Microsatellite Instabilitypredictor Of Adjuvant Treatment Response

The different tumor characteristics could be used to develop improved and more individualized chemotherapy in the future. There are promising data that MSI-H and MSS CRC respond differently to specific classes of chemotherapeutic agents. There is evidence that the effective treatment with methylating agents such as N-methyl-N'-nitro-nitrosoguanidine, N-methyl-N-nitro-sourea, and their chemotherapeutic analogs, streptozocin and temozolomide, requires functional MMR. Tumor cell lines with defective MSH2, MSH6, MLH1, or PMS2 genes as well as MSH2-deficient mouse embryonic cells are highly resistant to these drugs compared to the corresponding MMR-proficient cell lines. It is suggested that the absence of MGMT alkylated guanine will lead to incorrect incorporation of thymine into the newly synthesized strand. This mismatch will be recognized by MMR proteins, which, after a further replication round, leads to apoptosis by a not-yet-understood mechanism. This process seems to be interrupted in MSI-H tumors with inactivated MMR resulting in ''damage tolerance'' which should be considered in therapy stratification.

Another widely used chemotherapeutic drug targeting DNA is cisplatin leading to intrastrand DNA cross-links between adjacent purines and activation of DNA repair.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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