Tumor multi-drug resistance

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Fojo, A.T. Ueda, K. Slamon, D.J. Poplack, D.G. Gottesman, M.M. Pastan, M.M. Expression of a multi-drug-resistance gene in human tumors and tissues. Proc. Natl. Acad. Sci. USA 1987, 84, 265-269. 

DiOC6 (3) is rapidly removed from the cells that have active efflux pump (P glycoprotein), such as stem cells or multi-drug resistant tumor cells, which may simulate collapse of AW,. 

A synergistic effect of hyperthermia of 42 to 45°C was observed when delivered after or simultaneously to PDT [87-90] which could be of advantage in treating brain tumors. The PDT might be of advantage in the treatment of tumors not responding to chemotherapy because cells which express multi-drug resistance features are less likely to be cross-resistant to PDT [91]. 

P-gp is also concentrated in tumor cells and is primarily responsible for multi-drug resistance found in some patients undergoing chemotherapy (Bellamy 1996). 

Efflux pumps are transmembrane located transporter proteins which are expressed in various tissues including liver, placenta, the proximal tubule in the kidney, capillary endothelial cells of brain and testis, and epithelial cells of the intestine [1,2]. In addition, they are over-expressed in cancer cells and are involved in the multi drug resistance (MDR) mechanisms of tumors. Besides other mechanisms such as CYP3A, efflux pumps constitute an integral part of the body s natural detoxification system. Due to their loealisation in various tissue they affect absorption, distribution, metabolism and elimination [3]. They are... 

We have noted that multi-drug resistant variants of Gba-containing tumor cells... 

L. S. Jabr-Milane et al. Multi-functional nanocarriers to overcome tumor drug resistance. Cancer Treat. Rev. (2008). 

The success of cisplatin and carboplatin in treating cancer, combined with the intrinsic and acquired resistance of many tumors to traditional platinum chemotherapy, has generated considerable interest in developing next-generation platinum drugs. Since the discovery of the antitumor activity of cisplatin, researchers have reported the synthesis, characterization, and antitumor activity of thousands of platinum compounds [1] [2]. The previous two chapters in this section describe the promising activity of novel multi-nuclear Ptn and orally active PtIV complexes [3] [4],... 

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