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T cells AND metabolism

Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Danilo T Perez-Rivera, Veronica L Torres-Torres, Abraham E Torres-Colon, Maytee Cruz-Aponte
Diabetes mellitus is a disease characterized by a range of metabolic complications involving an individual's blood glucose levels, and its main regulator, insulin. These complications can vary largely from person to person depending on their current biophysical state. Biomedical research day-by-day makes strides to impact the lives of patients of a variety of diseases, including diabetes. One large stride that is being made is the generation of techniques to assist physicians to ``personalize medicine''. From available physiological data, biological understanding of the system, and dimensional analysis, a differential equation-based mathematical model was built in a sequential matter, to be able to elucidate clearly how each parameter correlates to the patient's current physiological state...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Kyle J Seamon, Namandje N Bumpus, James T Stivers
Sterile Alpha Motif and HD Domain Protein 1 (SAMHD1) is a unique enzyme that has important roles in nucleic acid metabolism, viral restriction, and the pathogenesis of autoimmune diseases and cancer. Although much attention has been focused on its dNTP triphosphohydrolase activity in viral restriction and disease, SAMHD1 also binds to single-stranded RNA and DNA. Here we utilize a UV crosslinking method using 5-bromodeoxyuridine-substituted oligonucleotides coupled with high-resolution mass spectrometry (HRMS) to identify the binding site for single-stranded nucleic acids (ssNA) on SAMHD1...
October 24, 2016: Biochemistry
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
Hena Naqvi, Mohammad Kaleem Ahmad, Syed Rizwan Hussain, Shalini Gupta, Mohammad Waseem, Abbas Ali Mahdi
BACKGROUND: Oral squamous cell carcinoma (OSCC) occurrence appears to be the number one among all cancers in India. Folate is a methyl donor during DNA methylation, as it provides substrate for methylenetetrahydrofolate reductase (MTHFR) to convert 5,10-MTHF to 5-MTHF and subsequently metabolizes it to methionine. The purpose of this study was to identify MTHFR C677T gene polymorphism in patients with OSCC. MATERIALS AND METHODS: A total of 350 OSCC cases and 350 healthy controls participated in this study...
October 24, 2016: Clinical Oral Investigations
Mazen Al-Hommrani, Paramita Chakraborty, Shilpak Chatterjee, Shikhar Mehrotra
Cell, the basic unit of life depends for its survival on nutrients and thereby energy to perform its physiological function. Cells of lymphoid and myeloid origin are key in evoking an immune response against "self" or "non-self" antigens. The thymus derived lymphoid cells called T cells are a heterogenous group with distinct phenotypic and molecular signatures that have been shown to respond against an infection (bacterial, viral, protozoan) or cancer. Recent studies have unearthed the key differences in energy metabolism between the various T cell subsets, natural killer cells, dendritic cells, macrophages and myeloid derived suppressor cells...
2016: J Immunol Res Ther
Mariela Arias-Hidalgo, Jan Hegermann, Georgios Tsiavaliaris, Fabrizio Carta, Claudiu T Supuran, Gerolf Gros, Volker Endeward
BACKGROUND/AIMS: Across the mitochondrial membrane an exceptionally intense exchange of O2 and CO2 occurs. We have asked, 1) whether the CO2 permeability, PM,CO2, of this membrane is also exceptionally high, and 2) whether the mitochondrial membrane is sufficiently permeable to HCO3- to make passage of this ion an alternative pathway for exit of metabolically produced CO2. METHODS: The two permeabilities were measured using the previously published mass spectrometric 18O exchange technique to study suspensions of mitochondria freshly isolated from rat livers...
October 24, 2016: Cellular Physiology and Biochemistry
Marcin M Kamiński, Swantje Liedmann, Sandra Milasta, Douglas R Green
T cell activation results in a rapidly proliferating T cell endowed with a metabolic phenotype necessary for growth and division. However, before the cell can proceed towards this burst of cell division a phase of quiescence occurs, during which the basic mechanisms governing regulation of metabolic reprograming are established. This review focuses on key cellular processes controlling early metabolic regulation and how these circuits of metabolic control dictate distinct cellular fates upon the first asymmetric division...
October 19, 2016: Seminars in Immunology
Po C Liu, Yi T Lee, Chun Y Wang, Ya-Tang Yang
We describe a low cost, configurable morbidostat for characterizing the evolutionary pathway of antibiotic resistance. The morbidostat is a bacterial culture device that continuously monitors bacterial growth and dynamically adjusts the drug concentration to constantly challenge the bacteria as they evolve to acquire drug resistance. The device features a working volume of ~10 ml and is fully automated and equipped with optical density measurement and micro-pumps for medium and drug delivery. To validate the platform, we measured the stepwise acquisition of trimethoprim resistance in Escherichia coli MG 1655, and integrated the device with a multiplexed microfluidic platform to investigate cell morphology and antibiotic susceptibility...
September 27, 2016: Journal of Visualized Experiments: JoVE
Víctor Resco de Dios, Arthur Gessler, Juan Pedro Ferrio, Josu G Alday, Michael Bahn, Jorge Del Castillo, Sébastien Devidal, Sonia García-Muñoz, Zachary Kayler, Damien Landais, Paula Martín-Gómez, Alexandru Milcu, Clément Piel, Karin Pirhofer-Walzl, Olivier Ravel, Serajis Salekin, David T Tissue, Mark G Tjoelker, Jordi Voltas, Jacques Roy
BACKGROUND: Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO2 and H2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron...
October 20, 2016: GigaScience
D Bogdanou, M Penna-Martinez, N Filmann, T L Chung, Y Moran-Auth, J Wehrle, C Cappel, S Huenecke, E Herrmann, U Koehl, K Badenhoop
BACKGROUND: Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T cell (Treg) defect. Vitamin D (VD) deficiency is highly prevalent in T1D which can aggravate immune dysfunction. High dose VD treatment may enhance Tregs and improve metabolism in T1D patients. METHODS: In a randomized, double-blind, placebo-controlled trial with cross-over design, patients received either for three months cholecalciferol 4000 IU/d, followed by three months placebo or the sequential alternative...
October 20, 2016: Diabetes/metabolism Research and Reviews
K Bilmin, T Kujawska, W Secomski, A Nowicki, P Grieb
Sonodynamic therapy (SDT) is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA) which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX...
2016: Folia Neuropathologica
Justus Mahnke, Valéa Schumacher, Stefanie Ahrens, Nadja Käding, Lea Marie Feldhoff, Magdalena Huber, Jan Rupp, Friederike Raczkowski, Hans-Willi Mittrücker
The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for TH2 and TH17 cell formation and controls peripheral CD8(+) T cell differentiation. We used Listeria monocytogenes infection to characterize the function of IRF4 in TH1 responses. IRF4(-/-) mice generated only marginal numbers of listeria-specific TH1 cells. After transfer into infected mice, IRF4(-/-) CD4(+) T cells failed to differentiate into TH1 cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation...
October 20, 2016: Scientific Reports
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
J A Molad, D T Blumenthal, F Bokstein, M Findler, I Finkel, N M Bornstein, S Yust-Katz, E Auriel
Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined...
October 18, 2016: Journal of Neuro-oncology
Yusuke Endo, Koutaro Yokote, Toshinori Nakayama
Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases...
October 18, 2016: Cellular and Molecular Life Sciences: CMLS
Prashant Trikha, Robert L Plews, Andrew Stiff, Shalini Gautam, Vincent Hsu, David Abood, Robert Wesolowski, Ian Landi, Xiaokui Mo, John Phay, Ching-Shih Chen, John Byrd, Michael Caligiuri, Susheela Tridandapani, William Carson
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored...
2016: Oncoimmunology
Piotr T Filipczak, Cynthia L Thomas, Wenshu Chen, Andrew Salzman, Jacob D McDonald, Yong Lin, Steven A Belinsky
Tuberous sclerosis complex (TSC) is a genetic multi-organ disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach...
October 18, 2016: Cancer Research
Anne-Segolene Cottereau, Sebastien Hapdey, Loic Chartier, Romain Modzelewski, Olivier Casasnovas, Emmanuel Itti, Herve Tilly, Pierre Vera, Michel A Meignan, Stéphanie Becker
: To compare in a large series of Peripheral T cell lymphoma (PTCL), as a model of diffuse disease, the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) measured on FDG-PET/CT with adaptive thresholding methods to TMTV measured with a fixed 41% SUVmax threshold method. METHODS: 106 patients with PTCL, staged with a PET/CT were enrolled from 5 LYSA centers. In this series TMTV computed with the 41% SUVmax threshold is a strong predictor of outcome (Ann Oncol, 2016)...
October 6, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Beata Banaszewska, Joanna Wrotyńska-Barczyńska, Robert Z Spaczynski, Leszek Pawelczyk, Antoni J Duleba
CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism is the central feature of PCOS. Studies on isolated ovarian theca-interstitial cells suggest that resveratrol, a natural polyphenol, reduces androgen production. OBJECTIVE: This study was designed to evaluate endocrine and metabolic effects of resveratrol on PCOS. DESIGN AND SETTING: This was a randomized (1:1) double-blind, placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
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