Showing papers on "Angiogenesis published in 1978"

Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin.

Abstract: Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cells cultures previously described.

Angiogenesis as a marker of preneoplastic lesions of the human breast

Abstract: At the time of biopsy or mastectomy, 947 tissue fragments from 42 patients were transplanted onto the rabbit iris to determine their capacity to elicit new formation of vessels. In all 10 carcinomas tested, at least 1 of the transplanted fragments induced a strong angiogenic response. Of 50 transplants from hyperplastic lobules, 28% also elicited new vessel formation. Fibrous or adipose tissue and tissues from normal lobules, fibrocystic disease, fibroadenoma, lipoma, and gynecomastia almost always failed to produce angiogenesis (Table 1). In the angiogenesis test the human mammary gland behaves like the mouse gland: a fraction of epithelial lesions, which morphologically appear hyperplastic, is already able to induce an angiogenic response just as the carcinomas. In the mouse, the frequency of neoplastic transformation is higher for those hyperplastic lesions with a high frequency of angiogenic response.13 These results suggest that a major effort may be warranted to ascertain whether the frequency of carcinomas is higher in human subjects whose mammary hyperplastic lesions elicit a strong angiogenic response. The angiogenic assay could distinguish lesions undergoing neoplastic transformation before morphological signs of „atypia” and invasion appear.

Regional differences in tumor growth: Studies of the vascular system

Abstract: We have previously shown that tumor cells inoculated into the thoracic region of the trunk grow much more rapidly and with a higher frequency than do an equivalent number of cells injected more posteriorly. We thought that these results might have been a reflection of an underlying difference in the vascular system supplying these regions of the trunk. The present experiments which were undertaken to characterize various aspects of the vascular system associated with the transplantation sites used in these studies include measurements of rates of diffusion of salt solutions, of protein clearance, and of the retention of radio-labelled cells and cellular debris. We have examined local differences in temperatures and studied the effect of change of ambient temperature on those local differences as well as on tumor growth. More directly, we have measured blood flow to the capillaries by intracardiac administration of radioactive microspheres, and assessed the ability of inoculated tumor cells to induce angiogenesis. We have been unable to detect any major differences in the parameters of the vascular system that we have analyzed. Thus we cannot offer any satisfactory explanation for the observed four-fold differences in tumor growth in anterior vs posterior inoculation sites. The results are discussed in terms of underlying developmental gradients which can be invoked to provide a basis for further experimentation.

Inhibition of lymphocyte-induced angiogenesis by enzymatically isolated rabbit cornea cells.

Abstract: Corneal and kidney cells were isolated from adult rabbits by enzymatic digestion. The were tested for anti-angiogeneic activity by the lymphocyte-induced angiogenesis assay. In this assay an intradermal injection of semi-allogeneic lymphocytes resulted in a new blood vessel formation visible after three days at the injection site. Isolated rabbit cells were mixed in 1:10 ratio with murine lymphocytes and injected into 600 R X-ray irradiated mice. Number of newly formed blood vessels evoked by lymphocytes injected alone or with rabbit cells added was counted. Corneal cells but not kidney cells decreased angiogenesis evoked by lymphocytes. This finding is discussed in view of corneal avascularity and pathological neo-vascularization.

Tumour angiogenesis and tumour immunity

Abstract: The capacity to induce new vessels from the host is one of the few properties that may be common to most, if not all, solid neoplasms. If, in fact, tumours can modify or reorganize their local environment to their own advantage, then the capacity for angiogenesis may be a pre-requisite for a ‘successful’ tumour.

Local graft-versus-host reaction in mice evoked by Peyer's patch and other lymphoid tissue cells tested in a lymphocyte-induced angiogenesis assay.

Abstract: The competence of murine Peyer's patch cells to evoke a local GVH reaction was compared with that displayed by lymphoid cells of spleen, lymph nodes, thymus, bone marrow, peritoneal cavity and peripheral blood. The local GVH reaction was assessed in a lymphocyte-induced angiogenesis assay in which an intradermal injection of lymphoid cells results in a new blood vessel formation at the injection site, and the number of vessels corresponds to the number of the immunocompetent cells injected. Peyer's patch cells were capable of mounting a local GVH reaction of intensity comparable to that evoked by the corresponding number of thymus cells or a four times lower number of spleen cells. The highest activity was exhibited by lymph node and peripheral blood cells while bone marrow cells were the least active. A striking increase in angiogenic response was observed after X-irradiation of the recipients with 700R.

Enhancing effect of X-ray irradiation on a new blood vessel formation in mice tested by lymphocyte induced angiogenesis assay.

Abstract: X-irradiation enhanced a new blood vessel formation occurring in the course of a local GvH reaction in mice. Maximal enhancing effect was exerted by single total body irradiation doses ranging from 700 to 1050 R. Fractionation in daily doses smaller than 200 R did not exhibit enhancing effect. Proliferative ability of angiogenesis inducing cells is not necessary for enhancing effect of irradiation.

Perineural angiogenesis in mice bearing subcutaneous tumours.

Abstract: Cells of myeloma or fibrosarcoma were inoculated s.c. into BALB/c mice. Intact skins and tissue sections from animals killed at periodic intervals after inoculation of tumor cells were examined macroscopically and microscopically. The development of new blood vessels, probably involved in vascularization of the tumor, was observed around the nerves adjacent to the deposit of tumour cells. This occurred 5 days after inoculation of cells and before the tumour had a mean diameter of less than 1 mm. Lesser degrees of "perineural angiogenesis" were noted after s.c. inoculation of mineral oil, Freund's complete adjuvant or implantation of intact spleen, but none was observed with killed tumour cells.

The tumor angiogenesis factor (TAF)

Abstract: The tumor Angiogenesis Factor (TAF) isolated from several human and animal neoplasms by J Folkman and S Kumar is a factor that induces the appearance of neovessels in the tumors After describing the methods of vasculor, physiological, experimental and in some cases pathological proliferation, the author has compared the Angiogenesis in both the natural and neoplastic tissues, then, he's studies the tumoral growth the rate of which regularized by the TAF The proving, the extraction and chemical nature of this factor have been reviewed Afterwards, the author has called to mind the notion of tumoral ecology and the various possibilities of inhibition of the tumoral growth, that is founded on the inhibition of the Angiogenesis and the therapeutical possibilities of the TAF in the fight against cancer To end up with his study, the author is now considering the possibility of using the TAF, extract of the sarcoma of sticker as a complement to the electontherapy in the treatment of this neoplasm