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https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#1
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28732077/mutations-in-the-caenorhabditis-elegans-orthologs-of-human-genes-required-for-mitochondrial-trna-modification-cause-similar-electron-transport-chain-defects-but-different-nuclear-responses
#2
Carmen Navarro-González, Ismaïl Moukadiri, Magda Villarroya, Ernesto López-Pascual, Simon Tuck, M-Eugenia Armengod
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28730636/the-reduction-in-maize-leaf-growth-under-mild-drought-affects-the-transition-between-cell-division-and-cell-expansion-and-cannot-be-restored-by-elevated-gibberellic-acid-levels
#3
Hilde Nelissen, Xiao-Huan Sun, Bart Rymen, Yusuke Jikumaru, Mikko Kojima, Yumiko Takebayashi, Rafael Abbeloos, Kirin Demuynck, Veronique Storme, Marnik Vuylsteke, Jolien De Block, Dorota Herman, Frederik Coppens, Steven Maere, Yuji Kamiya, Hitoshi Sakakibara, Gerrit T S Beemster, Dirk Inzé
Growth is characterized by the interplay between cell division and cell expansion, two processes that occur separated along the growth zone at the maize leaf. To gain further insight into the transition between cell division and cell expansion, conditions were investigated in which the position of this transition zone was positively or negatively affected. High levels of gibberellic acid (GA) in plants overexpressing the GA biosynthesis gene GA20-OXIDASE (GA20OX-1(OE) ) shifted the transition zone more distally, whereas mild drought, which is associated with lowered GA biosynthesis, resulted in a more basal positioning...
July 21, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28730494/deconstructing-the-metabolic-networks-of-oncogenic-signaling-using-targeted-liquid-chromatography-tandem-mass-spectrometry-lc-ms-ms
#4
George Poulogiannis
Metabolic reprogramming is recognized as an emerging hallmark of oncogenic signaling and cancer development. Hence the need to identify novel quantitative analytical platforms for studying metabolism in vitro and in vivo has dramatically increased. Here, we describe the experimental workflow for a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach involving positive/negative ion switching to analyze >250 metabolites of central carbon metabolism, nucleotides, and amino acids.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730493/magnetic-resonance-spectroscopy-mrs-based-methods-for-examining-cancer-metabolism-in-response-to-oncogenic-kinase-drug-treatment
#5
Yuen-Li Chung
Magnetic resonance spectroscopy (MRS) is an analytical technique that has been extensively used to examine reprogrammed metabolism and treatment response in cancer cells and solid tumors both in vivo and ex vivo. High-resolution MRS (HR-MRS) is one of the best methods for metabolic profiling, as it is highly quantitative, robust, and reproducible. The protocols for dual-phase extraction of cancer cells and tumors and sample preparations for high-resolution (1)H and (31)P HR-MRS analysis are described here. Descriptions of spectra acquisition and analysis are also included in this chapter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730480/identification-and-validation-of-driver-kinases-from-next-generation-sequencing-data
#6
Andri Leonidou, Barrie Peck, Rachael Natrajan
It is well appreciated that activating mutations in kinase genes result in kinome reprogramming that leads to altered downstream signaling networks that drive tumor progression. Indeed small-molecule inhibition of activated kinases has heralded the wave of precision medicine in the past decade. The advent of next-generation sequencing has identified a plethora of potentially activating mutations and fusion genes in previously unreported kinase genes that can potentially be developed as targeted therapies. However, the bottleneck in the translation of these alterations into clinically useful therapies lies in their functional validation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730141/extracellular-vesicles-as-modulators-of-tumor-microenvironment-and-disease-progression-in-glioma
#7
REVIEW
Abir Mondal, Divya Kumari Singh, Suchismita Panda, Anjali Shiras
Diffuse gliomas are lethal tumors of the central nervous system (CNS) characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs) to be causal in driving tumor growth in glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729963/advances-in-applications-of-metabolomics-in-pluripotent-stem-cell-research
#8
Vijesh J Bhute, Xiaoping Bao, Sean P Palecek
Stem cells undergo extensive metabolic rewiring during reprogramming, proliferation and differentiation, and numerous studies have demonstrated a significant role of metabolism in controlling stem cell fates. Recent applications of metabolomics, the study of concentrations and fluxes of small molecules in cells, have advanced efforts to characterize and maturate stem cell fates, assess drug toxicity in stem cell tissue models, identify biomarkers, and study the effects of environment on metabolic pathways in stem cells and their progeny...
February 2017: Current Opinion in Chemical Engineering
https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#9
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28729418/myc-regulated-mevalonate-metabolism-maintains-brain-tumor-initiating-cells
#10
Xiuxing Wang, Zhi Huang, Qiulian Wu, Briana C Prager, Stephen C Mack, Kailin Yang, Leo J Y Kim, Ryan C Gimple, Yu Shi, Sisi Lai, Qi Xie, Tyler E Miller, Christopher G Hubert, Anne Song, Zhen Dong, Wenchao Zhou, Xiaoguang Fang, Zhe Zhu, Vaidehi Mahadev, Shideng Bao, Jeremy N Rich
Metabolic dysregulation drives tumor initiation in a subset of glioblastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastomas with wildtype IDH are poorly understood. MYC promotes metabolic reprogramming in cancer, but targeting MYC has proven notoriously challenging. Here, we link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which can be inhibited by statin or 6-fluoromevalonate treatment...
July 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28728836/chromosome-intermingling-mechanical-hotspots-for-genome-regulation
#11
REVIEW
Caroline Uhler, G V Shivashankar
Cells sense physical and chemical signals from their local microenvironment and transduce them to the nucleus to regulate genomic programs. In this review, we first discuss different modes of mechanotransduction to the nucleus. We then highlight the role of the spatial organization of chromosomes for integrating these signals. In particular, we emphasize the importance of chromosome intermingling for gene regulation. We also discuss various geometric models and recent advances in microscopy and genomics that have allowed access to these nanoscale chromosome intermingling regions...
July 17, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#12
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28728135/prostate-cancer-risk-and-dna-methylation-signatures-in-aging-rats-following-developmental-bpa-exposure-a-dose-response-analysis
#13
Gail S Prins, Shu-Hua Ye, Lynn Birch, Xiang Zhang, Ana Cheong, Han Lin, Esther Calderon-Gierszal, Jacob Groen, Wen-Yang Hu, Shuk-Mei Ho, Richard B van Breemen
BACKGROUND: Previous studies have uncovered heightened prostatic susceptibility to hormone-induced neoplasia from early-life exposure to low-dose bisphenol A (BPA). However, significant data gaps remain that are essential to address for biological relevance and necessary risk assessment. OBJECTIVES: A complete BPA dose-response analysis of prostate lesions across multiple prostatic lobes was conducted that included internal BPA dosimetry, progression to adenocarcinoma with aging and mechanistic connections to epigenetically reprogramed genes...
July 11, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28726588/reconstituting-mouse-lungs-with-conditionally-reprogrammed-human-bronchial-epithelial-cells
#14
Ryan LaRanger, Jennifer R Peters-Hall, Melissa Coquelin, Busola R Alabi, Chris Chen, Woodring E Wright, Jerry Shay
We developed methods for conditionally reprogramming (CR) primary human bronchial epithelial cells (HBECs) to extend their functional life span and permit their differentiation into both upper and lower airway lung epithelium. We also developed a bioreactor to support vascular perfusion and rhythmic breathing of decellularized mouse lungs reconstituted with CR HBECs isolated from patients with and without cystic fibrosis (CF). While conditionally reprogrammed cells only differentiate into an upper airway epithelium after 35 days at the air liquid interface, in reconstituted lungs these cells differentiate into upper airway bronchial epithelium and lower airway alveolar structures after 12 days...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28726153/immunological-issues-after-stem-cell-based-%C3%AE-cell-replacement
#15
REVIEW
Valeria Sordi, Silvia Pellegrini, Lorenzo Piemonti
PURPOSE OF REVIEW: Islet and pancreas transplantation prove that β cell replacement can cure the glycemic derangements in type 1 diabetes (T1D). Induced pluripotent stem cells (iPSCs) can differentiate into functional insulin-producing cells, able to restore normoglycemia in diabetic animal models. iPSCs in particular can be derived from the somatic cells of a person with T1D. This review aims to clarify if it is possible to transplant autologous iPSC-derived β cells without immunosuppression or which are the alternative approaches...
September 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28725426/colony-stimulating-factor-1-receptor-csf1r-inhibitors-in-cancer-therapy
#16
REVIEW
Michael A Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H Ries, Dominik Rüttinger
The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development. Emerging data on the tolerability of CSF1/CSF1R-targeting agents suggest a favorable safety profile, making them attractive combination partners for both standard treatment modalities and immunotherapeutic agents...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725231/chloroplast-redox-status-modulates-genome-wide-plant-responses-during-the-non-host-interaction-of-tobacco-with-the-hemibiotrophic-bacterium-xanthomonas-campestris-pv-vesicatoria
#17
Juan J Pierella Karlusich, Matias D Zurbriggen, Fahimeh Shahinnia, Sophia Sonnewald, Uwe Sonnewald, Seyed A Hosseini, Mohammad-Reza Hajirezaei, Néstor Carrillo
Non-host resistance is the most ample and durable form of plant resistance against pathogen infection. It includes induction of defense-associated genes, massive metabolic reprogramming, and in many instances, a form of localized cell death (LCD) at the site of infection, purportedly designed to limit the spread of biotrophic and hemibiotrophic microorganisms. Reactive oxygen species (ROS) have been proposed to act as signals for LCD orchestration. They are produced in various cellular compartments including chloroplasts, mitochondria and apoplast...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28724614/nuclear-mtor-acts-as-a-transcriptional-integrator-of-the-androgen-signaling-pathway-in-prostate-cancer
#18
Étienne Audet-Walsh, Catherine R Dufour, Tracey Yee, Fatima Z Zouanat, Ming Yan, Georges Kalloghlian, Mathieu Vernier, Maxime Caron, Guillaume Bourque, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Armen G Aprikian, Jacques Lapointe, Simone Chevalier, Vincent Giguère
Androgen receptor (AR) signaling reprograms cellular metabolism to support prostate cancer (PCa) growth and survival. Another key regulator of cellular metabolism is mTOR, a kinase found in diverse protein complexes and cellular localizations, including the nucleus. However, whether nuclear mTOR plays a role in PCa progression and participates in direct transcriptional cross-talk with the AR is unknown. Here, via the intersection of gene expression, genomic, and metabolic studies, we reveal the existence of a nuclear mTOR-AR transcriptional axis integral to the metabolic rewiring of PCa cells...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28723896/maternal-h3k27me3-controls-dna-methylation-independent-imprinting
#19
Azusa Inoue, Lan Jiang, Falong Lu, Tsukasa Suzuki, Yi Zhang
Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashions. After fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci, including imprinting control regions. How parental chromatin becomes equalized and how imprinting control regions escape from this reprogramming is largely unknown. Here we profile parental allele-specific DNase I hypersensitive sites in mouse zygotes and morula embryos, and investigate the epigenetic mechanisms underlying these allelic sites...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723729/wnt-signaling-in-cardiovascular-disease-opportunities-and-challenges
#20
Austin Gay, Dwight A Towler
PURPOSE OF REVIEW: Cardiometabolic diseases increasingly afflict our aging, dysmetabolic population. Complex signals regulating low-density lipoprotein receptor-related protein (LRP) and frizzled protein family members - the plasma membrane receptors for the cadre of Wnt polypeptide morphogens - contribute to the control of cardiovascular homeostasis. RECENT FINDINGS: Both canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) Wnt signaling programs control vascular smooth muscle (VSM) cell phenotypic modulation in cardiometabolic disease...
July 18, 2017: Current Opinion in Lipidology
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