Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a 42-year-old man with a cerebral glioblastoma multiforme associated with marked neovascularization of the arachnoid of the brain stem and spinal cord is reported. All of the neurological symptoms and signs were referrable to the glioblastoma and resultant craniotomies. The arachnoid contained a proliferation of well differentiated blood vessels. This neovascularization occurred in the absence of local tumor or inflammation. We suggest that the neovascularization resulted from release of a tumor angiogenesis factor into the cerebrospinal fluid.
Clin Neuropathol
PMID:Distant angiogenesis in a patient with glioblastoma multiforme. 169 77

Significant proliferation of capillaries with hyperplastic vascular endothelium is one of the characteristic histologic features of glioblastoma multiforme (GBM). It has been shown that the renin-angiotensin II cascade stimulates new vessel formation. The presence of renin in several types of highly vascularized neoplasm suggests that it may also be implicated in the mechanism of tumor angiogenesis. In order to study the possible relationship of renin to GBM, immunohistochemical search for human renin was carried out in ten instances of such a tumor. Eight of these cases demonstrated renin-containing neoplastic astrocytes, whereas seven cases of reactive gliosis and six cases of low-grade astrocytoma revealed no renin-containing cells. The immunostaining was not present after preabsorption of the renin antiserum with pure human renin or substitution of preimmune serum for the specific renin antiserum. Because it has also been demonstrated that a product of renin, angiotensin II, has angiogenic properties, it seems reasonable to postulate that renin, through angiotensin II, may play a role in the mechanism of GBM-associated neovascularization.
Am J Clin Pathol 1988 Oct
PMID:Renin in glioblastoma multiforme and its role in neovascularization. 245 55

This report provides fine structural evidence that, dependent upon the malignancy, tumor as well as mesenchymal cells may participate actively in the neovascularization of experimental tumors grown in transparent tissue chambers implanted into skinfolds of syrian hamsters. Such non-endothelial cells may help to promote angiogenesis in two different ways: (1) They are incorporated into capillary sprouts thereby accelerating the growth rate of the latter independent of endothelial cell proliferation. (2) Extravascular cells (tumor and mesenchymal elements) become integrated in varying numbers into the linings of comparatively large blood-perfused vessels. This facilitates the rapid establishment and functional remodelling of the microvascular bed to adapt the microcirculation to the varying local demands of the growing tumor. If these results can be confirmed for other tumors, and if they are independent of the tumor's environment and the experimental protocol, then we will have to reconsider the significance of tumor angiogenesis as a realistic biological model from which general conclusions with regard to neovascularization in non-tumorous tissues may be drawn.
Int J Microcirc Clin Exp 1985
PMID:The fine structure of tumor blood vessels. I. Participation of non-endothelial cells in tumor angiogenesis. 258 Aug 10

The study of human endothelial cells in tissue culture has been previously limited to umbilical vein, a large vessel source, and microvascular endothelium from human foreskin, spleen, and adrenal. Microvascular endothelium cultured from these sources have required matrix-coated culture flasks, tumor-conditioned medium, or 50% human serum for growth and subcultivation. To obtain cultures of microvascular endothelium with less stringent growth requirements, human adipose tissue was digested with collagenase and endothelial cells were separated from other stromal elements by sequential filtration and layering cells onto 5% albumin. Using standard medium containing 10% fetal calf serum, these cells grew readily to confluence and survived serial passages. When the cultures were subconfluent, cytoplasmic extensions and a capillary-like morphology were observed. Confluent cultures displayed the "cobblestone" appearance characteristic of other endothelial preparations. Electron microscopy demonstrated the presence of characteristic tight junctions and pinocytotic vesicles. Immunofluorescent staining for Factor VIII was positive, and cultures contained angiotensin-converting enzyme activity. Thus, cultures of human microvascular endothelium were readily obtained from adipose tissue and required only standard medium with 10% serum for growth and subcultivation. This system can be used to study human endothelial cell biology and may prove useful in the study of pathologic states such as diabetic microvasculopathy and tumor angiogenesis.
J Clin Invest 1983 Jun
PMID:Isolation and culture of microvascular endothelium from human adipose tissue. 630 56

Morphology of blood vessels in cancer of the larynx, which as other solid tumors has great neoangiogenic abilities, was studied on microcorrosion casts in SEM. Most evident changes of the endothelial patterns were seen on the casts of capillaries, venules, and veins. Capillaries, especially the newly formed, are the most numerous constituent of the vascular bed in all zones of cancer of the larynx. These vessels exhibit great morphological differentiation varying from the single, blind-ended pipes via relatively long hairpin loops spirally twisted in the long axis, to strongly spiralled and convoluted loops, resembling pseudoglomeruli. The newly formed capillaries deriving predominantly from the host's capillaries, venules, and veins have a embryonal character. It seems reasonable to presume that the neoangiogenesis process triggered by active influence of the tumor angiogenesis factor, is in principle, a repetition of the mechanism of the embryonal angiogenesis.
J Cancer Res Clin Oncol 1981
PMID:Morphology of arteries, veins, and capillaries in cancer of the larynx: scanning electron-microscopical study on microcorrosion casts. 727 63

Human prostatic cancer cells have a remarkably low rate of proliferation even when they have metastasized to the bone and have become androgen independent (Berges et al., Clin. Cancer Res., 1:473-480, 1995). Due to this low proliferation, patients with such androgen-independent metastatic prostatic cancer cells are rarely treated successfully with the presently available chemotherapeutic agents. Therefore, new approaches are urgently needed which are not dependent on the rate of cancer cell proliferation for their effectiveness. One such approach is to inhibit the angiogenic response within localized and metastatic cancer deposits, since the resultant hypoxia-induced tumor cell death does not require cell proliferation. We have previously demonstrated that the quinoline-3-carboxamide, linomide, is an p.o. active agent which inhibits tumor angiogenesis and thus blood flow in a variety of rat prostatic cancers independent of their growth rate, androgen sensitivity, or metastatic ability. Because of its antiangiogenic effects, linomide treatment induces the hypoxic death of rat prostatic cancer cells, thus inhibiting their net growth and metastases. To determine whether human prostatic cancer cells are similarly sensitive to hypoxia-induced death caused by linomide inhibition of tumor angiogenesis, androgen-independent TSU and PC-3 human prostatic cancer cells were xenotransplanted into SCID mice that were either untreated or treated p.o. with linomide. These studies demonstrated that linomide treatment decreases microvessel density in both androgen-independent human prostatic cancers. Microvessel density was decreased from 1.8 +/- 0.4% of the total area in control tumors to 1.0 +/- 0.2% in linomide-treated TSU tumors [i.e., a 44% decrease in microvessel density (P < 0.05)]. Similarly, a 56% decrease (P < 0.05) was observed in the microvessel density of PC-3 tumors (i.e., 2.7 +/- 0.8% of the area in control tumor versus 1.2 +/- 0.2% in the linomide-treated tumors). This inhibition of angiogenesis increased cell death in both TSU and PC-3 cancer cells. This is reflected in both an increase in the area of necrosis and an increase in the apoptotic index in non-necrotic areas. In untreated TSU tumors, 40 +/- 2% of tumor volume was necrotic. Linomide treatment increased this necrotic percentage to 59 +/- 2% [i.e., 48% increase (P < 0.05)]. Linomide therapy also increased apoptotic cell death in non-necrotic tumor areas. In the untreated TSU tumors, 2.9 +/- 0.6% of tumor cells were apoptotic in the non-necrotic areas, and in the linomide-treated TSU tumors this percentage increased to 3.6 +/- 0.4% [i.e., 24% increase (P < 0.05)].(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Human prostatic cancer cells are sensitive to programmed (apoptotic) death induced by the antiangiogenic agent linomide. 754 15

Human hepatocellular carcinoma (HCC) is characterized by hypervascularity and tumor staining in angiograms, and tumor angiogenesis is considered indispensable for tumor growth. HCC is also characterized by an obvious multistage process of tumor progression. To find out in which stage of human hepatocarcinogenesis angiogenesis occurs, we have carried out a pathological study, of the phenotypic changes in tumor vessels taken from surgically resected liver tumors showing each step of the progression. Eleven early advanced HCCs (advanced HCC component in early HCC nodule, eAd HCC), seven early HCCs (eHCC) and six adenomatous hyperplasias (AH), the non-tumorous liver surrounding each and five normal livers were studied by lectin histochemistry and immunohistochemistry. The sinusoidal endothelial cells from the non-tumorous liver were shown to be negative for UEA-I (Ulex europaeus I), but the endothelial cells from the sinusoidal tumor vessels in advanced HCC components were strongly positive. In AH and eHCC, half the tumors were negative and the other half focally positive. In the early HCC lesion of eAdHCC, the rate of positivity for UEA-I was a little higher than in AH and eHCC but lower than in advanced HCC lesions in eAdHCC. Immunohistochemically, laminin was not detected in the sinusoids in the non-tumorous liver or in the sinusoidal tumor vessels in AH and eHCC. In eAdHCC, however, two early HCC lesions and four advanced HCC lesions were positive. An immunohistochemical examination for muscle actin revealed an increase in arterial tumor vessels in six advanced HCC lesions and one early HCC lesion of eAdHCC. The results indicate the emergence of UEA-I-positive sinusoidal tumor vessels to be most pronounced during the progression from eHCC to advanced HCC, and laminin-positive sinusoidal tumor vessels or actin-positive arterial tumor vessels to emerge mainly in advanced HCC.
Jpn J Clin Oncol 1993 Apr
PMID:Phenotype changes in tumor vessels associated with the progression of hepatocellular carcinoma. 768 37

We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (bFGF) mRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-bFGF antibody. In in vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of bFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, bFGF mRNA levels and angiogenesis in mice. The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by bFGF, possibly via paracrine control.
J Clin Invest 1993 Jul
PMID:Induction of vascular endothelial tubular morphogenesis by human glioma cells. A model system for tumor angiogenesis. 768 24

Metastatic disease is one of the major causes of death from cancer in human beings. Several enzyme systems have been implicated in the metastatic process, but the metalloproteinases (MPs) appear to be the major group involved in most instances of neoplastic invasion. Increased MP activity has been correlated with the metastatic potential of many cancers, including breast cancer. MPs also play a role in tumor angiogenesis. Tetracyclines are antimicrobial agents that can suppress MP activity in a variety of tissues, including gingiva, bone, and cartilage. Several reports have indicated that tetracyclines can suppress tumor MPs as well. A synthetic tetracycline, doxycycline, inhibits migration of human MDA-MB-435 breast adenocarcinoma cells through a reconstituted basement membrane (Matrigel), an assay used as an in vitro surrogate for the in vivo process of tumor invasion through basement membranes. Additionally, doxycycline diminishes the proliferation of this breast cancer cell line and also decreases its gelatinolytic activity, as determined by gel zymography.
J Lab Clin Med 1995 Mar
PMID:Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells. 789 8

General principles for anticancer drug development include traditional drug-screening methods in biological test systems. Today, testing of a drug in a panel of selected human tumor xenografts in mice is assumed to have the best predictive value for clinical efficacy. Chemical modification of well-known antitumor drugs from compound groups such as purine analogs, vinca alkaloids, antifolates and platinum analogs are carried out to increase anticancer activity, to reduce toxic side-effects and to improve pharmacokinetic properties of the drugs. In the last decade the enormous development in molecular techniques has led to the discovery of key proteins that are intimately involved in the regulation of cancer growth control. Cell growth inhibitors could be developed by structure-based design, creating small organic molecules ("peptide mimetics") to target crucial enzymes, oncogenes or oncogene products, tumor-suppressor genes and their products as well as growth factors and their corresponding receptors. Drugs representing new leading structures, like alkylphosphocholines, topoisomerase I inhibitors, taxoids and suramin, have already entered the clinic. Novel therapeutic approaches may provide substantial progress in cancer treatment in the very near future. Examples are the concept of high-dose chemotherapy with hematopoietic stem cell support, the various strategies of gene therapy, the modulation of multi-drug resistance of cancer cells, and strategies to inhibit tumor angiogenesis.
J Cancer Res Clin Oncol 1996
PMID:Current concepts of treatment in medical oncology: new anticancer drugs. 860 70


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