Although a large number of pharmaceutical therapies are available to treat cardiovascular diseases like heart failure, in many medical conditions treatment is still not optimal and, therefore, the need for innovative, safe and efficacious drugs is still very high in this indication. Biomarkers are an important tool in the preclinical and clinical drug development process; they allow patient selection for clinical studies as well as therapy monitoring during studies. Biomarker concepts in cardiovascular indications differ very much from those in oncology and are very diverse. The present article gives an overview of the pathomechanisms of heart failure and describes the socioeconomic impact of the disease and the biomarker strategies being applied in the development of new heart failure drugs. The focus lies on protein biomarkers that can be measured in the blood and on functional biomarkers that can be derived from implanted and wearable medical devices.
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or R/R systemic anaplastic large-cell lymphoma (sALCL) treated with brentuximab vedotin (BV) experienced high remission rates in two Phase II trials. With increased response rates and survival times, patient-reported outcomes (PROs) and health-related quality of life (HRQoL) are becoming increasingly important and can help inform treatment decisions to enhance care of cancer patients.
The objective was to qualitatively assess HRQoL in long-term survivors treated with BV.
An eight-question survey assessing PRO-related aspects was developed and fielded to a subset of patients with HL or sALCL who remained in long-term follow-up after completing BV treatment in the two pivotal studies.
The survey was completed by 25 of 38 patients (12 with HL, 13 with sALCL). The majority of patients reported that their energy level, outlook on life, difficulties with daily activities, ability to participate in physical activities, and overall HRQoL improved compared to those before BV treatment.
Small sample size and lack of a baseline questionnaire or validated assessment instrument limit broad applicability of these findings to large populations of patients with HL or sALCL.
This is the first report of BV PRO data in R/R HL and sALCL. Given the patients’ poor prognostic outcomes before stem cell transplant, these encouraging results warrant formal evaluation of PRO end points in BV trials.

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The secretion of IL-1β is a central event in the initiation of inflammation. Unlike most other cytokines, the secretion of IL-1β requires two signals: one signal to induce the intracellular up-regulation of pro-IL-1β and a second signal to drive secretion of the bioactive molecule. The release of pro-IL-1β is a complex process involving proteolytic cleavage by caspase-1. However, the exact mechanism of secretion is poorly understood. Here we sought to identify novel proteins involved in IL-1β secretion and intracellular processing to gain further insights into the mechanism of IL-1 release. A human proteome microarray containing 19,951 unique proteins was used to identify proteins that bind human recombinant pro-IL-1β. Probes with a signal-to-noise ratio of >3 were defined as biologically relevant. In these analyses, calmodulin was identified as a particularly strong hit, with a signal-to-noise ratio of ∼ 11. Using an ELISA-based protein-binding assay, the interaction of recombinant calmodulin with pro-IL-1β, but not mature IL-1β, was confirmed and shown to be calcium-dependent. Finally, using small molecule inhibitors, it was demonstrated that both calcium and calmodulin were required for nigericin-induced IL-1β secretion in THP-1 cells and primary human monocytes. Together, these data suggest that, following calcium influx into the cell, pro-IL-1β interacts with calmodulin and that this interaction is important for IL-1β processing and release.
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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The Cell Index Database, (CELLX) (View Source) provides a computational framework for integrating expression, copy number variation, mutation, compound activity, and meta data from cancer cells. CELLX provides the computational biologist a quick way to perform routine analyses as well as the means to rapidly integrate data for offline analysis. Data is accessible through a web interface which utilizes R to generate plots and perform clustering, correlations, and statistical tests for associations within and between data types for ~20,000 samples from TCGA, CCLE, Sanger, GSK, GEO, GTEx, and other public sources. We show how CELLX supports precision oncology through indications discovery, biomarker evaluation, and cell line screening analysis.

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This phase 2 study evaluated the efficacy and safety of inotuzumab ozogamicin (InO) in patients with indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab alone, rituximab plus chemotherapy or anti-CD20 radioimmunotherapy. Patients received InO 1·8 mg/m(2) intravenously on a 28-d cycle for a planned 4-8 cycles. The initial InO dose and schedule could be adjusted for tolerability and patients were allowed to receive 2 additional cycles (up to 8 total) after achieving a complete response (CR). The primary endpoint was overall response. Eighty-one patients were enrolled, among whom 48 (59%) received ≥3 InO cycles and 13 (16%) completed the treatment phase. The overall response rate was 67% (CR, 31%). Median (95% confidence interval) progression-free survival was 12·7 (8·9-26·9) months; median overall survival was not reached. Haematological adverse events (AEs) were common, particularly thrombocytopenia (74%) and neutropenia (56%). These were also the most common AEs leading to treatment discontinuation (37% and 11%, respectively); 58% of patients reported AEs leading to treatment discontinuation. InO demonstrated robust activity in these heavily pretreated patients, although treatment duration was limited by haematological toxicities. Additional studies may determine dosing regimens that allow for reduced toxicity.
© 2016 John Wiley & Sons Ltd.

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