of hematoporphyrin derivative (15 mg/kg), chambers were exposed to red light (632 +/- 2 nm, eight light dose values, 0 to 270 J/cm2). After an initial blanching (ischemia) of the tumor accompanied by apparent vasoconstriction, reperfusion was observed with a slowing down of the tumor circulation, vasodilatation, and eventually a complete stasis, together with diffuse hemorrhages and subsequent necrosis. Besides, in large normal tissue vessels, platelet aggregates were observed, but no hemorrhage. Tumor regrowth occurred unless the tumor circulation and the adjacent normal tissue circulation were both destroyed. Tumor cell viability after treatment was assessed by transplanting the tumor from the chamber into the flank of the same animal. Even after a combined porphyrin and light dose 4 times the lethal dose for all tissues in the chamber, five of five transplanted tumors did regrow. This leads to the conclusion that, in our model system, tumor cell death after photoradiation occurs secondary to destruction of the microcirculation. In order to obtain additional information on normal tissue damage, rat ears were also irradiated. For the same light dose, the biological effect was only slightly larger than that of the normal tissue in the observation chambers, even though the measured ratio of porphyrin concentrations in ears and normal tissue in the chambers (subcutis) was about six. MH - Animal ; Dose-Response Relationship, Drug ; Ear/BLOOD SUPPLY ; Female ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/ THERAPEUTIC USE ; Mammary Neoplasms, Experimental/BLOOD SUPPLY/ *DRUG THERAPY ; Microcirculation/*DRUG EFFECTS ; Neoplasm Transplantation ; *Photochemotherapy ; Rats ; Support, Non-U.S. Gov't SO - Cancer Res 1986 May;46(5):2532-40 93 UI - 86189519 AU - Kessel D TI - Localization and photosensitization of murine tumors in vivo and in vitro by a chlorin-porphyrin ester. AB - Preparation of the tumor-localizing preparation called hematoporphyrin derivative involves a two-step reaction wherein hematoporphyrin is acetylated and the reaction product subjected to alkaline hydrolysis. We have proposed that the tumor-localizing fraction of this product is composed of hematoporphyrin units joined by ester linkages. Using an analogous synthetic procedure, we prepared some new sensitizers in which hematoporphyrin is esterified to chlorins (reduced porphyrins). Because of the differences in absorption spectra, the porphyrin-chlorin esters are 5-fold more potent photosensitizers than are the porphyrin-porphyrin esters, with light of wavelength greater than 600 nm. MH - Animal ; Cell Survival/DRUG EFFECTS ; Chromatography, High Pressure Liquid ; Female ; Hematoporphyrin Photoradiation/ *METHODS ; Hematoporphyrins/*CHEM SYNTHESIS/METABOLISM/ PHARMACODYNAMICS ; Mice ; Neoplasms, Experimental/METABOLISM ; Photochemotherapy/*METHODS ; Porphyrins ; Spectrometry, Fluorescence ; Spectrum Analysis ; Support, U.S. Gov't, P.H.S. ; Tissue Distribution SO - Cancer Res 1986 May;46(5):2248-51 94 UI - 86186931 AU - Wiebel FJ ; Kiefer F ; Krupski G ; Schuller HM TI - Expression of glutathione S-transferase and phenol sulfotransferase, but not of UDP-glucuronosyltransferase, in the human lung tumor cell lines NCI-H322 and NCI-H358. AB - The expression of xenobiotic-metabolizing enzymes was studied in the human lung tumour cell lines NCI-H322 and NCI-H358. These cells are derived from adenocarcinomas and exhibit features of Clara cells and alveolar type II cells, respectively. Examination of the in vitro activities showed that both cell lines lack UDP-glucuronosyltransferase against the substrates 3-hydroxybenzo[a]pyrene (3-OH-BaP) and 4-hydroxybiphenyl (4-OH-Bph) and that in vitro conjugation of sulfate with 3-OH-BaP was only just detectable. In contrast, both cell lines showed fairly high levels of glutathione-S transferase activity with the substrate 1-chloro-2,4-dinitro-benzene (54.4 and 83.0 nmol/min X mg protein, respectively) and of glutathione (81 and 41 nmole/mg protein, respectively). The metabolic capacity of intact NCI-H322 and NCI-H358 cells was examined using benzo[a]pyrene (BaP) and 3-OH-BaP as substrates. The cell lines formed sulfate conjugates from 3-OH-BaP (4.5 and 0.4 pmol/min X mg protein, respectively) but did not produce any detectable glucuronides. When cultures of the two cell lines were exposed to BaP, phenolic products accumulated in the growth medium. NCI-H322 cells also formed some sulfate conjugates, whereas such conjugates were barely detectable in the medium of NCI-H358 cells. In contrast A549, a human pulmonary adenocarcinoma cell line known to contain UDP-glucuronosyltransferase activity, efficiently conjugated 3-OH-BaP to glucuronic acid and converted the primary phenolic products formed from BaP to glucuronides. Thus the NCI-H322 and NCI-H358 cells are exceptional in that they possess no or very little glucuronosyltransferase activity but exhibit appreciable monooxygenase activity. The cell lines may therefore be of interest for examining the biological effects of potentially toxic chemicals which are otherwise detoxified by glucuronic acid conjugation. The cells may also be useful as test systems for evaluating the potential cytotoxicity and genotoxicity of chemicals to human lung. MH - Benzo(a)pyrene/METABOLISM ; Benzopyrenes/PHARMACODYNAMICS ; Cell Line ; Cell Survival/DRUG EFFECTS ; Fluorescence ; Glucuronates/ METABOLISM ; Glucuronidase/ANALYSIS ; Glutathione Transferases/ *ANALYSIS ; Human ; Hydroxylation ; Lung Neoplasms/*ENZYMOLOGY/ PATHOLOGY ; Phenols/METABOLISM ; Sulfurtransferases/*ANALYSIS ; UDP Glucuronosyltransferase/*ANALYSIS SO - Biochem Pharmacol 1986 Apr 15;35(8):1337-43 95 UI - 86184344 AU - Wieman TJ TI - Lasers and the surgeon. AB - The evolution of laser technology in medicine has progressed rapidly over the past 25 years, and these devices are widely used in surgical treatment today. Three different types of lasers are predominantly used: the carbon dioxide, argon ion, and neodymium-YAG instruments. Each operates on similar principles but because of the different wavelengths of light emitted, their applications differ. However, by and large, all of them utilize thermal energy generated by light and tissue interactions. Recently, the combination of an argon ion and a dye laser used with photosensitizing drugs has shown promise in the treatment of cancers, and this represents a nonthermal application of laser technology. In order to use lasers effectively, a knowledge of the specific laser and tissue properties is essential. In the future, lasers will be used not only as thermal scalpels but also as instruments than can provide a very precise delivery of energy to parts of the body that are otherwise inaccessible without operation. The use of photodynamic therapy will provide a mechanism of selectively destroying tumors while leaving normal tissues intact. MH - Animal ; Atherosclerosis/SURGERY ; Bladder Neoplasms/DRUG THERAPY ; Colonic Neoplasms/SURGERY ; Endoscopy/METHODS ; Esophageal Neoplasms/SURGERY ; Heat/THERAPEUTIC USE ; Hemorrhage, Gastrointestinal/SURGERY ; Human ; Lasers/HISTORY/*THERAPEUTIC USE ; Light Coagulation ; Lung Neoplasms/DRUG THERAPY ; Photochemotherapy/INSTRUMENTATION ; Rectal Neoplasms/SURGERY ; Surgery/*METHODS SO - Am J Surg 1986 Apr;151(4):493-500 96 UI - 86183537 AU - Grzelewska-Rzymowska I ; Szmidt M ; Kowalski ML ; Ro:zniecki J TI - Sensitivity and tolerance to tartrazine in aspirin-sensitive asthmatics. AB - The occurrence of sensitivity to tartrazine was examined in 51 patients with asthma and aspirin sensitivity. All patients underwent oral challenge tests with aspirin and tartrazine. Sensitivity to tartrazine was found in 16 i.e. 31.4% of tested asthmatics. The symptoms of sensitivity to tartrazine were similar to those of aspirin. Tolerance to tartrazine was induced in 5 aspirin and tartrazine sensitive asthmatics. Sensitivity to both substances was manifested in these 5 persons as dyspnea but 2 of them had additional extrabronchial symptoms. A good tolerance of 40 mg tartrazine was achieved in all the challenged patients who did not refer any dyspnea and extrabronchial symptoms. It was also proven that, being in the aspirin tolerance state the patients could be given tartrazine with no sensitivity symptoms. The authors think that the possibility of inducing tartrazine and aspirin tolerance, as well as the course of sensitivity reaction to both substances, both point to a similar pathogenetic background. MH - Adult ; Aspirin/*ADVERSE EFFECTS/DIAGNOSTIC USE ; Asthma/ *CHEMICALLY INDUCED/IMMUNOLOGY ; Azo Compounds/*ADVERSE EFFECTS ; Drug Hypersensitivity/*ETIOLOGY ; Female ; Forced Expiratory Volume ; Human ; Hypersensitivity, Immediate/COMPLICATIONS ; Male ; Middle Age ; Nasal Polyps/ETIOLOGY ; Tartrazine/*ADVERSE EFFECTS/DIAGNOSTIC USE SO - Allergol Immunopathol (Madr) 1986 Jan-Feb;14(1):31-6 97 UI - 86180373 AU - Cheng MK ; McKean J ; Boisvert D ; Tulip J TI - Photoradiation therapy: current status and applications in the treatment of brain tumors. AB - Photoradiation therapy is achieved when a photosensitizing drug is activated by light to form products that are lethal to tumor cells. The most commonly used drug is hematoporphyrin derivative, which is preferentially taken up and retained by malignant tissue. Photoactivation is usually produced by using a dye laser tuned at 630 nm (red light). The primary mechanism of neoplastic cell damage in photoradiation therapy involves the production of free radicals formed during illumination of hematoporphyrin derivative by light of this wavelength. The treatment would seem to damage first the tumor cell membrane, then the cytoplasmic inclusions, and finally the nucleus. Photoradiation therapy has been quite effective in the treatment of superficial malignancies, especially in skin, breast, eye, bladder, bronchus, and stomach. Experience with brain tumors is still limited. Important unresolved problems in the application of photoradiation therapy to gliomas include relative uptake of hematoporphyrin derivative into the tumor, limited light penetration of the tissue, local heating, and damage induced in normal brain by photoradiation therapy. MH - Brain Neoplasms/PHYSIOPATHOLOGY/*THERAPY ; Carcinoma/ PHYSIOPATHOLOGY/*THERAPY ; Chemistry ; Glioma/PHYSIOPATHOLOGY/ *THERAPY ; Hematoporphyrins/ADMINISTRATION & DOSAGE/METABOLISM/ THERAPEUTIC USE ; Human ; *Phototherapy/ADVERSE EFFECTS/METHODS ; Support, Non-U.S. Gov't ; Thermodynamics SO - Surg Neurol 1986 May;25(5):423-35 98 UI - 86179878 AU - Wade MH ; Trosko JE ; Schindler M TI - A fluorescence photobleaching assay of gap junction-mediated communication between human cells. AB - Gap junction-mediated communication between contiguous cells has been implicated in the regulation of cell proliferation and differentiation. This report describes a new technique to measure cell-cell communication, gap fluorescence redistribution after photobleaching, which is based on the diffusion-dependent return of 6-carboxyfluorescein-mediated fluorescence in a photobleached cell that is in contact with other fluorescently labeled cells. Fluorescence recovery rates are interpreted as dye transport across gap junctions. Results of experiments on normal human fibroblasts and human teratocarcinoma cells show that this technique can measure rapid dye transfer and detect inhibition of communication (between teratocarcinoma cells) by the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate and the pesticide dieldrin. MH - *Cell Communication/DRUG EFFECTS ; Dieldrin/PHARMACODYNAMICS ; Fibroblasts/ULTRASTRUCTURE ; Fluoresceins/*DIAGNOSTIC USE ; Human ; Intercellular Junctions/DRUG EFFECTS/*ULTRASTRUCTURE ; Microscopy, Fluorescence ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Teratoma/ULTRASTRUCTURE ; Tetradecanoylphorbol Acetate/PHARMACODYNAMICS SO - Science 1986 Apr 25;232(4749):525-8 99 UI - 86177983 AU - Wilson BC ; Muller PJ ; Yanch JC TI - Instrumentation and light dosimetry for intra-operative photodynamic therapy (PDT) of malignant brain tumours. AB - A technique is described for uniform light irradiation of the tumour cavity after radical subtotal malignant brain tumour resection in patients whose tumours have been photosensitized by intravenous injection of hematoporphyrin derivative. The cavity is maintained by an inflatable rubber 'balloon' filled with a light-scattering liquid, within which is placed a single-strand optical fibre coupled to an argon/dye laser operating at 630 nm. Details of the construction of the applicator are given, together with measurements of the uniformity of irradiation and the light loss within the scattering medium. The device has been assessed in nine patients in a phase I trial. In two of these patients, the penetration depth of 630 nm light in brain tissue has also been measured in vivo using an optical-fibre probe, indicating that the penetration depth of 630 nm light in human brain is greater than that found in vitro. MH - Adolescence ; Adult ; Astrocytoma/DRUG THERAPY/SURGERY ; Brain Neoplasms/*DRUG THERAPY/SURGERY ; Combined Modality Therapy ; Female ; Glioblastoma Multiforme/DRUG THERAPY/SURGERY ; Human ; Intraoperative Period ; Male ; Middle Age ; Photochemotherapy/ INSTRUMENTATION/*METHODS ; Support, Non-U.S. Gov't SO - Phys Med Biol 1986 Feb;31(2):125-33 100 UI - 86173862 AU - Gregory RO ; Goldman L TI - Application of photodynamic therapy in plastic surgery. AB - Photodynamic therapy is a technique for administering a sensitizer, hematoporphyrin derivative, which is selectively retained in malignant tissue. This is then activated by light, usually of 630 nm resulting in selective deterioration of the malignant tissue. This technique has been used for detecting and treating a variety of cancers in experimental animals and human beings. In plastic surgery, it has been applied to both basal and squamous cell carcinomas as well as to other skin lesions. Metastatic deposits will also respond to this treatment. Advantages include ease of treatment, sometimes requiring little or no anesthesia, low incidence of reactions, ability to repeat the treatment any number of times, and sparing of normal tissue. Photodynamic therapy has been used as a salvage operation, to clear tissue of suspected or probable remaining malignant disease, and to alleviate the need for a radical operation, allowing a more conservative one. Photodynamic therapy continues to be an investigational tool, and it should be used only as an adjunct to commonly accepted techniques, and then only when needed. Common disadvantages include a severe photosensitivity of the patient for several weeks following administration of the drug as well as inability to treat adequately bulky tumors. New techniques of administration and methods of activation will make this an increasingly common and useful tool in the practice of plastic surgery. MH - Aged ; Bowen's Disease/THERAPY ; Carcinoma, Basal Cell/*THERAPY ; Carcinoma, Squamous Cell/*THERAPY ; Case Report ; Female ; Human ; Male ; *Photochemotherapy ; Skin Neoplasms/*THERAPY ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Lasers Surg Med 1986;6(1):62-6 101 UI - 86172725 AU - Evarts RP ; Raab M ; Marsden E ; Thorgeirsson SS TI - Histochemical changes in livers from portacaval-shunted rats. AB - Portacaval shunt (PCS) operations were performed on male inbred SD rats. The activity of liver gamma-glutamyltranspeptidase (GGT) increased a few days after the operation and remained high after several months. However, the activity was only present in periportal areas of liver lobules and was mainly restricted to the endothelial lining cells of periportal blood vessels. Phenobarbital sodium (CAS: 57-03-7) administration did not change the distribution of GGT. The activity of liver glucose-6-phosphatase disappeared in the centrilobular areas a few days after the operation but was present in the periportal areas. The distribution of this activity returned to normal after several months. The capacity of liver cells to store glycogen was significantly decreased following the PCS operation. Morphologic changes in hepatocytes observed after the PCS operation did not show similarities to those seen in preneoplastic livers. The nuclei of the small compact hepatocytes found in the animals with PCS were irregular in shape and stained intensively with hematoxylin and eosin. The large pale-staining cells in the periphery of liver lobes were GGT negative and their nuclei had a normal morphology. Neither morphologic nor histochemical changes consistent with preneoplastic and/or neoplastic stage were observed after 10 months in the liver when the PCS operation was performed on rats having received an ip dose (10 mg/kg) of diethylnitrosamine (CAS: 55-18-5) 2 weeks prior to the operation. MH - Animal ; Cocarcinogenesis ; Diethylnitrosamine ; Eosin/DIAGNOSTIC USE ; Gamma-Glutamyltransferase/ANALYSIS ; Glucosephosphatase/ ANALYSIS ; Hematoxylin/DIAGNOSTIC USE ; Histocytochemistry ; Liver/*ANALYSIS/PATHOLOGY ; Liver Glycogen/ANALYSIS ; Liver Neoplasms, Experimental/ETIOLOGY ; Organ Weight ; Portacaval Shunt, Surgical/*ADVERSE EFFECTS ; Precancerous Conditions/ ETIOLOGY ; Rats ; Rats, Inbred Strains SO - JNCI 1986 Apr;76(4):731-8 102 UI - 86172103 AU - Flanigan RC ; Pavlik EJ ; Van Nagell JR ; Keaton K ; Kenady DE TI - Proliferation, esterase activity, and propidium iodide exclusion in urologic tumor cells after in vitro exposure to chemotherapeutic agents. AB - After exposing urological tumor cells to anticancer agents in vitro, cellular esterase activity and the ability to exclude propidium iodide (PI) were examined as dual indicators of functionality or "viability.: High esterase activity/PI exclusion was observed in assays in which anticancer agents failed to inhibit cellular proliferation, while low esterase activity/PI exclusion was often observed when proliferation had been significantly inhibited. In a number of instances, exposure to anticancer agents did produce significant inhibition of proliferation without lowering viability. In this setting, the recovery of proliferative capacity could be demonstrated with several transitional cell carcinoma cell lines, and this recovery was always associated with high esterase activity/PI exclusion. When the proliferation of primary urological tumor preparations was inhibited by drug exposure, estimates of elevated viability were obtained in 27 per cent of the determinations. Thus, viability estimates may be an indicator of the potential for tumor-cell recovery from exposure to anticancer agents. Moreover, the potential for recovery may explain differences between the results of chemosensitivity testing and actual clinical events by reconciling clinical failures with elevated viabilities indicative of this potential. MH - Antineoplastic Agents/*PHARMACODYNAMICS ; Bladder Neoplasms/ *METABOLISM/PATHOLOGY ; Carcinoma, Transitional Cell/*METABOLISM/ PATHOLOGY ; Cell Adhesion ; Cell Division/DRUG EFFECTS ; Cell Line ; Cell Survival/DRUG EFFECTS ; Esterases/*METABOLISM ; Flow Cytometry ; Fluorescence ; Human ; Microscopy, Fluorescence ; Phenanthridines/*METABOLISM ; Propidium/*METABOLISM ; Support, Non-U.S. Gov't SO - J Urol 1986 May;135(5):1091-100 103 UI - 86171056 AU - Makino S ; Nakojo T ; Tsuchida Y ; Hashizume K ; Nakajima M ; Atsumi K ; Tulip J TI - Experimental studies of photo radiation therapy on neuroblastoma. AB - A combination of Photo Radiation Therapy (PRT) using Argon-Dye Laser with hematoporphyrin derivatives (HpD) was used experimentally on a cytogenetically highly malignant neuroblastoma xenograft, which exhibited a homogeneously staining region and caused DNA amplifications in chromosomes. The tumor tissue was treated with 500 joules/cm2 of laser. The dosage of HpD was 50 mg per kg body weight. Necrosis of over 50% of the tumor was observed in half the specimens. Swollen cytoplasmic organelles and ruptured cell and nuclear membranes were observed by electron microscopy after PRT. PRT may be used with other treatment modalities for the removal of residual and metastatic tumors. MH - Animal ; *Hematoporphyrin Photoradiation ; Human ; Mice ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Neoplasm Transplantation ; Neuroblastoma/*DRUG THERAPY/ULTRASTRUCTURE ; *Photochemotherapy ; Time Factors ; Transplantation, Heterologous SO - J Pediatr Surg 1986 Mar;21(3):240-3 104 UI - 86170144 AU - O'Donoghue GM TI - The migration theory of cholesteatoma formation. Some experimental observations. AB - The migration theory of cholesteatoma formation considers that stratified squamous epithelium from the external auditory meatus migrates into the middle ear, giving rise to cholesteatoma. To test the ability of squamous epithelium to migrate in this manner, 73 stains were placed in relation to 23 chronic perforations. In no instance did epithelium migrate into the middle ear cleft. The limitations of the migration theory are discussed. MH - Adolescence ; Adult ; Child ; Cholesteatoma/*ETIOLOGY/PATHOLOGY ; Ear Diseases/ETIOLOGY/PATHOLOGY ; Ear, Middle/*PATHOLOGY ; Female ; Gentian Violet/DIAGNOSTIC USE ; Human ; Male ; Middle Age ; Rupture, Spontaneous ; Tympanic Membrane/INJURIES/PATHOLOGY SO - J Laryngol Otol 1986 Apr;100(4):395-8 105 UI - 86168951 AU - Chen KC ; Bevan PC ; Matthews JG TI - Analysis of G banded karyotypes in myeloma cells. AB - Karyotypes of bone marrow cells from 24 patients with multiple myeloma (MM) and two patients with de novo plasma cell leukaemia (PCL) were analysed by Giemsa banding (G banding). Chromosome aberrations were found in 13 patients with MM and both patients with PCL. Hyperdiploid and hypodiploid lines were present in eight and five of the patients with MM, respectively. Marker chromosomes derived from structural rearrangements were present in all eight cases of MM with hyperdiploid lines, although markers of uncertain origin were rare in those patients with hypodiploid lines. Chromosome 1 participated most often, and chromosomes 5 and 9 often played a part in the structural rearrangements. Chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 were subject to numerical aberrations. In the two patients with PCL one had a hypodiploid line with a 14q + marker derived from a t(11;14) and the other a hyperdiploid line. The breakpoints on the chromosomes participating in the structural rearrangements in myeloma showed a good correlation with known fragile sites and oncogene locations on the corresponding chromosomes. MH - Adult ; Aged ; Azure Stains/DIAGNOSTIC USE ; Bone Marrow/ ULTRASTRUCTURE ; *Chromosome Aberrations ; *Chromosome Banding ; Chromosome Fragile Sites ; Female ; Genetic Marker ; Human ; Karyotyping ; Leukemia, Plasmacytic/PATHOLOGY ; Male ; Middle Age ; Multiple Myeloma/*FAMILIAL & GENETIC/PATHOLOGY ; Oncogenes ; Support, Non-U.S. Gov't SO - J Clin Pathol 1986 Mar;39(3):260-6 106 UI - 86166984 AU - de Jong S ; Zijlstra JG ; Timmer-Bosscha H ; Mulder NH ; de Vries EG TI - Detection of DNA cross-links in tumor cells with the ethidium bromide fluorescence assay. AB - Until now the fluorescence assay with ethidium bromide has only been used on pure DNA. This assay depends on the difference in fluorescence between single- and double-stranded DNA (dsDNA). Cross-links in DNA are measured by the return of fluorescence of dsDNA after heat denaturation at pH 12. Under these conditions denatured DNA gives very low fluorescence. In the present study this assay was applied to tumor cells. The mouse Ehrlich ascites tumor cell line (EAT) and a human small-cell carcinoma line (GLC4) were incubated for 4 hr at 37 degrees C, with the cross-linking agent cis-diamino-dichloro platinum (cDDP). The samples of whole cells were thereafter resuspended in potassium phosphate buffer with 10 mM EDTA, 4M NaCl, 0.1% Sarkosyl pH 7.2, for 16 hr at 37 degrees C. Measurements were performed with a spectrofluorometer with excitation wavelength 525 nm, emission wavelength 580 nm. There was a linear relationship for cDDP concentrations of 0-150 microM and the extent of DNA cross-links in EAT (r = 0.958). In GLC4 there was a linear relationship at low cDDP concentrations of 0-50 microM (r = 0.968) while between 50 and 150 microM a plateau was reached. RNase added to the lysate of whole cells had no influence on the extent of cross-links. This assay was compared with the alkaline elution assay, and results were identical. MH - Animal ; Carcinoma, Ehrlich Tumor/ANALYSIS ; Carcinoma, Oat Cell/ ANALYSIS ; Cells, Cultured ; DNA, Neoplasm/*ANALYSIS ; Ethidium/ *DIAGNOSTIC USE ; Fluorescence ; Human ; Hydrogen-Ion Concentration ; Lung Neoplasms/ANALYSIS ; Mice ; Neoplasms/ *ANALYSIS ; Nucleic Acid Denaturation ; Ribonucleases/ PHARMACODYNAMICS SO - Int J Cancer 1986 Apr 15;37(4):557-61 107 UI - 86164973 AU - Masotti L ; Cavatorta P ; Ferrari MB ; Casali E ; Arcioni A ; Zannoni C ; Borrello S ; Minotti G ; Galeotti T TI - O2-dependent lipid peroxidation does not affect the molecular order in hepatoma microsomes. AB - Microsomal membranes from rat liver and from the fast-growing Morris hepatoma 3942A have been peroxidized to different extents and the order parameter of the membranes measured by fluorescence depolarization of the probe 1,6-diphenyl-1,3,5-hexatriene. The data have been analysed by applying a mathematical approach that takes into account simultaneously static and dynamic fluorescence parameters. It appears that tumour membranes are more ordered than the control and their order parameter does not increase with greater exposure to the action of O2 radicals in contrast to liver membranes. The fatty acid composition of the membrane lipids has been studied under different experimental conditions and correlated to the behaviour of the physical parameter. MH - Animal ; Diphenylhexatriene/DIAGNOSTIC USE ; Fatty Acids/ANALYSIS ; Fluorescence ; Lipid Bilayers/METABOLISM ; Lipid Peroxides/ *METABOLISM ; Liver Neoplasms, Experimental/*METABOLISM ; Male ; Membrane Lipids/ANALYSIS ; Microsomes, Liver/*METABOLISM ; Oxygen/ *METABOLISM ; Rats ; Support, Non-U.S. Gov't ; Temperature SO - FEBS Lett 1986 Mar 31;198(2):301-6 108 UI - 86163706 AU - Hamilton JW ; Thune RG ; Morrissey JF TI - Symptomatic ectopic gastric epithelium of the cervical esophagus. Demonstration of acid production with Congo red. AB - Four patients were found with patches of gastric fundal type epithelium just distal to the cricopharyngeus, separated from the gastroesophageal junction by 15-20 cm of normal squamous epithelium. Three of the four had symptoms of dysphagia localized to the area of the esophagus containing the epithelium. Congo red dye (a pH indicator) applied to the mucosa during endoscopy revealed acid production by the mucosa after stimulation with pentagastrin. Interestingly, the patients' symptoms decreased during treatment with cimetidine only to return on cessation of therapy. MH - Adult ; Case Report ; Choristoma/PATHOLOGY/*SECRETION ; Congo Red/ DIAGNOSTIC USE ; Epithelium/PATHOLOGY ; Esophageal Neoplasms/ PATHOLOGY/*SECRETION ; Esophagoscopy ; Female ; Gastric Acid/ *SECRETION ; Gastric Fundus ; Gastric Mucosa/PATHOLOGY/*SECRETION ; Human ; Hydrogen-Ion Concentration ; Male ; Middle Age SO - Dig Dis Sci 1986 Apr;31(4):337-42 109 UI - 86163510 AU - Cortese DA TI - Endobronchial management of lung cancer. AB - Bronchoscopic phototherapy is available now for 2 distinct categories of tracheobronchial cancer: roentgenographically occult superficial squamous cell carcinoma and advanced malignancy causing significant airway obstruction. Laboratory and clinical experience show that the photodynamic effect of hematoporphyrin derivative phototherapy (HpD-PT) may be useful for treating superficial cancers that penetrate less than 5 mm into bronchial mucosa. The larger, obstructing cancers are better managed by high-power laser sources, such as the YAG laser, which are effective by hyperthermal photocoagulation, thermal necrosis, and tissue vaporization. MH - Airway Obstruction/ETIOLOGY ; Bronchial Neoplasms/SURGERY/THERAPY ; *Bronchoscopy ; Carcinoma, Squamous Cell/COMPLICATIONS/ DIAGNOSIS/SURGERY/*THERAPY ; Fiber Optics ; Human ; Lasers/ THERAPEUTIC USE ; Lung Neoplasms/COMPLICATIONS/DIAGNOSIS/SURGERY/ *THERAPY ; *Phototherapy/METHODS ; Review ; Support, U.S. Gov't, P.H.S. ; Tracheal Neoplasms/THERAPY SO - Chest 1986 Apr;89(4 Suppl):234S-236S 110 UI - 86161115 AU - Sarnat HB ; Curry B ; Rewcastle NB ; Trevenen CL TI - Cytoplasmic RNA in nervous system tumours in children: a fluorochromic histochemical study using acridine orange. AB - Acridine orange was used as a fluorochromic histochemical stain of nucleic acids, applied to 78 neoplasms of the central and peripheral nervous systems of 60 children. Some cases were compared with 5 adults and 4 other cases of chronic reactive gemistocytic gliosis. Opposite concentration gradients of cytoplasmic ribonucleic acid (RNA) was demonstrated in tumours of the neuronal/neuroectodermal series, and those of the glial/neuroepithelial series. Minimal AO-RNA fluorescence was seen in 8 cerebellar medulloblastomas and in a retinoblastoma; strong AO-RNA fluorescence occurred in one cerebellar medulloblastoma and in 3 primitive neuroectodemal tumours of the cerebral cortex. Intermediate intensity of fluorescence was found in neuroblastomas, and strong fluorescence was shown in well differentiated ganglioneuroma cells and in cells of chromaffin tumours. Among glial tumours, by contrast, the most anaplastic cells displayed the most RNA fluorescence, while better differentiated astrocytoma cells showed much less. Gradients also were found within some astrocytomas, corresponding to zones of relative anaplasia. Minimal or no fluorescence was detected in reactive gemistocytes or in oligodendroglioma cells. Ependymomas were weakly fluorescent and choroid plexus papillomas showed more fluorescence, similar to the findings in normal ependyma and choroid plexus. Several non-neuroepithelial tumours of the nervous system and Schwannomas also were studied. The acridine orange technique applied to either frozen or paraffin sections of nervous system tumours, has value as an adjunct in the diagnosis and grading of these neoplasms and perhaps in distinguishing reactive gliosis from benign astrocytoma. MH - Acridine Orange/*DIAGNOSTIC USE ; Adolescence ; Adult ; Child ; Child, Preschool ; Connective Tissue/METABOLISM ; Cytoplasm/ *METABOLISM ; Fluorescence ; Histocytochemistry ; Human ; Infant ; Nervous System Neoplasms/CLASSIFICATION/*METABOLISM ; Neurons/ METABOLISM ; RNA/*METABOLISM ; Support, Non-U.S. Gov't SO - Can J Neurol Sci 1986 Feb;13(1):31-41 111 UI - 86159536 AU - Chan WS ; Svensen R ; Phillips D ; Hart IR TI - Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer. AB - The uptake, retention and effects of aluminium chloro sulphonated phthalocyanine (AlSPc) were measured in two cell lines, UV-2237 a murine fibrosarcoma and the non-tumorigenic NIH/3T3 fibroblast line. The behaviour of cells treated with AlSPc was compared with that of those treated with haematoporphyrin derivative (HpD), a photosensitizer often used in photodynamic therapy (PDT) of cancer. AlSPc absorbs light strongly in the red region, is taken up by cells in a dose dependent fashion and is retained in vitro over a period of days (5 days after exposure greater than 40% remains cell-associated versus less than 25% of HpD). Additionally AlSPc was less cytotoxic to cells, maintained in darkness or exposed to room light, compared to HpD (100% viability versus 0% viability 3 days after 60 min exposure to room light). However red light (approximately 600-700 nm) caused greater toxicity in AlSPc-treated cells (100%) than in similarly exposed HpD-treated cells (less than 60%). No significant differences were detected between the responses of the fibrosarcoma and the fibroblast cell lines. These characteristics of AlSPc suggest that it may prove to be a useful photosensitizer for PDT of cancer and this possibility is discussed. MH - Animal ; Cell Line ; Cell Survival/DRUG EFFECTS ; Comparative Study ; Dose-Response Relationship, Drug ; Fibrosarcoma/*DRUG THERAPY ; Hematoporphyrins/THERAPEUTIC USE ; Indoles/*THERAPEUTIC USE ; Mice ; Organometallic Compounds/*THERAPEUTIC USE ; *Photochemotherapy ; Spectrophotometry ; Sulfonic Acids/ THERAPEUTIC USE SO - Br J Cancer 1986 Feb;53(2):255-63 112 UI - 86157333 AU - Yagi N TI - Comparison of thread test of lacrimation to Schirmer test. AB - A modified Schirmer test using thread instead of filter paper has been previously reported. The present report compares the characteristics of thread and filter paper and establishes the normal range for the tear flow rate. The moisture absorption by a 5-mm wide strip of filter paper was 0.765 microL/mm and that by a thread was 0.054 microL/mm. The thread was 14 times more sensitive in detecting small amounts of fluid than was the filter paper. The thread test was used in 42 normal subjects. The normal range was 60% to 140% (+/- 3 SD), so a value of less than 60% was considered to indicate lacrimal hypofunction, and over 140%, hyperfunction. MH - Cerebellar Neoplasms/SURGERY ; Cerebellopontile Angle ; Comparative Study ; Cotton ; Eyelid Diseases/ETIOLOGY ; Facial Nerve/SURGERY ; Facial Paralysis/*DIAGNOSIS/ETIOLOGY ; Filtration ; Fluoresceins/DIAGNOSTIC USE ; Human ; Methods ; Paper ; Postoperative Complications ; Reference Values ; Tears/*SECRETION SO - Ann Otol Rhinol Laryngol [Suppl] 1986 Jan-Feb;122:3-6 113 UI - 86156521 AU - Hill JH ; Plant RL ; Harris DM ; Grossweiner LI ; Rok B ; Seter AJ TI - The nude mouse xenograft system: a model for photodetection and photodynamic therapy in head and neck squamous cell carcinoma. AB - Mechanisms for hematoporphyrin derivative (HPD) localization in malignant tissue and in photodynamic therapy (PDT) have not been established. The authors' experience with human cancer xenografts in nude mice as a tumor system for the experimental study of these mechanisms is described. Human mucosal head and neck squamous cell carcinoma was successfully transplanted to nude mice in 29 per cent of trials and serially passed through multiple generations in three tumor lines. Time required for progressive growth averaged 13.9 days, and 300 mm3 tumors were obtained in four weeks. Take rates per passage varied, in part because of infection, and exponential growth rates varied among the three lines. However, within a single line exponential growth rates were similar. Average growth constants for the period of exponential growth were 0.14, 0.13, and 0.09 for the three lines. Fluorescent microscopy of excised xenografts revealed HPD fluorescence principally in connective tissue cells. Minimal fluorescence was seen in malignant epithelial cells. Spectrophotometric measures of HPD uptake in homogenized tissue showed highest values in liver. Tumor HPD levels were higher than those for either skin or muscle. The authors conclude that this tumor system can be used effectively to study HPD and PDT in head and neck cancer. MH - Animal ; Carcinoma, Squamous Cell/*PATHOLOGY ; *Disease Models, Animal ; Female ; Head and Neck Neoplasms/*PATHOLOGY ; Hematoporphyrins/DIAGNOSTIC USE ; Human ; Laryngeal Neoplasms/ PATHOLOGY ; Male ; Mice ; *Mice, Nude ; Microscopy, Fluorescence ; Mouth Neoplasms/PATHOLOGY ; Neoplasm Staging ; *Neoplasm Transplantation ; Pharyngeal Neoplasms/PATHOLOGY ; Photochemotherapy ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. ; *Transplantation, Heterologous SO - Am J Otolaryngol 1986 Jan-Feb;7(1):17-27 114 UI - 86156426 AU - Poppiti RJ Jr ; Margulies M ; Cabello B ; Rywlin AM TI - Membranous fat necrosis. AB - We report the case of a 66-year-old man with nodular lesions on the chest that were clinically diagnosed as epidermal cysts. Histologically the lesions consisted of fat necrosis with cystic spaces lined by striking membranous structures, mimicking a parasitic cuticle and exhibiting all the staining reactions of ceroid. Retrospective review of 33 consecutive cases of fat necrosis revealed similar membranous changes in 21% of the cases. The etiology and pathogenesis of this variant of fat necrosis are uncertain. MH - Adipose Tissue/*PATHOLOGY ; Aged ; Case Report ; Cysts/*PATHOLOGY ; Fat Necrosis/*PATHOLOGY ; Fluorescence ; Human ; Male ; Necrosis/*PATHOLOGY ; Skin Diseases/*PATHOLOGY SO - Am J Surg Pathol 1986 Jan;10(1):62-9 115 UI - 86145622 AU - Walle AJ TI - Identification of L3 leukemia and Burkitt's lymphoma cells by flow cytometric quantitation of nuclear and cellular RNA and DNA content. AB - Separate quantitations of nucleic acids of isolated nuclei and cells of L3 leukemia/Burkitt's lymphoma cell populations of peripheral blood (PB), bone marrow (BM) and lymph node (LN) cell suspensions of 17 patients were performed by acridine orange (AO) flow cytometry (FCM). The cell populations were analysed with respect to cell cycle characteristics and DNA/RNA distribution histograms of cells in various compartments of the cell cycle using mean value, coefficient of variation (CV), third moment about the mean as a measure of skewness (MOM3). The correlations between numbers of L3 blasts detected by microscopy and aneuploid cells quantified by FCM in 10 patients with aneuploid disease were r = 0.75 and r = 0.85 for BM and PB cell populations, respectively. Content of both nuclear and cellular RNA was 3-4 times higher in L3 cells than in normal donor lymphocytes. Percentages of cells in SG2M phase of L3 populations were significantly different from control populations in BM (p less than 0.01) and PB (p less than 0.0001). All samples with L3 blasts had abnormal CV of the DNA, and abnormal CV and MOM3 of the RNA peaks of G0/1 cell histograms. All samples with no blasts by morphology had normal DNA and RNA patterns. AO FCM correctly classified all specimens as involved or not involved with disease in accordance with the cytomorphological diagnoses. Combining AO FCM with prior cell separation increased the sensitivity of the method to detect abnormal cells to 0.02%, or 0.5 L3 cells per microliter of blood. MH - Acridine Orange/DIAGNOSTIC USE ; Burkitt's Lymphoma/*ANALYSIS ; Cell Cycle ; Cell Nucleus/*ANALYSIS ; DNA, Neoplasm/*ANALYSIS ; *Flow Cytometry ; Human ; Leukemia/*BLOOD ; RNA, Neoplasm/ *ANALYSIS ; Support, Non-U.S. Gov't SO - Leuk Res 1986;10(3):303-12 116 UI - 86144923 AU - Reynolds CP ; Biedler JL ; Spengler BA ; Reynolds DA ; Ross RA ; Frenkel EP ; Smith RG TI - Characterization of human neuroblastoma cell lines established before and after therapy. AB - Six new cell lines have been established from human neuroblastomas. Cell line SMS-KAN, from primary tumor before therapy, and line SMS-KANR, from bone marrow after chemotherapy and radiotherapy, were established from the same patient. Cell lines SMS-KCN (from primary tumor before any therapy) and SMS-KCNR (from bone marrow after chemotherapy) were established from another patient. Two other lines (SMS-MSN and SMS-SAN) were established from different patients before any therapy was given. Cell lines established from recurrent disease after chemotherapy (SMS-KANR and SMS-KCNR) had significantly shorter doubling times and increased plating efficiencies compared to those of cell lines derived from the same patient before chemotherapy (SMS-KAN and SMS-KCN). All cell lines contained tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine-beta-hydroxylase. Measurable amounts of choline acetyltransferase were also detected in SMS-KAN and SMS-KANR. Karyotype analysis showed all cell lines except SMS-MSN to be pseudodiploid with modal numbers of 46 and deletions of the short arm of chromosome 1; SMS-MSN had a modal number of 57-58 chromosomes. All cell lines had double-minute chromosomes, except SMS-KANR, which had abnormally banding regions. These new cell lines provide in vitro models of neuroblastoma suitable for the study of differences in neuroblastoma cell populations before chemotherapy as compared to the cell populations that proliferate after therapy. MH - Catecholamines/ANALYSIS ; Cell Line ; Child, Preschool ; Chromosome Aberrations ; Female ; Fluorescence ; Gene Amplification ; Human ; Infant ; Karyotyping ; Male ; Microscopy, Electron ; Neuroblastoma/FAMILIAL & GENETIC/*PATHOLOGY/THERAPY ; Norepinephrine/BIOSYNTHESIS ; Oncogenes ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - JNCI 1986 Mar;76(3):375-87 117 UI - 86141022 AU - Tuyp E ; MacKie RM TI - Combination therapy for psoriasis with methotrexate and etretinate. AB - Two young male patients with severe erythrodermic psoriasis and pustular episodes have both been successfully treated with a combination of methotrexate and etretinate for a period of 21/2 years. On this regimen, relative clearing of the psoriatic lesions has been achieved with no significant side effects. Neither patient has developed evidence of hepatotoxicity. The safety of and indications for combination therapy with methotrexate and etretinate are discussed, and the recent reports in the literature of experience with this combination regimen are considered. MH - Adult ; Carcinoma, Basal Cell/ETIOLOGY ; Case Report ; Drug Therapy, Combination ; Etretinate/*THERAPEUTIC USE ; Human ; Liver Function Tests ; Male ; Methotrexate/*THERAPEUTIC USE ; Middle Age ; Neoplasms, Radiation-Induced/ETIOLOGY ; Psoriasis/ *DRUG THERAPY ; PUVA Therapy/ADVERSE EFFECTS ; Skin Neoplasms/ ETIOLOGY SO - J Am Acad Dermatol 1986 Jan;14(1):70-3 118 UI - 86137506 AU - Vrabec F TI - "Displaced nerve cells: in the human retina. AB - Several kinds of nerve cells in the vertebrate retina can be found in retinal layers other that to which they belong. The present paper discusses all such cells within the human retina, as the author was able to stain them selectively using different neurohistological methods. MH - *Choristoma/PATHOLOGY ; *Eye Neoplasms/PATHOLOGY ; Human ; Methylene Blue/DIAGNOSTIC USE ; Neurons/*CYTOLOGY/ULTRASTRUCTURE ; Retina/*CYTOLOGY ; *Retinal Diseases/PATHOLOGY ; Retinal Ganglion Cells/*CYTOLOGY/ULTRASTRUCTURE ; Stains and Staining SO - Graefes Arch Clin Exp Ophthalmol 1986;224(2):143-6 119 UI - 86135164 AU - Blair OC ; Carbone R ; Sartorelli AC TI - Differentiation of HL-60 promyelocytic leukemia cells: simultaneous determination of phagocytic activity and cell cycle distribution by flow cytometry. AB - Phagocytosis of fluorescent microspheres by HL-60 promyelocytic leukemia cells following induction of differentiation with dimethyl sulfoxide (DMSO) was monitored using flow cytometry. Initiation of phagocytic capability following initiation of differentiation with 1.5% DMSO coincided with the attainment of respiratory burst activity as measured by NBT (nitro blue tetrazolium) reduction; the degree of phagocytic activity was dependent upon parameters such as microsphere size, microsphere number, and exposure time. Ingestion of fluorescent microspheres did not interfere with the measurement of DNA content using propidium iodide; thus, simultaneous determination of phagocytic activity and the cell cycle phase was possible. Accumulation of cells in the G1/G0 phase of the cell cycle following DMSO treatment was correlated with the acquisition of the capacity to phagocytize. Analysis of two-parameter correlated data also indicated that phagocytosis is coupled with residence in the G1/G0 phase of the cell cycle, further suggesting that the ability to phagocytize fluorescent microspheres is associated with end-stage differentiation. MH - Cell Cycle ; Cell Differentiation ; Cell Separation ; Cells, Cultured ; Dimethyl Sulfoxide/PHARMACODYNAMICS ; Flow Cytometry ; Fluorescent Dyes/DIAGNOSTIC USE ; Human ; Leukemia, Myeloblastic/ IMMUNOLOGY/*PATHOLOGY ; Microspheres ; *Phagocytosis/DRUG EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cytometry 1986 Mar;7(2):171-7 120 UI - 86135163 AU - Storkus WJ ; Balber AE ; Dawson JR TI - Quantitation and sorting of vitally stained natural killer cell-target cell conjugates by dual beam flow cytometry. AB - We have detected formation of stable associations, or conjugates, between fluorescein diacetate-(FDA) stained human natural killer (NK) cells and Hoechst 33342-(HO342) stained tumor cells by dual laser flow cytometry. Conjugates in mixtures of effectors and targets emitted both green (FDA) and blue (HO342) fluorescence. This was confirmed by cell sorting. More than 90% of the conjugates included one target and one effector cell. Conjugate formation frequency was temperature independent between 4 and 37 degrees C, optimized by 10 min, and stable for 1 hr. Enrichment of effector populations for cells mediating lysis of standard NK targets and for cells reacting with OKM1, Leu-7, and Leu-11b monoclonal antibodies also enriched conjugate-forming cells. Lysis of either OKM1+, Leu-11b+ effector subpopulations with antibody and complement eliminated, but treatment with these antibodies alone had no effect on, conjugate formation. Effector pretreatment with Leu-4 or 3A1 and complement increased the frequency of conjugation slightly. Flow-determined frequencies of NK-conjugate formation with 14 target cell lines correlated well with data derived from standard microscopic assays. However, the flow method was more rapid, could be used when target and effector were of comparable size, and permitted isolation of conjugates by sorting. MH - Antibodies, Monoclonal/DIAGNOSTIC USE ; Cell Line ; Cell Separation ; Cytotoxicity, Immunologic ; Erythroleukemia/ IMMUNOLOGY/PATHOLOGY ; Flow Cytometry/*METHODS ; Fluorescent Antibody Technic ; Fluorescent Dyes/DIAGNOSTIC USE ; Human ; Killer Cells, Natural/*CYTOLOGY/IMMUNOLOGY ; Neoplasms/IMMUNOLOGY/ PATHOLOGY ; Phenotype ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cytometry 1986 Mar;7(2):163-70 121 UI - 86135150 AU - Jacobs RM ; Boyce JT ; Kociba GJ TI - Flow cytometric and radioisotopic determinations of platelet survival time in normal cats and feline leukemia virus-infected cats. AB - This study demonstrates the potential usefulness of a flow cytometric technique to measure platelet survival time in cats utilizing autologous platelets labeled in vitro with fluorescein isothiocyanate (FITC). When compared with a 51Cr method, no significant differences in estimated survival times were found. Both the 51Cr and FITC-labeling procedures induced similar changes in platelet shape and collagen-induced aggregation. Platelets labeled with FITC had significantly greater volumes compared with those of glutaraldehyde-fixed platelets. These changes were primarily related to the platelet centrifugation and washing procedures rather than the labels themselves. This novel technique potentially has wide applicability to cell circulation time studies as flow cytometry equipment becomes more readily available. Problems with the technique are discussed. In a preliminary study of the platelet survival time in feline leukemia virus (FeLV)-infected cats, two of three cats had significantly reduced survival times using both flow cytometric and radioisotopic methods. These data suggest increased platelet turnover in FeLV-infected cats. MH - Animal ; Blood Platelets/*PHYSIOLOGY ; Cats ; *Cell Survival ; Feline Leukemia Virus ; Female ; Flow Cytometry/*METHODS ; Fluoresceins/DIAGNOSTIC USE ; Leukemia, Experimental/*BLOOD ; Microscopy, Phase Contrast ; Platelet Aggregation ; Scattering, Radiation ; Spectrometry, Fluorescence ; Support, U.S. Gov't, P.H.S. ; Thiocyanates/DIAGNOSTIC USE SO - Cytometry 1986 Jan;7(1):64-9 122 UI - 86133298 AU - Sieber F ; Sieber-Blum M TI - Dye-mediated photosensitization of murine neuroblastoma cells. AB - The purpose of this study was to determine if photosensitization mediated by the fluorescent dye, merocyanine 540, could be used to preferentially kill murine neuroblastoma cells in simulated autologous remission marrow grafts. Simultaneous exposure of Neuro 2a or NB41A3 neuroblastoma cells to merocyanine 540 and white light reduced the concentration of in vitro-clonogenic tumor cells 50,000-fold. By contrast, the same treatment had little effect on the graft's ability to rescue lethally irradiated syngeneic hosts. Lethally irradiated C57BL/6J X A/J F1 mice transplanted with photosensitized mixtures of neuroblastoma cells and normal marrow cells (1:100 or 1:10) survived without developing neuroblastomas. It is conceivable that merocyanine 540-mediated photosensitization will prove useful for the extracorporeal purging of residual neuroblastoma cells from human autologous remission marrow grafts. MH - Animal ; Bone Marrow/DRUG EFFECTS/TRANSPLANTATION ; Cell Line ; Cell Survival/DRUG EFFECTS ; Female ; Hematopoietic Stem Cells/ DRUG EFFECTS ; Mice ; Mice, Inbred C57BL ; Neuroblastoma/*DRUG THERAPY ; *Photochemotherapy ; Pyrimidinones/*THERAPEUTIC USE ; Radiation-Sensitizing Agents/*THERAPEUTIC USE ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Transplantation, Autologous ; Trypsin/PHARMACODYNAMICS SO - Cancer Res 1986 Apr;46(4 Pt 2):2072-6 123 UI - 86127620 AU - Shulok JR ; Klaunig JE ; Selman SH ; Schafer PJ ; Goldblatt PJ TI - Cellular effects of hematoporphyrin derivative photodynamic therapy on normal and neoplastic rat bladder cells. AB - HPD is known to localize in neoplastic cells and when exposed to the appropriate wavelength of light causes cytotoxicity. The authors have established a rat urothelial cell model for use in comparing and contrasting the effects of HPD photodynamic therapy (PDT) in normal (RBL-01) and transitional cell carcinoma (AY27) bladder cell lines. Uptake, toxicity, and morphologic damage following exposure to HPD PDT were evaluated. Trypan blue exclusion was used for determination of the toxicity of several HPD concentrations (1, 10, 25, and 50 micrograms/ml) with increasing duration of incubation with HPD (0, 1, 2, 4, 12, 24, and 48 hours). Both cell lines displayed increased toxicity with higher concentrations of HPD; however, the AY27 cells were more susceptible to the toxic effects of HPD PDT than the RBL-01 cells at the higher HPD doses studied (25 and 50 micrograms/ml). Viability decreased with increased duration of HPD incubation in RBL-01 cells up until 4 hours, after which it showed a steady increase. Viability decreased in the AY27 cells with increased duration of HPD incubation. An increase in serum concentration in the medium resulted in an increase in viability for both cell lines. Both cell lines demonstrated fast initial uptake of HPD followed by slower uptake over the time studied. By 24 and 48 hours the AY27 cells contained twice the amount of methanol-extractable porphyrins as the RBL-01 cells. The initial morphologic change following HPD PDT was damage to mitochondria. Mitochondrial damage occurred immediately after PDT in the AY27 cells and 30 minutes after PDT in the RBL-01 cells. Both cell lines exhibited a similar progression of cell injury; however, morphologic damage was observed earlier after PDT and appeared more extensive in the AY27 cells. MH - Animal ; Bladder/*DRUG EFFECTS/METABOLISM ; Bladder Neoplasms/ *DRUG THERAPY/METABOLISM/PATHOLOGY ; Blood ; Carcinoma, Transitional Cell/METABOLISM/PATHOLOGY/*RADIOTHERAPY ; Cell Line ; Cell Survival/DRUG EFFECTS ; Comparative Study ; Culture Media ; Hematoporphyrins/METABOLISM/PHARMACODYNAMICS/*THERAPEUTIC USE ; Kinetics ; Male ; Microscopy, Electron ; Mitochondria/DRUG EFFECTS/PATHOLOGY ; *Photochemotherapy ; Rats ; Rats, Inbred F344 ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Am J Pathol 1986 Feb;122(2):277-83 124 UI - 86105732 AU - Kostron H ; Swartz MR ; Miller DC ; Martuza RL TI - The interaction of hematoporphyrin derivative, light, and ionizing radiation in a rat glioma model. AB - The effects of hematoporphyrin derivative, light, and cobalt 60 (60Co) irradiation were studied in a rat glioma model using an in vivo and an in vitro clonogenic assay. There was no effect on tumor growth by visible light or by a single dose of 60Co irradiation at 4 Gy or 8 Gy, whereas 16 Gy inhibited tumor growth to 40% versus the control. Hematoporphyrin derivative alone slightly stimulated growth (P less than 0.1). Light in the presence of 10 mg hematoporphyrin derivative/kg inhibited tumor growth to 32%. 60Co irradiation in the presence of hematoporphyrin derivative produced a significant tumor growth inhibition (P less than 0.02). This growth inhibition was directly related to the concentration of hematoporphyrin derivative. The addition of 60Co to light in the presence of hematoporphyrin derivative produced a greater growth inhibition than light or 60Co irradiation alone. This effect was most pronounced when light was applied 30 minutes before 60Co irradiation. Our experiments in a subcutaneous rat glioma model suggest a radiosensitizing effect of hematoporphyrin derivative. Furthermore, the photodynamic inactivation is enhanced by the addition of 60Co irradiation. These findings may be of importance in planning new treatment modalities in malignant brain tumors. MH - Animal ; Cobalt Radioisotopes/*THERAPEUTIC USE ; Combined Modality Therapy ; Comparative Study ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Glioma/*DRUG THERAPY/PATHOLOGY/ RADIOTHERAPY ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/ ADMINISTRATION & DOSAGE ; Male ; *Photochemotherapy ; Rats ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Time Factors ; Tumor Stem Cell Assay SO - Cancer 1986 Mar 1;57(5):964-70 125 UI - 86105670 AU - Herrera-Ornelas L ; Petrelli NJ ; Mittelman A ; Dougherty TJ ; Boyle DG TI - Photodynamic therapy in patients with colorectal cancer. AB - A pilot study was conducted, in which photodynamic therapy (PDT), a technique in which malignant cells are destroyed by light after being previously photosensitized by a chemical compound, was tried in a group of 14 patients with recurrent or residual colorectal cancer in the pelvis. Three of the six patients with unresectable pelvic recurrences experienced a significant relief of pain after PDT. In two of the five patients who had an incomplete resection of their pelvic recurrences, there was also a substantial relief of pelvic pain after surgery and PDT. In one of these patients subsequent biopsies proved the disappearance of the residual pelvic microscopic disease after several sessions of PDT. Three patients had a recurrence from a squamous cell carcinoma primary of the anal canal. All recurrences were amenable to surgical resection. In one of the patients, PDT was used in an attempt to sterilize an area of residual tumor that was located over the left ischial tuberosity. The patient experienced good relief of pain, but died of her disease 7 months after PDT. In the other two patients, PDT was used as an "adjunct: after resection of their recurrences. One of these patients was free of disease and died of an unrelated cause 12 months after PDT. The other is alive and well. This study demonstrated that PDT can be safe and tolerable in patients with pelvic malignancies. PDT is capable of tumor destruction, can be used repeatedly in areas previously exposed to ionizing radiation, and may have a role in the prevention and management of pelvic-perineal recurrences from colorectal cancer. MH - Adult ; Aged ; Colonic Neoplasms/*DRUG THERAPY/PATHOLOGY/SURGERY ; Combined Modality Therapy ; Female ; Human ; Male ; Middle Age ; Neoplasm Recurrence, Local ; *Photochemotherapy ; Rectal Neoplasms/*DRUG THERAPY/PATHOLOGY/SURGERY SO - Cancer 1986 Feb 1;57(3):677-84 126 UI - 86105633 AU - Heuser LS ; Miller FN TI - Differential macromolecular leakage from the vasculature of tumors. AB - Tumor-induced neovascularization is essential for invasion, metastases, and exponential growth of solid tumors. The authors studied the differences in macromolecular leakage from the neovasculature of a fast-growing, early-metastasizing tumor, the Walker 256 carcinosarcoma, and a slow-growing, nonmetastasizing tumor, a rat chondrosarcoma. A 1-mm3 piece of the Walker 256 carcinoma or the chondrosarcoma was implanted in the cremaster muscle of rats. Five days after surgery the cremaster muscle with the implanted tumor was placed in a special bath containing Krebs solution such that the circulation and nerves from the animal to the cremaster were intact. Fluorescein isothiocyanate-labeled rat serum albumin (FITC-RSA) was injected (intra-arterially) into each rat to permit visualization of the vasculature by fluorescent microscopy. A closed-circuit television system was used to quantitate macromolecular leakage as a change in interstitial fluorescent intensity. Data are given as a relative fluorescent intensity (mean +/- standard error of the mean) in an area of the cremaster with tumor-induced neovascularization. These studies demonstrated that the vasculature induced by rapidly growing Walker 256 carcinosarcoma leak albumin freely when compared with the vasculature induced by the slow-growing chondrosarcoma. Furthermore, there was a significant increase in fluorescent intensity (albumin leakage) in the Walker tumor from 1 minute (24 +/- 3.0) to 30 minutes (49 +/- 5.6). In the normal cremaster area there was a significantly lower fluorescent intensity in the interstitium and a very slight increase with time (4 +/- 1.5 at 1 minute vs. 7 +/- 1.4 at 30 minutes). One interpretation of these data is that the mechanisms responsible for protein leakage from the vasculature of the Walker tumor may be involved in the fast growth and metastases of this tumor as compared with slower-growing tumors such as the chondrosarcoma. MH - Animal ; Carcinoma 256, Walker/BLOOD SUPPLY ; Chondrosarcoma/ BLOOD SUPPLY ; Fluoresceins/DIAGNOSTIC USE ; Male ; Microcirculation ; Microscopy, Fluorescence ; Neoplasms, Experimental/*BLOOD SUPPLY/PATHOLOGY ; *Neovascularization ; Rats ; Rats, Inbred Strains ; Support, U.S. Gov't, P.H.S. ; Thiocyanates/DIAGNOSTIC USE SO - Cancer 1986 Feb 1;57(3):461-4 127 UI - 86090924 AU - Knobler RM ; Edelson RL TI - Cutaneous T cell lymphoma. AB - Cutaneous T cell lymphoma is a malignancy of helper T cells, which have a propensity to infiltrate the skin. The incidence of the disease appears to exceed that of Hodgkin's disease, making it the most common lymphoma of adults. Advances in our knowledge of the biology of the malignant T cells should facilitate new and more effective forms of treatment. MH - Administration, Topical ; Antineoplastic Agents/ADMINISTRATION & DOSAGE ; Antineoplastic Agents, Combined/THERAPEUTIC USE ; Combined Modality Therapy ; Lymphoma/COMPLICATIONS/PATHOLOGY/ *THERAPY ; Neoplasm Staging ; Photochemotherapy ; Prognosis ; Radiotherapy Dosage ; Review ; Skin Neoplasms/COMPLICATIONS/ PATHOLOGY/*THERAPY ; Support, U.S. Gov't, P.H.S. ; T Lymphocytes SO - Med Clin North Am 1986 Jan;70(1):109-38 128 UI - 86076554 AU - Shikowitz MJ ; Steinberg BM ; Abramson AL TI - Hematoporphyrin derivative therapy of papillomas. Experimental study. AB - Hematoporphyrin derivative has been shown to selectively localize in malignant tissues and chemically induced animal papillomas. It is a powerful photo-sensitizing agent that can cause destruction and death of tissues in which it has localized by the generation of singlet oxygen when activated by light of the appropriate wavelength (photodynamic therapy [PDT]). Laryngeal papillomas are rapidly growing benign epithelial neoplasms with a clinical course marked by multiple recurrences after surgical removal. Before considering PDT as a therapeutic modality in the treatment of this debilitating disease we developed an animal model for experimentation. Using the cottontail rabbit papillomavirus, sometimes referred to as the Shope papillomavirus, large cutaneous papillomas were induced on the backs of Dutch Belted rabbits. Following intravenous administration of hematoporphyrin derivative, PDT was delivered with white light. Marked regression of the papillomas was noted with replacement by normal hair-bearing skin. The clinical implications of this work to the control of laryngeal papillomatosis is discussed. MH - Animal ; *Hematoporphyrin Photoradiation ; Hematoporphyrins/ METABOLISM/*THERAPEUTIC USE ; Papilloma/*DRUG THERAPY/PATHOLOGY ; *Photochemotherapy ; Rabbits ; Shope Papilloma Virus ; Skin Neoplasms/*DRUG THERAPY/PATHOLOGY ; Support, Non-U.S. Gov't ; Time Factors ; Tissue Distribution ; Tumor Virus Infections/*DRUG THERAPY/PATHOLOGY SO - Arch Otolaryngol Head Neck Surg 1986 Jan;112(1):42-6 129 UI - 86053220 AU - Hilf R ; Murant RS ; Narayanan U ; Gibson SL TI - Relationship of mitochondrial function and cellular adenosine triphosphate levels to hematoporphyrin derivative-induced photosensitization in R3230AC mammary tumors. AB - The effects of hematoporphyrin derivative-induced photosensitization on the levels of adenosine triphosphate (ATP) in R3230AC mammary adenocarcinomas were studied. Enzymatically dissociated tumor cells were exposed to various doses of hematoporphyrin derivative (HPD) in vitro plus photoradiation. A drug and light dose-dependent decrease in cellular ATP levels was observed; ATP levels were reduced by 60% after treatment with 7.0 micrograms HPD per ml plus 0.72 J total energy density per cm2. Cell viability, assessed by exclusion of trypan blue, displayed an apparently coordinate behavior to ATP levels. The effects of hematoporphyrin derivative plus photoradiation were examined in the presence of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation, or iodoacetate, an inhibitor of glycolysis, experiments designed to elucidate the site of action leading to reduced ATP levels. The results indicated that HPD-induced photosensitization had little additive effects to oligomycin-sensitive ATP production, whereas significant further reduction in ATP levels was obtained by HPD-induced photosensitization in the presence of iodoacetate. Taken together, along with earlier studies of selected mitochondrial enzymes, we conclude that HPD plus photoradiation inhibits mitochondrial function leading to reduction in cellular ATP levels and loss of viability. MH - Adenosine Triphosphate/METABOLISM ; Animal ; Cell Survival/DRUG EFFECTS ; Cells, Cultured ; Dose-Response Relationship, Drug ; Female ; Glycolysis/DRUG EFFECTS ; *Hematoporphyrin Photoradiation ; Iodoacetates/PHARMACODYNAMICS ; Mammary Neoplasms, Experimental/*DRUG THERAPY/METABOLISM ; Mitochondria/ *PHYSIOLOGY ; Oligomycins/PHARMACODYNAMICS ; Oxidative Phosphorylation/DRUG EFFECTS ; *Photochemotherapy ; Rats ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Jan;46(1):211-7 130 UI - 86053210 AU - Crute JJ ; Wahl AF ; Bambara RA ; Murant RS ; Gibson SL ; Hilf R TI - Inhibition of mammalian DNA polymerases by hematoporphyrin derivative and photoradiation. AB - Hematoporphyrin derivative (HPD) plus photoradiation caused the inactivation of DNA polymerases from calf thymus and R3230AC rat mammary tumor. Photosensitization of purified DNA polymerase-alpha as well as two forms of DNA polymerase-delta (I and II) from calf thymus were evaluated. Although all polymerase enzyme forms were inactivated at 70 micrograms HPD/ml, DNA polymerase-delta II was the most sensitive, displaying a 90% inactivation under conditions that did not cause significant inactivation of the other polymerase forms. Unlike DNA polymerase-alpha, the delta-forms have an associated 3'- to 5'-exonuclease activity. The exonuclease associated with DNA polymerase-delta II was uniquely sensitive to a low level of HPD and light exposure. DNA polymerase-delta II can be distinguished from other polymerase forms in cell extracts by its relative insensitivity to the polymerase inhibitor N2-(p-n-butylphenyl)deoxyadenosine 5'-triphosphate. In cytosols prepared from calf thymus and R3230AC rat mammary tumors, DNA polymerase-delta II was preferentially inhibited by HPD plus light. Furthermore, in experiments in which tumor-bearing rats were administered HPD prior to preparation of tumor cytosols, DNA polymerase-delta II was specifically inactivated by exposure to light. These results are discussed in view of their possible role in cancer therapy, and the potential use of HPD as a specific inhibitory agent of DNA polymerase-delta II is suggested. MH - Animal ; Cattle ; Cytosol/ENZYMOLOGY ; DNA Polymerases/ *ANTAGONISTS & INHIBITORS/RADIATION EFFECTS ; *Hematoporphyrin Photoradiation ; Mammary Neoplasms, Experimental/ENZYMOLOGY ; *Photochemotherapy ; Rats ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Thymus Gland/ENZYMOLOGY SO - Cancer Res 1986 Jan;46(1):153-9