Transcription errors induce proteotoxic stress and shorten cellular lifespan

Transcription errors occur in all living cells; however, it is unknown how these errors affect cellular health. To answer this question, we monitored yeast cells that were genetically engineered to display error-prone transcription. We discovered that these cells suffer from a profound loss in proteostasis, which sensitizes them to the expression of genes that are associated with protein-folding diseases in humans; thus, transcription errors represent a new molecular mechanism by which cells can acquire disease. We further found that the error rate of transcription increases as cells age, suggesting that transcription errors affect proteostasis particularly in aging cells. Accordingly, transcription errors accelerate the aggregation of a peptide that is implicated in Alzheimer’s disease, and shorten the lifespan of cells. These experiments reveal a novel, basic biological process that directly affects cellular health and aging

Incidence and risk factors of clinically significant chemotherapy-induced thrombocytopenia in patients with solid tumors

Purpose and relevance. Chemotherapy-induced thrombocytopenia (CIT) can be a significant problem in patients with cancer, leading to numerous clinical complications. Understanding the types of patients at risk for these complications is essential to improve monitoring, counseling, and provide future targeted prophylaxis measures. Previous studies have limited prospective utility since they do not examine risk factors associated with complications from multi-agent regimens. This evaluation aims to identify the incidence and risk factors associated with clinical complications of CIT in patients receiving common chemotherapy regimens. Methods. Retrospective evaluation of adult patients receiving first or second line regimens for the most common solid tumors associated with high rates (≥5%) of laboratory diagnosed thrombocytopenia. Patients were examined for clinically significant CIT (defined as platelet count &lt;75,000 cells/µL as well as the presence of one of the following: bleeding, dose reduction/delay, platelet transfusion, or therapy cessation) and associated risk factors. Results. About 254 patients receiving a total of 278 regimens were evaluated. The incidence of clinically significant CIT = 10.1%; complications were most common in patients receiving cisplatin/gemcitabine for bladder cancer (57%), or carboplatin/gemcitabine (29%) or cisplatin/etoposide (18%) for lung cancer. Bladder cancer (OR = 13.7 (2.89–64.7); p = 0.001) and concurrent or recent infection (OR = 3.8 (1.45–10.1); p = 0.007) was found to increase the risk of clinical complications while smoking was found to have a protective effect (OR = 0.17 (0.04–0.71)). Conclusions. The incidence of clinically significant CIT is most commonly seen in patients using cisplatin/gemcitabine for bladder cancer, or carboplatin/gemcitabine or cisplatin/etoposide for lung cancer. Further evaluation of these patients is warranted. </jats:p

Description of Current Practices of Empiric Chemotherapy Dose Adjustment in Obese Adult Patients

Medical literature is not clear on the best method to empirically dose chemotherapy in obese adult patients. This study sought to characterize current practices and identify factors affecting such decisions