Loss of mismatch repair (MMR) leads to a complex mutator phenotype that appears to drive the development of a subset of colon cancers. Here we show that MMR-deficient tumour cell lines are highly sensitive to the toxic effects of thymidine relative to MMR-proficient lines. This sensitivity was not a direct consequence of MMR deficiency or alterations of DNA precursor metabolism. Instead, MMR-de...

We have reported that transfer of chromosome 3 (Chr3) containing a single wild-type copy of the hMLH1 gene into HCT116 colon cancer cells, a cell line deficient in DNA mismatch repair (MMR) activity attributable to inactivating hMLH1 mutations, corrects all of the aspects of the MMR repair-deficient phenotype. We inhibited the expression of the wild-type hMLH1 gene using antisense RNA in HCT116...

Loss of expression of mismatch repair (MMR) proteins leads to resistance of tumor cells to a variety of DNA-damaging agents, including bifunctional alkylating and monofunctional methylating agents such as cis-diaminedichloroplatinum II (CDDP) and N'-methyl-N-nitrosourea (MNU). It has been suggested that coupling to cell death does not occur in the absence of MMR, but instead, DNA lesions are by...

The human colon tumor cell line HCT116 is deficient in wild-type liMIJII. is defective in mismatch repair (MMR), exhibits microsatellite instability, and is tolerant to JV-methylWV'-nitro-JV-nitrosoguanidine (MNNG). Transferring a normal copy of li.MI.III on chromosome 3 into the cell line restores MMR activity, stabilizes microsatellite loci, and increases the sensitivity of the cell to MNNG. ...

Loss of DNA mismatch repair (MMR) causes genomic instability by markedly increasing the frequency of sporadic mutations in both coding and noncoding sequences. Little is known about how loss of MMR affects sensitivity to the mutagenic effect of chemotherapeutic agents. We wanted to determine how loss of MMR affects the ability of cisplatin, a known mutagen, to generate human tumor cell variants...

wnloaded DNA mismatch repair (MMR) system provides critical genetic housekeeping, and its failure is ased with tumorigenesis. Through distinct domains on the DNA MMR proteins, the system recognizes pairs errors occurring during DNA synthesis, but signals apoptosis when the DNA damage cannot aired. Certain missense mutations in the MMR genes can selectively alter just one of these functions. ffe...

BACKGROUND We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens Biograph mMR PET/MR system. We perform regular cross-calibrations (Xcal) of our PET systems, including the PET/MR, using a Siemens mCT water phantom. LONG-TERM STABILITY The mMR calibration stability was evaluated over a 3-year period whe...

In countries where routine varicella vaccination is implemented, it is usually given at the same age as that recommended for measles-mumps-rubella (MMR) vaccination. A combined multivalent measles-mumps-rubella-varicella (MMRV) vaccine would offer the convenience of a single injection and facilitate implementation of varicella vaccination into routine childhood immunisation schedules. We evalua...

We have reported that transfer of chromosome 3 (Chr3) containing a single wild-type copy of the hMLH1 gene into HCT116 colon cancer cells, a cell line deficient in DNA mismatch repair (MMR) activity attributable to inactivating hMLH1 mutations, corrects all of the aspects of the MMR repair-deficient phenotype. We inhibited the expression of the wild-type hMLH1 gene using antisense RNA in HCT116...

We have reported that transfer of chromosome 3 (Chr3) containing a single wild-type copy of the hMLH1 gene into HCT116 colon cancer cells, a cell line deficient in DNA mismatch repair (MMR) activity attributable to inactivating hMLH1 mutations, corrects all of the aspects of the MMR repair-deficient phenotype. We inhibited the expression of the wild-type hMLH1 gene using antisense RNA in HCT116...