UMLS:C1519670 - FACTA Search

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Query: UMLS:C1519670 (tumor angiogenesis)
6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The natural history and survival of breast cancer are extremely variable although the advances and improvement in treatment in recent years led to a lower mortality. In fact, in spite of the administration of systemic adjuvant therapy, women with metastatic lymph nodes at diagnosis have a risk of disease progression at 5 years of 40-50%. The disease heterogeneity and the intrinsic tumor cell resistance to therapies are determining factors of the problem. The role of parameters as tumor size, grading, vascular spread, axillary lymph node status, are well defined. However the increasingly early diagnosis and changes in clinical practice have led to the need for non morphologic parameters as estrogen and progesteron receptors, cell proliferation index, labelling index, growth factors tumor-dependent genes (p53, HER2), cell cycle regulators (cyclins). Specific cellular and molecular alterations are studied to identify diagnosticoinstrumental images (MRI) of tumor angiogenesis, the cause of the different tumor aggressiveness. In the surgical and consequently clinico-oncologic approach there is the problem of the interpretation and prognostic role of sentinel lymph node when it is positive for micrometastasis only, if diagnosed by immunohistochemistry.
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PMID:Biological factors and therapeutic modulation in breast cancer radiotherapy. 1269 49

Hepatocellular carcinoma (HCC) is becoming one of the most common malignant tumors worldwide and is characterized by a high vascularity. Angiogenesis, formation of new microvessels, is critical for the growth and progression of various human solid tumors. Vascular endothelial growth factor (VEGF) and angiopoietins (Ang1 and Ang2) are endothelial cell-specific vasculogenic and angiogenic growth factors, but their expression and roles in HCC have not been extensively explored. The aim of this study was to determine the expression and cellular localization of VEGF, Ang1, and Ang2 in specimens of resected human HCC using in situ hybridization and immunohistochemical staining and to examine their relationship to microvessel density (MVD) and tumor size. We also investigated whether mutation of p53 protein might affect the expression of the above angiogenic growth factors. VEGF and Ang2 were strongly expressed and localized predominantly to cancer cells, whereas Ang1 was detected in supportive cells of large blood vessels, stromal cells, endothelial cells, and tumor cells. Expression of the VEGF protein and the Ang2 (but not Ang1) mRNA were strongly correlated with MVD (P <.05, P =.001) and tumor size (P <.05). There was also a strong correlation between VEGF protein and Ang2 mRNA expression (P <.001). However, no significant correlation was found between overexpression of p53 and the expression of VEGF, angiopoietins, or MVD. These findings suggest that overproduction of the angiogenic growth factors VEGF and Ang2 by HCC cells may increase vascularity and tumor growth in a paracrine manner. Our findings also suggest that interaction between VEGF and Ang2 may play a critical role in tumor angiogenesis in HCC.
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PMID:Overexpression of VEGF and angiopoietin 2: a key to high vascularity of hepatocellular carcinoma? 1280 60

The most common genetic alterations found in a wide variety of cancers are p53 tumor suppressor gene mutations. p53 appears to be a nuclear transcription factor that plays a role in the control of cell proliferation, apoptosis, and the maintenance of genetic stability. Angiogenesis is a critical process in solid tumor growth and metastasis. Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, may be a major tumor angiogenesis regulator. Few studies have investigated the association between p53 and VEGF expressions and prognosis in esophageal carcinoma. Forty-seven specimens resected from patients with stage II and III squamous cell carcinoma (SCC) of the esophagus were studied using immunohistochemical staining. VEGF and p53 expressions were observed in 40% and 53% of the tumors, respectively. The p53 and VEGF staining statuses were coincident in only 21% of the tumors, and no significant correlation was found between p53 and VEGF statuses. No clinicopathologic factors were significantly correlated with p53 or VEGF expression. No significant association between p53 and VEGF expressions and poor prognosis was found. In conclusion, p53 and VEGF were not correlated with prognosis in patients with stage II and III SCC of the esophagus.
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PMID:Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of the esophagus. 1282 9

Among novel promising approaches that have recently entered the scene of anti-cancer therapy angiogenesis inhibition and targeting cancer-causing genes (e.g. oncogenes) are of particular interest as potentially highly synergistic. One reason for this is that transforming genetic lesions driving cancer progression (e.g. mutations of ras and/or p53) are thought to be causative for the onset of tumor angiogenesis and thereby responsible for build up of vascular supply which is essential for cancer cell survival, malignant growth, invasion and metastasis. However, many of the same genetic alterations that emerge during disease progression and repeated rounds of mutagenic and/or apoptosis causing therapy could alter cellular hypoxia-, growth factor- and apoptotic pathways in such a manner, as to also render cancer cells (partially) refractory to the detrimental consequences of poor blood vessel accessibility (density), ischemia, hypoxia and growth factor deprivation. As recent experimental evidence suggests, such cancer cells could therefore display a reduced vascular demand and remain viable even in poorly perfused regions of the tumor as well as possess an overall growth/survival advantage. The latter circumstance may lead to (predict) diminished efficacy of anti-angiogenic agents in certain malignancies. Therefore, we propose that analysis of oncogenic pathways and gene expression profiling of cancer cells may lead to important clues as to potential efficacy of anti-angiogenic therapies, the direct target of which is the host vasculature, but which are ultimately aimed at (indirect) destruction/control of the cancer cells population. We also suggest that oncogene (tumor suppressor)-directed therapies may help reverse diminished vascular demand of highly transformed cancer cells and thereby facilitate (sensitize tumors to) therapies directed against vascular supply of cancers and their metastases.
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PMID:Oncogenes and tumor angiogenesis: the question of vascular "supply" and vascular "demand". 1501 93

We have developed a novel gene therapy that targets genetic alterations in pancreatic cancer using oncolytic replication-selective adenoviruses in tumor cells. E1B-55kDa-deleted adenovirus (AxE1AdB) can selectively replicate in TP53-deficient human cancer cells but not cells with functional TP53. Consecutive injection with AxE1AdB markedly inhibited the growth of human pancreatic tumors in severe combined immunodeficiency disease mice. Furthermore, AxE1AdB displayed the ability to enhance gene expression as a virus vector. It is reported that uracil phosphoribosyl transferase (UPRT) overcomes 5-FU resistance. The therapeutic advantage of a replication-selective adenovirus that expresses UPRT (AxE1AdB-UPRT) was thus evaluated in an intraperitoneum-disseminated tumor model. Combined treatment with 5-FU and AxE1AdB-UPRT dramatically reduced the disseminated tumor burden without causing toxicity in normal tissues. We also clarified the process of AxE1AdB-inhibited tumor angiogenesis through the preserved E1A region: an adenoviral E1A protein binds to pRB, forcing the quiescent cell into the S phase. We constructed a double-mutant, replication-selective adenovirus (AxdAdB-3) containing a mutation in the RB-binding motif of the E1A region and a deletion of large E1B-55kDa. AxdAdB-3 swiftly induced cancer cell death in vitro and showed a potent antitumor effect in vivo. These results strongly suggest that AxdAdB-3 possesses a wider therapeutic potential than previously believed, given that most pancreatic cancers have abnormalities in both the TP53 and RB pathways.
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PMID:Oncolytic virotherapy as a novel strategy for pancreatic cancer. 1508 81

We have previously reported that p53 mutations, loss of bax expression or decreased spontaneous tumor apoptosis were associated with poorer prognoses in maxillary sinus squamous cell carcinoma (SCC)(Cancer 94: 1968-1980, 2002). In the present study, we analyzed tumor angiogenesis monitored by expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and tumor microvessel density, in correlation with p53 status, spontaneous apoptosis or disease prognosis in the same group of 70 maxillary sinus SCC patients. Tumor biopsy specimens obtained prior to initiation of treatment were examined for expression of VEGF and bFGF and tumor microvessel density using immunohistological methods. Average vessel density (AVD) (range: 3-75; median: 25) and maximum vessel density (MVD) (range: 4-125; median: 53) were assessed by the number of microvessels stained with anti-CD31 mAb in tumor lesions. VEGF was expressed in 35 (50%) of 70 patients and bFGF was in 43 (61%). Patients with VEGF expression showed significantly higher levels of MVD than those without VEGF expression (57 vs. 38; P=0.019). The VEGF expression was observed more frequently in patients with p53 overexpression and/or mutation than in those with normal p53 status (P=0.048). The MVD inversely correlated with the apoptotic index (AI) defined as the number of single stranded (ss)-DNA-positive cells per 1000 tumor cells (r= -0.23; P=0.022). Patients with neck lymph node and/or distant metastases after surgery showed significantly higher levels of MVD than patients without any metastasis (64 vs. 42; P=0.048). Low histological effectiveness of radiochemotherapy correlated with bFGF expression (P=0.0059). To clarify actual prognostic factors for maxillary sinus SCC, we selected 57 patients treated uniformly with preoperative radiochemotherapy followed by maxillectomy. Kaplan-Meier analysis showed that survival was significantly worse in patients with high MVD (> or =80) than in those with low MVD (<80) (P=0.042). These data suggest that the VEGF expression in association with the p53 overexpression and/or mutations may cause increased microvascularity, decreased spontaneous apoptosis or metastases, while the bFGF expression may be associated with resistance to radiochemotherapy, thereby resulting in poorer prognoses in maxillary sinus SCC. VEGF and bFGF expression and tumor microvessel density in tumor lesions were analyzed in 70 patients with maxillary sinus squamous cell carcinoma. The VEGF expression dependent of p53 overexpression and/or mutations was associated with angiogenesis, decreased spontaneous tumor apoptosis and metastases, while the bFGF expression was associated with resistance to radiochemotherapy, resulting in poor prognosis.
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PMID:VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis. 1514 81

Endometrial carcinoma occurs mostly in post-menopausal women. Classical methods of prognostication, as FIGO stage and histopathologic grade, could be improved by applying additional techniques, utilizing molecular biology and immunochemistry. p-53 tumor suppressor gene, the most commonly mutated gene in human cancers has been shown to play an important role in the biology of gynecologic carcinomas. Angiogenesis, a process of formation of new vessels, being connected to tumors progression and metastatic potential was shown to be linked with tumor suppressor genes expression. The aim of the study was to evaluate relationships between intensity of tumor angiogenesis, serum levels of Vascular Endothelial Growth Factor (VEGF) and tissue p-53 protein expression in endometrial adenocarcinoma. Angiogenic Point's Density (APD) was calculated in hot spots areas using the morphometric appliance. For detection of p53 protein in tumor samples, LSAB + Kit Alkaline Phosphatase (DAKO) was used. VEGF levels were assessed in patient's blood sampled before the operation. Overexpression of p53 protein was found in tumor tissue in 35.2% of cases and mean angiogenic points density was greater in p53 positive cases. Serum levels of VEGF were above the cut off level in 54.5% of patients, in those cases angiogenesis was also elevated. In cases of p53 overexpression, VEGF levels tended to be greater as compared with p53 negative cases. In conclusion, our study demonstrated that angiogenesis was more intensive in p53 positive cases, confirming the hypothesis of tumor suppressor-gene regulation of the process of neovascularization. Serum levels of VEGF were borderline-significantly higher in cases of p53 overexpression, they were also correlated to the angiogenesis. Joint assessment of angiogenesis and tumor suppressor genes expression may contribute to reliable evaluation of the biology of endometrial carcinoma.
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PMID:Evaluation of angiogenesis, p-53 tissue protein expression and serum VEGF in patients with endometrial cancer. 1525 72

Hypoxia-induced angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Rho family small GTPases are involved in this process, and Racl, a prominent member of the Rho family, may be critical in regulating hypoxia-induced gene activation of several angiogenesis factors and tumor suppressors. To fur-ther define Racl function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock down gene expression of Racl in gastric cancer cell line AGS that expresses a high level of Racl. Both the mRNA and protein levels of Racl in the AGS cells were decreased dramatically after transfection with a Racl-specific siRNA vector. When the conditioned medium derived from the Racl downregulated AGS cells was applied to the human endothelial cells. it could significantly inhibit the cell proliferation. Further study proved that, VEGF and HIF-la, two angiogenesis promoting factors, were found to be downregulated whereas p53 and VHL, which are tumor suppressors and angiogenesis inhibitors. were upregulated in the Racl siRNA transfected cells. Our results suggest that Racl may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting the Racl GTPase.
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PMID:Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells. 1530 76

Thymidine phosphorylase (TP) is a unique enzyme involved not only in angiogenesis, but in 5-fluorouracil (5-FU) metabolism as well. TP is produced by both tumor and stromal cells. The aim of this study was to reveal the clinical implication of TP localization in tumor tissues. Advanced colorectal cancer specimens (n=97) were prepared for immunohistochemical staining using monoclonal antibodies against TP, p53, vascular endothelial growth factor (VEGF), factor VIII, CD68 and thymidylate synthase (TS). Clinicopathological factors and the clinical prognosis were examined for each indicator. High tumor TP expression and high stromal TP expression were observed in 38% (36/95 cases) and 49% (47/95 cases) of the cases, respectively. High tumor TP expression tended to correlate with microvessel density (MVD) (p=0.0511). Among patients who underwent curative resection, those with high stromal TP expression had a favorable prognosis (p=0.0127). High stromal TP status was also a strong prognostic factor in the group receiving adjuvant 5-FU derivatives (p=0.0222). TP produced by tumor cells has a stimulatory effect on tumor angiogenesis, while that produced by stromal cells plays an entirely different role. The latter may enhance the anticancer effect of 5-FU via its catalyzed function.
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PMID:Importance of thymidine phosphorylase expression in tumor stroma as a prognostic factor in patients with advanced colorectal carcinoma. 1570 8

Apigenin is a nontoxic dietary flavonoid that has been shown to possess anti-tumor properties and therefore poses special interest for the development of a novel chemopreventive and/or chemotherapeutic agent for cancer. Ovarian cancer is one of the most common causes of cancer death among women. Here we demonstrate that apigenin inhibits expression of vascular endothelial growth factor (VEGF) in human ovarian cancer cells. VEGF plays an important role in tumor angiogenesis and growth. We found that apigenin inhibited VEGF expression at the transcriptional level through expression of hypoxia-inducible factor 1alpha (HIF-1alpha). Apigenin inhibited expression of HIF-1alpha and VEGF via the PI3K/AKT/p70S6K1 and HDM2/p53 pathways. Apigenin inhibited tube formation in vitro by endothelial cells. These findings reveal a novel role of apigenin in inhibiting HIF-1 and VEGF expression that is important for tumor angiogenesis and growth, identifying new signaling molecules that mediate this regulation.
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PMID:Apigenin inhibits VEGF and HIF-1 expression via PI3K/AKT/p70S6K1 and HDM2/p53 pathways. 1574 77

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