==================================BSR38================================== 38. Experimental neovascularization of rat cornea. This is one model of neovascularization of the ocular tissue (retina, iris, cornea). 1 UI - 87048875 AU - Polverini PJ ; Novak RF TI - Inhibition of angiogenesis by the antineoplastic agents mitoxantrone and bisantrene. AB - The effects of mitoxantrone and bisantrene on angiogenic responses induced by tumor cell-conditioned media in the avascular cornea of rat eye have been evaluated. Both mitoxantrone and bisantrene effectively inhibited, in a concentration-dependent manner, angiogenesis induced by conditioned media obtained from either a hamster buccal pouch carcinoma cell line or P388D1 murine macrophage-like cells. Whereas vessel ingrowth in corneas containing tumor cell-conditioned media was detected as early as day 2 or 3 and was maximal by day 7, inclusion of mitoxantrone or bisantrene in the conditioned media at a 1:1 ratio (160 microM mitoxantrone or 32 microM bisantrene) resulted in complete inhibition of angiogenesis throughout the 14-day evaluation period. When concentrations of 64 and 32 microM mitoxantrone or 13 and 6.4 microM bisantrene were employed there was a marked delay in the appearance of capillary blood vessels (day 5 to 7) and a reduction in the intensity of angiogenic responses. No untoward toxicity to the tissue was observed at the concentrations of mitoxantrone or bisantrene employed. MH - Animal ; Anthracenes/PHARMACODYNAMICS ; Antineoplastic Agents/ *PHARMACODYNAMICS ; Cornea/BLOOD SUPPLY ; Culture Media ; Mitoxantrone/ *PHARMACODYNAMICS ; Neovascularization/*PHYSIOPATHOLOGY ; Rats ; Support, Non-U.S. Gov't SO - Biochem Biophys Res Commun 1986 Nov 14;140(3):901-7 2 UI - 87023860 AU - Leure-Dupree AE TI - Vascularization of the rat cornea after prolonged zinc deficiency. AB - Neovascularization of the anterior stroma of the rat cornea was associated with prolonged zinc deficiency (in this model). There was also an increase in the myelinated nerves of the cornea. Blood vessels were not observed in the corneas of the pair-fed and ad-libitum-fed control animals. The invading blood vessels were frequently associated with Schwann cells and neurites. Unmyelinated nerves were observed in the corneal stroma of all three experimental groups. MH - Animal ; Cornea/*BLOOD SUPPLY/INNERVATION/ULTRASTRUCTURE ; Fibroblasts/ ULTRASTRUCTURE ; Male ; *Neovascularization ; Rats ; Rats, Inbred Strains ; Schwann Cells/ULTRASTRUCTURE ; Support, U.S. Gov't, P.H.S. ; Zinc/ *DEFICIENCY SO - Anat Rec 1986 Sep;216(1):27-32 3 UI - 86277247 AU - Alessandri G ; Raju KS ; Gullino PM TI - Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastasis. AB - Mobilization of the capillary endothelium is one of the first events observed during angiogenesis, and the study of conditions that control or influence the mobilization of the endothelium in vitro has been assumed to offer information relevant to the understanding of angiogenesis in vivo. In vitro mobilization of the bovine capillary endothelium was substantially enhanced by addition of gangliosides to the culture medium. Optimal mobilization was obtained when the endothelium incorporated the gangliosides first and was then seeded on fibronectin anchored to collagen type I. Preincubation of the capillary endothelium with gangliosides, trisialoganglioside in particular, doubled the amount of fibronectin bound to the cells and enhanced the migration about 5-fold. 'Blockage' of ganglioside binding with cholera toxin or gamma-interferon substantially reduced migration. Rabbit corneas, treated in vivo with a variety of angiogenesis effectors to induce neovascularization, consistently showed an increase in sialic acid content just prior to the time the tissue would be penetrated by the capillaries. This finding was interpreted to indicate that an increment of the ganglioside content of the capillary endothelial cell membranes may play a determinant role in the mobilization of the capillary endothelium in vivo as shown here to take place in vitro. Since the formation of a tumor from a micrometastasis requires formation of new capillaries and highly metastasizing tumors very frequently have high levels of sialic acid on the cell surface, it is hypothesized that production and shedding of gangliosides from the surface of neoplastic cells may be a factor in promoting angiogenesis and metastatic growth. MH - Animal ; Capillaries/DRUG EFFECTS/*METABOLISM ; Cattle ; Cell Movement/ DRUG EFFECTS ; Cornea/ANALYSIS/DRUG EFFECTS ; Endothelium/DRUG EFFECTS/ METABOLISM ; Fibronectins/PHARMACODYNAMICS/*PHYSIOLOGY ; Gangliosides/ PHARMACODYNAMICS/*PHYSIOLOGY ; Growth Substances/PHARMACODYNAMICS ; *Neoplasm Metastasis ; *Neovascularization ; Rabbits ; Rats ; Sialic Acids/ANALYSIS ; Support, Non-U.S. Gov't SO - Invasion Metastasis 1986;6(3):145-65 4 UI - 86269696 AU - Oikawa T ; Matsuzawa A ; Iwaguchi T TI - Progression from hormone dependence to autonomy and angiogenesis in mouse mammary tumours. AB - The transplantable pregnancy-dependent mammary tumour (TPDMT-4), the related hormone-dependent (TPDMT-4EP) and autonomous (T4-0I320 and T4-0I96) subline tumours, and the mammary glands from DDD mice were compared for angiogenic activity on the rabbit cornea by tissue implantation. The TPDMT-4EP tumour was established by serially transplanting TPDMT-4 tumour fragments in oestradiol plus progesterone treated mice. The T4-0I320 and T4-0I96 tumours directly derived from the TPDMT-4 and TPDMT-4EP tumours, respectively. Angiogenic activity was graded by macroscopic and microscopic examinations into 3 classes; negative, partial and complete angiogenesis. These tumours were comparable to mammary glands in activity and induced complete angiogenesis in only 15-23% of the implants. However, when partial and complete responses were combined as positive angiogenesis, TPDMT-4, T4-0I320, TPDMT-4EP and T4-0I96 tumour implants were angiogenic in 25, 29, 42 and 54%, respectively. The T4-0I96 tumour was significantly more angiogenic than the parent tumour but this was not so for the TPDMT-4EP tumour. Spontaneous C3H mouse mammary tumours, human gliomas from nude mice, rat Walker 256 carcinomas and rabbit VX-2 tumours induced complete angiogenesis in 54, 63, 59 and 92% of the implants, respectively. The results suggest that the TPDMT-4 tumour is unique in being weakly angiogenic and able to progress toward greater autonomy with or without augmented angiogenic activity in different conditions. MH - Animal ; Carcinoma 256, Walker/BLOOD SUPPLY ; Cornea/BLOOD SUPPLY ; Estradiol/PHYSIOLOGY ; Female ; Male ; Mammary Neoplasms, Experimental/ *BLOOD SUPPLY/PHYSIOPATHOLOGY ; Mice ; Mice, Inbred C3H ; Neoplasm Transplantation ; *Neovascularization ; Pregnancy ; Progesterone/ PHYSIOLOGY ; Rabbits ; Rats ; Support, Non-U.S. Gov't SO - Br J Cancer 1986 Jul;54(1):91-6 5 UI - 86212516 AU - Hoban BP ; Collin HB TI - Effects of salicylate and steroid on neutrophil migration and corneal blood vessel growth. AB - Cauterization of the cornea results in emigration of neutrophils from the limbal blood vessels into the corneal tissue. Blood vessel proliferation follows, the stimulus for which is unknown. In this study, 0.1 M sodium salicylate drops administered topically to cauterized rat corneas over a 48-h period had an inhibitory effect on the migration of neutrophils from the limbal vessels 6 h after injury, but this was not maintained at 48 h. After 6 days of treatment, the salicylate had no effect on vessel growth into the cauterized rat cornea. Application of prednisolone disodium phosphate ointment to cauterized corneas also inhibited neutrophil migration at 6 h, but increased the extravascular neutrophils at 48 h. After 6 days of treatment, corneal blood vessel growth was significantly reduced. It was concluded that there is no consistent relation between the number of extravascular neutrophils at the corneal limbus and the extent of corneal blood vessel growth. MH - Animal ; Cell Movement/DRUG EFFECTS ; Cornea/*BLOOD SUPPLY/DRUG EFFECTS/ *INJURIES ; Female ; Leukocyte Count ; Male ; Neovascularization ; Neutrophils/*DRUG EFFECTS ; Prednisolone/*ANALOGS & DERIVATIVES/ PHARMACODYNAMICS ; Rats ; Rats, Inbred Strains ; Sodium Salicylate/ *PHARMACODYNAMICS ; Support, Non-U.S. Gov't SO - Am J Optom Physiol Opt 1986 Apr;63(4):271-6 6 UI - 86087676 AU - Koch AE ; Polverini PJ ; Leibovich SJ TI - Induction of neovascularization by activated human monocytes. AB - Neovascularization, the process of new blood vessel growth, is an important feature of many pathologic and physiologic processes. Monocytes were isolated from citrated blood buffy coat of healthy adult human donors on Ficoll-Hypaque gradients. Mononuclear cells from these gradients were fractionated on discontinuous Percoll gradients; monocyte-enriched fractions were isolated and assessed for angiogenic activity in rat corneas. Freshly isolated monocytes as well as monocytes cultured for 20 hr on fibronectin-coated collagen gels failed to stimulate neovascularization. In contrast, adherent monocytes activated with concanavalin A (25 micrograms/ml) or endotoxin (5 micrograms/ml) for 20 hr were found to be potently angiogenic. We conclude that peripheral blood monocytes must be activated to acquire the ability to induce new blood vessel growth, a process central to inflammation, wound healing, and tumor development. MH - Adult ; Animal ; Cell Separation ; Cells, Cultured ; Concanavalin A/ PHARMACODYNAMICS ; Cornea/BLOOD SUPPLY ; Endotoxins/PHARMACODYNAMICS ; Fibronectins ; Human ; Macrophage Activation ; Macrophages/DRUG EFFECTS/ *PHYSIOLOGY ; Monocytes/DRUG EFFECTS/*PHYSIOLOGY ; *Neovascularization ; Rats ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. SO - J Leukocyte Biol 1986 Feb;39(2):233-8