Background Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. Objective Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. Data sources We searched various databases including PubMed (1946–2015), EMBASE (1947–2015), and Cochrane Central Register of Controlled Trials (1898–2015). Eligibility criteria Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. Included studies A total of 28 articles met these criteria and are summarized in this manuscript. Conclusion Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies.

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Multiple myeloma (MM) is genetically complex disease. Identification of mutations and aberrant signaling pathways that contribute to the progression of MM and drug resistance has potential to lead to specific targets and personalized treatment. Aberrant signal pathways include: RAS pathway activation due to RAS or BRAF mutations (targeted by vermurafenib alone or combined with cobimetinib), BCL2 overexpression especially in t(11:14) (targeted by venetoclax), JAK2 pathway activation (targeted by ruxolitinib), NF-kB pathway activation (treated with DANFIN

Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. After fusing with late endosomes, lysosomes are reformed from the resulting hybrid organelles through a process that involves budding of a nascent lysosome, extension of the nascent lysosome from the hybrid organelle, while remaining connected by a membrane bridge, and scission of the membrane bridge to release the newly formed lysosome. The newly formed lysosomes undergo cycles of homotypic fusion and fission reactions to form mature lysosomes. In this study, we used a forward genetic screen in Caenorhabditis elegans to identify six regulators of lysosome biology. We show that these proteins function in different steps of lysosome biology, regulating lysosome formation, lysosome fusion, and lysosome degradation.

Response to cardiovascular drugs can vary greatly between individuals, and the role of the microbiome in this variability is being increasingly appreciated. Recent evidence indicates that bacteria and other microbes are responsible for direct and indirect effects on drug efficacy and toxicity. Pharmacomicrobiomics aims to uncover variability in drug response due to microbes in the human body, which may alter drug disposition through microbial metabolism, interference by microbial metabolites, or modification of host enzymes. In this review, we present recent advances in our understanding of the interplay between microbes, host metabolism, and cardiovascular drugs. We report numerous cardiovascular drugs with evidence of, or potential for, gut-microbe interactions. However, the effects of gut microbiota on many cardiovascular drugs are yet uninvestigated. Finally, we consider potential clinical applications for the described findings.