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Most cancer cells overexpress the anti-apoptotic protein survivin and display redox dysregulation originating from genotypic and phenotypic alterations. These disturbances contribute to the uncontrolled proliferation, invasion, and chemoresistance of cancer cells, yet they also represent a specific vulnerability that could be exploited therapeutically in selected tumors. YM155 (sepantronium bromide) is a naphthoquinone-containing imidazolebased compound that selectively inhibits survivin expression at the transcriptional and post-transcriptional levels. Here, we performed a systematic review and meta-analysis of clinical studies in which YM155 was administered as monotherapy or combination therapy for patients with cancer. We assessed fully or partially reported clinical outcomes and pharmacological parameters, and further performed subgroup analysis based on tumor type and treatment regimen. Our comprehensive analysis, which included patients of many ethnicities, demonstrated that YM155 was effective as a monotherapy or combination therapy. Clinical benefits, including regression and/or stabilization of tumor progression and prolonged survival, were observed within a reasonable time after treatment initiation, and YM155 displayed good synergistic effects with combination drugs. YM155 appears to be effective against a wide range of tumor types and has an acceptable safety profile, with the main toxicities being decreased blood cell counts; fatigue/weakness; renal, hepatic, and/or cardiac issues; and electrolyte disturbance. [ABSTRACT FROM AUTHOR]

Background/Aim: We have recently shown that oral recombinant methionase (o-rMETase) prevents obesity and diabetes onset in mice on a high-fat (HF) diet. The present study aimed to determine if o-rMETase can inhibit the onset of nonalcoholic fatty liver disease (NAFLD) onset in mice on a high-fat diet. Materials and Methods: Male C57BL/6J mice in the control group were fed a normal-fat diet (NFD) (+6.5% fat), and other mice were fed a high-fat (HF) diet (+34.3% fat). Then, the mice on the HF diet were divided into two dietary groups: i) HF+phosphate buffered saline (PBS) group, and ii) HF+o-rMETase group. Result: The fatty change score in the livers of mice treated with HF+PBS increased to an average of 2.6 during the experimental period of 8 weeks. In contrast, the fatty change in the livers of mice on the HF+o-rMETase group had an average score of 0.92 (p=0.04, HF+PBS vs HF+o-rMETase). Conclusion: o-rMETase inhibited the onset of NAFLD as well as prevented obesity and the onset of diabetes on a high-fat diet, offering a possibility of a new paradigm to prevent liver cirrhosis or liver cancer via NAFLD. [ABSTRACT FROM AUTHOR]