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https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#1
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723573/proteomic-and-metabolomic-characterization-of-a-mammalian-cellular-transition-from-quiescence-to-proliferation
#2
Ho-Joon Lee, Mark P Jedrychowski, Arunachalam Vinayagam, Ning Wu, Ng Shyh-Chang, Yanhui Hu, Chua Min-Wen, Jodene K Moore, John M Asara, Costas A Lyssiotis, Norbert Perrimon, Steven P Gygi, Lewis C Cantley, Marc W Kirschner
There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#3
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28722313/cellular-glycosylation-senses-metabolic-changes-and-modulates-cell-plasticity-during-emt
#4
REVIEW
P Carvalho-Cruz, F Alisson-Silva, A R Todeschini, W B Dias
Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward Hexosamine Biosynthesis Pathway (HBP) which fuels aberrant glycosylation patterns that are extensively observed in cancer cells...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28721450/smad3-and-bmal1-regulate-p21-and-s100a4-expression-in-myocardial-stromal-fibroblasts-via-tnf-%C3%AE
#5
Fuyuki Sato, Akira Kohsaka, Kana Takahashi, Saki Otao, Yusuke Kitada, Yoshiyuki Iwasaki, Yasuteru Muragaki
Bmal1, a clock gene, is associated with depression, hypertrophy, metabolic syndrome and diabetes. Smad3, which is involved in the TGF-β signaling pathway, plays an important role in the regulation of tumor progression, fibrosis, obesity and diabetes. Our previous report showed that Smad3 has circadian expression in mouse livers. In the current study, we focused on the heart, especially on the myocardial stromal fibroblasts because the roles of Bmal1 and Smad3 in this tissue are poorly understood. Bmal1 and Smad3 have circadian expression in mouse hearts, and their circadian expression patterns were similar...
July 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28721154/obesity-and-inflammation-the-linking-mechanism-and-the-complications
#6
Mohammed S Ellulu, Ismail Patimah, Huzwah Khaza'ai, Asmah Rahmat, Yehia Abed
Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28720669/muc1-mediated-metabolic-alterations-regulate-response-to-radiotherapy-in-pancreatic-cancer
#7
Venugopal Gunda, Joshua J Souchek, Jaime Abrego, Surendra K Shukla, Gennifer D Goode, Enza Vernucci, Aneesha Dasgupta, Nina CHaika, Ryan J King, Sicong Li, Shuo Wang, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K Singh
Purpose: MUC1, an oncogene overexpressed in multiple solid tumors including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models. <p>Experimental design: We used MUC1 knockdown and overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response and metabolomic evaluations...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720668/efficient-mitochondrial-glutamine-targeting-prevails-over-glioblastoma-metabolic-plasticity
#8
Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M Vallette, Claire Pecqueur
Purpose Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer, however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof-of concept for personalized metabolic targeting of GBM. <p> Experimental Design We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays and mitochondrial respirometry...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#9
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720588/ews-fli-is-a-master-regulator-of-metabolic-reprogramming-in-ewing-sarcoma
#10
Jason M Tanner, Claire Bensard, Peng Wei, Nathan M Krah, John C Schell, Jamie D Gardiner, Joshua D Schiffman, Stephen L Lessnick, Jared Rutter
Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology...
July 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28719905/childhood-onset-adult-growth-hormone-deficiency-clinical-hormonal-and-radiological-assessment-in-a-single-center-in-china
#11
Hongbo Yang, Huijuan Zhu, Xuemin Yan, Hui Pan
BACKGROUND: Although growth hormone deficiency (GHD) is an important issue in pediatric patients, adult GHD (AGHD) is a neglected field of endocrinology in China. The aim of this study is to characterize the clinical, hormonal, and radiological features in childhood-onset AGHD (CO AGHD) in a single center in China and to compare them with counterparts from Japan. METHODS: The medical records of 78 Chinese patients with CO AGHD were reviewed and compared with data from the HypoCCS database study from Japan (N = 69)...
July 18, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28719220/egfr-targeted-cationic-polymeric-mixed-micelles-for-co-delivery-of-gemcitabine-and-mir-205-for-treating-advanced-pancreatic-cancer
#12
Goutam Mondal, Saud Almawash, Amit Kumar Chaudhary, Ram I Mahato
Gemcitabine (GEM), a first-line chemotherapy for pancreatic cancer undergoes rapid metabolism and develops chemoresistance after repeated administration. We previously demonstrated that the combination of GEM and miR-205 provides an effective therapeutic strategy to sensitize GEM-resistant pancreatic cancer cells. Since epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer cells, in this study, we aimed to deliver mixed micelles containing GEM and miR-205 decorated with EGFR-targeting cetuximab (C225) monoclonal antibody for targeted therapy...
July 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28719152/a-first-in-human-phase-i-multicenter-open-label-dose-escalation-study-of-the-oral-raf-vegfr-2-inhibitor-raf265-in-locally-advanced-or-metastatic-melanoma-independent-from-braf-mutation-status
#13
Benjamin Izar, William Sharfman, F Stephen Hodi, Donald Lawrence, Keith T Flaherty, Ravi Amaravadi, Kevin B Kim, Igor Puzanov, Jeffrey Sosman, Reinhard Dummer, Simone M Goldinger, Lyhping Lam, Shefali Kakar, Zhongwen Tang, Oliver Krieter, David F McDermott, Michael B Atkins
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718696/tumor-induced-disorder-of-iron-metabolism-in-major-organs-a-new-insight-from-chemical-speciation-of-iron
#14
Rujie Chen, Guangcun Chen
Objective To investigate the evolution of iron speciation in major organs of tumor-bearing mice and its role in cancer formation and cancer-associated complications. Methods The concentration and chemical speciation of iron in the spleen, liver, lung, kidney, heart, blood, muscle, and tumor tissue of healthy mice and tumor-bearing mice were studied by synchrotron radiation-based total reflection X-ray fluorescence spectrometry (SR-TXRF) coupled with X-ray absorption spectroscopy (XAS). Results The TXRF and XAS results showed that the iron content, especially the ferritin content, significantly decreased in the blood and spleen but significantly increased in the liver, lung, and muscle of mice after tumor implantation...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28718423/angiogenesis-and-metabolism-entwined-for-therapy-resistance
#15
REVIEW
Gabriela Jiménez-Valerio, Oriol Casanovas
Angiogenesis and metabolism are entwined processes that permit tumor growth and progression. Blood vessel supply is necessary for tumor survival not only by providing oxygen and nutrients for anabolism but also by removing waste products from cellular metabolism. On the other hand, blocking angiogenesis with antiangiogenic therapies shows clinical benefits in treating several tumor types. Nevertheless, resistance to therapy emerges over time. In this review we discuss a novel mechanism of adaptive resistance involving metabolic adaptation of tumor cells, and we also provide examples of tumor adaptation to therapy, which may represent a new mechanism of resistance in several types of cancer...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716817/pi3k%C3%AE-%C3%AE-and-notch1-cross-regulate-pathways-that-define-the-t-cell-acute-lymphoblastic-leukemia-disease-signature
#16
Evgeni Efimenko, Utpal P Davé, Irina V Lebedeva, Yao Shen, Maria J Sanchez-Quintero, Daniel Diolaiti, Andrew Kung, Brian J Lannutti, Jianchung Chen, Ronald Realubit, Zoya Niatsetskiya, Vadim Ten, Charles Karan, Xi Chen, Andrea Califano, Thomas G Diacovo
PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using a Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716678/cancer-recurrence-monitoring-using-hyperpolarized-1-13-c-pyruvate-metabolic-imaging-in-murine-breast-cancer-model
#17
Peter J Shin, Zihan Zhu, Roman Camarda, Robert A Bok, Alicia Y Zhou, John Kurhanewicz, Andrei Goga, Daniel B Vigneron
The purpose of this work was to study the anatomic and metabolic changes that occur with tumor progression, regression and recurrence in a switchable MYC-driven murine breast cancer model. Serial (1)H MRI and hyperpolarized [1-(13)C]pyruvate metabolic imaging were used to investigate the changes in tumor volume and glycolytic metabolism over time during the multistage tumorigenesis. We show that acute de-induction of MYC expression in established tumors results in rapid tumor regression and significantly reduced glycolytic metabolism as measured by pyruvate-to-lactate conversion...
July 14, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28716144/macrophage-type-2-differentiation-in-a-patient-with-laryngeal-squamous-cell-carcinoma-and-metastatic-prostate-adenocarcinoma-to-the-cervical-lymph-nodes
#18
Michael C Topf, Madalina Tuluc, Larry A Harshyne, Adam Luginbuhl
BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28714409/ampk-therapeutic-target-for-diabetes-and-cancer-prevention
#19
Shotaro Umezawa, Takuma Higurashi, Atsushi Nakajima
BACKGROUND: AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28714013/glioblastoma-entities-express-subtle-differences-in-molecular-composition-and-response-to-treatment
#20
Joana Balça-Silva, Diana Matias, Anália Do Carmo, Luiz Gustavo Dubois, Ana Cristina Gonçalves, Henrique Girão, Nathalie Henriques Silva Canedo, Ana Helena Correia, Jorge Marcondes De Souza, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-Neto
Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines...
July 7, 2017: Oncology Reports
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