On April 8, 2016 Delcath Systems, Inc. (NASDAQ: DCTH), a specialty pharmaceutical and medical device company focused on the treatment of primary and metastatic liver cancers, reported that the Hacettepe University Clinic in Ankara, Turkey has been activated as a treatment center for the Delcath Hepatic CHEMOSAT Delivery System (CHEMOSAT) for the treatment of cancers of the liver (Press release, Delcath Systems, APR 8, 2016, View Source;p=RssLanding&cat=news&id=2155549 [SID:1234510558]). Hacettepe University Clinic successfully completed its first CHEMOSAT treatments in March, and the center represents the first CHEMOSAT commercial location to be activated outside of the European Union.

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"We are especially pleased to be expanding access to CHEMOSAT to benefit the thousands of patients in Turkey suffering with these life-threatening cancers of the liver for which there are limited treatment options," said Dr. Jennifer K. Simpson, Ph.D., MSN, CRNP, President and Chief Executive Office of Delcath. "With its high level of clinical expertise, we believe that Hacettepe University can serve as an important hub for CHEMOSAT treatment to patients in Turkey and throughout the region. We are selectively evaluating other markets in the wider European region in order to continue our geographic expansion and the steady growth in clinical adoption of CHEMOSAT as a treatment for patients with cancers of the liver."

The design of efficacious and cost-effective therapeutic vaccines against cancer remains both a research priority and a challenge. For more than a decade, our laboratory has been involved in the development of synthetic peptide-based anti-cancer therapeutic vaccines. We first dedicated our efforts in the identification and validation of peptide epitopes for both CD8 and CD4 T cells from tumor-associated antigens (TAAs). Because of suboptimal immune responses and lack of therapeutic benefit of peptide vaccines containing these epitopes, we have focused our recent efforts in optimizing peptide vaccinations in mouse tumor models using numerous TAA epitopes. In this focused research review, we describe how after taking lessons from the immune system’s way of dealing with acute viral infections, we have designed peptide vaccination strategies capable of generating very high numbers of therapeutically effective CD8 T cells. We also discuss some of the remaining challenges to translate these findings into the clinical setting.

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Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal cancers, in part, due to resistance to both conventional and targeted therapeutics. Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) directly induces apoptosis through engagement of cell surface Death Receptors (DR4 and DR5), and has been explored as a molecular target for cancer treatment. Clinical trials with recombinant TRAIL and DR-targeting agents, however, have failed to show overall positive outcomes. Herein,we identify a novel TRAIL resistance mechanism governed by Hu antigen R (HuR, ELAV1), a stress-response protein abundant and functional in PDA cells. Exogenous HuR overexpression in TRAIL-sensitive PDA cell lines increases TRAIL resistance whereas silencing HuR in TRAIL-resistant PDA cells, by siRNA oligo-transfection, decreases TRAIL resistance. PDA cell exposure to soluble TRAIL induces HuR translocation from the nucleus to the cytoplasm. Furthermore, it is demonstrated that HuR interacts with the 3′-untranslated region (UTR) of DR4 mRNA. Pre-treatment of PDA cells with MS-444 (Novartis), an established small molecule inhibitor of HuR, substantially increased DR4 and DR5 cell surface levels and enhanced TRAIL sensitivity, further validating HuR’s role in affecting TRAIL apoptotic-resistance. NanoString{trade mark, serif} analyses on the transcriptome of TRAIL-exposed PDA cells identified global HuR-mediated increases in anti-apoptotic processes. Taken together, these data extend HuR’s role as a key regulator of TRAIL-induced apoptosis.
Discovery of an important new HuR-mediated TRAIL resistance mechanism suggests that tumor-targeted HuR inhibition increases sensitivity to TRAILPage-based therapeutics and supports their re-evaluation as an effective treatment for PDA patients.
Copyright ©2016, American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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To assess real-world use of everolimus in the treatment of hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic-breast-cancer (mBC).
Postmenopausal women with HR+/HER2- mBC who initiated a new therapy for mBC between July 20, 2012 and March 31, 2014 after a non-steroidal-aromatase-inhibitor were identified from two commercial claims databases. Multivariate logistic regressions were used to identify factors associated with everolimus use versus endocrine-monotherapy or chemotherapy. Dosing patterns and adherence to everolimus were summarized.
A total of 940 everolimus, 6,134 endocrine-monotherapy, and 3,410 chemotherapy regimens were included across patients’ first four lines of therapy. Patients with bone and visceral metastases were more likely to use everolimus versus endocrine-monotherapy. Patients with more comorbidities, visceral or central-nervous-system metastases, and prior chemotherapy use for mBC were less likely to use everolimus versus chemotherapy. Approximately 80% of patients initiated everolimus at label-recommended-dose of 10mg daily; 60-70% of patients had a medical possession ratio >0.8 to everolimus, and consistently high adherence was observed across lines of therapy.
For HR+/HER2- mBC, patients treated with everolimus had more severe disease than patients treated with endocrine-monotherapy but less severe disease than patients treated with chemotherapy. Most patients used everolimus according to label-recommended-dose and adherence was high across lines of therapy.

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In recent years, biodistribution analyses of pharmaceutical compounds in preclinical animal models have become an integral part of drug development. Here we report on the use of optical imaging biodistribution analyses in a mouse xenograft model to identify tissues that nonspecifically retained a bispecific antibody under development. Although our bispecific antibody bound both the epidermal growth factor receptor and insulin growth factor 1 receptor are expressed on H358, nonsmall-cell lung carcinoma cells, the fluorescence from labeled bispecific antibody was less intense than expected in xenografted tumors. Imaging analyses of live mice and major organs revealed that the majority of the Alexa Fluor 750 labeled bispecific antibody was sequestered in the liver within 2 h of injection. However, results varied depending on which near-infrared fluorophore was used, and fluorescence from the livers of mice injected with bispecific antibody labeled with Alexa Fluor 680 was less pronounced than those labeled with Alexa Fluor 750. The tissue distribution of control antibodies remained unaffected by label and suggests that the retention of fluorophores in the liver may differ. Given these precautions, these results support the incorporation of optical imaging biodistribution analyses in biotherapeutic development strategies.

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