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Asciminib, a Specific Allosteric BCR-ABL1 Inhibitor, in Patients with Chronic Myeloid Leukemia Carrying the T315I Mutation in a Phase 1 Trial
We report results from the largest cohort: pts with confirmed T315I mut at screening (tested locally by Sanger sequencing) and treated with asciminib 200 mg BID, which showed the most robust efficacy (data cutoff: April 30, 2018).At the data cutoff, treatment was ongoing in 23/24 pts (95.8%) (Table); 1 pt (4.2%) had ended treatment. Median duration of follow-up and asciminib exposure were both 28.5 wk (range, 0.1-74.7 wk). Most pts had received multiple prior TKIs, and PON was the most recent TKI for 12/24 (50.0%). Pts who were PON naive had underlying conditions, such as CV risk factors. Eight of 24 pts achieved MMR by 24...
Source: Blood - November 21, 2018 Category: Hematology Authors: Rea, D., Lang, F., Kim, D.-W., Cortes, J. E., Hughes, T. P., Minami, H., Breccia, M., Deangelo, D. J., Hochhaus, A., Talpaz, M., Goh, Y. T., le Coutre, P., Deininger, M. W., Etienne, G., Sondhi, M., Mishra, K., Aimone, P., Ng-Sikorski, J., Mauro, M. J. Tags: 632. Chronic Myeloid Leukemia: Therapy: TFR Failure, Resistance, and New Drug Development Source Type: research

6-Bromoindirubin-3 ′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver
In this study, we aimed to investigate the anti-aging effect, and molecular mechanism, of the novel anti-aging drug 6BIO on naturally aged mouse liver. Rapamycin, a well-known promising anti-aging drug that delays aging through mTOR-dependent autophagy (Zhou and Ye, 2018), was used as the positive control in the study. To our knowledge, this is the first study to demonstrate the effects of 6BIO treatment in models of natural aging. Our results indicated that 6BIO ameliorates the decline of liver function with age, including lipid metabolism disorder, and attenuates hepatocyte senescence in aged mice, as revealed by altera...
Source: Frontiers in Pharmacology - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Neuroimmunology of Human T-Lymphotropic Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis
Conclusion Recent advances in research on HTLV-1 provide better understanding of the molecular pathogenesis and mechanisms of HAM/TSP, and several clinical trials of novel therapies for patients with HAM/TSP have been initiated. However, long-term improvement of motor disability and quality of life still have not been achieved in HAM/TSP patients, and the clinical management remains challenging. Given that HAM/TSP is characterized by activated T-cells in both the periphery and CNS, studies in HAM/TSP will be highly informative for clarifying the pathogenesis of other neuroinflammatory disorders such as multiple sclerosis....
Source: Frontiers in Microbiology - April 23, 2019 Category: Microbiology Source Type: research

NAMPT as a Dedifferentiation-Inducer Gene: NAD+ as Core Axis for Glioma Cancer Stem-Like Cells Maintenance
Conclusion and Perspectives Gliomas are the most prevalent primary brain cancer in adults and include a broad category of tumors including astrocytoma, oligodendroglioma, and GBM. Regardless of tumor aggressiveness, malignancy, and infiltration, these glia-derived tumors rarely exceed a median survival time of 12–14 months. Driven by the infiltrative nature of these tumors, the clinical approach is difficult and relapses often occur with fatal consequences. These unsuccessful attempts to control glioma's fate have fostered research looking for more effective therapies. (GSCs) are a small subset of CD133&#...
Source: Frontiers in Oncology - May 2, 2019 Category: Cancer & Oncology Source Type: research

Sex Difference of Radiation Response in Occupational and Accidental Exposure
Conclusion and Outlook This review summarizes the data from major human studies on the health risks of radiation exposure and shows that sex can potentially influence the prolonged response to radiation exposure (Figure 1 and Tables 1, 2). These data suggest that long-term radiosensitivity in females is higher than that in males who receive a comparable dose of radiation. Our analysis of the literature agrees with the conclusions of the recent report on the Biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences (NAS), United States (National Research Council, 2006). The B...
Source: Frontiers in Genetics - May 2, 2019 Category: Genetics & Stem Cells Source Type: research