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novel agents

Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Pei-Hui Wang, Sin-Yee Fung, Wei-Wei Gao, Jian-Jun Deng, Yun Cheng, Vidyanath Chaudhary, Kit-San Yuen, Ting-Hin Ho, Ching-Ping Chan, Yan Zhang, Kin-Hang Kok, Wanling Yang, Chi-Ping Chan, Dong-Yan Jin
STING is a core adaptor in innate nucleic acid sensing in mammalian cells, on which different sensing pathways converge to induce type I interferon (IFN) production. Particularly, STING is activated by 2'3'-cGAMP, a cyclic dinucleotide containing mixed phosphodiester linkages and produced by cytoplasmic DNA sensor cGAS. Here, we reported on a novel transcript isoform of STING designated STING-β that dominantly inhibits innate nucleic acid sensing. STING-β without transmembrane domains was widely expressed at low levels in various human tissues and viral induction of STING-β correlated inversely with IFN-β production...
March 14, 2018: Nucleic Acids Research
Nicole M Revie, Kali R Iyer, Nicole Robbins, Leah E Cowen
Microorganisms have a remarkable capacity to evolve resistance to antimicrobial agents, threatening the efficacy of the limited arsenal of antimicrobials and becoming a dire public health crisis. This is of particular concern for fungal pathogens, which cause devastating invasive infections with treatment options limited to only three major classes of antifungal drugs. The paucity of antifungals with clinical utility is in part due to close evolutionary relationships between these eukaryotic pathogens and their human hosts, which limits the unique targets to be exploited therapeutically...
March 12, 2018: Current Opinion in Microbiology
Lucia Panzella, Thomas Eidenberger, Alessandra Napolitano
Black sesame pigment (BSP) represents a low cost, easily accessible material of plant origin exhibiting marked antioxidant and heavy metal-binding properties with potential as a food supplement. We report herein the inhibitory properties of the potentially bioaccessible fraction of BSP following simulated gastrointestinal digestion against key enzymes involved in Alzheimer's disease (AD). HPLC analysis indicated that BSP is transformed under the pH conditions mimicking the intestinal environment and the most abundant of the released compounds was identified as vanillic acid...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Julia Robertson, Marija Gizdavic-Nikolaidis, Simon Swift
Antimicrobial surfaces can be applied to break transmission pathways in hospitals. Polyaniline (PANI) and poly(3-aminobenzoic acid) (P3ABA) are novel antimicrobial agents with potential as non-leaching additives to provide contamination resistant surfaces. The activity of PANI and P3ABA were investigated in suspension and as part of absorbent and non-absorbent surfaces. The effect of inoculum size and the presence of organic matter on surface activity was determined. PANI and P3ABA both demonstrated bactericidal activity against Escherichia coli and Staphylococcus aureus in suspension and as part of an absorbent surface...
March 16, 2018: Materials
Jane Hawkey, David B Ascher, Louise M Judd, Ryan R Wick, Xenia Kostoulias, Heather Cleland, Denis W Spelman, Alex Padiglione, Anton Y Peleg, Kathryn E Holt
Acinetobacter baumannii is a common causative agent of hospital-acquired infections and a leading cause of infection in burns patients. Carbapenem-resistant A. baumannii is considered a major public-health threat and has been identified by the World Health Organization as the top priority organism requiring new antimicrobials. The most common mechanism for carbapenem resistance in A. baumannii is via horizontal acquisition of carbapenemase genes. In this study, we sampled 20 A. baumannii isolates from a patient with extensive burns, and characterized the evolution of carbapenem resistance over a 45 day period via Illumina and Oxford Nanopore sequencing...
March 16, 2018: Microbial Genomics
Bryan Markinson, Mahmoud Ghannoum, Tate Winter, Anthony Rycerz, Fernando Rock, Aditya K Gupta
Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed...
January 2018: Journal of the American Podiatric Medical Association
Kheireddine El-Boubbou
Magnetic nanoparticles (MNPs), particularly made of iron oxides, have been extensively studied as diagnostic imaging agents and therapeutic delivery vehicles. In this review, special emphasis is set on the 'recent advancements of drug-conjugated MNPs used for therapeutic applications'. The most prevalent preparation methods and chemical functionalization strategies required for translational biomedical nanoformulations are outlined. Particular attention is, then, devoted to the tailored conjugation of drugs to the MNP carrier according to either noncovalent or covalent attachments, with advantages and drawbacks of both pathways conferred...
March 16, 2018: Nanomedicine
Paula V Monje
This chapter describes protocols to establish simplified in vitro assays of Schwann cell (SC) differentiation in the absence of neurons. The assays are based on the capacity of isolated primary SCs to increase or decrease the expression of myelination-associated genes in response to the presence or absence of cell permeable analogs of cyclic adenosine monophosphate (cAMP). No special conditions of media or substrates beyond the administration or removal of cAMP analogs are required to obtain a synchronous response on differentiation and dedifferentiation...
2018: Methods in Molecular Biology
Xin Deng, Wen Zhao, Laijun Song, Wei Ying, Xinbin Guo
Glioma is one of the most common aggressive neuroepithelial malignant tumors in the central nervous system. It has a high recurrence rate and poor prognosis, primarily due to the fact that novel therapeutic agents cannot penetrate the blood-brain barrier (BBB). Endothelial progenitor cells (EPCs) have been reported to move across the BBB and access the tumor site. However, whether EPCs expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce glioma cell apoptosis requires further investigation...
April 2018: Oncology Letters
Naira F Z Schneider, Claudia Cerella, Jin-Young Lee, Aloran Mazumder, Kyung Rok Kim, Annelise de Carvalho, Jennifer Munkert, Rodrigo M Pádua, Wolfgang Kreis, Kyu-Won Kim, Christo Christov, Mario Dicato, Hyun-Jung Kim, Byung Woo Han, Fernão C Braga, Cláudia M O Simões, Marc Diederich
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+ /K+ -ATPase α subunit, assessed by computational docking...
2018: Frontiers in Pharmacology
Ken Matsui, Makoto Ozawa, Maki Kiso, Makoto Yamashita, Toshihiko Maekawa, Minoru Kubota, Sumio Sugano, Yoshihiro Kawaoka
Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro...
March 15, 2018: Scientific Reports
Sen Xu, Zong-Yuan Yang, Ping Jin, Xin Yang, Xiaoting Li, Xiao Wei, Ya Wang, Sixiang Long, Taoran Zhang, Gang Chen, Chaoyang Sun, Ding Ma, Qinglei Gao
Ovarian cancer (OC) is a devastating disease due to its high incidence of relapse and chemoresistance. The tumor microenvironment, especially the tumor stroma compartment, was proven to contribute tremendously to the unsatisfactory chemotherapeutic efficacy in OC. Cytotoxic agents not only effect tumor cells, but also modulate the phenotype and characteristics of the vast stromal cell population, which can in turn alter the tumor cell response to chemointervention. In this study, we focused on the tumor stroma response to cytotoxic agents and the subsequent effect on the OC tumor cells...
March 15, 2018: Molecular Cancer Therapeutics
Yuh-Charn Lin, Chun-Yu Liu, Reiji Kannagi, Ruey-Bing Yang
OBJECTIVE: SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), expressed on the endothelial cell surface, functions as a novel coreceptor for VEGFR2 (vascular endothelial growth factor receptor 2) and enhances VEGF-induced signaling in adult angiogenesis. However, whether SCUBE2 plays a role in pathological angiogenesis and whether anti-SCUBE2 antibody is an effective strategy for blocking tumor angiogenesis remain unknown. The aim of this study was to investigate the pathological role and targeting therapy of SCUBE2 in tumor vasculature...
March 15, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Marina E Eremeeva, Lindsey M Weiner, Maria L Zambrano, Gregory A Dasch, Renjie Hu, Inger Vilcins, Martin B Castro, Denise L Bonilla, Kerry A Padgett
The rabbit tick, Haemaphysalis leporispalustris Packard, is known for its association with Rickettsia rickettsii as it harbors both virulent and avirulent strains of this pathogen. In this manuscript we report findings and preliminary characterization of a novel spotted fever group rickettsia (SFGR) in rabbit ticks from California, USA. Rickettsia sp. CA6269 (proposed "Candidatus Rickettsia lanei") is most related to known R. rickettsii isolates but belongs to its own well-supported branch different from those of all R...
March 1, 2018: Ticks and Tick-borne Diseases
Amarjeet Singh, Bhavana Sharma, Renu Deswal
In the present study, we report perhaps for the first time the use of novel varieties of Brassica oleracea var. botrytis and Raphanus sativus as potential bioreductant, to synthesize highly stable silver nanoparticles (AgNPs, no aggregation observed for six months), which is a significant finding as plant extract-directed AgNPs are intrinsically unstable and tend to aggregate. The reduction of Ag+ to Ag0 nanostructures was confirmed using UVVis spectroscopy showing SPR spectra at 400-435 nm. Nanosight and transmission electron microscope (TEM) analysis showed monodisperse spherical AgNPs (4-18 nm)...
May 2018: Journal of Trace Elements in Medicine and Biology
Xingxing Yuan, Bingyu Wang, Lei Yang, Yali Zhang
Hepatocellular carcinoma (HCC) is a main cause of cancer-related mortality and its etiology is not fully understood. As prominent factors that regulate cellular homeostasis, both reactive oxygen species (ROS) and autophagy are considered to play an essential role in the liver carcinogenesis. However, the crosstalk between ROS and autophagy is not well characterized in the pathogenesis of HCC. This review summarizes the roles of autophagy in ROS-mediated hepatocarcinogenesis and discusses the role of ROS-induced autophagy in HCC cell fate decision following treatment with chemotherapeutic agents in preclinical settings, which may allow the identification of novel strategies for the treatment of HCC...
March 12, 2018: Clinics and Research in Hepatology and Gastroenterology
Stefania Ferrari, Leda Severi, Cecilia Pozzi, Antonio Quotadamo, Glauco Ponterini, Lorena Losi, Gaetano Marverti, Maria Paola Costi
Human thymidylate synthase (hTS) has an important role in DNA biosynthesis, thus it is essential for cell survival. TS is involved in the folate pathways, specifically in the de novo pyrimidine biosynthesis. Structure and functions are intimately correlated, account for cellular activity and, in a broader view, with in vivo mechanisms. hTS is a target for anticancer agents, some of which are clinical drugs. The understanding of the detailed mechanism of TS inhibition by currently used drugs and of the interaction with the mechanism of action of other anticancer agents can suggest new perspective of TS inhibition able to improve the anticancer effect and to overcome drug resistance...
2018: Vitamins and Hormones
Dev R Sahni, Steven R Feldman, Sarah L Taylor
Rosacea is a chronic and recurrent disease with a variety of cutaneous manifestations. The disorder is a centrofacial inflammatory dermatosis with significant financial, physical and psychological impacts. There are a number of topical, oral and systemic treatments available. Yet, treatment for rosacea remains difficult. The multifactorial nature of the disease combined with an incomplete understanding of the pathophysiology is challenging for providers and patients. Areas covered: This article provides an in-depth review of rosacea treatment and emerging use of ivermectin 1% cream for papulopustular rosacea based on multiple clinical trials...
March 16, 2018: Expert Opinion on Pharmacotherapy
Antonio Rossi, Rebecca Tay, Jaseela Chiramel, Arsela Prelaj, Raffaele Califano
Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC. Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC. Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results...
March 15, 2018: Expert Review of Anticancer Therapy
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