The present global, open-label, single-arm, multicenter, phase IIb study was designed to determine the efficacy and tolerability of oral vorinostat combined with standard doses of bortezomib in patients with multiple myeloma considered refractory to novel myeloma agents.
Eligible patients were age ≥ 18 years, had received ≥ 2 previous regimens, had disease refractory to ≥ 1 previous bortezomib-containing regimen, and had received ≥ 1 dose of an immunomodulatory drug (thalidomide or lenalidomide)-based regimen. The patients received 21-day cycles of bortezomib (1.3 mg/m(2) intravenously on days 1, 4, 8, and 11) plus oral vorinostat (400 mg/d on days 1-14). Oral dexamethasone, 20 mg, on the day of and the day after each dose of bortezomib could be added for patients with progressive disease after 2 cycles or no change after 4 cycles. The primary endpoint was the objective response rate.
The objective response rate was 11.3% (95% confidence interval, 6.6%-17.7%), and the median duration of response was 211 days (range, 64-550 days). The median overall survival duration was 11.2 months (95% confidence interval, 8.5-14.4 months), with a 2-year survival rate of 32%. The frequently reported adverse events were thrombocytopenia (69.7%), nausea (57.0%), diarrhea (53.5%), anemia (52.1%), and fatigue (48.6%); the overall safety profile was consistent with that of bortezomib and vorinostat.
The combination of vorinostat and bortezomib is active in patients with multiple myeloma refractory to novel treatment modalities and offers a new therapeutic option for this difficult-to-treat patient population (ClinicalTrials.gov identifier, NCT00773838).
Copyright © 2016 Elsevier Inc. All rights reserved.

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Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA’s anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1α, IL-1β, tumor necrosis factor-α, IFN-β, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-κB and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.
© The Author 2016. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

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On March 31, 2016 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported positive preclinical findings generated using the Company’s Immune Repertoire Capture technology, presented at the Gordon Research Conference: Antibody Biology & Engineering, which took place in Galveston, TX, March 20-25, 2016 (Press release, Atreca, MAR 31, 2016, View Source [SID1234522967]). In a poster titled, "Protective Anti-Malarial Human Antibodies identified from P. falciparum CSP Immunized Kymice using Immune Repertoire Capture (IRC)", a research team including scientists at Atreca and collaborators at leading institutions reported key preclinical research findings, including:

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Atreca’s Immune Repertoire Capture technology applied in combination with Kymab’s Kymice, an Ig-gene humanized mouse platform, identified and generated potent antibodies comprised of human variable genes.
•Atreca identified diverse lineages (or families) of antibodies that bind to a key target, the circumsporozoite protein (CSP) of P. falciparum. Two of these lineages provided potent protection in an in vivo malaria-challenge model, resulting in >99% reduction of liver-stage parasite load.
Daniel Emerling, Ph.D., Atreca’s Senior Vice President, Research, stated, "IRC enabled identification of multiple lineages containing potent, anti-malarial human antibodies generated by activated mouse B cells. The diversified antibody library that we generated had a high hit rate of binding against the CSP target (34%). Our analyses also provide the foundation for understanding structure-activity relationships that mediate the binding of the antibodies that are efficacious in vivo. Furthermore, we have identified many other antibody sequences in these and other lineages that are highly similar to the efficacious antibodies and may therefore also be active in vivo."

Dr. Emerling continued, "We are grateful to both the Bill & Melinda Gates Foundation and the PATH Malaria Vaccine Initiative for supporting this critical research."

"These results disclosed at the Gordon Conference demonstrate the ability of Atreca’s Immune Repertoire Capture technology to generate novel antibodies with high in vivo potency from immune responses, as well as multiple lineages containing such antibodies," commented Tito A. Serafini, Ph.D., Atreca’s President, Chief Executive Officer, and Co-Founder. "While our primary focus continues to be on cancer immunotherapy, our IRC technology allows us to mine the key phenomenon driving efficacious immune responses in humans and animals in diverse disease settings, including infectious and autoimmune diseases."

Atreca recently reported use of its Immune Repertoire Capture technology to analyze the successful anti-tumor responses in individuals with non-progressing lung adenocarcinoma. Based on this and related research, select antibodies discovered by Atreca have progressed to preclinical testing in in vivo models of cancer, with the goal of selecting candidates to enter into more advanced preclinical studies.

Transcriptional activation of telomerase reverse transcriptase (TERT) gene is a rate-limiting determinant in the reactivation of telomerase expression in cancers. TERT promoter mutations represent one of the fundamental mechanisms of TERT reactivation in cancer development. We review recent studies that elucidate the molecular mechanisms underscoring activation of mutant TERT promoters.

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On March 31, 2016 Celator Pharmaceuticals, Inc. (Nasdaq: CPXX) reported that data for VYXEOS (cytarabine:daunorubicin) Liposome for Injection (also known as CPX-351), its lead product candidate, will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA, April 16-20, 2016 (Press release, Celator Pharmaceuticals, MAR 31, 2016, View Source [SID:1234510229]).

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The research was conducted in the laboratory of Dr. Jeffrey Tyner at Oregon Health & Science University. The objective of the research was to examine the ex vivo sensitivity of acute myeloid leukemia (AML) cells derived from newly diagnosed patients to VYXEOS. This work supports the observed clinical benefit of VYXEOS in high-risk AML patients and may provide a means of identifying patient genotypes/phenotypes most sensitive to VYXEOS.

"We continue to learn more about the unique activity of VYXEOS in AML and enhance our ability to match this performance with specific patient characteristics that could be predictive of improved outcomes," said Lawrence Mayer, Ph.D., President and Chief Scientific Officer at Celator. "The research being undertaken by Dr. Tyner reflects Celator’s goal to elucidate the clinical benefits of VYXEOS by expanding our scientific understanding of its mechanism of action, particularly in AML cells with important molecular phenotypes."

Details on the AACR (Free AACR Whitepaper) poster presentation:

Presentation Title:
CPX-351 cytotoxicity against fresh AML blasts is increased for FLT3-ITD+ cells and correlates with drug uptake and clinical outcomes
Date/Time:
Sunday, April 17, 2016 – 1:00pm-5:00pm
Session Category:
Poster Presentation
Session Title:
ET01-03, Combination Chemotherapy
Location:
New Orleans Convention Center, Halls G-J Poster Section 15
Abstract Number:
287

The poster will be available on Celator’s website (www.celatorpharma.com) at the conclusion of the AACR (Free AACR Whitepaper) meeting.