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Journal of Translational Medicine

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https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#1
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
#2
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
https://www.readbyqxmd.com/read/28298232/elutriated-lymphocytes-for-manufacturing-chimeric-antigen-receptor-t-cells
#3
David F Stroncek, Daniel W Lee, Jiaqiang Ren, Marianna Sabatino, Steven Highfill, Hanh Khuu, Nirali N Shah, Rosandra N Kaplan, Terry J Fry, Crystal L Mackall
BACKGROUND: Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. METHODS: Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes...
March 16, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28298211/fty720-inhibits-mesothelioma-growth-in-vitro-and-in-a-syngeneic-mouse-model
#4
Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang
BACKGROUND: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. METHODS: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy...
March 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28292332/aberrant-t-cell-responses-in-the-bone-marrow-microenvironment-of-patients-with-poor-graft-function-after-allogeneic-hematopoietic-stem-cell-transplantation
#5
Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD)...
March 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28288654/non-invasive-in-vivo-imaging-of-cardiac-stem-progenitor-cell-biodistribution-and-retention-after-intracoronary-and-intramyocardial-delivery-in-a-swine-model-of-chronic-ischemia-reperfusion-injury
#6
María Collantes, Beatriz Pelacho, María José García-Velloso, Juán José Gavira, Gloria Abizanda, Itziar Palacios, Luis Rodriguez-Borlado, Virginia Álvarez, Elena Prieto, Margarita Ecay, Eduardo Larequi, Iván Peñuelas, Felipe Prósper
BACKGROUND: The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia-reperfusion...
March 13, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28264687/hyperglycemia-enhances-arsenic-induced-platelet-and-megakaryocyte-activation
#7
Jonathan D Newman, Christina T Echagarruga, Yoscar M Ogando, Emilie Montenont, Yu Chen, Edward A Fisher, Jeffrey S Berger
OBJECTIVE: Low to moderate inorganic arsenic (iAs) exposure is independently associated with cardiovascular disease (CVD), particularly for patients with diabetes mellitus (DM). The mechanism of increased CVD risk from iAs exposure in DM has not been adequately characterized. We evaluated whether increasing concentrations of glucose enhance the effects of iAs on platelet and megakaryocyte activity, key steps in atherothrombosis. METHODS: Healthy donor whole blood was prepared in a standard fashion and incubated with sodium arsenite in a range from 0 to 10 µM...
March 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28257636/endothelial-and-smooth-muscle-cells-derived-from-human-cardiac-explants-demonstrate-angiogenic-potential-and-suitable-for-design-of-cell-containing-vascular-grafts
#8
I S Zakharova, M K Zhiven', Sh B Saaya, A I Shevchenko, A M Smirnova, A Strunov, A A Karpenko, E A Pokushalov, L N Ivanova, P I Makarevich, Y V Parfyonova, E Aboian, S M Zakian
BACKGROUND: Endothelial and smooth muscle cells are considered promising resources for regenerative medicine and cell replacement therapy. It has been shown that both types of cells are heterogeneous depending on the type of vessels and organs in which they are located. Therefore, isolation of endothelial and smooth muscle cells from tissues relevant to the area of research is necessary for the adequate study of specific pathologies. However, sources of specialized human endothelial and smooth muscle cells are limited, and the search for new sources is still relevant...
March 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28253888/stability-of-pro-and-anti-inflammatory-immune-biomarkers-for-human-cohort-studies
#9
C Graham, R Chooniedass, W P Stefura, L Lotoski, P Lopez, A D Befus, A B Becker, K T HayGlass
BACKGROUND: Although discovery research has identified the importance of dozens of pro- and anti-inflammatory immune mediators in the pathogenesis, maintenance, exacerbation and resolution of inflammatory diseases, most human cohort studies have incorporated few or no immunological intermediate phenotypes in their analyses. Significant hindrances have been (1) the limited panel of biomarkers known to be readily detected in healthy human populations and (2) the stability, hence utility, of such biomarkers to repeated analysis...
March 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28241766/luteolin-suppresses-gastric-cancer-progression-by-reversing-epithelial-mesenchymal-transition-via-suppression-of-the-notch-signaling-pathway
#10
Ming-de Zang, Lei Hu, Zhi-Yuan Fan, He-Xiao Wang, Zheng-Lun Zhu, Shu Cao, Xiong-Yan Wu, Jian-Fang Li, Li-Ping Su, Chen Li, Zheng-Gang Zhu, Min Yan, Bing-Ya Liu
BACKGROUND: Gastric cancer (GC) is one of the most malignant tumors and the second leading cause of cancer-related deaths in the world. Luteolin, a flavonoid present in many fruits and green plants, suppresses cancer progression. The effects of luteolin on GC cells and their underlying mechanisms remain unclear. METHODS: Effects of luteolin on cell proliferation, migration, invasion, and apoptosis were examined in vitro and in vivo by cell counting kit-8 (CCK-8), transwell assays, and flow cytometry, respectively...
February 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28241765/heterogeneity-of-toll-like-receptor-9-signaling-in-b-cell-malignancies-and-its-potential-therapeutic-application
#11
REVIEW
Ling Bai, Wei Chen, Jingtao Chen, Wei Li, Lei Zhou, Chao Niu, Wei Han, Jiuwei Cui
Toll-like receptor 9 (TLR9) is expressed in a variety of B-cell malignancies and works as a bridge between innate and adaptive immunity. CpG oligodeoxynucleotides (CpG ODNs), TLR9 agonists, are able to induce anticancer immune responses and exert direct effects against cancer cells, serving as cancer therapeutic agents. Therefore, TLR9 might be a potential therapeutic target for drug development. However, several new evidences have revealed that direct effects of TLR9 agonists on B-cell malignancies is controversial...
February 27, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28235425/therapeutic-strategies-for-cell-based-neovascularization-in-critical-limb-ischemia
#12
REVIEW
Makoto Samura, Tohru Hosoyama, Yuriko Takeuchi, Koji Ueno, Noriyasu Morikage, Kimikazu Hamano
Critical limb ischemia (CLI) causes severe ischemic rest pain, ulcer, and gangrene in the lower limbs. In spite of angioplasty and surgery, CLI patients without suitable artery inflow or enough vascular bed in the lesions are often forced to undergo amputation of a major limb. Cell-based therapeutic angiogenesis has the potential to treat ischemic lesions by promoting the formation of collateral vessel networks and the vascular bed. Peripheral blood mononuclear cells and bone marrow-derived mononuclear cells are the most frequently employed cell types in CLI clinical trials...
February 24, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28235424/comparative-analysis-of-curative-effect-of-bone-marrow-mesenchymal-stem-cell-and-bone-marrow-mononuclear-cell-transplantation-for-spastic-cerebral-palsy
#13
Xuebin Liu, Xiaojun Fu, Guanghui Dai, Xiaodong Wang, Zan Zhang, Hongbin Cheng, Pei Zheng, Yihua An
BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) and bone marrow mononuclear cells (BMMNCs) are both used to treat spastic cerebral palsy. However, the differences in therapeutic effect remain unknown. METHODS: A total of 105 patients with spastic cerebral palsy were enrolled and randomly assigned to three groups: the BMMSC group, the BMMNC group and the control group. Patients in both transplantation groups received four intrathecal cell injections. Patients in the control group received Bobath therapy...
February 24, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28235419/a-rabbit-model-for-experimental-alveolar-cleft-grafting
#14
Mohammad Kamal, Lars Andersson, Rene Tolba, Alexander Bartella, Felix Gremse, Frank Hölzle, Peter Kessler, Bernd Lethaus
OBJECTIVES: The purpose of the present study was to develop an animal model for creating alveolar cleft defects with properly simulated clinical defect environment for tissue-engineered bone-substitute materials testing without compromising the health of the animal. Cleft creation surgery was aimed at creating a complete alveolar cleft with a wide bone defect with an epithelial lining (oral mucosa) overlying the cleft defect. METHODS: A postmortem skull of a New Zealand White (NZW) rabbit skull (Oryctolagus cuniculus) underwent an osteological and imaging survey...
February 24, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28241774/erratum-to-walking-performance-is-positively-correlated-to%C3%A2-calf-muscle-fiber-size-in%C3%A2-peripheral-artery-disease-subjects-but-fibers-show-aberrant-mitophagy-an-observational-study
#15
Sarah H White, Mary M McDermott, Robert L Sufit, Kate Kosmac, Alex W Bugg, Marta Gonzalez-Freire, Luigi Ferrucci, Lu Tian, Lihui Zhao, Ying Gao, Melina R Kibbe, Michael H Criqui, Christiaan Leeuwenburgh, Charlotte A Peterson
No abstract text is available yet for this article.
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28231855/cox-2-expression-positively-correlates-with-pd-l1-expression-in-human-melanoma-cells
#16
Gerardo Botti, Federica Fratangelo, Margherita Cerrone, Giuseppina Liguori, Monica Cantile, Anna Maria Anniciello, Stefania Scala, Crescenzo D'Alterio, Chiara Trimarco, Angela Ianaro, Giuseppe Cirino, Corrado Caracò, Maria Colombino, Giuseppe Palmieri, Stefano Pepe, Paolo Antonio Ascierto, Francesco Sabbatino, Giosuè Scognamiglio
BACKGROUND: The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28231806/imatinib-increases-oxygen-delivery-in-extracellular-matrix-rich-but-not-in-matrix-poor-experimental-carcinoma
#17
Mikhail Burmakin, Tijs van Wieringen, P Olof Olsson, Linda Stuhr, Aive Åhgren, Carl-Henrik Heldin, Rolf K Reed, Kristofer Rubin, Carina Hellberg
BACKGROUND: Imatinib causes increased turnover of stromal collagen, reduces collagen fibril diameter, enhances extracellular fluid turnover and lowers interstitial fluid pressure (IFP) in the human colonic carcinoma KAT-4/HT-29 (KAT-4) xenograft model. METHODS: We compared the effects of imatinib on oxygen levels, vascular morphology and IFP in three experimental tumor models differing in their content of a collagenous extracellular matrix. RESULTS: Neither the KAT4 and CT-26 colonic carcinoma models, nor B16BB melanoma expressed PDGF β-receptors in the malignant cells...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#18
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222799/assessment-of-plasma-chitotriosidase-activity-ccl18-parc-concentration-and-np-c-suspicion-index-in-the-diagnosis-of-niemann-pick-disease-type-c-a-prospective-observational-study
#19
Isabel De Castro-Orós, Pilar Irún, Jorge Javier Cebolla, Victor Rodriguez-Sureda, Miguel Mallén, María Jesús Pueyo, Pilar Mozas, Carmen Dominguez, Miguel Pocoví
BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28222797/melanoma-antigen-specific-effector-t-cell-cytokine-secretion-patterns-in-patients-treated-with-ipilimumab
#20
Yana G Najjar, Fei Ding, Yan Lin, Robert VanderWeele, Lisa H Butterfield, Ahmad A Tarhini
BACKGROUND: In a previously reported study, patients with regionally advanced melanoma were treated with neoadjuvant ipilimumab (ipi) (Tarhini in PLoS ONE 9(2): e87705, 3). Significant changes in circulating myeloid derived suppressor cells (MDSC), regulatory T cells (Treg) and peptide specific type I CD4(+) and CD8(+) T cells were noted at week 6 that correlated with clinical outcome. Characterization of antigen-specific effector T cell secreted cytokines may shed insights into ipi associated T cell activation and function...
February 21, 2017: Journal of Translational Medicine
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