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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/28427434/adenovirus-mediated-cd40l-gene-transfer-increases-teffector-tregulatory-cell-ratio-and-upregulates-death-receptors-in-metastatic-melanoma-patients
#1
A Schiza, J Wenthe, S Mangsbo, E Eriksson, Anders Nilsson, T H Tötterman, A Loskog, G Ullenhag
BACKGROUND AND AIMS: Malignant melanoma is an aggressive tumor sensitive for immunotherapy such as checkpoint blockade antibodies. Still, most patients with late stage disease do not respond, and the side effects can be severe. Stimulation of the CD40 pathway to initiate anti-tumor immunity is a promising alternative. Herein, we demonstrate immune profiling data from melanoma patients treated with an adenovirus-based CD40 ligand gene therapy (AdCD40L). METHODS: Peripheral blood mononuclear cells and plasma were collected from malignant melanoma patients (n = 15) enrolled in a phase I/IIa study investigating intratumoral delivery of AdCD40L with or without low dose cyclophosphamide...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28427417/novel-trigenic-cacna1c-des-mypn-mutations-in-a-family-of-hypertrophic-cardiomyopathy-with-early-repolarization-and-short-qt-syndrome
#2
Yanhong Chen, Hector Barajas-Martinez, Dongxiao Zhu, Xihui Wang, Chonghao Chen, Ruijuan Zhuang, Jingjing Shi, Xueming Wu, Yijia Tao, Weidong Jin, Xiaoyan Wang, Dan Hu
BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients with early repolarization (ER) pattern are at higher risk of ventricular arrhythmia, yet the genetic background of this situation has not been well investigated. Here we report novel trigenic mutations detected in a Chinese family of obstructive HCM with ER and short QT syndrome (SQTS). METHODS: Proband and family members underwent detailed medical assessments. DNAs were extracted from peripheral blood leukocytes for genetic screening with next generation method...
April 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28410599/the-role-of-vitamin-c-in-the-treatment-of-pain-new-insights
#3
REVIEW
Anitra C Carr, Cate McCall
The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms...
April 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28399937/specific-circulating-microrna-signature-of-bicuspid-aortic-valve-disease
#4
Neus Martínez-Micaelo, Raúl Beltrán-Debón, Isabel Baiges, Marta Faiges, Josep M Alegret
BACKGROUND: We aimed to determine the circulating miRNA expression profile associated with BAV and aortic dilation to provide diagnostic and prognostic biomarkers for BAV and/or aortic dilation. METHODS AND RESULTS: We applied a miRNome-wide microarray approach using plasma samples (n = 24) from healthy tricuspid aortic valve individuals, BAV patients and BAV patients with aortic dilation to compare and identify the specific miRNAs associated with BAV and aortic dilation...
April 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28399886/levels-of-hepatic-th17-cells-and-regulatory-t-cells-upregulated-by-hepatic-stellate-cells-in-advanced-hbv-related-liver-fibrosis
#5
Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao
BACKGROUND: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. METHODS: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University...
April 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28390420/partnering-with-patients-in-translational-oncology-research-ethical-approach
#6
Marie-France Mamzer, Nathalie Duchange, Darquy Sylviane, Patrice Marvanne, Claude Rambaud, Giovanna Marsico, Catherine Cerisey, Florian Scotté, Anita Burgun, Cécile Badoual, Pierre Laurent-Puig, Christian Hervé
BACKGROUND: The research program CARPEM (cancer research and personalized medicine) brings together the expertise of researchers and hospital-based oncologists to develop translational research in the context of personalized or "precision" medicine for cancer. There is recognition that patient involvement can help to take into account their needs and priorities in the development of this emerging practice but there is currently no consensus about how this can be achieved. In this study, we developed an empirical ethical research action aiming to improve patient representatives' involvement in the development of the translational research program together with health professionals...
April 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28388917/influence-of-diet-on-the-gut-microbiome-and-implications-for-human-health
#7
REVIEW
Rasnik K Singh, Hsin-Wen Chang, Di Yan, Kristina M Lee, Derya Ucmak, Kirsten Wong, Michael Abrouk, Benjamin Farahnik, Mio Nakamura, Tian Hao Zhu, Tina Bhutani, Wilson Liao
Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet...
April 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28385150/combination-of-serum-histidine-and-plasma-tryptophan-as-a-potential-biomarker-to-detect-clear-cell-renal-cell-carcinoma
#8
Hyung-Ok Lee, Robert G Uzzo, Debra Kister, Warren D Kruger
BACKGROUND: In previous work, we showed that serum-free amino acid (SFAA) profiles were different between kidney cancer patients and age and sex matched controls. The goals of the current study are to: (1) confirm our initial observation on an independent sample set; (2) examine if there were similar differences in plasma-free amino acids (PFAA); and (3) determine if removal of tumors changed SFAA and PFAA profiles. METHODS: SFAA and PFAA profiles were measured in 484 samples taken from 124 healthy controls and 56 clear cell renal cell carcinoma (ccRCC) patients both before and after resection of renal tumors...
April 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28381281/association-of-atrial-fibrillation-susceptibility-genes-atrial-fibrillation-phenotypes-and-response-to-catheter-ablation-a-gene-based-analysis-of-gwas-data
#9
Daniela Husser, Petra Büttner, Laura Ueberham, Borislav Dinov, Philipp Sommer, Arash Arya, Gerhard Hindricks, Andreas Bollmann
BACKGROUND: Previous studies have suggested PITX2, KCNN3 and ZFHX3 as atrial fibrillation (AF) susceptibility genes. Single common genetic polymorphisms of those genes have been linked with AF phenotypes and rhythm outcome of AF catheter ablation although their mechanisms remain elusive. New gene-based association tests may help clarifying genotype-phenotype correlations. Therefore, we hypothesized that PITX2, KCNN3 and ZFHX3 associate with left atrial enlargement and persistent AF and subsequently with ablation outcome...
April 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28381232/detection-of-newly-produced-t-and-b-lymphocytes-by-digital-pcr-in-blood-stored-dry-on-nylon-flocked-swabs
#10
Marion Vaglio Tessitore, Alessandra Sottini, Aldo M Roccaro, Claudia Ghidini, Simona Bernardi, Giovanni Martellosio, Federico Serana, Luisa Imberti
BACKGROUND: A normal number of T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) is considered a biomarker for adequate new T- and B-cell production. In newborns, detection of TRECs and KRECs by real time PCR from dried blood spotted on filter paper is used for the screening of severe immunodeficiency. In adults, elderly and during diseases, where the number of TRECs is lower than in newborns and children, a large amount of DNA and a sensitive method of amplification are necessary to identify newly produced lymphocytes...
April 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28372590/proteomic-analysis-of-protein-purified-derivative-of-mycobacterium-bovis
#11
Sante Roperto, Mariaconcetta Varano, Valeria Russo, Roberta Lucà, Monica Cagiola, Marco Gaspari, Dora Maria Ceccarelli, Giovanni Cuda, Franco Roperto
BACKGROUND: Tuberculin skin test based on in vivo intradermal inoculation of purified protein derivative from Mycobacterium bovis (bPPD) is the diagnostic test for the control and surveillance of bovine tuberculosis (bTB). METHODS: Proteomic analysis was performed on different bPPD preparations from M. bovis, strain AN5. Proteins were precipitated from bPPD solutions by TCA precipitation. The proteome of bPPD preparations was investigated by bottom-up proteomics, which consisted in protein digestion and nano-LC-MS/MS analysis...
April 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28372585/multiple-gene-variations-contributed-to-congenital-heart-disease-via-gata-family-transcriptional-regulation
#12
Yanyan Qian, Deyong Xiao, Xiao Guo, Hongbo Chen, Lili Hao, Xiaojing Ma, Guoying Huang, Duan Ma, Huijun Wang
BACKGROUND: Congenital heart disease (CHD) is a common birth defect, and most cases occur sporadically. Mutations in key genes that are responsible for cardiac development could contribute to CHD. To date, the genetic causes of CHD remain largely unknown. METHODS: In this study, twenty-nine candidate genes in CHD were sequenced in 106 patients with Tetralogy of Fallot (TOF) using target exome sequencing (TES). The co-immunoprecipitation (CO-IP) and luciferase reporter gene assays were performed in HEK293T cells, and wild-type and mutant mRNA of ZFPM2 were microinjected into zebrafish embryos...
April 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28364777/in-vivo-mri-and-ex-vivo-histological-assessment-of-the-cardioprotection-induced-by-ischemic-preconditioning-postconditioning-and-remote-conditioning-in-a-closed-chest-porcine-model-of-reperfused-acute-myocardial-infarction-importance-of-microvasculature
#13
Tamás Baranyai, Zoltán Giricz, Zoltán V Varga, Gábor Koncsos, Dominika Lukovic, András Makkos, Márta Sárközy, Noémi Pávó, András Jakab, Csilla Czimbalmos, Hajnalka Vágó, Zoltán Ruzsa, Levente Tóth, Rita Garamvölgyi, Béla Merkely, Rainer Schulz, Mariann Gyöngyösi, Péter Ferdinandy
BACKGROUND: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis...
April 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28359318/24h-gene-variation-effect-of-combined-bevacizumab-erlotinib-in-advanced-non-squamous-non-small-cell-lung-cancer-using-exon-array-blood-profiling
#14
Florent Baty, Markus Joerger, Martin Früh, Dirk Klingbiel, Francesco Zappa, Martin Brutsche
BACKGROUND: The SAKK 19/05 trial investigated the safety and efficacy of the combined targeted therapy bevacizumab and erlotinib (BE) in unselected patients with advanced non-squamous non-small cell lung cancer (NSCLC). Although activating EGFR mutations were the strongest predictors of the response to BE, some patients not harboring driver mutations could benefit from the combined therapy. The identification of predictive biomarkers before or short after initiation of therapy is therefore paramount for proper patient selection, especially among EGFR wild-types...
March 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28340574/myocyte-enhancer-factor-2d-provides-a-cross-talk-between-chronic-inflammation-and-lung-cancer
#15
Hai-Xing Zhu, Lin Shi, Yong Zhang, Yi-Chun Zhu, Chun-Xue Bai, Xiang-Dong Wang, Jie-Bai Zhou
BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. METHODS: We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition...
March 24, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28330473/dynamic-and-specific-immune-responses-against-multiple-tumor-antigens-were-elicited-in-patients-with-hepatocellular-carcinoma-after-cell-based-immunotherapy
#16
Yanyan Han, Yeting Wu, Chou Yang, Jing Huang, Yabing Guo, Li Liu, Ping Chen, Dongyun Wu, Junyun Liu, Jin Li, Xiangjun Zhou, Jinlin Hou
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in China and frequently occurs with chronic hepatitis B virus infection. To investigate whether cell-based cancer immunotherapy induces tumor specific immune responses in patients with HCC and provides clinical benefits, as well as to elucidate the most immunogenic tumor associated antigens (TAAs), multiple antigen stimulating cellular therapy (MASCT) was applied in addition to standard of care. METHODS: Mature dendritic cells (DCs) and activated T cells prepared for MASCT were generated from autologous peripheral blood mononuclear cells (PBMCs)...
March 22, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28320414/epidermal-growth-factor-receptor-and-epididymis-invasion-as-prognostic-biomarkers-in-clinical-stage-i-testicular-germ-cell-tumours
#17
Miguel F Sanmamed, E Esteban, E Uriol, R Zarate, M Capelan, C Muriel, G Crespo, J P Berros, P Pardo-Coto, Q Perez, C Alvarez-Fernández, P Jiménez Fonseca, M Luque, A Astudillo
BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28320405/urinary-collagen-degradation-products-as-early-markers-of-progressive-renal-fibrosis
#18
Ryanne S Hijmans, Daniel Guldager Kring Rasmussen, Saleh Yazdani, Gerjan Navis, Harry van Goor, Morten Asser Karsdal, Federica Genovese, Jacob van den Born
BACKGROUND: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. METHODS: Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12)...
March 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#19
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28302133/activin-b-is-a-novel-biomarker-for-chronic-fatigue-syndrome-myalgic-encephalomyelitis-cfs-me-diagnosis-a-cross-sectional-study
#20
Brett A Lidbury, Badia Kita, Donald P Lewis, Susan Hayward, Helen Ludlow, Mark P Hedger, David M de Kretser
BACKGROUND: Investigations of activin family proteins as serum biomarkers for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). CFS/ME is a disease with complex, wide-ranging symptoms, featuring persistent fatigue of 6 months or longer, particularly post exertion. No definitive biomarkers are available. METHODS: A cross-sectional, observational study of CFS/ME patients fulfilling the 2003 Canadian Consensus Criteria, in parallel with healthy non-fatigued controls, was conducted...
March 16, 2017: Journal of Translational Medicine
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