Showing papers on "Angiogenesis published in 1976"

Tumor angiogenesis activity in cells grown in tissue culture.

Abstract: Normal, viral transformed and tumor-derived cells grown in tissue culture and representing different species were tested for their ability to produce an extracellular tumor angiogenesis factor (TAF). TAF was assayed by measuring the host-mediated vascular response of the chorioallantoic membrane to TAF preparations. All of the viral transformed and tumor-derived cells tested, including SVT2, SVW126, Welker 256 rat carcinoma, B-16 mouse melanoma, human glioblastoma, and human meningioma cells, produced TAF. The potency of the TAF preparations, as measured by the number of cells needed to induce a positive vascular response on the chorioallantoic membrane, varied from cell line to cell line. The most potent cells tested were the glioblastoma and maningioma brain tumor cells. Since these brain tumors are found to be the most highly vascularized tumors in vivo, it was concluded that a correlation exists between the vascularity of a tumor in vivo and the potency of TAF in vitro. There was no detectable angiogenesis activity induced by density-inhibited BALB/c primary mouse embryo or early-passage human skin fibroblasts, even when relatively large numbers of cells were used to make a sample. However, density-inhibited BALB/c 3T3 aan W138 human embryonic lung fibroblasts, two cell lines widely regarded as demonstrating "normal" growth behavior in culture, produced TAF. From these and other observations, it was suggested that BALB/c 3T3 and W138 are not fully "normal" cells. Furthermore, it was suggested that the production of TAF is an early event in the cell transformation process that precedes the loss of density inhibition of growth in vitro.

Angiogenesis induction by tumors, embryonic tissues, and lymphocytes.

Abstract: Summary Although it is well established that tumors can induce endothelial cell mitosis and angiogenesis leading to extensive neovascularization, little is known concerning the spectrum of normal cells or tissues that may have similar inductive capabilities. A variety of developmentally active tissues were tested: mouse embryonic organ rudiments, mouse and rabbit trophoblast and placenta, and blastemal fragments obtained from regenerating deer antlers. Assays for angiogenesis included grafts made to the chorioallantoic membrane of chick embryos and grafts placed intracorneally in adult rabbit eyes. Virtually all of these test tissues were negative, the only exceptions being some antler grafts and some grafts obtained from metanephric tubules of the embryonic mouse kidney. In contrast, a striking vascular reaction could be evoked by foreign lymphocytes obtained from spleen or lymph node. Originally examined by intradermal inoculation into adult allogeneic mice, competent lymphocytes were shown to evoke extensive vascular responses in host animals, characterized by increased visualization of blood vessels, vascular divarication, and marked endothelial cell activity. When tested in the chick chorioallantoic membrane assay, mouse lymph node and spleen cells induced a typical angiogenesis response, and, similarly, mouse lymph nodes as well as allogeneic rabbit lymph nodes elicited the characteristic neovascularization reaction when grafted intracorneally into adult rabbits.

The role of vascular proliferation in the growth of brain tumors.

Abstract: The formation of new blood vessels, i.e., angiogenesis, is a critical step in the evolution of a brain tumor from the earliest avascular phase to the clinically overt, vascular stage. For cerebral astrocytomas, intense capillary proliferation is a poor prognostic sign, associated with rapidly growing tumors. The in vivo production of a vasoformative substance can be demonstrated by transplanting human and experimental gliomas to the rabbit cornea. Intense neovascularization is elicited by the tumor and not by control tissues. If the same tumor is transplanted to the vitreous, thereby interrupting the vasoformative signal, the tumor remains in a dormant state for a prolonged period of time, despite its malignant potential. Inhibition of angiogenesis would be an important adjunct to the surgical treatment of gliomas.

Lymphocyte-induced angiogenesis in tumor-bearing mice

Abstract: The presence of a growing tumor can lead to a significant curtailment of a graft-versus-host reaction as measured by the ability of allogeneic spleen cells to induce a host vascular response. This interference with the normal pattern of immunological reactions may be a reason for the survival of tumors in an immunologically alien environment.

Humoral control of cell proliferation: the role of fibroblast growth factor in regeneration, angiogenesis, wound healing, and neoplastic growth

Abstract: The Fibroblast Growth Factor (FGF) is a mitogenic agent in the brain and pituitary of mammals. Recent investigations of the effect of FGF on diverse cell types has shown that FGF stimulates the division of cells from a wide variety of tissues of mesodermal origin including fibroblasts, chondrocytes, myoblasts, smooth muscle cells, glial cells, normal adrenal cells, and the Y1 adrenal cell line. Cell types of endodermal or ectodermal origin do not appear to be sensitive to FGF. Since FGF can be found in neural tissues and since it induces the proliferation of two cell types involved in the formation of regeneration blastemas (chondrocytes and myoblasts), we have investigated the possibility that FGF could be similar or identical to the neurotrophic factors present in nerve and responsible for the regeneration of limbs in lower vertebrates. Our results have shown that FGF could indeed substitute for the neurotropic factor and replace the nerves in inducing blastema formation and sustaining proliferation of mesenchymal cells which can differentiate into chrondrocytes and myoblasts. Since the blastema has been described as a benign tumor, the role of FGF in the formation of blastemas and benign tumors is currently under investigation. In addition to stimulating fibroblasts, FGF also has a striking growth-promoting effect on primary cultures of vascular endothelial cells. This suggests that FGF could be an angiogenesis factor. Thus, FGF, one of the most potent mitogenic agents found in tissue extracts has two properties expected of an agent which could induce tumors: it can induce blastema formation (direct mitogenic effect) and, through its mitogenic effect on endothelial cells, it could induce formation of capillaries (amplification step), permitting unlimited growth. Repair processes under FGF control will, under normal circumstances, lead to wound healing. In contrast, if cells become transplanted to the wrong environment (hormonal imbalance), growth factors such as FGF could make them proliferate in an anarchic way since negative feedback from surrounding cells will be lacking.

Endothelial growth factor present in tissue culture of CNS tumors.

Abstract: ✓ Human endothelial cells obtained from postpartum umbilical veins and placed in primary tissue cultures were treated with media from cultures of human and experimental central nervous system tumors. Endothelial proliferation was determined by the uptake of 3H thymidine with autoradiography and represented as the thymidine labeling index (TI), which is the proportion of 3H thymidine-labeled endothelial cells to total number of cells counted. There was a marked increase in the TI when tumor-conditioned medium was added to endothelial cultures (range 28.7% to 98.3%) when compared to controls (2.1%) and endothelium with conditioned media from fibroblasts (4.5%). This study demonstrates the presence of a chemical substance produced by tumor cells which results in endothelial proliferation. The system described provides a useful assay technique for the further characterization of this endothelial growth factor.

Melanoma. Tumor angiogenesis and human neoplasia.

Abstract: Transparent hamster-cheek-pouch chambers were used to document angiogenesis induced by implants of human malignant melanoma. Capillary proliferation was observed with direct implantation of melanoma fragments and with tumor implants placed on microporous membrane Filters. The pattern of capillary neovascularization was recorded and correlated with clinical and histopatho-logic parameters.

The fine structural study on blood vessels within human brain tumors.

Abstract: The blood vessels of human brain tumors were studied in comparison with normal architecture under electron microscope. 1) In benign glial tumors, their blood vessels were apperently similar to those of normal tissue. 2) In malignant glial tumors, immature vessels were observed as might be expected in young, immature cells. The nucleus-cytoplasm ratio was high, and cytoplasm was filled with an abundance of organelles, especially free ribosomes and mitochondria. These findings suggest a high metabolic activity of endothelium. Opened intercellular junction, increased pinocytotic and coated vesicles were recognized in the endothelial cells, and proliferated endothelial cells had irregular luminal surface and elongated processes. These facts suggest an increased capacity to trasfer materials between the luman and the parenchyma. 3) In non-glial tumors, a fenestrated endothelium was commonly observed. The perivascular basement membrane was often reduplicated and was composed of several layers. 4) Adhesive devices between adjacent endothelial cells presented commonly macula adherens and desmosome-like pattern. 5) Tubular bodies were observed in the vascular endothelial cytoplasm of glioblastoma multiforme, pinealoma, craniopharyngioma, astrocytoma, teratoma with choriocarcinoma and pituitary adenoma. These tubular bodies showed various spectra from immature type to mature, might reflect a marked vascular reaction in angiogenesis with brain tumor formation. 6) Furthermore, in the case of pinealoma, its vascular basement membrane filled with collagen fibers and some dense materials merged continuously into the intercellular space of tumor tissue as seen in meningioma. These facts suggest that the origin of the pinealoma might be the mesodermal tissue.