Vascular Endothelial Growth Factor In Cancer Research Articles

Molecular docking and interactions between vascular endothelial growth factor (VEGF) receptors and phytochemicals: An in-silico study

Abstract Vascular endothelial growth factor (VEGF) is a mitogen, which plays a vital role in angiogenesis and neovascularization. Numerous medications have been developed to inhibit VEGF in cancer, because of its significance in tumor development and its survival. Hence, the current study is focused on identifying phytocompounds to directly target VEGF receptors using in-silico approach. In this study, a computational approach has been applied to elucidate the role of the phytocompounds in inhibition of angiogenesis through modulation of VEGF receptors responsible for angiogenesis. Molecular docking analysis was performed using AutoDock 4.2 software. In addition, the in silico ADMET analysis was carried out to predict the pharmacokinetic properties. Among the 50 phytocompounds tested, 6 compounds (Eriodyctiol, Epicatechin, Scutellarin, Ginkgolide A, Tetrandrine and Bassic acid) showed a better interaction profile than standard drug (Triamcinolone). Our study suggests a potential therapeutic effect of these phytocompounds for inhibiting angiogenesis, thereby providing inkling for novel drug design for proangiogenic diseases such as DR.

Colon Cancer Liver Metastasis: Addition of Antiangiogenesis or EGFR Inhibitors to Chemotherapy

For patients with unresectable colorectal liver metastases (CRLM), selection of adequate drug combinations, with or without biological agents, for immediate use is crucial for success of conversion to resectable CRLM with potentially curative results. This paper addresses the use of biological agents directed against the two main targets in colorectal cancer—vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). Addition of the anti-angiogenic monoclonal antibody (MAb) bevacizumab to chemotherapy may increase resection of CRLM for patients with KRAS mutated or for unselected patients. Caution must be exercised with wound healing complications when surgery is performed after bevacizumab use. Patients with KRAS wild-type should be considered for combination therapy with EGFR inhibitors, because this strategy has led to promising results with improved R0 resection.

Fighting on the border

Colorectal cancer (CRC) is a public healthproblem inmost develped countries. It is potentially curable in its early stages, but a elevant proportion of patients still presents with or ultimately evelops metastatic disease. Over the past 10 years, significant advances have been made in he molecular profiling and clinico-pathological characterization f CRC. In particular, the expanding body of information on cancer iology may provide the biological rationale for new therapeutic trategies. The interesting manuscript published in this issue of igestive and Liver Disease by Cianchi et al. further demonstrates ow molecular studies may help therapy to be tailored to cancer’s iology [1]. COX2 gene expression is virtually undetectable in the normal ntestine, but frequently upregulated in CRC [2]. In vivo and in itro studies have demonstrated that COX2 gene product promotes ngiogenesis, supporting both tumour growth and metastatic mplants [3]. A direct correlation between COX2 expression and icrovessel density has also been documented. As in several ther epithelial malignancies, COX2 protein over-expression conistently correlates with an unfavourable prognosis. In a study on large cohort of CRC patients, Soumaoro et al. associated COX2ositive cancers with a significantly shorter overall survival, and his unfavourable outcomewas also confirmedwhen different caner stages were considered separately [4]. In the Soumaoro study, OX2 over-expression was consistently found in primary tumours, s well in all liver metastases and almost in all metastatic regional ymph nodes. Vascular endothelial growth factor (VEGF) is a glycoproteinwith itogenic effects on endothelium and its activation results in sigalling cascades that promote both new endothelial cell growth nd the survival of existing vessels. The role of VEGF in cancer has een extensively studied and a higher expression of VEGF has been ssociated with COX2 upregulation [2]. Cianchi et al. provide original, interesting data on this hot issue 1]. They tested the expression of a panel of well-known angio-

Vascular Endothelial Growth Factor in Thyroid Cancers

Vascular endothelial growth factor (VEGF) is an essential peptide in new vessel growth in physiology (endometrial growth, embryonic development); pathological conditions (diabetic retinopathy, rheumatoid arthritis); as well as in tumor cell growth, particularly distant metastases. This study focused on VEGF structure, receptors, and angiogensis in tumors, especially their roles in thyroid cancer. The VEGF mRNA undergoes alternative splicing events that generate four homodimeric isoforms, including VEGF121, VEGF165, VEGF189, or VEGF206. Using VEGF purified from a culture medium conditioned by A-431 human epidermoid carcinoma cells, VEGF-binding site complexes of 230, 170, and 125 kDa were detected on human umbilical vein endothelial cells. The VEGF specifically induced the tyrosine phosphorylation of a 190-kDa polypeptide, which had similar mass to the largest binding site detected through affinity cross-linking. A transmembrane receptor belongs to the tyrosine kinase family, fms-like tyrosine kinase (FLT). These receptor tyrosine kinases encoded by the FLT gene family have distinct functions in regulating blood vessel growth and differentiation. Regulation of VEGF is a complex, multistep mechanism in various kinds of cells and tissues. Hypoxia-dependent and -independent mechanisms are illustrated in different cancer tissues. Hypoxic tumor cells may switch to a proangiogenic phenotype, which increases VEGF transcription. Clinical applications of VEGF in cancer have included diagnosis, prediction of prognosis, and treatment in different solid tumors, including thyroid tumors. Studies involving thyroid cancer cell lines, serum level determination, immunohistocytochemical staining, molecular biological studies, and gene therapy to the in vivo clinical trials, have shown that antiangiogensis therapy can provide another treatment modality for thyroid cancer. Future studies focused on recombinant human anti-VEGF research involving patients with advanced thyroid cancer, and investigation of the protection of high-risk patients by using novel antiangiogenic vaccines, are warranted.

Expression of Vascular Endothelial Growth Factor (VEGF) Associated with Its Receptor (VEGFR) in Relation to Tissue Factor (TF) in Human Breast Cancer Tissue.

New blood vessel formation is an important process in tumor growth and dissemination. The relationship between vessel density and survival of patients was documented in breast cancer patients. Vascular endothelial growth factor (VEGF) is of paramount importance in new blood vessel development. VEGF exerts its biological function through binding to specific receptors (VEGFR-1/Flt-1 and VEGFR-2/KDR/Flk-1). Recent studies revealed that tissue factor (TF), apart from being the main procoagulant in cancer patients, is endowed with biological activities that do not relate to its hemostatic function. There exists a large body of evidence that TF is one of the key regulators of angiogenesis. In vitro experiments demonstrated that TF stimulates the synthesis of VEGF in different cell types. The purpose of the study was to assess the expression of VEGF and VEGF coupled to its receptor in relation to the expression of TF. Studies were performed on breast cancer fragments and metastatic axillary lymph node tissues obtained during surgical treatment of previously untreated patients. The tissues were fixed according to AMeX method and embedded in paraffin. Immunohistochemical staining procedures according to the ABC method and Envision Double Staining System (DAKO) were employed using polyclonal antibodies directed to TF and VEGF and a novel monoclonal antibody that binds to VEGF only when it is associated with its receptor - VEGFR. In breast cancer and lymph node tissues the co-localization of TF and VEGF in cancer cells was observed. Of particular interest was the co-expression of TF and VEGF in association with its receptor - VEGFR in cancer cells and endothelial cells of small blood vessels. Furthermore, VEGF coupled to its receptor was localized in dendritic cells in metastatic lymph nodes, which may indicate its influence on the host immune response system. The observed co-localization of TF and VEGF (including VEGF in association with VEGFR) suggests a functional interrelationship that exists between TF and VEGF in breast cancer in vivo.

Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma

OBJECTIVE: Vascular endothelial growth factor (VEGF) promotes proliferation of various tumor cells by stimulating angiogenesis. Experimentally, hypoxia and energy depletion are known to induce angiogenesis by increasing VEGF expression. We investigated whether factors reflecting the general condition of the patients influence the tissue concentration of VEGF in colorectal carcinoma. METHODS: Tissue concentrations of VEGF in 81 colorectal carcinomas, 81 normal mucosas, and 30 colonic adenomas were determined. The expressions of VEGF and its receptor in cancer tissue were evaluated immunohistochemically. For the assessment of the general preoperative condition of the patients, the nutritional status was evaluated and arterial blood gas was analyzed. RESULTS: The mean concentration of VEGF in the cancer tissue was significantly higher than that in the normal colonic mucosa and colonic adenoma. Tumor size, histological grade, serum cholinesterase, and arterial level of PO 2 were the independent factors that influenced the tissue concentration of VEGF in colorectal cancer. Immunohistochemically, the VEGF-positive cancer tended to have an increased expression of VEGF receptor, kinase insert domain–containing receptor (KDR). In patients with positive KDR in the tumor, the arterial levels of PO 2 and O 2 saturation were significantly lower than those in patients without its expression. CONCLUSION: Tissue content of VEGF or expression of KDR in colorectal carcinoma may be associated with disease status, including nutritional status, systemic oxygenation, and tumor progression. The systemic-local regulating mechanism of VEGF or KDR may play an important role in the constant growth of tumor cells, especially in wasted colorectal cancer patients.

Factors influencing tissue concentration of vascular endothelial growth factor in colorectal carcinoma.

Vascular endothelial growth factor (VEGF) promotes proliferation of various tumor cells by stimulating angiogenesis. Experimentally, hypoxia and energy depletion are known to induce angiogenesis by increasing VEGF expression. We investigated whether factors reflecting the general condition of the patients influence the tissue concentration of VEGF in colorectal carcinoma. Tissue concentrations of VEGF in 81 colorectal carcinomas, 81 normal mucosas, and 30 colonic adenomas were determined. The expressions of VEGF and its receptor in cancer tissue were evaluated immunohistochemically. For the assessment of the general preoperative condition of the patients, the nutritional status was evaluated and arterial blood gas was analyzed. The mean concentration of VEGF in the cancer tissue was significantly higher than that in the normal colonic mucosa and colonic adenoma. Tumor size, histological grade, serum cholinesterase, and arterial level of PO2 were the independent factors that influenced the tissue concentration of VEGF in colorectal cancer. Immunohistochemically, the VEGF-positive cancer tended to have an increased expression of VEGF receptor, kinase insert domain-containing receptor (KDR). In patients with positive KDR in the tumor, the arterial levels of PO2 and O2 saturation were significantly lower than those in patients without its expression. Tissue content of VEGF or expression of KDR in colorectal carcinoma may be associated with disease status, including nutritional status, systemic oxygenation, and tumor progression. The systemic-local regulating mechanism of VEGF or KDR may play an important role in the constant growth of tumor cells, especially in wasted colorectal cancer patients.