The Journal of urology
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DNA mismatch repair is one of the correcting mechanisms that preserves genetic stability during replication or chemically induced damage. We hypothesized that genetic instability is due to a defect in mismatch repair genes in renal cell carcinoma. To test this hypothesis mismatch repair genes hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2 were analyzed in renal cell carcinoma cell lines and tissues. We further investigated the mechanisms of inactivation of these genes through CpG methylation pathways. ⋯ To our knowledge this is the first comprehensive study demonstrating the down-regulation of mismatch repair genes in renal cell carcinoma. Selective defect in some mismatch repair genes can cause genomic instability and activate the malignant transformation as well as the progression of renal cell carcinoma.
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The Journal of urology · Jun 2003
The urinary response to an oral oxalate load in recurrent calcium stone formers.
Dietary oxalate may contribute up to 50% to 80% of the oxalate excreted in urine. We studied the urinary response to an oral oxalate load in male and female idiopathic recurrent calcium oxalate stone formers with and without mild hyperoxaluria to evaluate the potential pathophysiological significance of dietary oxalate. ⋯ Recurrent calcium stone formers with mild hyperoxaluria have higher fasting urinary oxalate and an exaggerated urinary response to an oral oxalate load compared with recurrent calcium stone formers with normal urinary oxalate excretion. Men and women stone formers without hyperoxaluria excrete similar fractions of an oral oxalate load. Increased gastrointestinal absorption and renal excretion of dietary oxalate may be a significant pathophysiological mechanism of stone formation in patients with mild hyperoxaluria.
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The Journal of urology · Jun 2003
Modifying the American Society for Therapeutic Radiology and Oncology definition of biochemical failure to minimize the influence of backdating in patients with prostate cancer treated with 3-dimensional conformal radiation therapy alone.
Adoption of the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition has been critical for evaluating and comparing outcome following treatment with radiation. However, since its almost universal adoption, several points have remained controversial, notably backdating the date of failure to the point midway between the posttreatment prostate specific antigen (PSA) nadir and the first increase. We evaluated the impact of backdating on no biochemical evidence of disease (bNED) control and suggest changes in the definition. ⋯ Adoption of the ASTRO consensus definition has been crucial for evaluating outcome in the radiation oncology community. However, the date of failure should be moved from the current point to one closer to the point at which failure is declared. Additional analysis with large numbers of patients from multiple institutions is necessary to determine the point.