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Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
Alexandre Chlenski, Marija Dobratic, Helen R Salwen, Mark Applebaum, Lisa J Guerrero, Ryan Miller, Gillian DeWane, Elena Solomaha, Jeremy D Marks, Susan L Cohn
SPARC is a matrix protein that mediates interactions between cells and the microenvironment. In cancer, SPARC may either promote or inhibit tumor growth depending upon the tumor type. In neuroblastoma, SPARC is expressed in the stromal Schwannian cells and functions as a tumor suppressor. Here, we developed a novel in vivo model of stroma-rich neuroblastoma using non-tumorigenic SHEP cells with modulated levels of SPARC, mixed with tumorigenic KCNR cells. Tumors with stroma-derived SPARC displayed suppressed growth, inhibited angiogenesis and increased lipid accumulation...
October 20, 2016: Oncotarget
Sheng-Ren Chen, Yi-Yu Ke, Teng-Kuang Yeh, Shu-Yu Lin, Li-Chin Ou, Shu-Chun Chen, Wan-Ting Chang, Hsiao-Fu Chang, Zih-Huei Wu, Chih-Chien Hsieh, Ping-Yee Law, Horace H Loh, Chuan Shih, Yiu-Kay Lai, Shiu-Hwa Yeh, Shau-Hua Ueng
μ-Opioid receptor (MOR) agonists are analgesics used clinically for the treatment of moderate to severe pain, but their use is associated with severe adverse effects such as respiratory depression, constipation, tolerance, dependence, and rewarding effects. In this study, we identified N-({2-[(4-bromo-2-trifluoromethoxyphenyl)sulfonyl]-1,2,3,4-tetrahydro-1-isoquinolinyl}methyl)cyclohexanecarboxamide (1) as a novel opioid receptor agonist by high-throughput screening. Structural modifications made to 1 to improve potency and blood-brain-barrier (BBB) penetration resulted in compounds 45 and 46...
September 20, 2016: European Journal of Medicinal Chemistry
Christina Cimenti, Axel Schlagenhauf, Bettina Leschnik, Elke Fröhlich-Reiterer, Hildegard Jasser-Nitsche, Harald Haidl, Elisabeth Suppan, Gudrun Weinhandl, Maximilian Leberl, Martin Borkenstein, Wolfgang E Muntean
BACKGROUND: Micro- and macrovascular diseases are frequent complications in patients with diabetes. Hypercoagulability may contribute to microvascular alterations. OBJECTIVE: In this study, we investigated whether type 1 diabetes in children is associated with a hypercoagulable state by performing a global function test of coagulation - the thrombin generation assay. SUBJECTS: 75 patients with type 1 diabetes aged between 2 and 19years were compared to an age-matched healthy control group...
October 17, 2016: Thrombosis Research
Silvia Beatriz Gorban de Lapertosa, Gustavo Frechtel, Elise Hardy, Leobardo Sauque-Reyna
AIMS: Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. METHODS: This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin...
October 8, 2016: Diabetes Research and Clinical Practice
Bin Wang, Suijun Liu, Ling Li, Qiuming Yao, Ronghua Song, Xiaoqing Shao, Qian Li, Xiaohong Shi, Jin-An Zhang
BACKGROUND: Non-thyroidal illness syndrome (NTIS) is characterized by decreased serum triiodothyronine level without increased thyroid-stimulating hormone level during critical illness. The summary data on the prevalence of NTIS in cardiovascular patients are lacking, and its prognostic role in cardiovascular patients is also unclear. METHODS: We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of NTIS in cardiovascular patients...
October 18, 2016: International Journal of Cardiology
Natalia Proskura, Joanna Podlasińska, Lidia Skopicz-Radkiewicz
: The aim of the study was to determine content of 17 elements (Co, Cd, Cu, Cr, Ni, Pb, Zn, Mn, Fe, Mg, Na, Ca, K, N, C, S and P) and their bioaccumulation factors (BCF) in bay bolete (Boletus badius (Fr.) Fr.) fruiting bodies (caps and stalks) and underneath soil samples collected from forest sites in lubuskie voivodeship in Poland. Forty-eight samples of Boletus badius (Fr.) Fr. fruiting bodies and the same number of underneath soil substrate samples were collected in forest sites of Sulęcin Forest District in western Poland...
October 21, 2016: Chemosphere
Martin Paparella, Annamaria Colacci, Miriam N Jacobs
An approach for a systematic description of the uncertainties and complexity of the standard animal testing and assessment approach for carcinogenicity is explored by using a draft OECD Guidance document that was originally developed for reporting defined in vitro approaches to testing and assessment (OECD, 2016). The format is suitable for this re-purposing and it appears that the potential multitude of approaches for integrating and interpreting data from standard animal testing may ultimately be conceptually similar to the challenge of integrating relevant in vitro and in silico data...
October 24, 2016: ALTEX
Christine Gross, Veit Wiesmann, Sebastian Millen, Martina Kalmer, Thomas Wittenberg, Jan Gettemans, Andrea K Thoma-Kress
The delta-retrovirus Human T-cell leukemia virus type 1 (HTLV-1) preferentially infects CD4+ T-cells via cell-to-cell transmission. Viruses are transmitted by polarized budding and by transfer of viral biofilms at the virological synapse (VS). Formation of the VS requires the viral Tax protein and polarization of the host cytoskeleton, however, molecular mechanisms of HTLV-1 cell-to-cell transmission remain incompletely understood. Recently, we could show Tax-dependent upregulation of the actin-bundling protein Fascin (FSCN-1) in HTLV-1-infected T-cells...
October 2016: PLoS Pathogens
Bruna Bellincanta Nicoletto, Thaiana Cirino Krolikowski, Daisy Crispim, Luis Henrique Canani
Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1...
2016: PloS One
Thanh Tam Tran, Joel Adams-Bedford, Vasoontara Yiengprugsawan, Sam-Ang Seubsman, Adrian Sleigh
INTRODUCTION: Injury and psychological distress are public health priorities because of their high occurrence in the population. This study examines the longitudinal effects of injury characteristics on psychological distress. METHODS: Study participants were enrolled distance learning Thai adults (N = 42,785 at 2013 follow-up) residing nationwide. We analysed 2009 and 2013 data. Injury questions included injury prevalence, causes and levels of severity. Distress was measured using the standard Kessler-6...
2016: PloS One
Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Doyeon Kim, You Me Sung, Jinman Park, Sukjun Kim, Jongkyu Kim, Junhee Park, Haeok Ha, Jung Yoon Bae, SoHui Kim, Daehyun Baek
The functional rules for microRNA (miRNA) targeting remain controversial despite their biological importance because only a small fraction of distinct interactions, called site types, have been examined among an astronomical number of site types that can occur between miRNAs and their target mRNAs. To systematically discover functional site types and to evaluate the contradicting rules reported previously, we used large-scale transcriptome data and statistically examined whether each of approximately 2 billion site types is enriched in differentially downregulated mRNAs responding to overexpressed miRNAs...
October 24, 2016: Nature Genetics
Dallas M Smuin, William L Hennrikus
BACKGROUND: The pucker sign, also called skin tenting, indicates significant displacement of the supracondylar fracture and can be a cause for alarm. The purpose of this study is to compare a cohort of patients with type III supracondylar fractures presenting with a pucker sign to a group without a pucker sign by evaluating neurovascular injury at presentation, need for open reduction, persistent neurovascular injury, range of motion, and carrying angle at final follow-up. METHODS: A retrospective review was performed for Gartland type III extension type supracondylar fractures...
October 21, 2016: Journal of Pediatric Orthopedics
Marianges Zadrozny Gouvêa da Costa, Júlia Glória Lucatelli Pires, Paulo Dominguez Nasser, Camila da Silva Ferreira, Ana Cristina de Sá Teixeira, Denise Cerqueira Paranaguá-Vezozzo, Dulce Reis Guarita, Flair José Carrilho, Suzane Kioko Ono
OBJECTIVE: This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. METHODS: The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. RESULTS: Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73...
October 2016: Pancreas
Friedrich Kommoss, Asma Faruqi, C Blake Gilks, Sarah Lamshang Leen, Naveena Singh, Nafisa Wilkinson, W Glenn McCluggage
We investigated the frequency, histopathologic, and immunohistochemical characteristics of tubal involvement in uterine serous carcinoma (USC) and aimed to clarify the relationship between "serous tubal intraepithelial carcinoma (STIC)" and USC in these cases. Cases of USC with complete tubal examination were prospectively collected and reviewed for the presence of tubal involvement. Immunohistochemical analysis for p53 and WT1 was performed on the endometrial and tubal tumor in cases with tubal involvement...
October 21, 2016: American Journal of Surgical Pathology
Shane Virani, Colin Russell, Megan L Bruschetta, Kevin Ngoc Hua, Brigitte M Potvin, David Cox, Stephen N Robinovitch
INTRODUCTION: Shoulder-to-head contact is the most common cause of concussions in ice hockey, accounting for 42% of cases in the National Hockey League (NHL). The goal of this project was to determine how shoulder pad stiffness, modified by adding foam padding over the shoulder cap of existing shoulder pads, affected head impact severity when participants delivered checks to an instrumented dummy. METHODS: Fifteen participants administered "the hardest shoulder checks they were comfortable delivering" to the head of a dummy equipped with tri-axial accelerometers and gyros mounted in its helmet...
October 21, 2016: Medicine and Science in Sports and Exercise
Bing Kan, Li Yang, Yan-Jun Wen, Jin-Rong Yang, Ting Niu, Jiong Li, Hong-Xin Deng, Wei Wei, Li-Gong Chen, Quan Zhang, Wei Wang, Yu-Quan Wei
Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine...
October 21, 2016: Anti-cancer Drugs
Hyungchul Park, Ji Yong Ahn, Hwoon-Yong Jung, Joo Hyun Chun, Kwangwoo Nam, Jeong Hoon Lee, Kee Wook Jung, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee, Jin-Ho Kim
BACKGROUND: Gastric bleeding is not rare and difficult to treat in gastric cancer patients. We investigated whether this affects survival and if successful bleeding control improves the prognosis. PATIENTS/MATERIAL AND METHODS: We retrospectively reviewed medical records for 64 subjects who underwent endoscopic therapy for gastric cancer bleeding at Asan Medical Center from January 2012 to December 2014 (bleeding group). Each subject was matched 1:2 by age, sex, and American Joint Committee on Cancer staging with 128 randomly selected patients treated for stomach cancer during the same period (control group)...
October 21, 2016: Journal of Clinical Gastroenterology
Sanjay K Agarwal, Dipankar Bhowmik, Sandeep Mahajan, Soumita Bagchi
INTRODUCTION: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipient (RTR). Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. METHODS: In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded...
October 24, 2016: Transplant Infectious Disease: An Official Journal of the Transplantation Society
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