The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pan-demic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, David C. Fajgenbaum and Johnson S. Khor contributed equally to this study.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer. While the localized form of this disease can be treated surgically, advanced and metastatic stages are resistant to chemotherapies. Although more innovative treatments, such as targeted or immune-based therapies, exist, the need for new therapeutic options remains. ccRCC presents unique metabolic signatures and multiple studies have reported a significant increase in levels of reduced glutathione (GSH) and its precursors in ccRCC tumor samples compared with normal kidney tissues. These observations led us to investigate the effects of blocking the GSH pathway, particularly the gamma-glutamyltransferase 1 (GGT1) enzyme, in multiple ccRCC cell lines. In this study, we provide in vitro and in vivo evidence that GGT1/GSH pathway inhibition impacts ccRCC cell growth, through increased cell-cycle arrest. Of note, GGT1 inhibition also impairs ccRCC cell migration. Finally, pharmacologic GSH pathway inhibition decreases ccRCC cell proliferation and increases sensitivity to standard chemotherapy. Our results suggest that GGT1/GSH pathway inhibition represents a new strategy to overcome ccRCC chemoresistance. Implications: GGT1/GSH pathway inhibition represents a promising therapeutic strategy to overcome chemoresistance and inhibit progression of ccRCC tumors.
High quality comprehensive care for SCD can be delivered for a low income, aboriginal population in India through a community driven network of care. This model can serve as a template for healthcare delivery for SCD in low-income communities.
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