Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of central nervous system (CNS) and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors. Incidence of the disease is 1/36,000. CNS hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on 3p25-26, is a tumor-suppressor gene which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 70-99% of the patients. Mutations associated with VHL type 2 (with pheochromocytoma) are mainly missense mutations with hot-spot at codon 167. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic renal cell carcinoma. For endocrinologists search for VHL disease (as for MEN) should be imperative in presence of a patient with pheochromocytoma and neuroendocrine pancreatic tumor.
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PMID:[Von Hippel-Lindau disease: recent genetic progress and patient management. Francophone Study Group of von Hippel-Lindau Disease (GEFVH)]. 1018 87

The induction of tumor angiogenesis is mediated in particular by an increased production of VEGF. As ras oncogene is implicated in tumorigenesis, the inhibition of farnesyl transferase activity has recently been developed. The purpose of this study was to evaluate whether expression of mutated Ha-ras oncogene is associated with an altered expression of VEGF in an in vitro model of human skin carcinogenesis and to appreciate the effect of a new farnesyl transferase inhibitor on this VEGF expression. The amounts of VEGF secreted by an HaCaT cell line and two cell clones (metastatic or not) obtained after mutated c-Ha-ras transfection were compared. Our findings showed that the release of VEGF is greater for HaCaT-ras than for HaCaT cells and could be down-regulated using a protein farnesyl transferase inhibitor, in a reversible and dose-dependent manner. These results confirm that the Ha-ras oncogene can contribute to tumor development and progression of epidermal tumors through neoangiogenesis and that farnesyl transferase inhibitors as anticancer drugs may be efficient for the reduction of skin tumor growth.
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PMID:The up-regulation of vascular endothelial growth factor in mutated Ha-ras HaCaT cell lines is reduced by a farnesyl transferase inhibitor. 1022 98

Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-beta-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.
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PMID:A novel gene delivery system targeting cells expressing VEGF receptors. 1032 85

Recent studies have shown that systemic injection of anti-VEGF antibody into tumor-bearing mice results in decreases in tumor vascular permeability, vessel diameters, and tumor regression. Using a similar animal model, we have applied anti-VEGF antibody directly to the tumor tissue growing in transparent window chambers in SCID mice. Similar to the results obtained with systemic injection, vascular permeability was greatly reduced, but the response was reached at much lower concentrations with local application. Implications of these findings on local control of tumors are discussed.
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PMID:Effect of local anti-VEGF antibody treatment on tumor microvessel permeability. 1032 63

We previously reported that in vitro hypoxic condition enhanced VEGF level and its receptor expression in hepatic cancer cell line, HepG2. Transcatheter hepatic arterial embolization (TAE) therapy is one of the vasculo-occlusive and hypoxic challenges to hepatocellular carcinoma (HCC). Therefore, we examined the level of VEGF in sera of patients with HCC who underwent TAE during the course of the treatment. Thirty-eight patients with HCC and hepatitis C virus-positive cirrhosis were studied. Peripheral blood samples were taken before and 1, 3 and 7 days after TAE with informed consent. The serum levels of VEGF as well as hepatocyte growth factor (HGF), another hepatic remodeling factor, were measured. The molar ratio (BTR) of serum branched chain amino acid (BCAA) to tyrosine (Tyr), the serum levels of AST, ALT and LDH were also examined. Although the level of AST, ALT and LDH reached the peak value within 1 day after TAE, VEGF level increased significantly 7 days later. On the other hand, there were no significant alterations in the levels of HGF and BTR during the course of TAE. Although the level of HGF was significantly correlated with the level of VEGF before TAE, this correlation was no more observed after TAE. These data collectively suggest that VEGF may be secreted in response to clinical hypoxic intervention, TAE, independent of HGF or altered amino acid metabolism. VEGF may play a role as a sensitive marker for tumor ischemia.
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PMID:Serum vascular endothelial growth factor in the course of transcatheter arterial embolization of hepatocellular carcinoma. 1033 62

Malignant gliomas are a prominent target for cancer gene therapy approaches because of their poor prognosis despite all currently available therapies. Gene therapy strategies developed to interfere with the normal function of vascular endothelial growth factor receptors have been successfully used in different experimental models to block tumor angiogenesis and to inhibit tumor growth. In this study we examined whether retroviruses encoding a mutant VEGF receptor 2 (VEGFR-2) could suppress tumor angiogenesis and thereby prolong the survival of rats bearing syngeneic intracerebral glioma tumors. Survival time of rats with intracerebral tumors was significantly prolonged in a dose-dependent manner when retroviruses carrying a VEGFR-2 mutant were cotransplanted with tumor cells. No effect on survival was observed in rats that received virus-producing cells or virus supernatant intracerebrally after 5 days of tumor injection. In established subcutaneous tumors treatment with multiple injections of virus-producing cells also inhibited tumor growth in a dose-dependent manner. After implantation of tumor cells stably transfected with a truncated form of VEGFR-2, rats exhibited a rate of survival similar to that of animals treated with high numbers of virus-producing cells encoding the truncated form of VEGFR-2. Morphologically, tumors showed signs of impaired angiogenesis, such as extensive necrosis and reduced tumor vascular density. These results suggest a dual mode of function of truncated VEGFR-2, namely dominant-negative inhibition of VEGFR-2 function and VEGF depletion by receptor binding. We further explored the safety of retrovirus-mediated gene transfer. Although virus sequences were found in different tissues after intracerebral injection of virus-producing cells, no morphological changes were observed in any tissue after a follow-up time of 6 months. Our results indicate that VEGFR-2 inhibition is useful for the treatment of malignant gliomas.
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PMID:Antiangiogenic gene therapy in a rat glioma model using a dominant-negative vascular endothelial growth factor receptor 2. 1034 May 44

We have reported that bcl-2 is expressed in normal human thyroid epithelium and that its expression is down-regulated in undifferentiated thyroid tumors. Production of IL-6 was concomitantly down-regulated in these forms. Based on these observations, we analyzed whether insertion of bcl-2 would reverse the highly malignant phenotype of a thyroid cell line (ARO) derived from an undifferentiated carcinoma. This cell line fails to produce Bcl-2 and IL-6. By infection with a bcl-2 retroviral vector, ARO cells expressing bcl-2 (ARObcl-2) were obtained. Compared with parental cells, expression of bcl-2 was associated with enhancement of growth potential (DNA synthesis, in vitro proliferation rate, anchorage-independent growth in semi-solid media). Chemotaxis and invasive potential in Boyden chambers were also increased. bcl-2-expressing cells showed a reduced response to apoptotic stimuli (low-serum conditions or anti-neoplastic drugs). Large branched colonies were formed in Matrigel from ARObcl-2 cells but not from parental cells. Finally, ARObcl-2 cells showed a decreased latency of tumor appearance when injected into immunodeficient mice. Potentiation of the malignant phenotype of ARO cells by bcl-2 was not ascribed to altered expression of (i) cytokine/growth factors (IL-4, IL-6, IL-8, IL-10, IL-12, TGF-alpha, TGF-beta), (ii) thyroid-specific transcripts (TG, TPO, TSH-R, PIGF, PAX-8) or (iii) genes influencing tumor aggressiveness [VEGF, HMGI (Y), HMGI-C]. Our data indicate that bcl-2 potentiates the malignant phenotype of ARO cells not only by limiting the response to apoptotic stimuli but also by enhancing proliferation and tumor aggressiveness.
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PMID:Potentiation of the malignant phenotype of the undifferentiated ARO thyroid cell line by insertion of the bcl-2 gene. 1036 45

Angiogenesis, the formation of new blood vessels from pre-existing endothelium, is a crucial process for tumor growth, metastasis and inflammation. Therefore, it is focused on the anti-tumor therapy to prohibit angiogenesis in animal model and clinical studies. Eicosapentaenoic acid (EPA 20: 5,n-3) can restrain tumor growth and inflammation. In this paper, we examined the effects of EPA on tube formation. In EPA-pretreated endothelial cells angiogenesis was attenuated and also proliferation induced by VEGF, but not by b-FGF, was suppressed. The reason why EPA suppressed endothelial cell proliferation induced by VEGF was that EPA selectively inhibited the expression of KDR. As we mentioned, the regulation of angiogenesis in vivo may be involved in the expression of VEGF receptors.
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PMID:[Regulation of angiogenesis-expression of VEGF receptors]. 1036 59

Malignant gliomas are associated with a dysfunctional blood-tumor barrier (BTB) that causes substantial morbidity. Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional growth factor that correlates with glioma malignancy and has several biological properties that suggest a role in enhancing blood-glioma barrier permeability. In this study, we examined the effects of glioma cell SF/HGF expression on BTB permeability to horseradish peroxidase (HRP). Fischer 344 rats bearing intrastriatal 9L tumors engineered to secrete SF/HGF (9L-SF) and SF/HGF-negative control tumors (9L-neo) received intracardiac injections of HRP and were rapidly decapitated. Densitometric analysis of brain sections reacted with diaminobenzidine showed significantly greater extravascular HRP surrounding SF/HGF-secreting tumors than 9L-neo tumors of comparable size (p<0.05). HRP enzymatic activity associated with striata containing SF/HGF-expressing tumors was 1. 6-fold greater than that of striata containing control tumors (p<0. 05). Northern analysis showed that expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) did not differ between 9L-neo and 9L-SF tumors. These data demonstrate that SF/HGF expression by intracerebral glial tumors can enhance BTB permeability independent of changes in VEGF/VPF expression.
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PMID:Scatter factor/hepatocyte growth factor gene transfer increases rat blood-glioma barrier permeability. 1037 92

The biomolecules described in this article generally have been studied as possible diagnostic or clinically prognostic markers in the context of melanoma disease progression as measured by the gold standards of tumor thickness and development of metastasis. Most of the markers showed variations in expression phenotype only during the deeply invasive or metastatic stage of tumor progression and were thus predictive of clinical outcome only for these subgroups of patients. Some of the markers may have utility in identifying patients with deeply invasive primary tumors who are likely to develop metastasis and thus should receive earlier, more aggressive treatments. In addition, some of the markers may identify patients likely to respond better to a new type of therapy (e.g., anti-angiogenic therapy in a patient whose tumor is overexpressing VEGF or immunotherapy for a patient whose tumor is expressing high levels of MART-1). In the future, it will probably be possible to employ new techniques, such as laser-guided microdissection of tissues, to isolate individual melanocytes in order to identify the earliest stage-specific defects that contribute to an aggressive biological behavior. Identifying the subset of patients with superficially invasive melanomas who will develop metastatic disease will continue to provide a challenge.
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PMID:Update of diagnostic and prognostic markers in cutaneous malignant melanoma. 1041 Aug 63


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