Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although derived from the host tissue, the tumor vasculature is under the influence of the tumor microenvironment and needs to adapt to the resistance to blood flow inherent to the dynamics of tumor growth. Such vascular remodeling can offer selective targets to pharmacologically modulate tumor perfusion and thereby improve the efficacy of conventional anticancer treatments. Radiotherapy and chemotherapy can, indeed, take advantage of a better tumor oxygenation and drug delivery, respectively, both partly dependent on the tumor blood supply. Here, we showed that isolated tumor arterioles mounted in a pressure myograph have the ability, contrary to size-matched healthy arterioles, to contract in response to a transluminal pressure increase. This myogenic tone was exquisitely dependent on the endothelin-1 pathway because it was completely abolished by the selective endothelin receptor A (ETA) antagonist BQ123. This selectivity was additionally supported by the large increase in endothelin-1 abundance in tumors and the higher density of the ETA receptors in tumor vessels. We also documented by using laser Doppler microprobes and imaging that administration of the ETA antagonist led to a significant increase in tumor blood flow, whereas the perfusion in control healthy tissue was not altered. Finally, we provided evidence that acute administration of the ETA antagonist could significantly stimulate tumor oxygenation, as determined by electron paramagnetic resonance oximetry, and increase the efficacy of low-dose, clinically relevant fractionated radiotherapy. Thus, blocking the tumor-selective increase in the vascular endothelin-1/ETA pathway led us to unravel an important reserve of vasorelaxation that can be exploited to selectively increase tumor response to radiotherapy.
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PMID:Endothelin-1 is a critical mediator of myogenic tone in tumor arterioles: implications for cancer treatment. 1512 61

Endothelin-1 (ET-1) causes vasodilatation via its endothelin-B receptors. ET-1, endothelin-3 and endothelin-B receptors are known to be overexpressed in breast carcinoma tissue. However, the functional role of ET-1 in tumor vasculature is still unknown. If ET-1 causes an increase in breast tumor perfusion, it could be used to increase delivery of chemotherapeutic agents to the tumor tissues. Female Sprague-Dawley rats (180-200 g) were treated with either saline or N-methyl, N-nitrosourea (50 mg/kg, intraperitoneally), a chemical carcinogen. Each group was treated with: (a) ET-1 (50 ng/kg/minute, 30 minute infusion) (n = 6); or (b) BQ788, an endothelin-B receptor antagonist (0.33 mg/kg/minute, 20 minute infusion) + ET-1 (50 ng/kg/minute, 30 minute infusion) (n = 5). Blood flow to tumor and normal breast tissue was measured using radioactive microspheres. Blood perfusion to the breast and tumor tissue was measured using laser Doppler flowmetry. Blood flow to tumor tissue increased (153%; P < 0.05) and vascular resistance decreased following ET-1 infusion. Blood flow to other organs was not affected. Laser Doppler flowmetry showed an increase (176%; P < 0.05) in breast tumor perfusion following ET-1 infusion. The increase in perfusion was attenuated (-25.2%; P < 0.05) with the administration of BQ788. Results indicate that ET-1 induced an increase in blood flow to tumors in tumor-bearing rats, which is mediated by endothelin-B receptors.
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PMID:Endothelin-1-induced vasodilatation in rat breast tumor is mediated through endothelin-B receptors. 1583 54