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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Walker 256 carcinosarcomas were transplanted under the skin and in the bone marrow of the femur of Wistar rats to investigate the tumor angiogenesis and effect of anticancerous agents on it. Microangiography was performed on tumors in different stages after transplantation and on treated tumors in different stages after a single shot of Adriacin or Endoxan into the intraperitoneum. The tumors were histologically examined. The results were as follows: 1. Angiogenesis was found at the host side near the tumor in the beginning of the subcutaneous transplantation and formation of vascaular network was seen at the peripheral area in the tumor after 5-7 days. No blood vessel was found at the central region of the tumor, and so-called "sinusoidal lake" was seen at the border zone of central and peripheral regions, suggesting the impending central necrosis. The vascular network became loose and blood vessels became of larger diameters and sinusoidal blood vessels were found afater about 14 days. In the case of intramedullary transplantation, blood flow stopped in the marrow already after about 10 days and rich network of blood vessels was observed in the spicula. 2. In the Adriacin group, only a weak inhibitory effect on tumor growh was found. There was no degeneration of tumor cells, but a little disorder of tumor cell cords. The effects of the drug on the capillaries were remarkable. The diameter of the capillary was narrowed, with fragmented vascularity and disappearance of capillary network. It was estimated that effective amount of the drug might not reach tumor cells because of circulatory disturbance due to obstruction of the capillaries caused by Adriacin. 3. In the Endoxan group, inhibitory effect of the drug was remarkable, and degeneration and transformation into giant cells of tumor cells, with a decrease of tumor cells and proliferation of interstitial connective tissues. The microvascular system maintained its network structure for rather a long period and the network was reduced with an increase of the connective tissue, but no fragmentation was found. It was suggested that sufficient Endoxan might have reached the tumor cells and cause their degeneration and destruction, followed by decrease of tumor angiogenesis factor (TAF) and by secondary reduction and disappearance of the microvascular system.
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PMID:[Effects of anticancerous agents on the microvascular system of experimental malignant tumors (author's transl)]. 738 Dec 70

To investigate the effects of copper (Cu)-depletion diet and D-penicillamine treatment (CDPT) on both tumor growth and angiogenesis, we studied Fischer-344 rats in which 9L gliosarcoma cells had been subcutaneously implanted. We focused primarily on the alteration of Cu contents and the vascular density. Compared with the normal diet group, the CDPT group showed a significant reduction of tumor weight and a decrease in Cu concentration. Furthermore, the CDPT group demonstrated smaller blood vessels with significantly lower vascular density. This decrease of tumor growth was achieved by angiosuppression. Our study indicated that CDPT selectively caused Cu chelation from the tumor tissue; the normal brain tissue did not show lower Cu concentration after the treatment. The prevention of tumor angiogenesis by this method may be very useful in cancer therapy and may help elucidate the microenvironmental mechanisms for cancer cells.
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PMID:Copper chelation inhibits tumor angiogenesis in the experimental 9L gliosarcoma model. 747 81

Formation of new blood vessels is essential for several physiological and pathological events, e.g. embryogenesis, wound healing and tumor growth and metastasis. In order to increase the insight into the mechanisms of angiogenesis we have visualized the different components of the microvasculature in human wounds and tumors by immunohistochemistry on the light and electronmicroscopic level. For this purpose, antibodies recognizing distinct markers for human endothelial cells, pericytes and basal lamina were used on freshly frozen or paraformaldehyde-fixed tissue samples. In terms of efficacy, the PAL-E antigen is highly specific for blood vessel endothelium. Its sensitivity is less than other endothelial markers, such as von Willebrand factor and CD 31, as it is not expressed in arterioles. Within the context of the microvasculature alpha-smooth muscle actin and the HMW-MAA chondroitin sulphate proteoglycan are useful markers for pericytes. Type IV Collagen and Laminin can be visualized consistently in the microvascular basal lamina. During the formation of granulation tissue in wound healing a heterogeneity of the expression of endothelial and pericyte markers is found. In the least matured zone in granulation tissue of decubitus lesions and experimental skin wounds microvessels already contained both endothelial cells and pericytes, suggesting a role for both cell types in the early steps of angiogenesis. Regarding the tumor microvasculature, antibodies to von Willebrand factor often failed to stain capillaries, that did show expression of the other endothelial markers studied. Broad staining in pericytes was found for the HMW-MAA chondroitin sulphate proteoglycan. In contrast, these cells only locally expressed alpha-smooth muscle actin. Staining of the basal lamina components Type IV Collagen and Laminin within tumors was not restricted to the microvasculature. Therefore, antibodies recognizing endothelial markers, particularly PAL-E and BMA 120, are preferable as tools to visualize the tumor microvasculature. In accordance with the situation in granulation tissue of wound healing the broad presence of pericytes in the microvasculature of human tumor suggests an involvement of this cell type in tumor angiogenesis. Recent immunohistochemical studies on human tumor lesions indicated that a high number of microvessels adjacent to the tumor as a measure of tumor angiogenesis is an unfavorable prognostic factor in cutaneous melanoma, mammary carcinoma and non-small cell pulmonary carcinoma. This new application of immunohistochemistry represents a valuable, clinically relevant adjunct to the repertoire of the surgical pathologist.
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PMID:Angiogenesis in wound healing and tumor metastasis. 750 53

The isolation, purification, and molecular cloning of an increasing number of cytokines and their receptors have allowed major advances in our understanding of the relevance of these proteins to the pathobiology and treatment of such human diseases as neoplasia. Cytokines produced by the multiple cell types present within the microenvironment of solid tumors from a complex, dynamic network, in which they have overlapping properties, induce other cytokines and alter the expression of soluble and cell surface-bound cytokine receptors. A broad number of such intratumoral cytokines have multiple effects on tumor progression. These include direct and indirect effects both on tumor cell growth and metastatic behaviors and on such cells in the stromal compartment as fibroblasts, infiltrating immune cells, and endothelial cells in the microvasculature. Here, we review the sites of production and multifaceted role of several key cytokines in the stimulation of a new blood supply within growing neoplasms. The clinical implications and new therapeutic targets suggested by this rapidly emerging picture of the cellular and molecular mechanisms subserving tumor angiogenesis are also discussed.
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PMID:Cytokine networks in solid human tumors: regulation of angiogenesis. 752 56

A more accurate method of detecting nodal disease in squamous cell carcinoma of the tongue is needed so that treatment of the neck with its associated morbidity can safely be reserved for patients who actually have metastatic disease. Tumor angiogenesis and the expression of the p53 antigen--which have each been shown to be predictive of metastasis in breast and colon cancer, respectively--are examined for their ability to predict neck metastasis in tongue cancer. Fifty-seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose neck disease was examined by dissection or by 2-year follow-up, were studied. Twenty-eight patients (49%) were node positive and 29 patients (51%) were node negative. The primary tumors were immunohistochemically stained for the p53 antigen and for factor VIII, which allowed the blood vessels within the tumor to be quantitated. The mean vessel counts per x200 high-power field were 59.8 and 61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node-positive patients showed overexpression of p53 43% of the time, vs. 61% for node-negative patients (p = 0.17). Multivariate analysis confirmed that no difference in tumor angiogenesis or the expression of the p53 antigen was found between tumors that had metastasized and those that had not. Therefore neither tumor angiogenesis nor the p53 tumor marker is clinically useful in determining lymph node metastasis in these patients.
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PMID:Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue. 752 5

Angiogenesis, the sprouting of capillaries from preexisting vessels, is of fundamental importance during embryonic development and is the principal process by which the brain and certain other organs become vascularized. Angiogenesis occurs during embryonic development but is almost absent in adult tissues. Transient and tightly controlled (physiological) angiogenesis in adult tissues occurs during the female reproductive cycle and during wound healing. In contrast, pathological angiogenesis is characterized by the persistent proliferation of endothelial cells, and is a prominent feature of diseases such as proliferative retinopathy, rheumathoid arthritis, and psoriasis. In addition, many tumors are able to attract blood vessels from neighbouring tissues. Tumor-induced angiogenesis requires a constitutive activation of endothelial cells. These endothelial cells dissolve their surrounding extracellular matrix, migrate toward the tumor, proliferate, and form a new vascular network, thus supplying the tumor with nutrients and oxygen and removing waste products. The onset of angiogenesis in human gliomas is characterized by the expression of genes encoding angiogenic growth factors such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) in tumor cells, and coordinate induction of genes in endothelial cells which encode the respective growth factor receptors. Developmental and tumor angiogenesis appear to be regulated by a paracrine mechanism involving VEGF and VEGF receptor-1 and -2.
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PMID:Molecular mechanisms of developmental and tumor angiogenesis. 752 60

Recent studies demonstrate the relationship of microvessel density to malignant progression in breast cancer (N. Weidner, J. P. Semple, W. R. Welch, and J. Folkman, N. Engl. J. Med., 324: 1-8, 1991), underscoring the importance of angiogenesis in this tumor. Crucial in tumor angiogenesis are the paracrine actions of tumor-secreted factors (e.g., vascular endothelial growth factor), which have been thought to derive from the tumor epithelial cells themselves. We demonstrate that in response to hypoxic conditions, human mammary fibroblasts dramatically up-regulate vascular endothelial growth factor mRNA and increase vascular endothelial growth factor protein levels in accordance with the degree of oxygen deprivation. Thus, mammary stromal cells, only recently considered in the regulation of breast carcinomas, may play a hitherto unrealized role in breast cancer angiogenesis.
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PMID:Mammary fibroblasts may influence breast tumor angiogenesis via hypoxia-induced vascular endothelial growth factor up-regulation and protein expression. 752 53

We have previously suggested that tumor angiogenesis in human gliomas is regulated by a paracrine mechanism involving vascular endothelial growth factor (VEGF) and flt-1 (VEGF-receptor 1). VEGF, an endothelial-cell-specific mitogen, is abundantly expressed in glioma cells which reside along necrotic areas, whereas flt-1, a tyrosine-kinase receptor for VEGF, is expressed in tumor endothelial cells, but not in endothelial cells in normal adult brain. Recently, a second tyrosine-kinase receptor which binds VEGF with high affinity, designated KDR or flk-1, has been described. We performed in situ hybridization for VEGF mRNA, flt-1 mRNA and KDR mRNA on serial sections of normal brain, low-grade and high-grade glioma specimens. We show that KDR mRNA is co-expressed with flt-1 in vascular cells in glioblastoma but not in low-grade glioma. Since flt-1 and KDR are not expressed in endothelial cells in the normal adult brain, the coordinate up-regulation of 2 receptors for VEGF appears to be a critical event which controls tumor angiogenesis. Immunocytochemistry with a monoclonal anti-VEGF antibody revealed significant amounts of VEGF protein in the same glioma cells that expressed VEGF mRNA. The largest amount of VEGF immunoreactivity, however, was detected on the vasculature of glioblastomas, the site where VEGF exerts its biological functions. These findings suggest that VEGF is produced and secreted by glioma cells and acts on tumor endothelial cells which express VEGF receptors. To further characterize VEGF-producer cells in vivo, we investigated cellular proliferation, immunoreactivity to the p53 tumor-suppressor gene product and epidermal-growth-factor-receptor (EGFR) expression on serial sections by immunocytochemistry. VEGF-producer cells did not show increased cellular proliferation, p53 immunoreactivity or EGFR immunoreactivity as compared with glioma cells which did not express VEGF. Our studies therefore do not demonstrate evidence for a growth advantage of VEGF-producer cells in vivo or VEGF induction by p53 mutation or EGFR over-expression.
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PMID:Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. 752 92

In primary malignant brain tumors increased vascularity and marked edema strongly suggest a possible role of the vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). This was confirmed by earlier in situ hybridization studies, by analysis of the expression of the mitogen in different subsets of glioblastoma cells, and by the fact that the VEGF/VPF receptor flt-1 (fms-like tyrosine kinase) is up-regulated in tumor cells in vivo. To assess and quantify the expression of the VEGF/VPF gene and of the receptor gene, 26 surgical specimens of brain tumor tissue from 24 patients were analyzed. In most malignant gliomas, the expression level of the VEGF/VPF gene is elevated and can be increased up to 20- to 50-fold in comparison with low-grade tumors. Using polymerase chain reaction-based amplification, it could be shown that the messenger RNAs of three different VEGF/VPF forms are synthesized in tumor tissue samples. Northern blot studies revealed that in some samples a significant expression of the gene coding for placenta growth factor, a growth factor closely related to VEGF/VPF, was observed. In addition, using a radioreceptor assay it was possible to detect high VEGF/VPF-like activity in the cyst fluids of brain tumors, indicating the accumulation of the mitogen and permeability factor in brain tumor cysts. Further investigations revealed that astrocytoma and glioblastoma cells in culture express the VEGF/VPF gene and secrete the VEGF/VPF protein, whereas gene expression of the two known VEGF/VPF receptors, kinase insert domain-containing receptor and flt-1, could not be detected. These data support previous reports, which stated that VEGF/VPF acts as a paracrine growth and permeability factor in brain tumors and may contribute to tumor growth by initiating tumor angiogenesis.
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PMID:Detection and quantification of vascular endothelial growth factor/vascular permeability factor in brain tumor tissue and cyst fluid: the key to angiogenesis? 752 59

We investigated the mechanism(s) by which systemic administration of doxorubicin (DXR) produced growth retardation of B16 melanomas in the subcutis of syngeneic mice. DXR or saline was injected intravenously (i.v.) into C57BL/6 mice, and B16-BL6 cells were implanted subcutaneously (s.c.) on day 3, 7, or 21 after DXR treatment. In the DXR-pretreated mice, the tumors grew at a slower rate than in control (saline-treated) mice. The experiments were repeated with a B16 variant resistant to DXR with similar results. Tumor growth retardation correlated with extent of myelosuppression monitored by counting bone marrow cells, circulating leukocytes and peritoneal macrophages. In DXR-pretreated mice reconstituted with 1 x 10(7) viable syngeneic spleen cells, the s.c. tumors grew at a rate similar to that in control mice. DXR treatment and spleen cell reconstitution experiments were repeated in BALB/c athymic nude mice. The results were very similar. The growth of s.c. tumors was directly correlated with the degree of peritumoral vascularity. These data indicate that in addition to its well-documented direct antitumor effects, DXR may produce retardation of tumor growth by producing myelosuppression and, hence, inhibition of host cell-induced tumor angiogenesis.
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PMID:Leukocyte-induced angiogenesis and subcutaneous growth of B16 melanoma. 752 86


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