期刊
CANCER CELL
卷 27, 期 1, 页码 123-137出版社
CELL PRESS
DOI: 10.1016/j.ccell.2014.10.015
关键词
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资金
- Association for International Cancer Research [12-1068]
- Medical Research Council [G0901609]
- Cancer Research UK [C82181/A12007, C18270/A12888, C18270/A14355]
- Pancreatic Cancer Research Fund
- European Union [317445]
- Cancer Research UK [12007, 18673] Funding Source: researchfish
- Medical Research Council [MC_UP_1502/1, G0901338, G0901609, 1365527] Funding Source: researchfish
- Worldwide Cancer Research [12-1068] Funding Source: researchfish
- MRC [MC_UP_1502/1, G0901609, G0901338] Funding Source: UKRI
Increasing chemotherapy delivery to tumors, while enhancing drug uptake and reducing side effects, is a primary goal of cancer research. In mouse and human cancer models in vivo, we show that coadministration of low-dose Cilengitide and Verapamil increases tumor angiogenesis, leakiness, blood flow, and Gemcitabine delivery. This approach reduces tumor growth, metastasis, and minimizes side effects while extending survival. At a molecular level, this strategy alters Gemcitabine transporter and metabolizing enzyme expression levels, enhancing the potency of Gemcitabine within tumor cells in vivo and in vitro. Thus, the dual action of low-dose Cilengitide, in vessels and tumor cells, improves chemotherapy efficacy. Overall, our data demonstrate that vascular promotion therapy is a means to improve cancer treatment.
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