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Journal of Translational Medicine

Martin Bialke, Thomas Bahls, Lars Geidel, Henriette Rau, Arne Blumentritt, Sandra Pasewald, Robert Wolff, Jonas Steinmann, Tobias Bronsch, Björn Bergh, Galina Tremper, Martin Lablans, Frank Ückert, Stefan Lang, Tarik Idris, Wolfgang Hoffmann
BACKGROUND: The use of medical data for research purposes requires an informed consent of the patient that is compliant with the EU General Data Protection Regulation. In the context of multi-centre research initiatives and a multitude of clinical and epidemiological studies scalable and automatable measures for digital consent management are required. Modular form, structure, and contents render a patient's consent reusable for varying project settings in order to effectively manage and minimise organisational and technical efforts...
September 14, 2018: Journal of Translational Medicine
Jianqun Kou, Phillip R Musich, Ben Staal, Liang Kang, Yuan Qin, Zhi Q Yao, Boheng Zhang, Weizhong Wu, Angela Tam, Alan Huang, Huai-Xiang Hao, George F Vande Woude, Qian Xie
BACKGROUND: Aberrant MET tyrosine kinase signaling is known to cause cancer initiation and progression. While MET inhibitors are in clinical trials against several cancer types, the clinical efficacies are controversial and the molecular mechanisms toward sensitivity remain elusive. METHODS: With the goal to investigate the molecular basis of MET amplification (METamp ) and hepatocyte growth factor (HGF) autocrine-driven tumors in response to MET tyrosine kinase inhibitors (TKI) and neutralizing antibodies, we compared cancer cells harboring METamp (MKN45 and MHCCH97H) or HGF-autocrine (JHH5 and U87) for their sensitivity and downstream biological responses to a MET-TKI (INC280) and an anti-MET monoclonal antibody (MetMab) in vitro, and for tumor inhibition in vivo...
September 12, 2018: Journal of Translational Medicine
Chen-Yu Chen, Re-Wen Wu, Nai-Wen Tsai, Mel S Lee, Wei-Che Lin, Mei-Chi Hsu, Chih-Cheng Huang, Yun-Ru Lai, Chia-Te Kung, Hung-Chen Wang, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Ben-Chung Cheng, Yi-Fang Chiang, Cheng-Hsien Lu
BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. METHODS: The numbers of circulating EPCs [CD133+ /CD34+ (%), KDR+ /CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT)...
September 12, 2018: Journal of Translational Medicine
Maria Tsamou, Dries S Martens, Bianca Cox, Narjes Madhloum, Karen Vrijens, Tim S Nawrot
BACKGROUND: In the early-life environment, proper development of the placenta is essential for both fetal and maternal health. Telomere length at birth has been related to life expectancy. MicroRNAs (miRNAs) as potential epigenetic determinants of telomere length at birth have not been identified. In this study, we investigate whether placental miRNA expression is associated with placental telomere length at birth. METHODS: We measured the expression of seven candidate miRNAs (miR-16-5p, -20a-5p, -21-5p, -34a-5p, 146a-5p, -210-3p and -222-3p) in placental tissue at birth in 203 mother-newborn (51...
September 12, 2018: Journal of Translational Medicine
Mayte Delgado-Ureña, Francisco G Ortega, Diego de Miguel-Pérez, Alba Rodriguez-Martínez, Jose L García-Puche, Hugh Ilyine, Jose A Lorente, Jose Exposito-Hernandez, M Carmen Garrido-Navas, Miguel Delgado-Ramirez, M José Serrano
BACKGROUND: The use of circulating tumor cells (CTCs) as indicators of treatment response in metastatic colorectal cancer (mCRC) needs to be clarified. The objective of this study is to compare the Response Evaluation Criteria in Solid Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on the presence and phenotypic characterization of CTCs, as indicators of FOLFOX-bevacizumab treatment response. METHODS: 77 mCRC blood samples from FOLFOX-bevacizumab treated patients were analyzed to isolate CTCs before and after (12 and 24 weeks) treatment, using an immunomagnetic separation method...
September 6, 2018: Journal of Translational Medicine
Xuefen Chen, Xiaohuan Gong, Changhong Shi, Li Sun, Zheng Tang, Zhengping Yuan, Jiwei Wang, Jinming Yu
BACKGROUND: Even though multi-focused psychosocial residence rehabilitation intervention (MPRRI) programs are widely implemented by the Shanghai Cancer Rehabilitation Club, these programs have not been rigorously evaluated. In this study, we evaluated the effects of a 21-day MPRRI program, on the quality of life (QoL) among cancer survivors. METHODS: A total of 388 cancer patients were enrolled to either receive the 21-day MPRRI (n = 129) intervention or a waiting-list comparison (WLC) intervention (n = 259)...
September 6, 2018: Journal of Translational Medicine
Matteo Pallocca, Frauke Goeman, Francesca De Nicola, Elisa Melucci, Francesca Sperati, Irene Terrenato, Laura Pizzuti, Beatrice Casini, Enzo Gallo, Carla Azzurra Amoreo, Patrizia Vici, Luigi Di Lauro, Simonetta Buglioni, Maria Grazia Diodoro, Edoardo Pescarmona, Marco Mazzotta, Maddalena Barba, Maurizio Fanciulli, Ruggero De Maria, Gennaro Ciliberto, Marcello Maugeri-Saccà
We have previously reported that nuclear expression of the Hippo transducer TAZ in association with Wnt pathway mutations negatively impacts survival outcomes in advanced gastric cancer (GC) patients. Here, we extended these previous findings by investigating another oncogenic cooperation, namely, the interplay between YAP, the TAZ paralogue, and p53. The molecular output of the YAP-p53 cooperation is dependent on TP53 mutational status. In the absence of mutations, the YAP-p53 crosstalk elicits a pro-apoptotic response, whereas in the presence of TP53 mutations it activates a pro-proliferative transcriptional program...
September 4, 2018: Journal of Translational Medicine
Dirk Lassner, Christine S Siegismund, Uwe Kühl, Maria Rohde, Andrea Stroux, Felicitas Escher, Heinz-Peter Schultheiss
BACKGROUND: Enteroviral cardiomyopathy is a life-threatening disease, and detection of enterovirus (EV) RNA in the initial endomyocardial biopsy is associated with adverse prognosis and increased mortality. Some patients with EV infection may spontaneously eliminate the virus and recover, whereas those with virus persistence deteriorate and progress to heart failure. Interferon-beta (IFN-β) therapy eliminates the virus, resulting in increased survival of treated patients. CCR5 is expressed on antigen-presenting cells (both macrophages and dendritic cells) and immune effector cells (T-lymphocytes with memory/effector phenotype and natural killer cells)...
September 4, 2018: Journal of Translational Medicine
Abdellah Tebani, Lenaig Abily-Donval, Isabelle Schmitz-Afonso, Bénédicte Héron, Monique Piraud, Jérôme Ausseil, Farid Zerimech, Bruno Gonzalez, Stéphane Marret, Carlos Afonso, Soumeya Bekri
BACKGROUND: Metabolomics represent a valuable tool to recover biological information using body fluids and may help to characterize pathophysiological mechanisms of the studied disease. This approach has not been widely used to explore inherited metabolic diseases. This study investigates mucopolysaccharidosis type III (MPS III). A thorough and holistic understanding of metabolic remodeling in MPS III may allow the development, improvement and personalization of patient care. METHODS: We applied both targeted and untargeted metabolomics to urine samples obtained from a French cohort of 49 patients, consisting of 13 MPS IIIA, 16 MPS IIIB, 13 MPS IIIC, and 7 MPS IIID, along with 66 controls...
September 4, 2018: Journal of Translational Medicine
José O Alemán, Nicholas A Bokulich, Jonathan R Swann, Jeanne M Walker, Joel Correa De Rosa, Thomas Battaglia, Adele Costabile, Alexandros Pechlivanis, Yupu Liang, Jan L Breslow, Martin J Blaser, Peter R Holt
BACKGROUND: Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. METHODS: We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit...
September 3, 2018: Journal of Translational Medicine
Christian Ramos-Peñafiel, Irma Olarte-Carrillo, Rafael Cerón-Maldonado, Etta Rozen-Fuller, Juan Julio Kassack-Ipiña, Guillermo Meléndez-Mier, Juan Collazo-Jaloma, Adolfo Martínez-Tovar
BACKGROUND: In acute lymphoblastic leukemia (ALL), high ABCB1 gene expression has been associated with treatment resistance, which affects patient prognosis. Many preclinical reports and retrospective population studies have shown an anti-cancer effect of metformin. Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival...
September 3, 2018: Journal of Translational Medicine
Christopher Centeno, Jason Markle, Ehren Dodson, Ian Stemper, Christopher Williams, Matthew Hyzy, Thomas Ichim, Michael Freeman
BACKGROUND: Bone marrow concentrate (BMC) has shown promise in the treatment of several orthopedic conditions. This registry study investigated the use of autologous BMC and platelet products for percutaneous anterior cruciate ligament (ACL) treatment. METHODS: Twenty-nine patients presenting to a single outpatient interventional musculoskeletal and pain practice with symptomatic grade 1, 2, or 3 ACL tears with less than 1 cm retraction were enrolled. Patients were treated with a percutaneous ACL injection of autologous BMC and platelet products using fluoroscopic guidance...
September 3, 2018: Journal of Translational Medicine
Mohamed A Ghonim, Jeffrey Wang, Salome V Ibba, Hanh H Luu, Kusma Pyakurel, Ilyes Benslimane, Shaker Mousa, A Hamid Boulares
BACKGROUND: The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into harnessing the anti-inflammatory properties of LMWH but none have been used as therapy for asthma. Sulfated-non-anticoagulant heparin (S-NACH) is an ultra-LMWH with no systemic anticoagulant effects. OBJECTIVE: The present study explored the potential of S-NACH in blocking allergic asthma and examined the potential mechanism by which it exerts its effects...
September 1, 2018: Journal of Translational Medicine
Steven F Josephs, Thomas E Ichim, Stephen M Prince, Santosh Kesari, Francesco M Marincola, Anton Rolando Escobedo, Amir Jafri
Tumor necrosis factor (TNF)-alpha was originally identified in the 1970s as the serum mediator of innate immunity capable of inducing hemorrhagic necrosis in tumors. Today, a wide spectrum of biological activities have been attributed to this molecule, and clinical translation has mainly occurred not in using it to treat cancer, but rather to inhibit its effects to treat autoimmunity. Clinical trials utilizing systemic TNF-alpha administration have resulted in an unacceptable level of toxicities, which blocked its development...
August 31, 2018: Journal of Translational Medicine
Chaoxia Lu, Wei Wu, Fang Liu, Kunqi Yang, Jiacheng Li, Yaping Liu, Rongrong Wang, Nuo Si, Peng Gao, Yongtai Liu, Shuyang Zhang, Xue Zhang
BACKGROUND: Cardiomyopathies are the most common clinical and genetic heterogeneity cardiac diseases, and genetic contribution in particular plays a major role in patients with primary cardiomyopathies. The aim of this study is to investigate cases of inherited cardiomyopathy (IC) for potential disease-causing mutations in 64 genes reported to be associated with IC. METHODS: A total of 110 independent cases or families diagnosed with various primary cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular non-compaction, and undefined cardiomyopathy, were collected after informed consent...
August 30, 2018: Journal of Translational Medicine
Arthur F Vale, Juliana A Carneiro, Paulo C V Jardim, Thiago V Jardim, James Steele, James P Fisher, Paulo Gentil
BACKGROUND: Individuals with arterial hypertension often have an autonomic nervous system (ANS) imbalance with predominance of sympathetic ANS. This predominance can lead to injury of several organs affecting its functioning. There is evidence that performing high intensity resistance training (RT) with heavier loads and a lower number of repetitions results in lower cardiovascular stress when compared with lighter loads and a higher number of repetitions. However, the effects of different protocols of RT in autonomic modulation are not known...
August 30, 2018: Journal of Translational Medicine
Seah H Lim, Barbara A Methé, Bettina M Knoll, Alison Morris, Stephen K Obaro
Non-typhoidal Salmonella usually induces self-limiting gastroenteritis. However, in many parts of Africa, especially in individuals who are malnourished, infected with malaria, or have sickle cell disease, the organism causes serious and potentially fatal systemic infections. Since the portal of entry of non-typhoidal Salmonella into the systemic circulation is by way of the intestine, we argue that an increased gut permeability plays a vital role in the initiation of invasive non-typhoidal Salmonella in these patients...
August 30, 2018: Journal of Translational Medicine
Castiglia Sara, Adamini Aloe, Rustichelli Deborah, Castello Laura, Mareschi Katia, Pinnetta Giuseppe, Leone Marco, Mandese Alessandra, Ferrero Ivana, Mesiano Giulia, Fagioli Franca
BACKGROUND: Cytokine-induced killer (CIK) cells are a very promising cell population raising growing interest in the field of cellular antitumor therapy. The aim of our study was to validate the most advantageous expansion method for this advanced therapy medicinal product (ATMP) and to translate it from preclinical field to good manufacturing practices (GMP). GMP ensures that ATMP are consistently produced and controlled to the quality standards required to their intended use. For this reason, the use of the xenogenic sera tended to be minimized by GMP for their high variability and the associated risk of transmitting infectious agents...
August 29, 2018: Journal of Translational Medicine
Di Liu, Xi Chu, Hao Wang, Jing Dong, Si-Qi Ge, Zhong-Yao Zhao, Hong-Li Peng, Ming Sun, Li-Juan Wu, Man-Shu Song, Xiu-Hua Guo, Qun Meng, You-Xin Wang, Gordan Lauc, Wei Wang
BACKGROUND: Alternative N-glycosylation has significant structural and functional consequences on immunoglobulin G (IgG) and can affect immune responses, acting as a switch between pro- and anti-inflammatory IgG functionality. Studies have demonstrated that IgG N-glycosylation is associated with ageing, body mass index, type 2 diabetes and hypertension. METHODS: Herein, we have demonstrated patterns of IgG glycosylation that are associated with blood lipids in a cross-sectional study including 598 Han Chinese aged 20-68 years...
August 29, 2018: Journal of Translational Medicine
Inés Herrero-Fernández, Isaac Rosado-Sánchez, Miguel Genebat, Laura Tarancón-Díez, María Mar Rodríguez-Méndez, María Mar Pozo-Balado, Carmen Lozano, Ezequiel Ruiz-Mateos, Manuel Leal, Yolanda M Pacheco
BACKGROUND: Maraviroc-containing combined antiretroviral therapy (MVC-cART) improved the response to the hepatitis B virus (HBV) vaccine in HIV-infected subjects younger than 50 years old. We aimed here to explore the effect of this antiretroviral therapy on different immunological parameters that could account for this effect. METHODS: We analysed baseline samples of vaccinated subjects under 50 years old (n = 41). We characterized the maturational subsets and the expression of activation, senescence and prone-to-apoptosis markers on CD4 T-cells; we also quantified T-regulatory cells (Treg) and dendritic cell (DC) subsets...
August 29, 2018: Journal of Translational Medicine
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