Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Tumor angiogenesis activity in cells grown in tissue culture. 124 90

In this paper we present a simple mathematical model that adequately accounts for at least the initial vasculature that is established in a melanoma transplant. It is assumed that the tumor produces a substance (tumor angiogenesis factor--TAF) that elicits capillary sprouts from the vascular bed of the host. These sprouts then invade the tumor along the gradient of TAF and cross-connect forming a vascular pathway that is similar to the experimental patterns observed in a hamster cheek pouch. This model is then extended to include the migration of loops. The rupture and formation of sprouts from these loops is assumed to depend on the strength of the stimulus (TAF). Under the assumption that the production of TAF is significantly reduced in a neighborhood of an established vessel, the network formed by the vessels in the tumor corresponds to the observed arboreal patterns.
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PMID:Model for initial vascular patterns in melanoma transplants. 127 14

Previous reports on the slower growth of tumors in senescent mice have suggested a decrease in tumor angiogenesis in these animals, but such an observation has not yet been documented quantitatively. In this study, we report the relative amount of tumor angiogenesis and tumor volume for two different types of tumor in 11 young (8-9-wk old) versus nine older (19-mo old) male C57BL/10 mice. B16 melanoma or SP1 methylcholanthrene-induced fibrosarcoma cells were injected into the ventral skin of mice. After 3 days, the mice were killed and the injection sites were examined for angiogenesis surrounding the tumor (centrally directed tumor angiogenesis), nerve-associated angiogenesis, and tumor volume. In the older mice, there was significantly less centrally directed tumor angiogenesis for both tumors tested, and nerve-associated angiogenesis was decreased for B16 melanoma. The mean tumor volume for the B16 implants was smaller for the older animals, but the mean SP1 tumor volumes were identical for both age groups. These findings support the hypothesis that tumor growth in older animals is associated with less formation of new blood vessels, and this may explain the slower tumor growth observed in aged animals with certain experimental tumors.
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PMID:Effect of host age on tumor-associated angiogenesis in mice. 168 82

A simple and quantitative angiogenesis assay was developed. Using this assay, the angiostatic effect of cortisone acetate (CA) on three murine tumors was studied. Tumor cells were inoculated i.d. into the syngeneic or heterogeneic hosts (day 0) and the degree of angiogenesis was quantitated on day 3 by measuring the tumor vascular volumes using an Evan's blue perfusion technique. CA treatment (250 mg/kg for 3 days) significantly suppressed tumor angiogenesis; however, the degree of angiostatic effect was influenced by the tumor types and by the mouse strain used. MBT-2 bladder cancer angiogenesis was suppressed by 77%-80% of controls in C3H/HeN and C57B1/6 mice, whereas MBT-2 angiogenesis in BALB/c mice was significantly less suppressed by CA (65% inhibition) as compared with values obtained for C3H mice. B16 melanoma or Line-1 lung-cell carcinoma-induced angiogenesis was suppressed by 57%-66% in their syngeneic or heterogeneic hosts. The combined administration of CA and heparin (Sigma; 1,000 units/ml in drinking water) did not influence the outcomes. The data suggest that host factor(s) and tumor factor(s) influenced the expression of CA angiostatic activity. This colorimetric assay enabled a quantitative estimation of the degree of angiogenesis in mammalian animals.
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PMID:Cortisone inhibition of tumor angiogenesis measured by a quantitative colorimetric assay in mice. 169 79

We studied the expression of the angiogenic factor vascular permeability factor) (VPF, also called vascular endothelial growth factor), in human melanoma cells in vitro and in vivo. Melanoma lines that develop tumors with a low metastatic potential in nude mice were found to have low expression levels of VPF in vitro, and the VPF expression levels in melanoma lines that yield highly metastatic xenografts were high. However, in vivo the correlation between VPF mRNA levels and the frequency of metastasis was lost; in all xenografts equally high levels of VPF mRNA were found, independent of the parental cell line. Hence, in vivo VPF gene expression was upregulated in the low expressing lines. The external factor responsible for this induction may be hypoxia, given that we found that low oxygen tension caused a (reversible) increase in the VPF mRNA levels in otherwise low expressing melanoma lines in vitro. A melanoma line with an inducible VPF expression was engineered into a line with a constitutive VPF expression. In the xenografts from this line a change in the vascular architecture was seen, indicating that the pattern or the level of VPF expression is important for tumor angiogenesis in melanoma xenografts.
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PMID:Vascular permeability factor expression influences tumor angiogenesis in human melanoma lines xenografted to nude mice. 753 47

We developed and evaluated an in vivo athymic nude mouse model for tumor growth, angiogenesis, metastasis, and antineoplastic drug development. Melanoma cell lines expressing beta-galactosidase encoded by the Escherichia coli lac Z gene have been created by infecting an immortal murine melanocyte cell line with a recombinant retrovirus expressing the v-Ha-ras oncogene and lac Z to generate the MRB (melanoma, ras, beta-galactosidase) cell lines. The amelanotic, phorbol ester-independent, transformed melanoma cell lines developed tumors rapidly when injected subcutaneously into nude mice, as well as experimental lung metastases when injected i.v. into the tail vein. beta-galactosidase-expressing subcutaneous tumors and lung metastases stained blue with X-gal. The melanomas produced in nude mice have been characterized by using various histochemical and immunohistochemical staining methods to detect melanoma- and endothelial-cell-specific markers to determine the extent of neovascularization in MRB nude mouse tumors. Optimal staining of endothelial cells involved in tumor angiogenesis was observed by using ADPase activity and antiangiotensin-converting enzyme antibody staining. Attempts at indirect quantification of metastatic tumor cell number within the lung by either beta-galactosidase enzymatic activity or ELISA immunoreactivity were unsuccessful. However, the MRB cell lines should be useful in screening for and studying the mechanisms of action of antineoplastic, antimetastatic, and angiostatic drugs in vivo in athymic nude mice.
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PMID:Evaluation of a nude mouse tumor model using beta-galactosidase-expressing melanoma cells. 768 92

Although florid microvascular proliferation (MVP) in glioblastoma multiforme (GBM) has long been considered as proliferation of endothelial cells (EC), recent immuno-light microscopic studies demonstrated many alpha-smooth muscle actin (alpha-sm actin)-positive cells in this MVP, suggesting a major contribution of pericytes and/or vascular smooth muscle cells (VSMC). Under certain culture conditions, however, alpha-sm actin expression has also been described in EC. In order to further investigate to what extent pericytes/VSMC participate in MVP in GBM, we performed an immunohistochemical study at both the light and electron microscopic levels with anti-alpha-sm actin, with an antibody against EC (EN-4) and with an antibody recently described to react with "activated" pericytes in conditions with neovascularization (anti-high molecular weight-melanoma associated antigen). In this detailed study of MVP in GBM, two distinct cell types could be recognized on the basis of a consistent ultrastructural localization and immunophenotype: EC and pericytes/VSMC; no transitional forms were found between these two cell types. The contribution of pericytes/VSMC to MVP in GBM was extensive and already present in many delicate tumor capillaries, suggesting not only an essential but also an early role of these cells in this type of tumor angiogenesis.
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PMID:Early and extensive contribution of pericytes/vascular smooth muscle cells to microvascular proliferation in glioblastoma multiforme: an immuno-light and immuno-electron microscopic study. 774 29

Key growth factor-receptor interactions involved in angiogenesis are possible targets for therapy of CNS tumors. Vascular endothelial growth factor (VEGF) is a highly specific endothelial cell mitogen that has been shown to stimulate angiogenesis, a requirement for solid tumor growth. The expression of VEGF, the closely related placental growth factor (PIGF), the newly cloned endothelial high affinity VEGF receptors KDR and FLT1, and the endothelial orphan receptors FLT4 and Tie were analyzed by in situ hybridization in normal human brain tissue and in the following CNS tumors: gliomas, grades II, III, IV; meningiomas, grades I and II; and melanoma metastases to the cerebrum. VEGF mRNA was up-regulated in the majority of low grade tumors studied and was highly expressed in cells of malignant gliomas. Significantly elevated levels of Tie, KDR, and FLT1 mRNAs, but not FLT4 mRNA, were observed in malignant tumor endothelia, as well as in endothelia of tissues directly adjacent to the tumor margin. In comparison, there was little or no receptor expression in normal brain vasculature. Our results are consistent with the hypothesis that these endothelial receptors are induced during tumor progression and may play a role in tumor angiogenesis.
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PMID:Expression of endothelial cell-specific receptor tyrosine kinases and growth factors in human brain tumors. 785 49

The MUC18 protein, a member of the immunoglobulin superfamily and related to several adhesion molecules, shows an expression pattern in human malignant melanoma which is closely associated with tumor progression and the onset of metastasis. To determine the expression pattern of MUC18 in normal human tissues, immunohistochemical analysis was performed on frozen sections of a variety of normal human tissues using monoclonal antibodies against three different epitopes. This analysis showed that expression of MUC18 is limited to smooth muscle cells and to vascular endothelium. No reactivity could be observed with epithelial cells or with quiescent or activated hemopoetic cells. Smooth muscle cells in lung, skin, and in the gastrointestinal tract express MUC18 as does vascular smooth muscle, whereas myocardium or skeletal muscle appeared negative. Comparison of MUC18 staining with that of the panendothelial marker CD31 showed that MUC18 is expressed on the endothelia of a subset of blood capillaries and in tumor vessels but is absent on the endothelium of arterial vessels and large veins. The regulation of MUC18 expression was investigated in vascular smooth muscle cells and endothelial cells cultured in vitro. These studies revealed induction of the gene in endothelial cells upon proliferation. The observation that the MUC18 protein is not only present on melanoma cells but also on the endothelia of blood vessels penetrating primary and metastatic melanomas suggests a complex involvement of this potential cell adhesion molecule in tumor angiogenesis and metastasis.
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PMID:MUC18, a melanoma-progression associated molecule, and its potential role in tumor vascularization and hematogenous spread. 792 17

Tumor progression is frequently associated with changes in responsiveness of tumor cells to paracrine growth factors. A potential major source of such paracrine factors in solid tumors are endothelial cells since this type of cell can constitute a sizeable fraction of the cellular composition of solid tumors. As an initial step to examining the possible effects of endothelial cell-associated growth factors on tumor cell growth, a panel of human melanoma cell lines representative of different stages of tumor progression was employed for studies utilizing endothelial cell-derived growth modulators. Macrovascular or microvascular human endothelial cells from umbilical vein or from skin, respectively, inhibited melanoma cell growth in direct coculture experiments. The potency of this inhibitory effect diminished as a function of melanoma progression. Conditioned media from endothelial cell cultures mimicked the effect of the cell coculture experiments, suggesting the involvement of soluble growth factor(s). Approximately 50-75% of the conditioned media inhibitory effect was abrogated by addition of the neutralizing antibody to interleukin-6 (IL-6). Gel filtration chromatography revealed the presence of additional inhibitors in endothelial cell conditioned medium. Two peaks of activity were detected with apparent molecular weights of approximately 100-150 Kd and 20-30 Kd, the latter containing IL-6 activity. Whereas early-stage radial growth phase (RGP) primary tumor-derived melanoma cells were sensitive to at least three different endothelial products of high or low molecular weight (including IL-6), melanoma cells from more advanced metastatic lesions were resistant to the latter activities, and retained only partial sensitivity to the high molecular weight inhibitor. More advanced vertical growth phase (VGP) primary melanoma cell lines expressed intermediate inhibition-sensitive phenotypes. Thus human melanoma development appears to be associated with progressive loss of sensitivity to the growth inhibitory effects of IL-6 and other factors produced by endothelial cells. This is likely to be a result of a selection process when tumor cells are confronted with adjacent vasculature during the progress of tumor angiogenesis.
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PMID:Progressive loss of sensitivity to endothelium-derived growth inhibitors expressed by human melanoma cells during disease progression. 816 65


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