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https://www.readbyqxmd.com/read/29145561/clinical-significance-of-cd73-in-triple-negative-breast-cancer-multiplex-analysis-of-a-phase-iii-clinical-trial
#1
L Buisseret, S Pommey, B Allard, S Garaud, M Bergeron, I Cousineau, L Ameye, Y Bareche, M Paesmans, J P A Crown, A Di Leo, S Loi, M Piccart-Gebhart, K Willard-Gallo, C Sotiriou, J Stagg
Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29145370/reprogram-restore-regenerate
#2
Simon Makin
No abstract text is available yet for this article.
November 14, 2017: Scientific American
https://www.readbyqxmd.com/read/29144600/engineering-mammalian-designer-cells-for-the-treatment-of-metabolic-diseases
#3
REVIEW
Yidan Wang, Meiyan Wang, Kaili Dong, Haifeng Ye
Synthetic biology applies engineering principles to biological systems and has significantly advanced the design of synthetic gene circuits that can reprogram cell activities to perform new functions. The ability to engineer mammalian designer cells with robust therapeutic behaviors has brought new opportunities for treating metabolic diseases. In this review, we highlight the most recent advances in the development of synthetic designer cells uploaded with open-loop gene circuits or closed-loop gene circuits for the treatment of metabolic disorders including diabetes, hypertension, hyperuricemia and obesity, and discuss the current technologies and future perspectives in applying these designer cells for clinical applications...
November 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29144021/quantitative-extracellular-matrix-proteomics-suggests-cell-wall-reprogramming-in-host-specific-immunity-during-vascular-wilt-caused-by-fusarium-oxysporum-in-chickpea
#4
Eman Elagamey, Kanika Narula, Arunima Sinha, Sudip Ghosh, Magdi A E Abdellatef, Niranjan Chakraborty, Subhra Chakraborty
Extracellular matrix (ECM) is the unique organelle that perceives stress signals and reprograms molecular events of host cell during patho-stress. However, our understanding of how ECM dictates plant immunity is largely unknown. Vascular wilt caused by the soil borne filamentous fungus Fusarium oxysporum is a major impediment for global crop productivity. To elucidate the role of ECM proteins and molecular mechanism associated with cell wall mediated immunity, the temporal changes of ECM proteome was studied in vascular wilt resistant chickpea cultivar upon F...
November 16, 2017: Proteomics
https://www.readbyqxmd.com/read/29143975/sustained-cardiac-programming-by-short-term-juvenile-exercise-training-in-male-rats
#5
Y Asif, M E Wlodek, M J Black, A P Russell, P F Soeding, G D Wadley
The aim of this study was to investigate if endurance training during juvenile life 'reprograms' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days/week for four weeks in either juvenile (5-9 weeks of age), adolescent (11-15 weeks of age) or adult life (20-24 weeks of age). Juvenile exercise training, when compared to 24 week old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0...
November 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29143810/next-generation-pacemakers-from-small-devices-to-biological-pacemakers
#6
REVIEW
Eugenio Cingolani, Joshua I Goldhaber, Eduardo Marbán
Electrogenesis in the heart begins in the sinoatrial node and proceeds down the conduction system to originate the heartbeat. Conduction system disorders lead to slow heart rates that are insufficient to support the circulation, necessitating implantation of electronic pacemakers. The typical electronic pacemaker consists of a subcutaneous generator and battery module attached to one or more endocardial leads. New leadless pacemakers can be implanted directly into the right ventricular apex, providing single-chamber pacing without a subcutaneous generator...
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29143563/mammalian-target-of-rapamycin-complex-2-mtorc2-controls-glycolytic-gene-expression-by-regulating-histone-h3-lysine-56-acetylation
#7
Raghavendra Vadla, Devyani Haldar
Metabolic reprogramming is a hallmark of cancer cells, but the mechanisms are not well understood. The mammalian target of rapamycin complex 2 (mTORC2) controls cell growth and proliferation and plays a critical role in metabolic reprogramming in glioma. mTORC2 regulates cellular processes such as cell survival, metabolism, and proliferation by phosphorylation of AGC kinases. Components of mTORC2 are shown to localize to the nucleus, but whether mTORC2 modulates epigenetic modifications to regulate gene expression is not known...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29143560/induced-pluripotent-stem-cells-derived-from-human-amnion-in-chemically-defined-conditions
#8
Jaroslav Slamecka, Steven McClellan, Anna Wilk, Javier Laurini, Elizabeth Manci, Simon P Hoerstrup, Benedikt Weber, Laurie Owen
Fetal stem cells are a unique type of adult stem cells that have been suggested to be broadly multipotent with some features of pluripotency. Their clinical potential has been documented but their upgrade to full pluripotency could open up a wide range of cell-based therapies particularly suited for pediatric tissue engineering, longitudinal studies or disease modeling. Here we describe episomal reprogramming of mesenchymal stem cells from the human amnion to pluripotency (AM-iPSC) in chemically defined conditions...
November 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29143183/micrornas-important-regulators-of-induced-pluripotent-stem-cell-generation-and-differentiation
#9
REVIEW
Zhao-Lin Zeng, Xiao-Long Lin, Li-Lan Tan, Ya-Mi Liu, Kai Qu, Zuo Wang
Induced pluripotent stem (iPS) cells can differentiate into nearly all types of cells. In contrast to embryonic stem cells, iPS cells are not subject to immune rejection because they are derived from a patient's own cells without ethical concerns. These cells can be used in regenerative medical techniques, stem cell therapy, disease modelling and drug discovery investigations. However, this application faces many challenges, such as low efficiency, slow generation time, partially reprogrammed colonies and tumourigenicity...
November 15, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29143182/noncoding-rnas-in-the-regulation-of-pluripotency-and-reprogramming
#10
REVIEW
Vladimir V Sherstyuk, Sergey P Medvedev, Suren M Zakian
Pluripotent stem cells have great potential for developmental biology and regenerative medicine. Embryonic stem cells, which are obtained from blastocysts, and induced pluripotent stem cells, which are generated by the reprogramming of somatic cells, are two main types of pluripotent cells. It is important to understand the regulatory network that controls the pluripotency state and reprogramming process. Various types of noncoding RNAs (ncRNAs) have emerged as substantial components of regulatory networks...
November 15, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29141558/modulation-of-cancer-metabolism-by-phytochemicals-a-brief-overview
#11
Danina Muntean, Sturza Adrian, Ioana Pavel, Oana Duicu
Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141219/preventive-inhibition-of-liver-tumorigenesis-by-systemic-activation-of-innate-immune-functions
#12
Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M Varki, Shuang-Jian Qiu, Bing Ren, Wenxian Fu, Gen-Sheng Feng
Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141216/slc3a2-mediates-branched-chain-amino-acid-dependent-maintenance-of-regulatory-t-cells
#13
Kayo Ikeda, Makoto Kinoshita, Hisako Kayama, Shushi Nagamori, Pornparn Kongpracha, Eiji Umemoto, Ryu Okumura, Takashi Kurakawa, Mari Murakami, Norihisa Mikami, Yasunori Shintani, Satoko Ueno, Ayatoshi Andou, Morihiro Ito, Hideki Tsumura, Koji Yasutomo, Keiichi Ozono, Seiji Takashima, Shimon Sakaguchi, Yoshikatsu Kanai, Kiyoshi Takeda
Foxp3(+) regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3(+) Treg cells with defective in vivo proliferative capacity...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140550/lncrna-h19-interacts-with-polypyrimidine-tract-binding-protein-1-to-reprogram-hepatic-lipid-homeostasis
#14
Chune Liu, Zhihong Yang, Jianguo Wu, Li Zhang, Sangmin Lee, Dong-Ju Shin, Melanie Tran, Li Wang
H19 is an imprinted long non-coding RNA abundantly expressed in embryonic liver and repressed after birth. Here we show that H19 serves as a lipid sensor by synergizing with RNA-binding protein PTBP1 to modulate hepatic metabolic homeostasis. H19RNA interacts with PTBP1 to facilitate its association with SREBP1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are upregulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#15
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29139477/a-dietary-flavone-confers-communicable-protection-against-colitis-through-nlrp6-signaling-independently-of-inflammasome-activation
#16
K Radulovic, S Normand, A Rehman, A Delanoye-Crespin, J Chatagnon, M Delacre, N Waldschmitt, L F Poulin, J Iovanna, B Ryffel, P Rosenstiel, M Chamaillard
Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29138463/talen-mediated-shift-of-mitochondrial-dna-heteroplasmy-in-melas-ipscs-with-m-13513g-a-mutation
#17
Naoki Yahata, Yuji Matsumoto, Minoru Omi, Naoki Yamamoto, Ryuji Hata
Induced pluripotent stem cells (iPSCs) are suitable for studying mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations. Here, we generated iPSCs from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with the m.13513G>A mutation. The patient's dermal fibroblasts were reprogrammed, and we established two iPSC clones with and without mutant mtDNA. Furthermore, we tried to decrease mutant mtDNA level in iPSCs using transcription activator-like effector nucleases (TALENs)...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138417/association-of-predicted-pathogenic-mutations-in-mitochondrial-nd-genes-with-distant-metastasis-in-nsclc-and-colon-cancer
#18
Nobuko Koshikawa, Miho Akimoto, Jun-Ichi Hayashi, Hiroki Nagase, Keizo Takenaga
Cancer cells have more mutations in their mitochondrial DNA (mtDNA) than do normal cells, and pathogenic mutations in the genes encoding mitochondrial NADH dehydrogenase (ND) subunits have been found to enhance the invasive and metastatic ability of various tumour cells in animal experiments. However, it is unknown whether single-nucleotide variants (SNVs) of the ND genes that decrease complex I activity are involved in distant metastasis in human clinical samples. Here, we demonstrated the enhancement of the distant metastasis of Lewis lung carcinoma cells by the ND6 13885insC mutation, which is accompanied by the overexpression of metastasis-related genes, metabolic reprogramming, the enhancement of tumour angiogenesis and the acquisition of resistance to stress-induced cell death...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138396/polo-like-kinase-1-coordinates-biosynthesis-during-cell-cycle-progression-by-directly-activating-pentose-phosphate-pathway
#19
Xiaoyu Ma, Lin Wang, De Huang, Yunyan Li, Dongdong Yang, Tingting Li, Fudong Li, Linchong Sun, Haoran Wei, Kun He, Fazhi Yu, Debiao Zhao, Lan Hu, Songge Xing, Zhaoji Liu, Kui Li, Jing Guo, Zhenye Yang, Xin Pan, Ailing Li, Yunyu Shi, Junfeng Wang, Ping Gao, Huafeng Zhang
Two hallmarks for cancer cells are the accelerated cell cycle progression as well as the altered metabolism, however, how these changes are coordinated to optimize the growth advantage for cancer cells are still poorly understood. Here we identify that Polo-like kinase 1 (Plk1), a key regulator for cell mitosis, plays a critical role for biosynthesis in cancer cells through activating pentose phosphate pathway (PPP). We find that Plk1 interacts with and directly phosphorylates glucose-6-phosphate dehydrogenase (G6PD)...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138395/myokine-mediated-muscle-kidney-crosstalk-suppresses-metabolic-reprogramming-and-fibrosis-in-damaged-kidneys
#20
Hui Peng, Qianqian Wang, Tanqi Lou, Jun Qin, Sungyun Jung, Vivekananda Shetty, Feng Li, Yanlin Wang, Xin-Hua Feng, William E Mitch, Brett H Graham, Zhaoyong Hu
Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice...
November 14, 2017: Nature Communications
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