Search results for "vascular endothelial growth factor"
showing 10 items of 320 documents
How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.
2019
e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF an…
Comparative study of human colonic tumor-derived endothelial cells (HCTEC) and normal colonic microvascular endothelial cells (HCMEC): Hypoxia-induce…
2009
Colorectal carcinoma growth and progression is dependent on the vasculature of the tumor microenvironment. Tumor-derived endothelial cells differ functionally from their normal counterpart. For this reason we isolated microvascular endothelial cells from human colon cancer tissue (HCTEC) and compared them with endothelial cells from normal colonic tissue (HCMEC) of the same donor. Since hypoxia is a universal hallmark of carcinomas, we examined its effects on HCTEC of five patients in comparison with the corresponding HCMEC, with respect to the secretion of the soluble form of the two important vascular endothelial growth factor (VEGF) receptors, VEGFR-1 and -2. After dissociation by dispas…
PDGFRβ and FGFR2 mediate endothelial cell differentiation capability of triple negative breast carcinoma cells
2014
Triple negative breast cancer (TNBC) is a very aggressive subgroup of breast carcinoma, still lacking specific markers for an effective targeted therapy and with a poorer prognosis compared to other breast cancer subtypes. In this study we investigated the possibility that TNBC cells contribute to the establishment of tumor vascular network by the process known as vasculogenic mimicry, through endothelial cell differentiation. Vascular-like functional properties of breast cancer cell lines were investigated in vitro by tube formation assay and in vivo by confocal microscopy, immunofluorescence or immunohistochemistry on frozen tumor sections. TNBCs express endothelial markers and acquire th…
Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.
2008
This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expressi…
Prognostic and predictive factors in patients treated with ramucirumab (RAM) with advanced hepatocellular carcinoma (aHCC) and elevated alpha-fetopro…
2021
4146 Background: Elevated AFP in patients with aHCC is a poor prognostic factor with distinct molecular features, including high vascular endothelial growth factor (VEGF) signalling and increased angiogenesis. RAM, a human IgG1 monoclonal antibody, VEGF receptor 2 (VEGFR2) inhibitor, demonstrated improved survival vs placebo among patients with elevated AFP in the REACH-2 trial and is accepted as a standard of care for management of aHCC. We analyzed prognostic factors in patients with AFP ≥400 ng/mL and predictors of clinical benefit to RAM in an individual participant data (IPD) meta-analysis of the REACH and REACH-2 Phase III trials. Methods: Patients with aHCC, Child-Pugh A, ECOG perfo…
Tumor and its microenvironment: a synergistic interplay.
2013
The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species …
Analysis of Antiproliferative and Chemosensitizing Effects of Sunitinib on Human Esophagogastric Cancer Cells: Synergistic Interaction With Vandetani…
2009
The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti-proliferative and chemosensitizing properties of the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small-molecule inhibitors was examined by reverse transcriptase-polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, …
Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasi…
2013
Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused…
Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.
2012
3062 Background: ALN-VSP02 is an RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs targeting vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). In a phase 1 trial, ALN-VSP02 administered as an iv infusion q2 wks was well-tolerated and showed evidence of anti-VEGF pharmacology and antitumor activity. Methods: Patients treated on the phase I trial with stable disease (SD) or better after 4 months (8 doses) were eligible to continue on an extension study until disease progression. Main objectives included continued evaluation of safety/tolerability and assessment of disease response. Results: Seven of 37 patients …
Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns
2021
VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry. Differences in subcellular colocalization of VEGFR2 with endothelial, tumor and stem cell markers were determined by doub…