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https://www.readbyqxmd.com/read/28938091/targeting-metabolism-for-cancer-therapy
#1
REVIEW
Alba Luengo, Dan Y Gui, Matthew G Vander Heiden
Metabolic reprogramming contributes to tumor development and introduces metabolic liabilities that can be exploited to treat cancer. Chemotherapies targeting metabolism have been effective cancer treatments for decades, and the success of these therapies demonstrates that a therapeutic window exists to target malignant metabolism. New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in preclinical models or clinical trials...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937677/synthesis-and-materialization-of-a-reaction-diffusion-french-flag-pattern
#2
Anton S Zadorin, Yannick Rondelez, Guillaume Gines, Vadim Dilhas, Georg Urtel, Adrian Zambrano, Jean-Christophe Galas, André Estevez-Torres
During embryo development, patterns of protein concentration appear in response to morphogen gradients. These patterns provide spatial and chemical information that directs the fate of the underlying cells. Here, we emulate this process within non-living matter and demonstrate the autonomous structuration of a synthetic material. First, we use DNA-based reaction networks to synthesize a French flag, an archetypal pattern composed of three chemically distinct zones with sharp borders whose synthetic analogue has remained elusive...
October 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28936674/conditional-modulation-of-biological-processes-by-low-temperature-degrons
#3
Nico Dissmeyer
Conditional modulation of biological processes plays key roles in basic and applied research and in translation. It can be achieved on various levels via a multitude of approaches. One of the directions is manipulating target protein levels and activity by transcriptional, posttranscriptional, translational, and posttranslational control. Because in most of these techniques, the synthesis of the target proteins is adjusted to the needs, they all rely on the specific half-life of the target protein and its turn-over...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28936660/isolation-of-arabidopsis-pollen-sperm-cells-and-vegetative-nuclei-by-fluorescence-activated-cell-sorting-facs
#4
Mário R Santos, Cláudia Bispo, Jörg D Becker
Efficient methods to isolate highly purified Arabidopsis thaliana pollen and the subcellular components of the male gametophyte (the vegetative nucleus and two sperm cells) have enabled genome-scale studies revealing a highly dynamic reprogramming of the transcriptome and epigenome during pollen development. Here, we describe the isolation of uninucleate microspores, mature pollen, as well as sperm cells and vegetative nuclei by Fluorescence-Activated Cell Sorting.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28936623/acute-renal-metabolic-effect-of-metformin-assessed-with-hyperpolarised-mri-in-rats
#5
Haiyun Qi, Per M Nielsen, Marie Schroeder, Lotte B Bertelsen, Fredrik Palm, Christoffer Laustsen
AIMS/HYPOTHESIS: Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction-oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes...
September 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28936585/understanding-intestinal-glucose-transporter-expression-in-obese-compared-to-non-obese-subjects
#6
Rebecca A Deal, Yueming Tang, Reid Fletcher, Alfonso Torquati, Philip Omotosho
INTRODUCTION: The impact of Roux-en-Y gastric bypass (RYGB) on weight loss and co-morbid disease resolution is well established. However, the mechanisms underlying the procedure remain incompletely understood. Intestinal remodeling involving glucose transporters (GLUTs) may play a crucial role. Rat studies have demonstrated morphological adaptation of GLUTs within adipose and intestinal cells in association with the reprogramming of glucose metabolism. There is a limited understanding of the variations in expression amongst GLUT family receptors in the human intestine...
September 21, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28936211/regulation-of-human-macrophage-m1-m2-polarization-balance-by-hypoxia-and-the-triggering-receptor-expressed-on-myeloid-cells-1
#7
Federica Raggi, Simone Pelassa, Daniele Pierobon, Federica Penco, Marco Gattorno, Francesco Novelli, Alessandra Eva, Luigi Varesio, Mirella Giovarelli, Maria Carla Bosco
Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935813/asxl3-is-a-novel-pluripotency-factor-in-human-respiratory-epithelial-cells-and-a-potential-therapeutic-target-in-small-cell-lung-cancer
#8
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restfo, Thomas Ried, Paul S Meltzer, David S Schrump
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSC (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAEC. Of particular novelty, we identified the PRC2-associated protein, ASXL3 which was markedly upregulated in Lu-iPSC and small cell lung cancer (SCLC) lines and clinical specimens...
September 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28935711/distinct-regenerative-potential-of-trunk-and-appendages-of-drosophila-mediated-by-jnk-signalling
#9
Raquel Martín, Noelia Pinal, Ginés Morata
The Drosophila body comprises a central part, the trunk, and outgrowths of the trunk, the appendages. Much is known about appendage regeneration, but little about the trunk. As the wing imaginal disc contains a trunk component, the notum, and a wing appendage, we have investigated the response to ablation of these two components. We find that in contrast with the strong regenerative response of the wing, the notum does not regenerate. Nevertheless, the elimination of the wing primordium elicits a proliferative response of notum cells, but they do not regenerate wing; they form a notum duplicate...
September 21, 2017: Development
https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#10
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28935668/chemical-reprogramming-of-mouse-embryonic-and-adult-fibroblast-into-endoderm-lineage
#11
Shangtao Cao, Shengyong Yu, Yan Chen, Xiaoshang Wang, Chunhua Zhou, Yuting Liu, Junqi Kuang, He Liu, Dongwei Li, Jing Ye, Yue Qing, Shilong Chu, Linlin Wu, Lin Guo, Yinxiong Li, Xiaodong Shu, Jiekai Chen, Jing Liu, Duanqing Pei
We report here an approach to redirect somatic cell fate under chemically defined conditions without transcription factors. We start by converting mouse embryonic fibroblasts (MEFs) to epithelial-like cells (ciELC) with chemicals and growth factors. Subsequent cell fate mapping reveals a robust induction of SOX17 in the resulting ELCs that can be further reprogrammed to endodermal progenitor cells (ciEPC). Interestingly, these cells can self-renew in vitro and further differentiate into albumin-producing hepatocytes that can rescue mice from acute live injury...
September 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28934652/ecophysiological-responses-to-excess-iron-in-lowland-and-upland-rice-cultivars
#12
Caroline Müller, Solange Ferreira da Silveira Silveira, Danilo de Menezes Daloso, Giselle Camargo Mendes, Andrew Merchant, Kacilda Naomi Kuki, Marco Antonio Oliva, Marcelo Ehlers Loureiro, Andréa Miyasaka Almeida
Iron (Fe) is an essential nutrient for plants but under high concentrations, such as that found naturally in clay and waterlogged soils, its toxic effect can limit production. This study aimed to investigate the stress tolerance responses exhibited by different rice cultivars. Both lowland and upland cultivars were grown under excess Fe and hypoxic conditions. Lowland cultivars showed higher Fe accumulation in roots compared with upland cultivars suggesting the use of different strategies to tolerate excess Fe...
September 13, 2017: Chemosphere
https://www.readbyqxmd.com/read/28934501/model-based-design-of-rna-hybridization-networks-implemented-in-living-cells
#13
Guillermo Rodrigo, Satya Prakash, Shensi Shen, Eszter Majer, José-Antonio Daròs, Alfonso Jaramillo
Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#14
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933288/stem-cell-differentiation-stage-factors-and-their-role-in-triggering-symmetry-breaking-processes-during-cancer-development-a-quantum-field-theory-model-for-reprogramming-cancer-cells-to-healthy-phenotypes
#15
Pier Mario Biava, Fabio Burigana, Roberto Germano, Philip Kurian, Claudio Verzegnassi, Giuseppe Vitiello
A long history of research has pursued the use of embryonic factors isolated during cell differentiation processes for the express purpose of transforming cancer cells back to healthy phenotypes. Recent results have clarified that the substances present at different stages of cell differentiation-which we call stem cell differentiation stage factors (SCDSFs)-are proteins with low molecular weight and nucleic acids that regulate genomic expression. The present review summarizes how these substances, taken at different stages of cellular maturation, are able to retard proliferation of many human tumor cell lines and thereby reprogram cancer cells to healthy phenotypes...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932637/muc1-c-promotes-the-suppressive-immune-microenvironment-in-non-small-cell-lung-cancer
#16
Audrey Bouillez, Dennis Adeegbe, Caining Jin, Xiufeng Hu, Ashujit Tagde, Maroof Alam, Hasan Rajabi, Kwok-Kin Wong, Donald Kufe
The cancer immune microenvironment is of importance for the effectiveness of immunotherapy; however, its dysregulation is poorly understood. The MUC1-C oncoprotein is aberrantly overexpressed in non-small cell lung cancer (NSCLC) and has been linked to the induction of PD-L1. The present work investigated the effects of targeting MUC1-C in an immuno-competent MUC1 transgenic (MUC1.Tg) mouse model. We show that Lewis Lung Carcinoma cells expressing MUC1-C (LLC/MUC1) exhibit upregulation of PD-L1 and suppression of interferon-γ (IFN-γ)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28931827/altered-methylations-of-h19-snrpn-mest-and-peg3-are-reversible-by-developmental-reprogramming-in-kidney-tissue-of-icsi-derived-mice
#17
Qitao Zhan, Xuchen Qi, Ning Wang, Fang Le, Luna Mao, Xinyun Yang, Mu Yuan, Hangying Lou, Xiangrong Xu, Xijing Chen, Fan Jin
Although the prevalence of Intracytoplasmic sperm injection (ICSI) has increased year by year, there remains concern about the safety of these procedures because of reports of the increased risk for imprinting disorders. Previous research has demonstrated that gonadotropin stimulation contributes to an increased incidence of epimutations in ICSI-derived mice. However, the epimutations in ICSI offspring after removing the effect of gonadotropin stimulation and the possibility that epimutations are reversible by developmental reprogramming has not been investigated...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931519/beta-cell-replacement-in-mice-using-human-type-1-diabetes-nuclear-transfer-embryonic-stem-cells
#18
Lina Sui, Nichole Danzl, Sean R Campbell, Ryan Viola, Damian Williams, Yuan Xing, Yong Wang, Neil Phillips, Greg Poffenberger, Bjarki Johannesson, Jose Oberholzer, Alvin C Powers, Rudolph L Leibel, Xiaojuan Chen, Megan Sykes, Dieter Egli
Beta cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ES) derived from a type 1 diabetes patient to differentiate into beta cells, and provide a source of autologous islets for cell replacement. NT-ES cells differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature beta cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells...
September 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#19
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28930672/histone-h3-methylated-at-arginine-17-is-essential-for-reprogramming-the-paternal-genome-in-zygotes
#20
Yuki Hatanaka, Takeshi Tsusaka, Natsumi Shimizu, Kohtaro Morita, Takehiro Suzuki, Shinichi Machida, Manabu Satoh, Arata Honda, Michiko Hirose, Satoshi Kamimura, Narumi Ogonuki, Toshinobu Nakamura, Kimiko Inoue, Yoshihiko Hosoi, Naoshi Dohmae, Toru Nakano, Hitoshi Kurumizaka, Kazuya Matsumoto, Yoichi Shinkai, Atsuo Ogura
At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a...
September 19, 2017: Cell Reports
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