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Journal of Translational Medicine

Ae Ri Kim, Ji-Hye Kim, Aeryun Kim, Yongsung Sohn, Jeong-Heon Cha, Eun-Jung Bak, Yun-Jung Yoo
BACKGROUND: Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. Therefore, we investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis. METHODS: Rats were divided into control (C), diabetes with periodontitis (DP), and diabetes with periodontitis treated with SIM (DPS) groups. DP and DPS groups were intravenously injected with streptozotocin (50 mg/kg), and C group was injected with citrate buffer...
November 9, 2018: Journal of Translational Medicine
Wataru Goto, Shinichiro Kashiwagi, Koji Takada, Yuka Asano, Katsuyuki Takahashi, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The prognosis of breast cancer and the treatment response to neoadjuvant chemotherapy (NAC) differ depending on the intrinsic molecular subtypes. We evaluated the prognostic significance of immunohistological subtypes in patients with recurrent breast cancer after treatment with NAC and surgery. METHODS: A total of 237 patients with breast cancer treated with NAC and subsequent curative surgery between 2007 and 2015 were analyzed. The correlation between intrinsic molecular subtypes and clinicopathological features, prognosis, and pathological complete response (pCR) rate of NAC were investigated retrospectively...
November 9, 2018: Journal of Translational Medicine
Pandora Pound, Merel Ritskes-Hoitinga
BACKGROUND: The pharmaceutical industry is in the midst of a productivity crisis and rates of translation from bench to bedside are dismal. Patients are being let down by the current system of drug discovery; of the several 1000 diseases that affect humans, only a minority have any approved treatments and many of these cause adverse reactions in humans. A predominant reason for the poor rate of translation from bench to bedside is generally held to be the failure of preclinical animal models to predict clinical efficacy and safety...
November 7, 2018: Journal of Translational Medicine
Morten Lapin, Satu Oltedal, Kjersti Tjensvoll, Tove Buhl, Rune Smaaland, Herish Garresori, Milind Javle, Nils Idar Glenjen, Bente Kristin Abelseth, Bjørnar Gilje, Oddmund Nordgård
BACKGROUND: It was recently demonstrated that the size of cell-free DNA (cfDNA) fragments that originates from tumor cells are shorter than cfDNA fragments that originates from non-malignant cells. We investigated whether cfDNA fragment size and cfDNA levels might have prognostic value in patients with advanced pancreatic cancer. METHODS: Blood samples were obtained from patients with advanced pancreatic cancer, before (n = 61) initiation of chemotherapy and after the first cycle of chemotherapy (n = 39)...
November 6, 2018: Journal of Translational Medicine
Hyung Kyu Park, Mingi Kim, Minjung Sung, Seung Eun Lee, Yu Jin Kim, Yoon-La Choi
BACKGROUND: Sarcomas are challenging to study because of their rarity and histomorphological complexity. PD1 and PD-L1 inhibitors showed a promising anti-tumor effect in solid tumors, where a relationship between PD-L1 expression and the objective response has been evidenced. METHODS: In this study, we examined PD-L1 expression in 16 bone and soft tissue sarcoma cell lines of 11 different subtypes by means of western blot, flow cytometry and immunocytochemistry, and in 230 FFPE patient-derived tumor tissues by means of immunohistochemistry using three different antibody clones...
November 6, 2018: Journal of Translational Medicine
Miran A Jaffa, Mulugeta Gebregziabher, Sara M Garrett, Deirdre K Luttrell, Kenneth E Lipson, Louis M Luttrell, Ayad A Jaffa
BACKGROUND: Connective tissue growth factor (CTGF), is a secreted matricellular factor that has been linked to increased risk of cardiovascular disease in diabetic subjects. Despite the biological role of CTGF in diabetes, it still remains unclear how CTGF expression is regulated. In this study, we aim to identify the clinical parameters that modulate plasma CTGF levels measured longitudinally in type 1 diabetic patients over a period of 10 years. A number of patients had negligible measured values of plasma CTGF that formed a point mass at zero, whereas others had high positive values of CTGF that were measured on a continuous scale...
November 6, 2018: Journal of Translational Medicine
Rui Zhang, Xia-Hui Lin, Min Ma, Jie Chen, Jun Chen, Dong-Mei Gao, Jie-Feng Cui, Rong-Xin Chen
BACKGROUND: Incomplete thermal ablation may induce invasiveness of hepatocellular carcinoma (HCC). Here, we investigated whether activated hepatic stellate cells (HSCs) would accelerate the progression of residual HCC after sublethal heat treatment, and thus sought to identify the potential targets. METHODS: Hepatocellular carcinoma cells were exposed to sublethal heat treatment and then cultured with the conditioned medium from activated HSCs (HSC-CM). The cell proliferation, migration, invasion and parameters of epithelial-mesenchymal transition (EMT) were analyzed...
November 6, 2018: Journal of Translational Medicine
Clémentine Andre, Eric Piver, Romain Perault, Arnaud Bisson, Julien Pucheux, Emmanuelle Vermes, Bertrand Pierre, Laurent Fauchier, Dominique Babuty, Nicolas Clementy
BACKGROUND: Cardiac resynchronization therapy (CRT) reduces symptoms, morbidity and mortality in chronic heart failure patients with wide QRS complexes. However, approximately one third of CRT patients are non-responders. Myocardial fibrosis is known to be associated with absence of response. We sought to see whether galectin-3, a promising biomarker involved in fibrosis processes, could predict response and outcomes after CRT. METHODS: Consecutive patients eligible for implantation of a CRT device with a typical left bundle branch block ≥ 120 ms were prospectively included...
November 3, 2018: Journal of Translational Medicine
Muhammad Tahir Ul Qamar, Amna Bari, Muhammad Muzammal Adeel, Arooma Maryam, Usman Ali Ashfaq, Xiaoyong Du, Iqra Muneer, Hafiz Ishfaq Ahmad, Jia Wang
BACKGROUND: Chikungunya virus (CHIKV), causes massive outbreaks of chikungunya infection in several regions of Asia, Africa and Central/South America. Being positive sense RNA virus, CHIKV replication within the host resulting in its genome mutation and led to difficulties in creation of vaccine, drugs and treatment strategies. Vector control strategy has been a gold standard to combat spreading of CHIKV infection, but to eradicate a species from the face of earth is not an easy task...
October 27, 2018: Journal of Translational Medicine
Roxane Schaub, Stéphanie Badiou, Johannes Viljoen, Pierre Dujols, Karine Bolloré, Philippe Van de Perre, Marie-Louise Newell, Ruth Bland, Nicolas Nagot, Edouard Tuaillon
BACKGROUND: Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed. METHODS: In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study)...
October 25, 2018: Journal of Translational Medicine
Ning Pu, Guochao Zhao, Hanlin Yin, Jian-Ang Li, Abulimiti Nuerxiati, Dansong Wang, Xuefeng Xu, Tiantao Kuang, Dayong Jin, Wenhui Lou, Wenchuan Wu
BACKGROUND: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor due to the difficulty of disease diagnosis and therapy. Immunotherapy has had robust performance against several malignancies, including PDAC. In this study, we aim to analyze the expression of CD8 and FoxP3 on T lymphocytes and TGF-β expression in tumor tissues, and then analyze the possible clinical significance of these finding in order to find a novel effective immunotherapy target in PDAC using a murine model...
October 25, 2018: Journal of Translational Medicine
Kun Wang, Xiuqing Wang, Sainan Zheng, Yumei Niu, Wenyue Zheng, Xi Qin, Zhongcheng Li, Junyuan Luo, Wentao Jiang, Xuedong Zhou, Wei Li, Linglin Zhang
BACKGROUND: Human saliva is a protein-rich, easily accessible source of potential biomarkers for the diagnosis of oral and systemic diseases. However, little is known about the changes in salivary proteome associated with aging of patients with dental caries. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) in combination with multiple reaction monitoring mass spectrometry (MRM-MS) to characterize the salivary proteome profiles of subjects of different ages, presenting with and without caries, with the aim of identifying age-related biomarkers for dental caries...
October 25, 2018: Journal of Translational Medicine
Lin Wang, Zhong Sheng Sun, Bingwu Xiang, Chi-Ju Wei, Yan Wang, Kevin Sun, Guanjie Chen, Michael S Lan, Gilberto N Carmona, Abner L Notkins, Tao Cai
BACKGROUND: Neurogenin3 (Ngn3) and neurogenic differentiation 1 (NeuroD1), two crucial transcriptional factors involved in human diabetes (OMIM: 601724) and islet development, have been previously found to directly target to the E-boxes of the insulinoma-associated 2 (Insm2) gene promoter, thereby activating the expression of Insm2 in insulin-secretion cells. However, little is known about the function of Insm2 in pancreatic islets and glucose metabolisms. METHODS: Homozygous Insm2-/- mice were generated by using the CRISPR-Cas9 method...
October 25, 2018: Journal of Translational Medicine
M Cañadas-Garre, K Anderson, J McGoldrick, A P Maxwell, A J McKnight
BACKGROUND: Chronic kidney disease (CKD) is recognised as a global public health problem, more prevalent in older persons and associated with multiple co-morbidities. Diabetes mellitus and hypertension are common aetiologies for CKD, but IgA glomerulonephritis, membranous glomerulonephritis, lupus nephritis and autosomal dominant polycystic kidney disease are also common causes of CKD. MAIN BODY: Conventional biomarkers for CKD involving the use of estimated glomerular filtration rate (eGFR) derived from four variables (serum creatinine, age, gender and ethnicity) are recommended by clinical guidelines for the evaluation, classification, and stratification of CKD...
October 25, 2018: Journal of Translational Medicine
Matteo Sarocchi, Matteo Bauckneht, Eleonora Arboscello, Selene Capitanio, Cecilia Marini, Silvia Morbelli, Maurizio Miglino, Angela Giovanna Congiu, Giorgio Ghigliotti, Manrico Balbi, Claudio Brunelli, Gianmario Sambuceti, Pietro Ameri, Paolo Spallarossa
BACKGROUND: Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism. METHODS: By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (18 FDG-PET) scans before treatment (PETSTAGING ), after 2 cycles (PETINTERIM ) and at the end of treatment (PETEOT ); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHOPOST )...
October 25, 2018: Journal of Translational Medicine
Clémentine Mirabel, Eduard Puente-Massaguer, Anna Del Mazo-Barbara, Blanca Reyes, Philip Morton, Francesc Gòdia, Joaquim Vives
BACKGROUND: Successful delivery of cell-based therapeutics into patients is compromised by their short shelf-life upon release from production facilities due to the living nature of the active component that rapidly loses viability, and therefore its properties. In this context, the use of appropriate additives may contribute to the stabilisation of the cellular component within specifications for a longer time until administration. RESULTS: In the present study, we evaluated the effect of different formulations on the stability of viability, identity, and potency of clinical grade multipotent mesenchymal stromal cells in suspension, both electrolyte solution and protein content were found to impact on their shelf-life...
October 24, 2018: Journal of Translational Medicine
Yingfeng Liu, Wolin Hou, Xiyan Meng, Weijing Zhao, Jiemin Pan, Junling Tang, Yajuan Huang, Minfang Tao, Fang Liu
BACKGROUND: Insulin resistance and beta cell dysfunction were reported to be responsible for gestational diabetes mellitus (GDM). However, little is known about the heterogeneity of these factors and its influences on perinatal outcomes. We investigated whether subtypes of insulin resistance and beta cell dysfunction in gestational diabetes mellitus have different impacts on perinatal outcomes. METHODS: In this prospective cohort study, we followed 554 pregnant women and glucose challenge test was performed at 24-28th weeks of their gestation...
October 24, 2018: Journal of Translational Medicine
David Borg, Anna H Larsson, Charlotta Hedner, Björn Nodin, Anders Johnsson, Karin Jirström
BACKGROUND: We have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant ± adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS). METHODS: The neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant ± adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014...
October 24, 2018: Journal of Translational Medicine
Guang-Ran Guo, Liang Chen, Man Rao, Kai Chen, Jiang-Ping Song, Sheng-Shou Hu
BACKGROUND: Cardiomyocytes derived from animals and induced pluripotent stem cells (iPSCs) are two main cellular models to study cardiovascular diseases, however, neither provides precise modeling of the response of mature human cardiomyocytes to disease or stress conditions. Therefore, there are emerging needs for finding an optimized primary human cardiomyocytes isolation method to provide a bona fide cellular model. METHODS AND RESULTS: Previous established protocols for the isolation of primary human cardiomyocytes are limited in their application due to relatively low cell yield and the requirement of tissue integrity...
October 22, 2018: Journal of Translational Medicine
Yoshiya Horimoto, Emi Tokuda, Fumi Murakami, Toshitaka Uomori, Takanori Himuro, Katsuya Nakai, Gotaro Orihata, Kotaro Iijima, Shinsaku Togo, Hideo Shimizu, Mitsue Saito
BACKGROUND: Liquid biopsy approaches, such as measuring circulating tumour cells (CTCs), have recently been introduced in several clinical studies. However, the development of CTCs as a predictive marker for treatment effects on breast cancer remains an enormous task. We investigated CTCs, including epithelial mesenchymal transition (EMT) status, from metastatic breast cancer patients who had received eribulin-based treatment, which reportedly suppresses EMT as a means of tumour suppression...
October 20, 2018: Journal of Translational Medicine
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