Chemosensitizing agent

Chemosensitizing agents prepared by Lin (6) consisting of phenothiazine derivatives, (V), were effective against chloroquine-resistant Plasmodium falciparum. 

Another approach to overcome MDR involves the use of polymeric surfactants, such as Pluronic block copolymers, as chemosensitizing agents. The affect of Pluronic block copolymers on MDR cells has two components first, the polymers alter membrane micro viscosity and, second, they cause ATP depletion selectively in MDR cells Both effects... 

For non-suspension cultures, suitable matrices include liquid overlay on agarose (59), Matrigel , or Cultrex (48, 92). More recently, micropatterned arrays have been developed for adherent 3-D spheroid cultures (56) and have been used to show reduced chemosensitivity of colorectal carcinoma cells to irinotecan (58). In some cases, 3-D cultures can be enhanced by the addition of host cells. This increases complexity, but inevitably decreases flexibility and speed of analysis. However, important insights into the role of host cells have emerged stromal cells modify the gene expression and response of many tumor cell types to chemotherapeutic agents (93) and tumor-associated myofibroblasts can enhance tumor invasiveness (94). 

The MTT assay was initially developed as a quantitative assay for cell survival and proliferation, not as an in vitro assay for chemosensitivity testing. Further study was required to ascertain if the method accurately predicted the in vivo antitumor activities of anticancer agents. Shimoyama et al. [189] studied the predictability of the MTT assay with respect to a clonogenic assay (Sect. 4.1.1.3.) and showed excellent reproducibility and a close correlation to the in vivo predictability rate of the clonogenic assay. Another study [190] also showed that the MTT assay closely approximated (90%) the clinical activity of anticancer agents. Many authors have since utilized the MTT assay to determine the efficacy of polymeric anticancer drug conjugates. 

If accurate determination of chemosensitivity were predictable by gene expression analysis, the overall number of patients receiving cytotoxic treatment unnecessarily would decrease, and the overall survival benefit derived per patient treated would increase accordingly. Large increases in the absolute survival of patients diagnosed with breast cancer, however, will require the development of novel therapeutic agents. 

Iwadate Y, Sakaida T, Saegusa T, Hiwasa T, Takiguchi M, Fujimoto S, et al. Proteome-based identification of molecular markers predicting chemosensitivity to each category of anticancer agents in human gliomas. Int J Oncol 2005 26(4)993-998. 

Ulukaya, E., Colakogullari, M., and Wood, E.J. 2004. Interference by anti-cancer chemotherapeutic agents in the MTT-tumor chemosensitivity assay. Chemotherapy 50, 43-50. 

Albuquerque, E.X., S.S. Deshpande, M. Kawabuchi, Y. Aracava, M. Idriss, D.L. Rickett, and A.F. Boyne. 1985. Multiple actions of anticholinesterase agents on chemosensitive synapses Molecular basis for prophylaxis and treatment of organophosphate poisoning. Fund. Appl. Toxicol. 5 S182-S203. 

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