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Stem cell metabolism

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https://www.readbyqxmd.com/read/28926956/carbonic-anhydrase-inhibition-and-the-management-of-hypoxic-tumors
#1
REVIEW
Claudiu T Supuran
Hypoxia and acidosis are salient features of many tumors, leading to a completely different metabolism compared to normal cells. Two of the simplest metabolic products, protons and bicarbonate, are generated by the catalytic activity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), with at least two of its isoforms, CA IX and XII, mainly present in hypoxic tumors. Inhibition of tumor-associated CAs leads to an impaired growth of the primary tumors, metastases and reduces the population of cancer stem cells, leading thus to a complex and beneficial anticancer action for this class of enzyme inhibitors...
September 16, 2017: Metabolites
https://www.readbyqxmd.com/read/28926112/chronic-kidney-disease-and-vitamin-d-metabolism-in-human-bone-marrow-derived-mscs
#2
REVIEW
Shuanhu Zhou, Julie Glowacki
Vitamin D that is synthesized in the skin or is ingested undergoes sequential steps of metabolic activation via a cascade of cytochrome P450 enzymatic hydroxylations in the liver and kidney to produce 1α,25-dihydroxyvitamin D (1α,25(OH)2 D). There are many tissues that are able to synthesize 1α,25(OH)2 D, but the biological significance of extrarenal hydroxylases is unresolved. Human marrow-derived mesenchymal stem cells (marrow stromal cells, hMSCs) give rise to osteoblasts, and their differentiation is stimulated by 1α,25(OH)2 D...
August 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28926104/glucose-stimulates-intestinal-epithelial-crypt-proliferation-by-modulating-cellular-energy-metabolism
#3
Weinan Zhou, Deepti Ramachandran, Abdelhak Mansouri, Megan J Dailey
The intestinal epithelium plays an essential role in nutrient absorption, hormone release and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926101/the-metabolic-cross-talk-between-epithelial-cancer-cells-and-stromal-fibroblasts-in-ovarian-cancer-progression-autophagy-plays-a-role
#4
REVIEW
Chanitra Thuwajit, Alessandra Ferraresi, Rossella Titone, Peti Thuwajit, Ciro Isidoro
Cancer and stromal cells, which include (cancer-associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation...
September 19, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#5
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920013/transcriptional-regulation-of-stem-cell-and-cancer-stem-cell-metabolism
#6
Ahmet Alptekin, Bingwei Ye, Han-Fei Ding
PURPOSE OF REVIEW: Metabolism is increasingly recognized as a major player in control of stem cell function and fate. How stem cell metabolism is established, maintained, and regulated is a fundamental question of biology and medicine. In this review, we discuss major metabolic programs in stem cells and cancer stem cells, with a focus on key transcription factors that shape the stem cell metabolic phenotype. RECENT FINDINGS: Cancer stem cells primarily use oxidative phosphorylation for energy generation, in contrast to normal stem cells, which rely on glycolytic metabolism with the exception of mouse embryonic stem cells...
March 2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28916735/functional-screening-in-human-cardiac-organoids-reveals-a-metabolic-mechanism-for-cardiomyocyte-cell-cycle-arrest
#7
Richard J Mills, Drew M Titmarsh, Xaver Koenig, Benjamin L Parker, James G Ryall, Gregory A Quaife-Ryan, Holly K Voges, Mark P Hodson, Charles Ferguson, Lauren Drowley, Alleyn T Plowright, Elise J Needham, Qing-Dong Wang, Paul Gregorevic, Mei Xin, Walter G Thomas, Robert G Parton, Lars K Nielsen, Bradley S Launikonis, David E James, David A Elliott, Enzo R Porrello, James E Hudson
The mammalian heart undergoes maturation during postnatal life to meet the increased functional requirements of an adult. However, the key drivers of this process remain poorly defined. We are currently unable to recapitulate postnatal maturation in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), limiting their potential as a model system to discover regenerative therapeutics. Here, we provide a summary of our studies, where we developed a 96-well device for functional screening in human pluripotent stem cell-derived cardiac organoids (hCOs)...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916726/the-nqo1-bioactivatable-drug-%C3%AE-lapachone-alters-the-redox-state-of-nqo1-pancreatic-cancer-cells-causing-perturbation-in-central-carbon-metabolism
#8
Molly A Silvers, Stanislaw Deja, Naveen Singh, Robert A Egnatchik, Jessica Sudderth, Xiuquan Luo, Muhammad S Beg, Shawn C Burgess, Ralph J DeBerardinis, David A Boothman, Matthew E Merritt
Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide, then peroxide formation, which damages DNA and causes hyperactivation of poly (ADP-ribose) polymerase (PARP), resulting in extensive NAD+/ATP depletion...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915578/targeting-hypoxic-cancer-stem-cells-cscs-with-doxycycline-implications-for-optimizing-anti-angiogenic-therapy
#9
Ernestina Marianna De Francesco, Marcello Maggiolini, Herbert B Tanowitz, Federica Sotgia, Michael P Lisanti
Here, we report new mechanistic insight into how chronic hypoxia increases 'stemness' in cancer cells. Using chemical inhibitors, we provide direct experimental evidence that ROS production and mitochondrial biogenesis are both required for the hypoxia-induced propagation of CSCs. More specifically, we show that hypoxic CSCs can be effectively targeted with i) simple mitochondrial anti-oxidants (Mito-TEMPO) and/or ii) inhibitors of mitochondrial biogenesis (Doxycycline). In this context, we discuss the idea that mitochondrial biogenesis itself may be a primary driver of "stemness" in hypoxic cancer cells, with metabolic links to fatty acid oxidation (FAO)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#10
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28912794/histological-and-transcriptomic-analysis-during-bulbil-formation-in-lilium-lancifolium
#11
Panpan Yang, Leifeng Xu, Hua Xu, Yuchao Tang, Guoren He, Yuwei Cao, Yayan Feng, Suxia Yuan, Jun Ming
Aerial bulbils are an important propagative organ, playing an important role in population expansion. However, the detailed gene regulatory patterns and molecular mechanism underlying bulbil formation remain unclear. Triploid Lilium lancifolium, which develops many aerial bulbils on the leaf axils of middle-upper stem, is a useful species for investigating bulbil formation. To investigate the mechanism of bulbil formation in triploid L. lancifolium, we performed histological and transcriptomic analyses using samples of leaf axils located in the upper and lower stem of triploid L...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28912786/co-infection-of-sweet-orange-with-severe-and-mild-strains-of-citrus-tristeza-virus-is-overwhelmingly-dominated-by-the-severe-strain-on-both-the-transcriptional-and-biological-levels
#12
Shimin Fu, Jonathan Shao, Changyong Zhou, John S Hartung
Citrus tristeza is one of the most destructive citrus diseases and is caused by the phloem-restricted Closterovirus, Citrus tristeza virus. Mild strain CTV-B2 does not cause obvious symptoms on indicators whereas severe strain CTV-B6 causes symptoms, including stem pitting, cupping, yellowing, and stiffening of leaves, and vein corking. Our laboratory has previously characterized changes in transcription in sweet orange separately infected with CTV-B2 and CTV-B6. In the present study, transcriptome analysis of Citrus sinensis in response to double infection by CTV-B2 and CTV-B6 was carried out...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28910694/an-epidemiologic-perspective-on-the-stem-cell-hypothesis-in-human-carcinogenesis
#13
REVIEW
David Schottenfeld
BACKGROUND: Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue - specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28904337/toxoplasma-modulates-signature-pathways-of-human-epilepsy-neurodegeneration-cancer
#14
Huân M Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V Rajagopala, Craig W Roberts, Fiona L Henriquez, Alexandre Montpetit, Jenefer M Blackwell, Sarra E Jamieson, Kelsey Wheeler, Ian J Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G Davis, Liliana Soroceanu, Charles Cobbs, Dennis A Steindler, Kenneth Boyer, A Gwendolyn Noble, Charles N Swisher, Peter T Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima McLeod
One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904060/early-exposure-to-a-high-fat-high-sugar-diet-increases-the-mammary-stem-cell-compartment-and-mammary-tumor-risk-in-female-mice
#15
Isabel U Lambertz, Linjie Luo, Thomas R Berton, Scott L Schwartz, Stephen D Hursting, Claudio J Conti, Robin Fuchs-Young
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation and post-weaning. Analyses showed that a post-weaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence...
September 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28903047/caloric-restriction-promotes-structural-and-metabolic-changes-in-the-skin
#16
Maria Fernanda Forni, Julia Peloggia, Tárcio T Braga, Jesús Eduardo Ortega Chinchilla, Jorge Shinohara, Carlos Arturo Navas, Niels Olsen Saraiva Camara, Alicia J Kowaltowski
Caloric restriction (CR) is the most effective intervention known to enhance lifespan, but its effect on the skin is poorly understood. Here, we show that CR mice display fur coat remodeling associated with an expansion of the hair follicle stem cell (HFSC) pool. We also find that the dermal adipocyte depot (dWAT) is underdeveloped in CR animals. The dermal/vennule annulus vasculature is enlarged, and a vascular endothelial growth factor (VEGF) switch and metabolic reprogramming in both the dermis and the epidermis are observed...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28901500/cell-cycle-and-pluripotency-convergence-on-octamer%C3%A2-binding-transcription-factor-4-review
#17
Shiqi She, Qucheng Wei, Bo Kang, Ying-Jie Wang
Embryonic stem cells (ESCs) have unlimited expansion potential and the ability to differentiate into all somatic cell types for regenerative medicine and disease model studies. Octamer‑binding transcription factor 4 (OCT4), encoded by the POU domain, class 5, transcription factor 1 gene, is a transcription factor vital for maintaining ESC pluripotency and somatic reprogramming. Many studies have established that the cell cycle of ESCs is featured with an abbreviated G1 phase and a prolonged S phase. Changes in cell cycle dynamics are intimately associated with the state of ESC pluripotency, and manipulating cell‑cycle regulators could enable a controlled differentiation of ESCs...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901484/molecular-iodine-impairs-chemoresistance-mechanisms-enhances-doxorubicin-retention-and-induces-downregulation-of-the-cd44-cd24-and-e-cadherin-vimentin-subpopulations-in-mcf-7-cells-resistant-to-low-doses-of-doxorubicin
#18
Alexander Bontempo, Brenda Ugalde-Villanueva, Evangelina Delgado-González, Ángel Luis Rodríguez, Carmen Aceves
One of the most dreaded clinical events for an oncology patient is resistance to treatment. Chemoresistance is a complex phenomenon based on alterations in apoptosis, the cell cycle and drug metabolism, and it correlates with the cancer stem cell phenotype and/or epithelial-mesenchymal transition. Molecular iodine (I2) exerts an antitumor effect on different types of iodine-capturing neoplasms by its oxidant/antioxidant properties and formation of iodolipids. In the present study, wild-type breast carcinoma cells (MCF-7/W) were treated chronically with 10 nM doxorubicin (DOX) to establish a low-dose DOX-resistant mammary cancer model (MCF-7/D)...
September 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901391/protective-effects-of-heme-oxygenase-1-transduced-bone-marrow-derived-mesenchymal-stem-cells-on-reduced%C3%A2-size-liver-transplantation-role-of-autophagy-regulated-by-the-erk-mtor-signaling-pathway
#19
Raorao Wang, Zhongyang Shen, Liu Yang, Mingli Yin, Weiping Zheng, Bin Wu, Tao Liu, Hongli Song
Autophagy is a critical lysosomal pathway that degrades cytoplasmic components to maintain cell homeostasis and provide substrates for energy metabolism. A study revealed that heme oxygenase-1 (HO-1)-transduced bone marrow-derived mesenchymal stem cells (BM-MSCs) could protect 50% reduced-size liver transplantation (RSLT) in a rat model. However, the mechanisms remain mostly unknown. The aim of the present study was to explore the effects and related mechanism of autophagy on the protection conferred by HO-1-transduced BM-MSCs (HO-1/BM-MSCs) on 50% RSLT in a rat model...
September 6, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28900770/how-regularities-of-mortality-statistics-explain-why-we-age-despite-having-potentially-ageless-somatic-stem-cells
#20
Alexander V Khalyavkin, Vyacheslav N Krut'ko
Researchers working in the area of ageing have found numerous manifestations of this process at the molecular biological level, including DNA and protein damage, accumulation of metabolic by-products, lipids peroxidation, macromolecular cross-linking, non-enzymatic glycosylation, anti-oxidant/pro-oxidant misbalance, rising of pro-inflammatory cytokines, etc. This results in an increase in the proportion of cells in growth arrest, reduction of the rate of information processing, metabolic rate decrease, and decrease in rates of other processes characterizing dynamic aspects of the organism's interaction with its environment...
September 12, 2017: Biogerontology
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