Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis plays a major role in the pathogenesis of many disorders. Vascular endothelial growth factor has been shown to be the key regulator of normal and pathological angiogenesis. Increased expression of VEGF has been associated with tumor neovascularization, metastasis and proliferation of cancer cells. Bevacizumab, a monoclonal antibody against VEGF, has shown promising preclinical and clinical activity against different types of cancer, particularly in combination with chemotherapy. There is an increasing evidence that bevacizumab has a disease-modifying effect in metastatic colorectal carcinoma (CRC), and also in advanced hepatocellular carcinoma. Further investigation is needed to evaluate the role of antiangiogenic therapeutic strategies in other gastrointestinal malignancies. This review summarizes recent knowledge about antiangiogenic therapy for gastrointestinal cancers.
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PMID:[Antiangiogenic therapy for gastrointestinal tumors]. 1904 83

Vascular Endothelial Growth Factor (VEGF) plays an important role in proliferation of cancer cells, angiogenesis and vascular permeability in peritoneal dissemination. Now we investigated the efficacy of anti-VEGF therapy in peritoneal dissemination of gastric cancer considering of pharmacokinetics. We investigated pharmacokinetics of bevacizumab, humanized anti-VEGF monoclonal antibody in subcutaneous xenograft and peritoneal dissemination model of OCUM-2MD3, highly peritoneal-seeding cell line of human scirrhous gastric carcinoma. In the group of intraperitoneal administration, bevacizumab remains in the intraperitoneal cavity and transits slowly to blood pool. On the other hand, in the group of subcutaneous administration, bevacizumab transits faster to blood pool and is accumulated in subcutaneous tumors and peritoneal nodules. Bevacizumab administered intraperitoneally seemed to neutralize intraperitoneal VEGF. Bevacizumab administered in subcutaneous seemed to act on peritoneal wall and control vascular permeability. Systemic administration of anti-VEGF agent will be a potential therapy in peritoneal dissemination of gastric cancer.
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PMID:[Anti-VEGF therapy for peritoneal dissemination model of gastric cancer considering of pharmacokinetics]. 1910 5

The current FDA-approved standard of care for nonsmall cell lung cancer is Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however, patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30% mortality rate due to fatal hemoptysis. In this study we evaluated the role of cytomorphology and immunohistochemistry in differentiating SQCC from adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases of nonsmall cell lung carcinoma with surgical pathology follow-up. All FNA specimens were reviewed independently by a panel of cytopathologists to differentiate between SQCC and ADC. The cell block material was available in 23 cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF-1, CK7, CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%). By immunohistochemical staining, 14/23 (61%) cases expressed TTF-1. Nine cases were TTF-1 negative; eight of the TTF-1 negative cases (89%) were SQCC. Twenty-three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity. Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC cases showed this dual expression. Cytomorphology alone may not be able to stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA specimens. The immune-panel of TTF-1, CK7, CK20, P63, and CK5/6 is useful in differentiating SQCC from ADC.
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PMID:Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine-needle aspiration specimens. 1917 Jan 69

Neoplastic angiogenesis is an essential process in the progressive growth of neoplasms and the production of metastasis. Angiogenesis consists of a series of linked and sequential steps that ultimately leads to the development of a neovascular blood supply to the tumor mass. VEGF has got an essential role in neoplastic angiogenesis, therefore it is an important target in the treatment of neoplasms. Bevacizumab, a humanized monoclonal antibody, inhibits VEGF, and may also improve the delivery of chemotherapy to the tumor mass. Multi-kinase ihibitors (sorafenib and sunitinib) are orally administered small-molecules, that inhibit different receptors (essentials in the neoplastic angiogenesis), such as the VEGFR or PDGFR. These agents are useful in the treatment of advanced renal-cell carcinoma, and are under investigation in several tumors.
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PMID:[Neoplastic angiogenesis]. 1929

Although in recent years, chemotherapeutic options for colorectal carcinoma have expanded, overall response rates are still too low, with high rates of toxicity. Pharmacogenetics aim at predicting both treatment response and adverse effects in individual patients. This review describes the current knowledge of pharmacogenetic markers in the systemic treatment of colorectal cancer. UGT1A1*28 leads to reduced conjugation of SN-38, the active metabolite of irinotecan, resulting in an increased rate of adverse effects, especially neutropenia. To a lesser extent, increased 5-FU toxicity is predicted by DPYD*2A. A variable number of tandem repeats polymorphism in the thymidylate synthase enhancer region, in combination with a single nucleotide polymorphism C>G, may predict poorer response to 5-FU. Efficacy of oxaliplatin is influenced by polymorphisms in components of DNA repair systems, such as ERCC1 and XRCC1. Polymorphic changes in the endothelial growth factor receptor probably predict cetuximab efficacy. Furthermore, the antibody-depended cell-mediated cytotoxic effect of cetuximab may be reduced by polymorphisms in the immunoglobin G fragment C receptors. Bevacizumab efficacy is suspected to be influenced by polymorphisms in the VEGF gene and the hypoxia inducible factor 1alpha gene. Although the interpretation of pharmacogenetic studies is complicated, results imply a promising way of pretreatment prediction of chemotherapy efficacy and toxicity.
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PMID:Pharmacogenetics in chemotherapy of colorectal cancer. 1941 51

It has been suggested that immunosuppressive cytokines such as transforming growth factor beta (TGF-beta) and interleukin 10 play an important role in the induction and/or maintenance of regulatory T-cells (Tregs) in patients with cancer. In the present study, whether or not vascular endothelial growth factor (VEGF) contributes to the induction and/or maintenance of Tregs was examined, because of experience with a patient in whom a positive correlation between VEGF concentration and the percentage of Tregs (% Tregs) among the total CD4(+) T-cells in the pleural effusion was found during dendritic cell activated lymphocyte therapy. CD4(+)CD25(high) T-cells were estimated as Tregs in the present study. In an in vitro experimental system, VEGF-containing malignant effusions increased the % Tregs in autologous peripheral blood mononuclear cells (PBMCs), which could be suppressed by the addition of a humanized monoclonal anti-VEGF antibody (bevacizumab [Avastin]). When VEGF-producing hepatic carcinoma cells were mix-cultured with PBMCs, the % Tregs increased and this increase was also suppressed by the addition of bevacizumab. Whether or not bevacizumab can affect the % Tregs of PBMCs in patients with colon cancer was also examined. Three out of four patients showed a significant decrease of the % Tregs after intravenous injection of bevacizumab. Interestingly, the expression of VEGF receptor-2 (VEGFR-2) was higher in Tregs than in other CD4(+) T-cells. Taken together, the data presented here indicate a contribution of VEGF to induction and/or maintenance of Tregs in patients with cancer.
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PMID:The contribution of vascular endothelial growth factor to the induction of regulatory T-cells in malignant effusions. 1941 23

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy.
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PMID:Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer. 1982 39

Nowadays, the advancements of systemic chemotherapy for colorectal carcinoma improve a clinical response rate, and expand the possibility of resection which couldn't operable at the initial visit. In addition, the prognoses of the patients, who had a radical operation for metastasis, are clearly longer than the non-operable patients. Bevacizumab, anti-human VEGF monoclonal antibody, is significantly effective when used in combination with one of the systemic multi-agent chemotherapy such as FOLFOX regimen or FOLFIRI regimen. We report here two cases with colon carcinoma, which had initially unresectable liver metastases, were respond to the treatment of systemic multi-agent chemotherapy with bevacizumab. Then, both cases were able to undergo radical resections of primary tumor and liver metastases safely.
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PMID:[Two radically resected colorectal carcinoma cases with unresectable liver metastasis after adjuvant chemotherapy with bevacizumab]. 2003 59

Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing vascular endothelial growth factor. Adverse events resulting from its use include gastrointestinal perforation, wound-healing complications, hemorrhage, and arterial thromboembolism. We present a case of a 67-year-old man who developed Fournier's gangrene during treatment with bevacizumab 4 months after completing mFOLFOX6 (5-FU/leucovorin/oxaliplatin) for CRC. Other than bevacizumab, the patient had no medications and had no medical conditions that would predispose to Fournier's gangrene.
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PMID:Fournier's gangrene as a possible side effect of bevacizumab therapy for resected colorectal cancer. 2010 Jun 90

Photodynamic therapy (PDT) is an alternative cancer treatment modality that offers localized treatment using a photosensitizer and light. However, tumor angiogenesis is a major concern following PDT-induced hypoxia as it promotes recurrence. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), thus preventing angiogenesis. The combination of PDT with antiangiogenic agents such as bevacizumab has shown promise in preclinical studies. We use confocal endomicroscopy to study the antiangiogenic effects of PDT in combination with bevacizumab. This technique offers in vivo surface and subsurface fluorescence imaging of tissue. Mice bearing xenograft bladder carcinoma tumors were treated with PDT, bevacizumab, or PDT and bevacizumab combination therapy. In tumor regression experiments, combination therapy treated tumors show the most regression. Confocal fluorescence endomicroscopy enables visualization of tumor blood vessels following treatment. Combination therapy treated tumors show the most posttreatment damage with reduced cross-sectional area of vessels. Immunohistochemistry and immunofluorescence studies show that VEGF expression is significantly downregulated in the tumors treated by combination therapy. Overall, combining PDT and bevacizumab is a promising cancer treatment approach. We also demonstrate that confocal endomicroscopy is useful for visualization of vasculature and evaluation of angiogenic response following therapeutic intervention.
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PMID:Evaluation of hypericin-mediated photodynamic therapy in combination with angiogenesis inhibitor bevacizumab using in vivo fluorescence confocal endomicroscopy. 2021 Apr 40


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