Mismatch repair deficiency

Martin SA, Hewish M, Sims D et al (2011) Parallel high-throughput RNA interference screens identify PINKl as a potential therapeutic target for the treatment of DNA mismatch repair-deficient cancers. Cancer Res 71 1836-1848... 

Wei SC, Lin YS, Tsao PN, Wu-Tsai JJ, Wu CH, Wong JM. 2004. Comparison of the anti-proliferation and apoptosis-induction activities of sulindac, celecoxib, curcumin, and nifedipine in mismatch repair-deficient cell lines. J Formos Med Assoc 103 599-606. 

Metallointercalators that selectively and efficiently target single base mismatches have found several applications both as biologic probes and as potential chemotherapeutic agents. For instance, [Rh(bpy)2phzi] + was used to probe the relative frequency of mismatched sites in cell lines deficient versus proficient in their mismatch repair machinery (18). The relative cleavage observed with the phzi complex in healthy cell lines was low compared with that in cancer cell lines that carried mutations in essential repair proteins. These results support previous studies on the association of mismatch repair deficiency and cancer. 

Koi, M., Umar, A., Chauhan, D. P., Cherian, S. P., and Carethers, J. M., (1994) Human chromosome 3 corrects mismatch repair deficiency and reduces N-methyl-N -nitro-iV-nitrosoguanidine tolerance in colon tumor cells with homozygous hMLHl mutation. Cancer Res. 54,4308 4312. 

Drummond, J. T., Anthoney, A., Brown, R., and Modrich, P. (1996) Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line. J. Biol. Chem. 16, 19,645-19,648. 

It has long been considered that genetic instability is an integral component of human neoplasia. In a small fraction of tumors, mismatch repair deficiency leads to a microsateUite instability at the nucleotide sequence level. In other tumors, an abnormal chromosome number (aneuploidy) has suggested an instability. 

The model predicts that RER+ tumor initiation depends both on X (number of mitoses of the stem cell with mismatch repair deficiency) and on N... 

Lai et al. " note that the DNA mismatch-repair-deficient Min mouse model (Apc+/-Msh2-/-) has genetic features of both FAP and HNPCC and, most importantly, rapidly develops numerous small and large bowel adenomas as well as colonic aberrant ciypt foci. They investigated the effects of COX inhibitors on intestinal adenomas and colonic aberrant crypt foci in this accelerated-polyposis, mismatch-repair-deficient Min mouse model, in addition to a standard Min mouse model. Their smdy demonstrated that a specific COX-2 inhibitor is effective in preventing small-bowel polyps in mismatch-lepair-deficient Min mice and both small- and large-bowel polyps in standard Min mice. 

Liu 1, Taverna P, Whitacre CM et al. Pharmacological disruption of base excision repair sensitizes mismatch repair-deficient and -proficient colon cancer cells to methylating agents. Clin Cancer Res 1999 5 2908-2917. 

Curtin NJ, Wang L-Z, Yiakouvaki A et aL Novel PARP-1 inhibitor, AG 14361, restores sensitivity to temozolomide in mismatch repair deficient cells. Clin Cancer Res 2004 10 881-889. 

Mcllhatton, M.A., Tyler, J., Burkholder, S., Ruschoff, J., Rigas, B., Kopelovich, L., and Fishel, R. (2007). Nitric oxide-donating aspirin derivatives suppress microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells. Cancer Res. 67, 10966-10975. 

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