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Journal of Translational Medicine

Daniel S Green, Ana T Nunes, Virginia David-Ocampo, Irene B Ekwede, Nicole D Houston, Steven L Highfill, Hanh Khuu, David F Stroncek, Seth M Steinberg, Kathryn C Zoon, Christina M Annunziata
BACKGROUND: Ovarian cancer has no definitive second line therapeutic options, and largely recurs in the peritoneal cavity. Locoregional immune therapy using both interferons and monocytes can be used as a novel approach. Interferons have both cytostatic and cytotoxic properties, while monocytes stimulated with interferons have potent cytotoxic properties. Due to the highly immune suppressive properties of ovarian cancer, ex vivo stimulation of autologous patient monocytes with interferons and infusion of all three agents intraperitoneally (IP) can provide a strong pro-inflammatory environment at the site of disease to kill malignant cells...
July 16, 2018: Journal of Translational Medicine
Shou-Sheng Liu, Yuan-Zhong Yang, Chang Jiang, Qi Quan, Qian-Kun Xie, Xiao-Pai Wang, Wen-Zhuo He, Yu-Ming Rong, Ping Chen, Qiong Yang, Lin Yang, Bei Zhang, Xiao-Jun Xia, Peng-Fei Kong, Liang-Ping Xia
BACKGROUND: Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. METHODS: We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression...
July 13, 2018: Journal of Translational Medicine
Xue-Mei Zhang, Jiao Ma, Yang Sun, Bing-Qian Yu, Zhuo-Min Jiao, Duo Wang, Mei-Yu Yu, Jin-Yue Li, Jin Fu
BACKGROUND: Spinal cord injury (SCI) is one of the most severe central nervous system injuries. Currently, transplanting bone marrow mesenchymal stem cells (BMSCs) is considered a therapeutic option for SCI. Tanshinone IIA (TIIA) is one of the extracts obtained from Salvia miltiorrhiza Bunge, which has been shown to have some protective effects against SCI. The present research was aimed to explore whether TIIA would influence the fate of transplanted BMSCs in a rat model of SCI, especially with regard to their differentiation into neuronal cells...
July 13, 2018: Journal of Translational Medicine
Muaiad Kittaneh, Charles Berkelhammer
Germline mutations in the BRCA-1 associated tumor protein 1 (BAP1) increase susceptibility to mesothelioma and other cancers. We describe a patient with a family history of peritoneal mesothelioma, who developed malignant peritoneal mesothelioma at age 45 in the absence of known asbestos exposure. These findings lead us to hypothesize that the mesothelioma occurred in the setting of germline a BAP1 mutation. This was confirmed by genetic testing. The subsequent therapeutic choices for the patient and testing of at-risk family members highlight the importance of recognizing this genetic syndrome and screening for individuals at high risk...
July 13, 2018: Journal of Translational Medicine
Raymond Chong, Lauren Albor, Chandramohan Wakade, John Morgan
BACKGROUND: Fatigue is a common problem among individuals with Parkinson's disease (PD). It may occur before the overt symptoms of bradykinesia, rigidity and tremor. Little is understood about how to measure fatigue in PD. Here we determined the dimensionality of the constructs of fatigue. METHODS: Four recommended scales, the Fatigue Severity Scale, Functional Assessment of Chronic Illness Therapy-Fatigue, Parkinson Fatigue Scale and Visual Analog Fatigue Scale (VAFS) were tested against quality of life measures including cognition, depression, sleep, life orientation, physical activity and PD symptoms in 22 PD subjects and 15 caregivers...
July 11, 2018: Journal of Translational Medicine
Prakash C Thakur, Jennifer L Miller-Ocuin, Khanh Nguyen, Rina Matsuda, Aatur D Singhi, Herbert J Zeh, Nathan Bahary
BACKGROUND: Endoplasmic reticulum (ER) stress and its consequent unfolded protein response (UPR) are believed to be associated with progression, survival and chemoresistance of a variety of tumor cells through multiple cellular processes, including autophagy. Therefore, the ER stress-autophagy pathway presents a potential molecular target for therapeutic intervention. The objective of this study was to evaluate the therapeutic efficacy of ER stress and autophagy modulators in the context of pancreatic ductal adenocarcinoma (PDAC)...
July 9, 2018: Journal of Translational Medicine
Andrew J Pellatt, Lila E Mullany, Jennifer S Herrick, Lori C Sakoda, Roger K Wolff, Wade S Samowitz, Martha L Slattery
BACKGROUND: The TGFβ-signaling pathway plays an important role in the pathogenesis of colorectal cancer (CRC). Loss of function of several genes within this pathway, such as bone morphogenetic proteins (BMPs) have been seen as key events in CRC progression. METHODS: In this study we comprehensively evaluate differential gene expression (RNASeq) of 81 genes in the TGFβ-signaling pathway and evaluate how dysregulated genes are associated with miRNA expression (Agilent Human miRNA Microarray V19...
July 9, 2018: Journal of Translational Medicine
Xiao-Ming Chen, Tao Zhang, Dan Qiu, Jian-Yi Feng, Zhen-Yi Jin, Qiang Luo, Xin-Yu Wang, Xiu-Li Wu
BACKGROUND: γδ T cells are associated with the pathogenesis of coronary atherosclerotic heart disease, but the relationship between the development of acute myocardial infarction (AMI) and γδ T cells is not clear. So we attempt to investigate the expression pattern and clonality of T cell receptor (TCR) repertoire of γδ T cells in AMI patients, analyze the expression levels of regulatory genes Foxp3 and IL-17A, and characterize the correlation between γδ T cells and the pathogenesis of AMI...
July 5, 2018: Journal of Translational Medicine
Xinxin Chen, Fengjiao Huang, Yicheng Qi, Mengxi Zhou, Qinglei Yin, Ying Peng, Yulin Zhou, Guang Ning, Shu Wang
BACKGROUND: Abnormal microRNAs (miRNAs) were reported to be involved in the mechanism of Graves' disease (GD). Dysregulated miRNAs may be overlapping in different cells and can be secreted to circulation. We chose miRNAs which were previously reported to be differentially expressed in peripheral blood mononuclear cells (PBMCs) in patients with GD with different disease stage, detected the expression of those miRNAs in serum, corroborated the findings in thyroid tissue, and validated the target gene in vitro to investigate the possible role of circulating miRNAs in GD...
July 5, 2018: Journal of Translational Medicine
Qian Yang, Wen-Wen Gu, Yan Gu, Na-Na Yan, Yan-Yan Mao, Xing-Xing Zhen, Jian-Mei Wang, Jing Yang, Hui-Juan Shi, Xuan Zhang, Jian Wang
BACKGROUND: Implantation failure is not only a major cause of early pregnancy loss, but it is also an obstacle to assisted reproductive technologies. The identification of potential circulating biomarkers for recurrent miscarriage (RM) and/or recurrent implantation failure would contribute to the development of novel diagnosis and prediction techniques. METHODS: MiR (miR-23a-3p, 27a-3p, 29a-3p, 100-5p, 127-3p and 486-5p) expression in the villi, decidual tissues and peripheral blood plasma and serum were validated by qPCR, and the localization of miRs in the villi and decidual tissues of RM and normal pregnancy (NP) women were detected by in situ hybridization...
July 4, 2018: Journal of Translational Medicine
B Clynick, B Dessauvagie, G Sterrett, N T Harvey, R J N Allcock, C Saunders, W Erber, K Meehan
BACKGROUND: Carcinoma of unknown primary (CUP) is a metastatic epithelial malignancy in the absence of an identifiable primary tumour. Prognosis for patients with CUP is poor because treatment options are generally limited to broad spectrum chemotherapy. A shift towards personalised cancer management based on mutation profiling offers the possibility of new treatment paradigms. This study has explored whether actionable, oncogenic driver mutations are present in CUP that have potential to better inform treatment decisions...
July 4, 2018: Journal of Translational Medicine
Yanqiong Zhang, Hailong Wang, Xia Mao, Qiuyan Guo, Weijie Li, Xiaoyue Wang, Guangyao Li, Na Lin
BACKGROUND: Approximately 30% of rheumatoid arthritis (RA) patients treated with Tripterysium glycosides (TG) tablets fail to achieve clinical improvement, implying the essentiality of predictive biomarkers and tools. Herein, we aimed to identify possible biomarkers predictive of therapeutic effects of TG tablets in RA. METHODS: Gene expression profile in peripheral blood mononuclear cells obtained from a discovery cohort treated with TG tablets was detected by Affymetrix EG1...
July 4, 2018: Journal of Translational Medicine
Janet Retseck, Alexis Nasr, Yan Lin, Huang Lin, Prateek Mendiratta, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: We previously reported early on-treatment significant modulation in circulating regulatory T cell (Treg), myeloid derived suppressor cells (MDSC) and antigen-specific type I CD4+ and CD8+ T cells that correlated with clinical outcome in regionally advanced melanoma patients treated with neoadjuvant ipilimumab. Here, we investigated the long term immunologic impact of CTLA4 blockade. METHODS: Patients were treated with ipilimumab given at 10 mg/kg IV every 3 weeks for 2 doses bracketing surgery...
July 4, 2018: Journal of Translational Medicine
Xiqing Li, Zunlan Zhao, Shijiang Yi, Lei Ma, Ming Li, Mingyue Liu, Yaping Zhang, Guangzhi Liu
BACKGROUND: The functions of the protein expressed in the nucleus and cytoplasm were different or opposite. The previous study found that oncogene Klf4 played a role of tumor suppressor in the nasopharyngeal cytoplasm. Cetuximab targeted epidermal growth factor receptor (EGFR) for the treatment of nasopharyngeal carcinoma. METHODS: A cohort of 231 cases of advanced nasopharyngeal carcinoma (7th AJCC III-IVa) samples was assessed by immunohistochemistry (IHC), of which, 63 cases were treated with basic treatment without cetuximab, the basic treatment include chemotherapy and radiotherapy, the regent of the chemotherapy include cisplatin and fluorouracil and 168 cases were treated with cetuximab in addition to the basic treatment...
July 4, 2018: Journal of Translational Medicine
Zhenjiang Liu, Thomas Poiret, Qingda Meng, Martin Rao, Anna von Landenberg, Esther Schoutrop, Davide Valentini, Ernest Dodoo, Inti Peredo-Harvey, Markus Maeurer
BACKGROUND: Patients with brain tumor or pancreatic cancer exhibit the poorest prognosis, while immune fitness and cellular immune exhaustion impacts their survival immensely. This work identifies differences in the immune reactivity to the common human pathogens cytomegalovirus (CMV) and Epstein-Barr virus (EBV) between patients with brain tumor in comparison to those with pancreatic cancer and healthy individuals. METHODS: We characterized the humoral and cellular immune responses of patients with brain tumor or pancreatic cancer to cytomegalovirus structural protein pp65 (CMV-pp65) as well as Epstein-Barr nuclear antigen-1 (EBNA-1) by whole-blood assay and ELISA...
July 3, 2018: Journal of Translational Medicine
Gandharva Nagpal, Kumardeep Chaudhary, Piyush Agrawal, Gajendra P S Raghava
BACKGROUND: Evidences in literature strongly advocate the potential of immunomodulatory peptides for use as vaccine adjuvants. All the mechanisms of vaccine adjuvants ensuing immunostimulatory effects directly or indirectly stimulate antigen presenting cells (APCs). While numerous methods have been developed in the past for predicting B cell and T-cell epitopes; no method is available for predicting the peptides that can modulate the APCs. METHODS: We named the peptides that can activate APCs as A-cell epitopes and developed methods for their prediction in this study...
July 3, 2018: Journal of Translational Medicine
Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga
Following publication of the original article [1], a typesetting mistake is reported. For Fig. 7b, a copy of Fig. 6b has been published. The correct Fig. 7b is given in this correction and the original article has been updated.
July 2, 2018: Journal of Translational Medicine
Linda M Liau, Keyoumars Ashkan, David D Tran, Jian L Campian, John E Trusheim, Charles S Cobbs, Jason A Heth, Michael Salacz, Sarah Taylor, Stacy D D'Andre, Fabio M Iwamoto, Edward J Dropcho, Yaron A Moshel, Kevin A Walter, Clement P Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A Toms, Kevin O Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R Abram, Andrew J Brenner, Steven Brem, Matthew G Ewend, Simon Khagi, Jana Portnow, Lyndon J Kim, William G Loudon, Reid C Thompson, David E Avigan, Karen L Fink, Francois J Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P Davis, Christopher Duma, Arnold B Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S Baskin, Pamela Z New, Michel Lacroix, Sven-Axel May, Timothy J Pluard, Victor Tse, Richard M Green, John L Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P Taylor, Anthony E Maida, Robert M Prins, Timothy F Cloughesy, Paul Mulholland, Marnix L Bosch
Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section...
June 29, 2018: Journal of Translational Medicine
Hai-Min Hwang, Chang-Kyu Heo, Hye Jung Lee, Sang-Seob Kwak, Won-Hee Lim, Jong-Shin Yoo, Dae-Yuel Yu, Kook Jin Lim, Jeong-Yoon Kim, Eun-Wie Cho
BACKGROUND: Tumor-associated (TA) autoantibodies, which are generated by the immune system upon the recognition of abnormal TA antigens, are promising biomarkers for the early detection of tumors. In order to detect autoantibody biomarkers effectively, antibody-specific epitopes in the diagnostic test should maintain the specific conformations that are as close as possible to those presenting in the body. However, when using patients' serum as a source of TA autoantibodies the characterization of the autoantibody-specific epitope is not easy due to the limited amount of patient-derived serum...
June 28, 2018: Journal of Translational Medicine
Alexandra DeBose-Scarlett, Raymond Balise, Deukwoo Kwon, Susan Vadaparampil, Steven Xi Chen, Eugene R Schiff, Gladys Patricia Ayala, Emmanuel Thomas
BACKGROUND: Hepatitis C virus (HCV) treatment regimens (DAAs) are well tolerated, efficacious but costly. Their high cost and restricted availability, raises concerns about the outcome of treatment in uninsured patients. This study investigated sustained virologic response (SVR) outcomes in a predominately uninsured patient population and completion of four steps along the HCV treatment cascade. METHODS: A retrospective chart review was conducted to characterize the patient population and analyze covariates to determine association with insurance status, attainment of SVR and progression through the HCV treatment cascade...
June 28, 2018: Journal of Translational Medicine
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