Tumors chemosensitivity

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. 

Moolten F L (1986). Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes Paradigm for a prospective cancer control strategy. Cancer Res. 46 5276-5281. 

Shabbits, J.A., Hu, Y, and Mayer, L.D. (2003). Tumor chemosensitization strategies based on apoptosis manipulations. Mol. Cancer Then 2, 805-813. 

Bioluminescence in vitro chemosensitivity assays are now used to assess the sensitivity of tumor cells (obtained by surgical or needle biopsy) to different dmgs and combinations of dmgs. Cells are grown in microwell plates in the presence of the dmgs at various concentrations. If the tumor cells are sensitive to the dmg then they do not grow, hence total extracted cellular ATP, measured using the bioluminescence firefly luciferase reaction, is low. This method has been used to optimize therapy for different soHd tumors and for leukemias (306). 

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. 

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). 

A key question that cannot be answered using cell culture assays is whether dietary GAs can have similar effects. Importantly, evidence that dietary tomatine is effective against cancer was shown in a feeding study using rainbow trout, in which reduced tumor incidence was found in tomatine-fed trout (Friedman et al., 2007). Tomatidine has potential as a chemosensitizing... 

Key Words Bioinformatics chemosensitivity tumor cell cytotoxicity NC160 gene expression compoimd screen... 

Isshi K, Sakuyama T, Gen T et al. Predicting 5-FU sensitivity using human colorectal cancer specimens comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU. Int J Clin Oncol 2002 7 335-342. 

Matsuyama R, Togo S, Shimizu D et al. Predicting 5-fluorouracil chemosensitivity of liver metastases from eoloreetal eaneer using primary tumor specimens three-gene expression model predicts clinical response. Int J Cancer 2006 19 406-413. 

Garg AK, Buchholz TA, Aggarwal BB. 2005. Chemosensitization and radiosensitization of tumors by plant polyphenols. Antioxid Redox Signal 7 1630-1647. 

Additional monosaccharide derivatives have been involved in biological studies that do not fall into the previously listed chemical categories. Of these, the acetylated monosaccharide derivatives have attracted the highest consideration. In particular, the insulinotropic action of L-glucose pentaacetate has been evaluated in animal and clinical studies [243]. Similarly, the tetraacetate derivative of 2-deoxy-D-glucose has been evaluated because of its cytotoxic effects upon lymphocytes, fibroblasts, and melanoma cells [244]. 2-Deoxy-D-glucose tetraacetate has been shown to display cytostatic and cytotoxic activity in various lines of tumoral cells. It was found to inhibit cell growth and confer chemosensitivity to cisplatin in two lines of human melanoma cells, poorly responsive to cisplatin [245]. 

The in vitro phase II trial of RA-700 employed human tumor clonogenic assay. From the results using a human tumor cell line of lung cancer (PC-6), RA-700 appears to possess time-dependent antitumor activity. The chemosensitivity rate of RA-700 was 67%, 22%, 17% and 10% for ovarian cancer, non-small cell lung cancer, breast cancer and colorectal cancer, respectively. RA-700 showed almost the same chemosensitivity as that of five standard anticancer drugs (adryamycin, mitomycin C, cisplatin, vinbrastine and 5-FU), but the spectrum of RA-700 activity appeared to be different. Furthermore, the antitumor activity of RA-700 had no relationship with prior chemotherapy. These results indicated that RA-700 is a candidate for phase I study [89]. 

The in vitro phase II trial of RA-700 was studied by human tumor clonogenic assay. From the results of a study using the human lung cancer cell line (PC-6), RA-700 appears to possess time-dependent antitumor activity. The chemosensitivity rates of RA-700 were 67, 22, 17, and 10%... 

Djojosubroto MW et al. Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma. Hepatology 2005 42 1127-1136. 

The results obtained in vivo were largely consistent with those observed in vitro and suggest that Pgp expression is determinant on the chemosensitivity of tumor cells to doxorubicin, an important cytostatic used in the treatment of osteosarcoma, and can be detected non-invasively by [ Tc]MIBI imaging. According to these results, the uptake parameter is not so robust as the washout-related parameters to evaluate the functional activity of Pgp expressed in tumors, since [ TcJMIBI is not target specific and its uptake is markedly... 

Waldenmaier, D.S., Babarina, A., and Kischkel, F.C., Rapid in vitro chemosensitivity analysis of human colon tumor cell fines, Toxicol. Appl. Pharmacol., 192,237-245,2003. 

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