==================================BSR42================================== 42. Oncogenes and cervical cancer or Kaposi's sarcoma. RAS or SIS oncogenes: Sequences in human cancer. Papilloma Viruses and Interferon. 1 UI - 87064402 AU - McCoy MS ; Weinberg RA TI - A human Ki-ras oncogene encodes two transforming p21 proteins. AB - The human Ki-ras gene was previously reported to contain two alternative fourth exons which encode two distinct p21 proteins differing only at their carboxy termini. The present study shows that either p21 protein is able on its own to transform NIH 3T3 cells to a tumorigenic state. MH - *Cell Transformation, Neoplastic ; Exons ; Genes, Structural ; Human ; *Oncogenes ; Plasmids ; Proto-Oncogene Proteins, Cellular/*GENETICS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Mol Cell Biol 1986 Apr;6(4):1326-8 2 UI - 87051323 AU - Srivatsan ES ; Benedict WF ; Stanbridge EJ TI - Implication of chromosome 11 in the suppression of neoplastic expression in human cell hybrids. AB - Cytogenetic analyses of intraspecies human HeLa X fibroblast hybrid cell populations have provided tentative evidence for the correlation of loss of a single copy of chromosomes 11 and 14 with reexpression of tumorigenicity. In this study paired combinations of nontumorigenic and tumorigenic segregant HeLa X fibroblast hybrid cells from two independent fusion events were examined for the presence or absence of normal chromosomes 11 and 14. In human hybrid cell lines the parental origin of chromosomes can be distinguished on the basis of restriction fragment length polymorphisms. Genes for c-Ha-ras, insulin, and apolipoprotein A-1 on chromosome 11 and a polymorphic locus AW101 on chromosome 14 were used as Southern hybridization probes. Analysis of DNA from the parental fibroblast and HeLa cell lines and their nontumorigenic and tumorigenic hybrids showed the loss of a fibroblast chromosome 11 in four of the tumorigenic segregants and a HeLa chromosome 11 in a fifth hybrid cell line. This latter segregant has, interestingly, also lost a copy of chromosome 14 of fibroblast origin. There was no obvious correlation of loss of a copy of normal chromosome 14 and reexpression of tumorigenicity in any of the other hybrid cell populations. Our conclusion from these observations is that gene(s) that map to normal chromosome 11 might be involved in control of tumorigenic expression in these human hybrid cells. MH - Alleles ; Base Sequence ; Cell Line ; *Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 14 ; DNA/ANALYSIS ; Fibroblasts/ULTRASTRUCTURE ; Hela Cells/ULTRASTRUCTURE ; Human ; Hybrid Cells/ULTRASTRUCTURE ; Neoplasms/*FAMILIAL & GENETIC ; Restriction Fragment Length Polymorphisms ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - Cancer Res 1986 Dec;46(12 Pt 1):6174-9 3 UI - 87049562 AU - Byrne MA ; M:ller BR ; Taylor-Robinson D ; Harris JR ; Wickenden C ; Malcolm AD ; Anderson MC ; Coleman DV TI - The effect of interferon on human papillomaviruses associated with cervical intraepithelial neoplasia. AB - A double-blind, placebo-controlled, trial of leucocyte interferon showed that, contrary to previous reports, interferon had no significant effect on cervical intraepithelial neoplasia (CIN) when applied topically in a gel. DNA hybridization of cervical scrapes was used to monitor the effect of interferon on the human papillomaviruses (HPV) associated with CIN. There was, however, no significant difference in the expression of HPV 6 or 16 in the cervical epithelium of patients treated with interferon compared with those given a placebo. By using superficial cells scraped from the surface of the cervical epithelium as a source of DNA for viral studies, we were able to investigate the relation between HPV and CIN without interfering with the natural history of the disease. HPV 16 was detected in lesions which persisted while HPV 6 only was detected in one lesion that regressed. Regression was clearly associated with reduction in the number of copies of viral DNA per cell in this case. Dual infection with HPV types 6 and 16 were recorded in two patients with persistent lesions. In one patient, hybridization studies indicated that infection with HPV 16 could have occurred after infection with type 6 was established, and it is postulated that this may have changed the nature of the cervical lesion. MH - Adolescence ; Adult ; Cervix Neoplasms/COMPLICATIONS/MICROBIOLOGY/ *THERAPY ; Clinical Trials ; Double-Blind Method ; DNA, Viral/ANALYSIS ; Female ; Human ; Interferon Type I/*THERAPEUTIC USE ; Papillomaviruses/ DRUG EFFECTS ; Support, Non-U.S. Gov't ; Tumor Virus Infections/ COMPLICATIONS/*THERAPY SO - Br J Obstet Gynaecol 1986 Nov;93(11):1136-44 4 UI - 87039109 AU - Zerler B ; Moran B ; Maruyama K ; Moomaw J ; Grodzicker T ; Ruley HE TI - Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. AB - Plasmids expressing partial adenovirus early region 1A (E1A) coding sequences were tested for activities which facilitate in vitro establishment (immortalization) of primary baby rat kidney cells and which enable the T24 Harvey ras-related oncogene and the polyomavirus middle T antigen (pmt) gene to transform primary baby rat kidney cells. E1A cDNAs expressing the 289- and 243-amino acid proteins expressed both E1A transforming functions. Mutant hrA, which encodes a 140-amino acid protein derived from the amino-terminal domain shared by the 289- and 243-amino acid proteins, enabled ras (but not pmt) to transform and facilitated in vitro establishment to a low, but detectable, extent. These studies suggest that E1A functions which collaborate with ras oncogenes and those which facilitate establishment are linked. Furthermore, E1A transforming functions are not associated with activities of the 289-amino acid E1A proteins required for efficient transcriptional activation of viral early region promoters. MH - Adenoviruses, Human/GENETICS ; Animal ; Base Sequence ; Cell Line ; *Cell Transformation, Neoplastic ; DNA/METABOLISM ; *Genes, Structural ; *Genes, Viral ; Human ; Kidney ; Oncogene Proteins, Viral/*GENETICS ; *Oncogenes ; Plasmids ; Polyomaviruses/GENETICS ; Rats ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Translation, Genetic SO - Mol Cell Biol 1986 Mar;6(3):887-99 5 UI - 86304600 AU - Hu LF ; Li XL ; Jiang JQ ; Yao J ; Yu Y ; Cao SL ; Huang KM ; Shen DT ; Wang LP ; Gu JR TI - Transforming activity of human nasopharyngeal carcinoma DNA. AB - NIH 3T3 cells were transfected with the DNAs from biopsy specimens of human nasopharyngeal carcinoma (NPC, EBV DNA positive) using calcium phosphate precipitation method. The malignant, transformed foci of NIH 3T3 cells have been observed and cloned. The hybridization of transfectant DNA digested by EcoRI with total human leukocyte DNA as probe was performed. The strong signal of smear comparing with NIH 3T3 DNA as control was observed. It was implied that the putative human transforming sequences had been integrated into transformed cells. Employing soft agar culture, the transformed cells can grow and form cell colonies. Following transfer, the foci were able to grow and adhere to a glass wall. These cells were easily agglutinated by con A. The cloned foci have been inoculated into nude mice with the formation of highly malignant sarcomas. In preliminary experiments for characterizing the transforming sequences, Ha-ras and Blym 1 were found in transfectants derived from one of the NPC DNA samples. It is implicated that these two oncogenes might be responsible for the acquisition of malignant phenotypic character of some human NPC. The further identification of oncogenes in NPC is currently in progress. MH - Animal ; Base Sequence ; Cell Line ; *Cell Transformation, Neoplastic ; DNA Restriction Enzymes/METABOLISM ; DNA, Neoplasm/*METABOLISM ; Human ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms/*FAMILIAL & GENETIC ; Nucleic Acid Hybridization ; Support, Non-U.S. Gov't ; *Transfection SO - J Cell Physiol [Suppl] 1986;4:21-6 6 UI - 86283650 AU - Strander HA TI - Interferon in the treatment of human papilloma virus. AB - Human papilloma viruses have been associated with several diseases, of which the most studied have been warts, juvenile laryngeal papillomatosis, and condyloma acuminatum. This article discusses the use of interferon in the treatment of these three diseases. MH - Condylomata Acuminata/*THERAPY ; Human ; Interferons/*THERAPEUTIC USE ; Laryngeal Neoplasms/*THERAPY ; Papilloma/*THERAPY ; Papillomaviruses/DRUG EFFECTS ; Warts/*THERAPY SO - Med Clin North Am 1986 May;Suppl:19-23 7 UI - 86246695 AU - Androphy EJ TI - Papillomaviruses and interferon. AB - Papillomaviruses are infectious agents which cause benign tumours, or warts, of cutaneous, uterine cervical and laryngeal epithelia. These infections are very common, yet no uniformly effective therapy exists. Current treatments do not selectively inhibit viral processes but destroy the infected epithelial cells. Since interferons have antiviral effects in vivo and in vitro, it was hypothesized that they might be useful for treating papillomavirus-induced conditions. Interferons have now been demonstrated to be effective in several forms of papillomavirus infection. In vitro, chronic treatment of bovine papillomavirus-transformed cells led to the loss of the papillomavirus genomes and return of the cells to a normal morphology. In humans, interferons have been used for treating laryngeal papillomatosis, cutaneous and anogenital warts and epidermodysplasia verruciformis. Partial and total remissions have been achieved with both intralesional and systemic administration. Ongoing studies aim to identify which conditions are most responsive, the optimal dosage and regimen and the most effective class of interferon. The mechanisms by which these responses occur are unknown, but are thought to depend on interferon inducing specific cellular proteins. RF - REVIEW ARTICLE: 25 REFS. MH - Animal ; Cell Line ; Cell Transformation, Neoplastic ; Cell Transformation, Viral ; Cervix Dysplasia/THERAPY ; Condylomata Acuminata/ THERAPY ; Female ; Human ; Interferons/*THERAPEUTIC USE ; Laryngeal Neoplasms/THERAPY ; Male ; Mice ; Papilloma/THERAPY ; Papillomaviruses/ *PHYSIOLOGY ; Recurrence ; Review ; Skin Diseases/THERAPY ; Tumor Virus Infections/*THERAPY ; Warts/*THERAPY SO - Ciba Found Symp 1986;120:221-34 8 UI - 86246694 AU - Steinberg BM TI - Laryngeal papillomatosis is associated with a defect in cellular differentiation. AB - The effects of human papillomavirus infection, which can cause laryngeal papillomas, were studied in vitro in laryngeal stratified squamous epithelial cells. Interferon exposure had only minor effects on the outgrowth of primary cells from tissue fragments and the incorporation of tritiated amino acids by first-passage cells. There was a marked decrease in tritiated thymidine incorporation by papilloma cells when cultured in the presence of interferon, but no effect on thymidine incorporation by normal cells. Differentiation of laryngeal papillomas appears to be abnormal. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of keratins showed that the keratins of high relative molecular mass (Mr 51,000 and 59,000) associated with normal laryngeal differentiation were absent from papilloma tissue. Rather, both papilloma tissue and cultured papilloma cells contained a keratin of Mr 53,000 not normally present. Binding of the fluoresceinated lectin peanut agglutinin to cell surfaces suggested that there were alterations in the normal distribution of glycoproteins or glycolipids on papilloma tissues. Filaggrin, a protein synthesized by differentiating cells, was not detectable in most superficial papilloma cells after immunohistochemical staining. These studies strongly suggest that papilloma cells do not differentiate normally. We propose that this defect may be responsible for the hypertrophy of the tissue. MH - Adolescence ; Adult ; Autoradiography ; Cell Differentiation ; Cells, Cultured ; Child ; Child, Preschool ; DNA, Viral/ANALYSIS ; Electrophoresis, Polyacrylamide Gel ; Female ; Human ; Infant ; Infant, Newborn ; Interferons/PHARMACOLOGY ; Intermediate Filament Proteins/ ANALYSIS ; Keratin/ANALYSIS ; Laryngeal Neoplasms/*PATHOLOGY ; Male ; Middle Age ; Nucleic Acid Hybridization ; Papilloma/*PATHOLOGY ; Papillomaviruses/CLASSIFICATION/GENETICS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Tumor Virus Infections/*PATHOLOGY/ TRANSMISSION SO - Ciba Found Symp 1986;120:208-20 9 UI - 86246692 AU - Coleman DV ; Wickenden C ; Malcolm AD TI - Association of human papillomavirus with squamous carcinoma of the uterine cervix. AB - The frequent association of human papillomavirus infection with preinvasive and invasive cancers of the cervix has led to speculation that the viruses may be involved in the neoplastic process. We have carried out some epidemiological studies of the prevalence of human papillomavirus infection in the female genital tract to evaluate more fully the oncogenic potential of these viruses in the cervix. A non-invasive method of detecting the virus has been developed for this purpose using DNA hybridization of cervical scrapings. The technique has been used to carry out prospective studies of patients with cervical intraepithelial neoplasia (CIN) and to investigate infection in women treated by laser therapy for CIN. We have also studied women with normal cervices to determine the prevalence of human papillomaviruses in the normal population. Further studies have involved the investigation of the effect of interferon on virus replication and epithelial proliferation in women with CIN III. MH - Carcinoma in Situ/*ETIOLOGY/MICROBIOLOGY/THERAPY ; Carcinoma, Squamous Cell/*ETIOLOGY/MICROBIOLOGY ; Cell Transformation, Neoplastic ; Cervix Neoplasms/*ETIOLOGY/MICROBIOLOGY/THERAPY ; Cervix Uteri/MICROBIOLOGY ; DNA, Viral/ANALYSIS ; Female ; Human ; Interferons/THERAPEUTIC USE ; Male ; Nucleic Acid Hybridization ; Papillomaviruses/GENETICS ; Prospective Studies ; Retrospective Studies ; Tumor Virus Infections/*COMPLICATIONS/ TRANSMISSION SO - Ciba Found Symp 1986;120:175-89 10 UI - 86216639 AU - Rodenhuis S ; Bos JL ; Slater RM ; Behrendt H ; van 't Veer M ; Smets LA TI - Absence of oncogene amplifications and occasional activation of N-ras in lymphoblastic leukemia of childhood. AB - To examine whether determination of (1) the copynumber or restriction pattern of certain oncogenes or (2) the mutational activation of the N-ras gene might contribute to the risk classification of acute lymphoblastic leukemia of childhood (ALL), we investigated DNA isolated from lymphoblasts of untreated patients. Restriction enzyme analysis of cellular oncogenes was performed on DNA of 25 patients. No rearrangements could be demonstrated within or near the genes c-myc, c-myb, c-abl, bcr, c-Ki-ras, and N-ras. No amplifications of these genes nor of N-myc or c-Ha-ras were present. Eight of 21 patients were heterozygote for "rare: Ha-ras allelic restriction fragments that have been associated with an increased risk of developing a malignancy. These patients were clinically indistinguishable from patients lacking these fragments. The breakpoint cluster region (bcr) that is rearranged in all patients with Philadelphia chromosome positive chronic myeloid leukemia, was normal in all cases, including at least one patient with Philadelphia chromosome positive ALL. A 2.8 kb HindIII fragment of a hitherto unknown gene or pseudogene related to v-myb probably derives from the Y chromosome. Nineteen patients were examined for point mutations in the N-ras gene, using a novel synthetic oligonucleotide hybridization assay. In two patients activating point mutations were present, both in positions 1 of the 12th codon. Both patients were somewhat older than the others (16 and 11 years), had L2 morphology, and were shown to have high growth fractions of tumor in their bone marrow. MH - Adolescence ; Alleles ; Base Sequence ; Child ; Child, Preschool ; DNA Restriction Enzymes/METABOLISM ; Female ; *Gene Amplification ; Human ; Infant ; Leukemia, Lymphoblastic/*FAMILIAL & GENETIC ; Male ; Mutation ; Nucleic Acid Hybridization ; *Oncogenes ; Support, Non-U.S. Gov't SO - Blood 1986 Jun;67(6):1698-704 11 UI - 86195542 AU - Yamada H ; Sakamoto H ; Taira M ; Nishimura S ; Shimosato Y ; Terada M ; Sugimura T TI - Amplifications of both c-Ki-ras with a point mutation and c-myc in a primary pancreatic cancer and its metastatic tumors in lymph nodes. AB - Activated c-Ki-ras with a point mutation (GGT to CGT) at codon 12, resulting in the substitution of arginine for glycine, was found in DNA from metastatic pancreatic adenocarcinoma in a lymph node. By means of restriction endonuclease length polymorphism with SacI digestion, we were able to demonstrate that the same point mutation of c-Ki-ras was present in the primary tumor and in metastases in lymph nodes. DNA from the normal spleen of the patient did not have this type of point mutation. Moreover, amplifications of 3- to 6-fold of the activated c-Ki-ras and 50-fold of c-myc were found in the primary tumor and the metastases in the two lymph nodes, indicating that point mutation had occurred at a relatively early stage of the tumor development, before amplification of the gene. This is the first clear demonstration of amplification of activated c-Ki-ras accompanied by amplification of c-myc in both primary and metastatic human tumors in vivo. MH - Base Sequence ; Codon ; DNA/GENETICS ; DNA Restriction Enzymes ; *Gene Amplification ; Human ; Lymphatic Metastasis ; *Mutation ; Nucleic Acid Hybridization ; *Oncogenes ; Pancreatic Neoplasms/*FAMILIAL & GENETIC/ PATHOLOGY ; Support, Non-U.S. Gov't ; Transfection SO - Jpn J Cancer Res 1986 Apr;77(4):370-5 12 UI - 86164981 AU - Weich HA ; Sebald W ; Schairer HU ; Hoppe J TI - The human osteosarcoma cell line U-2 OS expresses a 3.8 kilobase mRNA which codes for the sequence of the PDGF-B chain [published erratum appears in FEBS Lett 1986 May 26;201(1):180] AB - A cDNA clone of about 2500 base pairs was prepared from the human osteosarcoma cell line U-2 OS by hybridizing with a v-sis probe. Sequence analysis showed that this cDNA contains the coding region for the PDGF-B chain. It is discussed that the mitogen secreted by these osteosarcoma cells contains the PDGF-B chain and is probably a homodimer of two B-chains. MH - Base Sequence ; Cell Line ; DNA/ANALYSIS ; Human ; Oncogenes ; Platelet-Derived Growth Factor/*GENETICS ; RNA, Messenger/*ANALYSIS ; Sarcoma, Osteogenic/*ANALYSIS SO - FEBS Lett 1986 Mar 31;198(2):344-8 13 UI - 86224193 AU - Krontiris TG ; DiMartino NA ; Colb M ; Mitcheson HD ; Parkinson DR TI - Human restriction fragment length polymorphisms and cancer risk assessment. AB - The polymorphic restriction fragments of the human Ha-ras locus, produced by the variable tandem repetition (VTR) of a short consensus sequence, fall into three classes based on allelic frequencies. Alleles of the "rare: class (individual frequencies less than 0.5%) have been detected only in white blood cell and tumor DNA of cancer patients. This phenomenon is independent of ethnic origin. No significant association of rare alleles with cancer patients has been demonstrated at an independent tandem repeat locus, VTR4.1. The results suggest that the Ha-ras restriction fragment length polymorphism is useful in cancer risk assessment. MH - Alleles ; DNA/GENETICS ; DNA Restriction Enzymes ; Ethnic Groups ; Female ; Gene Frequency ; Human ; Male ; Neoplasms/*FAMILIAL & GENETIC ; *Oncogenes ; Pedigree ; *Polymorphism (Genetics) ; Repetitive Sequences, Nucleic Acid ; Risk ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - J Cell Biochem 1986;30(4):319-29 14 UI - 86196722 AU - Lau AS ; Hannigan GE ; Freedman MH ; Williams BR TI - Regulation of interferon receptor expression in human blood lymphocytes in vitro and during interferon therapy. AB - Interferons (IFN) elicit antiviral and antineoplastic activities by binding to specific receptors on the cell surface. The binding characteristics of IFN to human lymphocytes were studied using IFN alpha 2 labeled with 125I to high specific activity. The specific binding curves generated were analyzed by the LIGAND program of Munson and Rodbard to determine receptor numbers. The number of receptors in peripheral blood lymphocytes (PBL) and tonsillar B-lymphocytes (TBL) from normal individuals were 505 +/- 293 (n = 10) and 393 +/- 147 (n = 3) respectively. When these cells were preincubated in vitro with unlabeled IFN alpha 2, the receptor number decreased to 82 +/- 45 and 61 +/- 16 respectively. Receptor binding activities recovered gradually over a period of 72 h when the cells were incubated in IFN-free medium. This recovery of receptors could be blocked by the addition of actinomycin D to the incubation medium. A similar decrease in receptor expression was observed in vivo in PBL from patients being treated daily with 5 X 10(6) units/m2 per d of IFN alpha 2 by subcutaneous injection, for acute lymphoblastic leukemia or papilloma virus infections. Receptor numbers in PBL in vivo were further reduced concurrent with the progression of IFN therapy. Thus the reduction in IFN receptor expression observed in vitro can be demonstrated in vivo. These studies indicate that monitoring IFN receptor expression in vivo can provide information regarding the availability of IFN receptors at the cell surface for the mediation of IFN actions during the course of IFN therapy. MH - Dactinomycin/PHARMACOLOGY ; Human ; In Vitro ; Interferon Type I/ METABOLISM/*THERAPEUTIC USE ; Iodine Radioisotopes/DIAGNOSTIC USE ; Leukemia, Lymphoblastic/THERAPY ; Lymphocytes/*ANALYSIS/DRUG EFFECTS ; Papillomaviruses ; Receptors, Immunologic/*ANALYSIS/DRUG EFFECTS ; Support, Non-U.S. Gov't ; Tumor Virus Infections/THERAPY SO - J Clin Invest 1986 May;77(5):1632-8 15 UI - 86175921 AU - Gall SA ; Hughes CE ; Mounts P ; Segriti A ; Weck PK ; Whisnant JK TI - Efficacy of human lymphoblastoid interferon in the therapy of resistant condyloma acuminata. AB - The efficacy and tolerance of human lymphoblastoid interferon (Wellferon) were studied in an open label trial of 17 patients with resistant and persistent condyloma acuminata. Patients were treated intramuscularly with 5 X 10(6) U (5 MU)/m2 daily for 28 days followed by thrice weekly injections for two weeks. Sixteen patients were considered evaluable; eight experienced complete clearance, seven had significant reduction (greater than 50%) in lesion size, and one showed no response during the course of this trial. Biologic side effects of interferon occurred in all patients during initial dosing and diminished during thrice weekly therapy. Intramuscular injections and associated side effects were tolerated well. This study shows that systemic human lymphoblastoid interferon is active in treating severe recurrent genital warts in women with a history of recalcitrant disease. MH - Adolescence ; Adult ; Blood Cell Count ; Clinical Trials ; Condylomata Acuminata/MICROBIOLOGY/PATHOLOGY/*THERAPY ; Dinitrochlorobenzene/ DIAGNOSTIC USE ; DNA, Viral/ANALYSIS ; Fatigue/CHEMICALLY INDUCED ; Female ; Fever/CHEMICALLY INDUCED ; Genital Neoplasms, Female/ MICROBIOLOGY/PATHOLOGY/*THERAPY ; Headache/CHEMICALLY INDUCED ; Human ; Immunoglobulins/ANALYSIS ; Interferon Type I/ADVERSE EFFECTS/ANALYSIS/ *THERAPEUTIC USE ; Lymphocytes/IMMUNOLOGY ; Middle Age ; Nausea/ CHEMICALLY INDUCED ; Papillomaviruses/GENETICS ; Podophyllin/THERAPEUTIC USE SO - Obstet Gynecol 1986 May;67(5):643-51 16 UI - 86120375 AU - Valenzuela DM ; Groffen J TI - Four human carcinoma cell lines with novel mutations in position 12 of c-K-ras oncogene. AB - We have used synthetic oligonucleotides to probe for mutations affecting amino acid 12 of the c-K-ras gene in human cell line DNA. Of seven carcinoma cell lines tested, four were found to contain a mutation at this position. In each the nucleotide G was replaced with an A resulting in a Gly to Asp substitution in three cases (cell lines A427, A1165 and A1663) and Gly to Ser in the fourth (A549). Neither of these substitutions have been previously reported in either human tumor or human tumor-derived cell line DNA's. These results indicate that association between mutations involving position 12 of the human c-K-ras oncogene and carcinomas may be stronger than previously recognized. MH - Base Sequence ; Cell Line ; Comparative Study ; DNA, Neoplasm/GENETICS/ ISOLATION & PURIFICATION ; Human ; *Mutation ; Neoplasms/*FAMILIAL & GENETIC ; Nucleic Acid Hybridization ; *Oncogenes ; Support, Non-U.S. Gov't SO - Nucleic Acids Res 1986 Jan 24;14(2):843-52 17 UI - 86079573 AU - Der CJ ; Finkel T ; Cooper GM TI - Biological and biochemical properties of human rasH genes mutated at codon 61. AB - Using site-directed mutagenesis, we have introduced mutations encoding 17 different amino acids at codon 61 of the human rasH gene. Fifteen of these substitutions increased rasH transforming activity. The remaining two mutants, encoding proline and glutamic acid, displayed transforming activities similar to the normal gene. Overall, these mutants vary over 1000-fold in transforming potency. Increased levels of p21 expression were required for transformation by weakly transforming mutants. The mutant proteins were unaltered in guanine nucleotide binding properties. However, all 17 different mutant proteins displayed equivalently reduced rates of GTP hydrolysis, 8- to 10-fold lower than the normal protein. There was no quantitative correlation between reduction in GTPase activity and transformation, indicating that reduced GTP hydrolysis is not sufficient to activate ras transforming potential. MH - Amino Acid Sequence ; Animal ; Base Sequence ; Cell Transformation, Neoplastic/*ETIOLOGY ; Fibroblasts ; Gene Expression Regulation ; Guanosine Triphosphate/METABOLISM ; GTP Phosphohydrolase/GENETICS/ METABOLISM/PHYSIOLOGY ; Human ; Mice ; Neoplasm Proteins/*GENETICS/ METABOLISM/PHYSIOLOGY ; Protein Conformation ; *Proto-Oncogenes ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; Transfection SO - Cell 1986 Jan 17;44(1):167-76 18 UI - 86066276 AU - Trofatter KF Jr ; English PC ; Hughes CE ; Gall SA TI - Human lymphoblastoid interferon (Wellferon) in primary therapy of two children with condylomata acuminata. AB - Human lymphoblastoid interferon (Wellferon) was administered parenterally to two prepubertal girls as primary therapy for genital condylomata acuminata. One child probably had contracted the disease as the result of sexual molestation. Both patients experienced minimal side effects during therapy and underwent complete remission within six weeks. These cases support use of interferon as primary therapy in young patients with extensive condylomata and in those who may have contracted the disease as the result of sexual abuse. MH - Case Report ; Cervix Neoplasms/PATHOLOGY/*THERAPY ; Child ; Condylomata Acuminata/PATHOLOGY/*THERAPY ; Female ; Human ; Interferon Type I/ *THERAPEUTIC USE ; Papillomaviruses ; Perineum ; Skin Neoplasms/PATHOLOGY/ *THERAPY ; Support, Non-U.S. Gov't SO - Obstet Gynecol 1986 Jan;67(1):137-40