Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esophageal cancer is a rare but highly virulent malignancy occurring in the United States and other Western countries. Adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy in the United States. Controversy continues about the optimal surgical approach for the treatment of locally advanced esophageal cancer. Combined chemoradiotherapy is the standard of care in the nonsurgical management of esophageal cancer. Trials of preoperative chemotherapy followed by surgery have not shown a consistent benefit for the addition of chemotherapy to surgery. Preoperative chemoradiotherapy followed by surgery continues to be actively studied in the surgical management of locally advanced esophageal cancer. Pathologic complete responses are seen in 20-40% of patients, with 5-year survival achieved in 30-35% of patients. Recent randomized trials evaluating the role of surgery after completion of chemoradiotherapy have not clearly shown a benefit for the routine use of surgery after chemoradiotherapy. The toxicity of conventional fluorouracil, cisplatin, and radiation have led researchers to evaluate newer agents, such as the taxanes and irinotecan, in combined chemoradiotherapy trials. These trials have indicated promising antitumor activity and therapy tolerance, depending on the dose and schedule of therapy administered. Increasing the dose of radiotherapy or adding a brachytherapy boost to chemoradiotherapy has not improved the outcome of treatment in clinical trials. The advent of newer, targeted therapies, including agents directed against growth factor receptor pathways, tumor angiogenesis, and tumor invasion and metastasis, is leading to a new generation of clinical trials combining these agents with conventional cytotoxic chemotherapy and radiation.
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PMID:New developments in the treatment of esophageal cancer. 1616 69

Angiogenesis is an essential process required for tumor growth and progression. The Notch signaling pathway has been identified as a key regulator of the neo-angiogenic process. Jagged-1 (Jag1) is a Notch ligand required for embryonic and retinal vascular development, which direct contribution to the regulation of tumor angiogenesis remains to be fully characterized. The current study addresses the role of endothelial Jagged1-mediated Notch signaling in the context of tumoral angiogenesis in two different mouse tumor models: subcutaneous Lewis Lung Carcinoma (LLC) tumor transplants and the autochthonous Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP). The role of endothelial Jagged1 in tumor growth and neo-angiogenesis was investigated with endothelial-specific Jag1 gain- and loss-of-function mouse mutants (eJag1OE and eJag1cKO). By modulating levels of endothelial Jag1, we observed that this ligand regulates tumor vessel density, branching, and perivascular maturation, thus affecting tumor vascular perfusion. The pro-angiogenic function is exerted by its ability to positively regulate levels of Vegfr-2 while negatively regulating Vegfr-1. Additionally, endothelial Jagged1 appears to exert an angiocrine function possibly by activating Notch3/Hey1 in tumor cells, promoting proliferation, survival and epithelial-to-mesenchymal transition (EMT), potentiating tumor development. These findings provide valuable mechanistic insights into the role of endothelial Jagged1 in promoting solid tumor development and support the notion that it may constitute a promising target for cancer therapy.
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PMID:Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions. 2621 36