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Cancer metabolism

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https://www.readbyqxmd.com/read/28651157/different-patterns-in-the-risk-of-newly-developed-fatty-liver-and-lipid-changes-with-tamoxifen-versus-aromatase-inhibitors-in-postmenopausal-women-with-early-breast-cancer-a-propensity-score-matched-cohort-study
#1
Namki Hong, Han Gyul Yoon, Da Hea Seo, Seho Park, Seung Il Kim, Joo Hyuk Sohn, Yumie Rhee
BACKGROUND: Management of metabolic complications of long-term adjuvant endocrine therapy in early breast cancer remained an unmet need. We aimed to compare the effects of tamoxifen (TMX) and aromatase inhibitors (AIs) on the risk of fatty liver in conjunction with longitudinal changes in the serum lipid parameters. METHODS: Among 1203 subjects who were taking adjuvant TMX or AI (anastrozole or letrozole) without fatty liver at baseline, those taking TMX or AI were 1:1 matched on the propensity score...
June 23, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28651114/isolation-and-functional-interrogation-of-adult-human-prostate-epithelial-stem-cells-at-single-cell-resolution
#2
Wen-Yang Hu, Dan-Ping Hu, Lishi Xie, Ye Li, Shyama Majumdar, Larisa Nonn, Hong Hu, Toshi Shioda, Gail S Prins
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers...
June 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28650993/a-novel-potential-biomarker-for-metabolic-syndrome-in-chinese-adults-circulating-protein-disulfide-isomerase-family-a-member-4
#3
Chu-Yen Chien, Yi-Jen Hung, Yi-Shing Shieh, Chang-Hsun Hsieh, Chieh-Hua Lu, Fu-Huang Lin, Sheng-Chiang Su, Chien-Hsing Lee
BACKGROUND/OBJECTIVES: Protein disulfide isomerase (PDI) family members are specific endoplasmic reticulum proteins that are involved in the pathogenesis of numerous diseases including neurodegenerative diseases, cancer and obesity. However, the metabolic effects of PDIA4 remain unclear in humans. The aims of this study were to investigate the associations of serum PDIA4 with the metabolic syndrome (MetS) and its components in Chinese adults. SUBJECTS/METHODS: A total of 669 adults (399 men and 270 women) were recruited...
2017: PloS One
https://www.readbyqxmd.com/read/28650854/recent-developments-in-deuterium-oxide-tracer-approaches-to-measure-rates-of-substrate-turnover-implications-for-protein-lipid-and-nucleic-acid-research
#4
Matthew S Brook, Daniel J Wilkinson, Philip J Atherton, Ken Smith
PURPOSE OF REVIEW: Methods that inform on dynamic metabolism that can be applied to clinical populations to understand disease progression and responses to therapeutic interventions are of great importance. This review perspective will highlight recent advances, development, and applications of the multivalent stable isotope tracer deuterium oxide (D2O) to the study of substrate metabolism with particular reference to protein, lipids, and nucleic acids, and how these methods can be readily applied within clinical and pharmaceutical research...
June 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28650702/a-case-report-of-methadone-associated-hypoglycemia-in-an-11-month-old-male
#5
Michael S Toce, Margaret A Stefater, David T Breault, Michele M Burns
BACKGROUND: Methadone is a synthetic μ-opioid receptor agonist that is used in the management of pain, neonatal abstinence withdrawal syndrome, and opioid dependence. Overdose can cause miosis, respiratory depression, and central nervous system depression. Rarely, hypoglycemia has been reported. We present the case of an 11-month-old male who developed hypoketotic, hyperinsulinemic, hypoglycemia after an acute, unintentional methadone exposure. CASE DETAILS: The patient was a previously healthy 11-month-old male who presented in respiratory failure...
June 26, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28650662/glucose-restriction-combined-with-autophagy-inhibition-and-chemotherapy-in-hct-116-spheroids-decreases-cell-clonogenicity-and-viability-regulated-by-tumor-suppressor-genes
#6
Monica M Schroll, Gabriel J LaBonia, Katelyn R Ludwig, Amanda B Hummon
Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells...
June 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650465/mcu-dependent-mitochondrial-ca-2-inhibits-nad-sirt3-sod2-pathway-to-promote-ros-production-and-metastasis-of-hcc-cells
#7
T Ren, H Zhang, J Wang, J Zhu, M Jin, Y Wu, X Guo, L Ji, Q Huang, H Zhang, H Yang, J Xing
Mitochondrial Ca(2+) signaling, which is strongly dependent on the mitochondrial Ca(2+) uniporter (MCU) complex, has a series of key roles in physiopathological processes, including energy metabolism, reactive oxygen species (ROS) production and cell apoptosis. However, a mechanistic understanding of how the mitochondrial Ca(2+) signaling is remodeled and its functional roles remains greatly limited in cancers, especially in hepatocellular carcinoma. Here we demonstrated that the MCU complex was dysregulated in hepatocellular carcinoma (HCC) cells and significantly correlated with metastasis and poor prognosis of HCC patients...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#8
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
June 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28649697/bioorthogonal-labeling-of-human-prostate-cancer-tissue-slice-cultures-for-glycoproteomics
#9
David R Spiciarich, Rosalie Nolley, Sophia L Maund, Sean C Purcell, Jason Herschel, Anthony T Iavarone, Donna M Peehl, Carolyn R Bertozzi
Sialylated glycans are found at elevated levels in many types of cancer and have been implicated in disease progression. However, the specific glycoproteins that contribute to the cancer cell-surface sialylation are not well characterized, specifically in bona fide human disease tissue. Metabolic and bioorthogonal labeling methods have previously enabled the enrichment and identification of sialoglycoproteins from cultured cells and model organisms. Herein, we report the first application of this glycoproteomic platform to human tissues cultured ex vivo...
June 26, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28649593/colonic-microbiota-encroachment-correlates-with-dysglycemia-in-humans
#10
Benoit Chassaing, Shreya M Raja, James D Lewis, Shanthi Srinivasan, Andrew T Gewirtz
BACKGROUND AND AIMS: Mucoid structures that coat the epithelium play an essential role in keeping the intestinal microbiota at a safe distance from host cells. Encroachment of bacteria into the normally almost-sterile inner mucus layer has been observed in inflammatory bowel disease and in mouse models of colitis. Moreover, such microbiota encroachment has also been observed in mouse models of metabolic syndrome, which are associated low-grade intestinal inflammation. Hence, we investigated if microbiota encroachment might correlate with indices of metabolic syndrome in humans...
September 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28649566/-68-ga-188-re-complexed-cdtmp-trans-1-2-cyclohexyldinitrilotetraphosphonic-acid-as-a-theranostic-agent-for-skeletal-metastases
#11
Ambika P Jaswal, Virendra K Meena, Surbhi Prakash, Ankita Pandey, Baljinder Singh, Anil K Mishra, Puja P Hazari
OBJECTIVE: Metastasis of the osseous tissue is one of the frequent and severe aggravations as a result of several neoplastic conditions, such as metabolic disorders, infections, and cancer. The objective of this study was to evaluate the pertinence of [(68)Ga]-trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid (CDTMP) as a potential bone imaging agent for positron emission tomography (PET) applications as well as to assess [(188)Re]-CDTMP for bone pain palliation in metastatic skeletal disorders...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28649509/fabry-disease-four-case-reports-of-meningioma-and-a-review-of-the-literature-on-other-malignancies
#12
Beth L Thurberg, Dominique P Germain, Fernando Perretta, Iulia E Jurca-Simina, Juan M Politei
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by loss of function mutations in the GLA gene at Xq22 with subsequent functional deficiency of alpha-galactosidase A, resulting in the accumulation of globotriaosylceramide (GL-3 or Gb3) in multiple cells types throughout the body. As with other rare metabolic disorders, little is known about the incidence of malignancies in these populations and the relationship to the underlying disease, if any. We report the occurrence of meningioma in four female patients with Fabry disease...
June 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28649368/wnt-target-genes-and-where-to-find-them
#13
REVIEW
Aravinda-Bharathi Ramakrishnan, Ken M Cadigan
Wnt/β-catenin signaling is highly conserved throughout metazoans, is required for numerous essential events in development, and serves as a stem cell niche signal in many contexts. Misregulation of the pathway is linked to several human pathologies, most notably cancer. Wnt stimulation results in stabilization and nuclear import of β-catenin, which then acts as a transcriptional co-activator. Transcription factors of the T-cell family (TCF) are the best-characterized nuclear binding partners of β-catenin and mediators of Wnt gene regulation...
2017: F1000Research
https://www.readbyqxmd.com/read/28649243/distinct-blood-and-visceral-adipose-tissue-regulatory-t-cell-and-innate-lymphocyte-profiles-characterize-obesity-and-colorectal-cancer
#14
Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D'Archivio, Roberta Masella, Lucia Conti, Sandra Gessani
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649145/do-ssris-and-snris-reduce-the-frequency-and-or-severity-of-hot-flashes-in-menopausal-women
#15
Chris Stubbs, Lisa Mattingly, Steven A Crawford, Elizabeth A Wickersham, Jessica L Brockhaus, Laine H McCarthy
CLINICAL QUESTION: In menopausal women who experience regular hot flashes, does treatment with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) reduce the frequency and/or severity of hot flashes? ANSWER: Yes. Review of the literature suggests that treatment with SSRIs or SNRIs reduces the frequency and severity of hot flashes in menopausal and post-menopausal women. Studies demonstrated that paroxetine (Paxil), citalopram (Celexa) and escitolapram (Lexapro) were the most effective SSRIs, and venlafaxine (Effexor) was the most effective first line SNRI, with desvenlafaxine as a second option...
May 2017: Journal of the Oklahoma State Medical Association
https://www.readbyqxmd.com/read/28649131/blocking-the-utilization-of-glucose-induces-the-switch-from-senescence-to-apoptosis-in-pseudolaric-acid-b-treated-human-lung-cancer-cells-in-vitro
#16
Guo-Dong Yao, Jing Yang, Xiu-Xiu Li, Xiao-Yu Song, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Shao-Jiang Song, Takashi Ikejima
Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, exerts anti-tumor effects in several cancer cell lines. Our previous study showed that PAB mainly induced senescence via p53-p21 activation rather than apoptosis in suppression of the growth of human lung cancer A549 cells (p53 wild-type). In p53-null human lung cancer H1299 cells, however, PAB caused apoptosis without senescence. In this study we investigated what mechanism was responsible for the switch from senescence to apoptosis in PAB-treated human lung cancer cell lines...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28648983/mitochondrial-dynamics-in-regulating-the-unique-phenotypes-of-cancer-and-stem-cells
#17
REVIEW
Hsiuchen Chen, David C Chan
Cancer and stem cells appear to share a common metabolic profile that is characterized by high utilization of glucose through aerobic glycolysis. In the presence of sufficient nutrients, this metabolic strategy provides sufficient cellular ATP while additionally providing important metabolites necessary for the biosynthetic demands of continuous cell proliferation. Recent studies indicate that this metabolic profile is dependent on genes that regulate the fusion and fission of mitochondria. High levels of mitochondrial fission activity are associated with high proliferation and invasiveness in some cancer cells and with self-renewal and resistance to differentiation in some stem cells...
June 15, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28648777/mtorc2-regulates-amino-acid-metabolism-in-cancer-by-phosphorylation-of-the-cystine-glutamate-antiporter-xct
#18
Yuchao Gu, Claudio P Albuquerque, Daniel Braas, Wei Zhang, Genaro R Villa, Junfeng Bi, Shiro Ikegami, Kenta Masui, Beatrice Gini, Huijun Yang, Timothy C Gahman, Andrew K Shiau, Timothy F Cloughesy, Heather R Christofk, Huilin Zhou, Kun-Liang Guan, Paul S Mischel
Mutations in cancer reprogram amino acid metabolism to drive tumor growth, but the molecular mechanisms are not well understood. Using an unbiased proteomic screen, we identified mTORC2 as a critical regulator of amino acid metabolism in cancer via phosphorylation of the cystine-glutamate antiporter xCT. mTORC2 phosphorylates serine 26 at the cytosolic N terminus of xCT, inhibiting its activity. Genetic inhibition of mTORC2, or pharmacologic inhibition of the mammalian target of rapamycin (mTOR) kinase, promotes glutamate secretion, cystine uptake, and incorporation into glutathione, linking growth factor receptor signaling with amino acid uptake and utilization...
June 22, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28648378/steroidogenic-metabolism-of-galeterone-reveals-a-diversity-of-biochemical-activities
#19
Mohammad Alyamani, Zhenfei Li, Michael Berk, Jianneng Li, Jingjie Tang, Sunil Upadhyay, Richard J Auchus, Nima Sharifi
Galeterone is a steroidal CYP17A1 inhibitor, androgen receptor (AR) antagonist, and AR degrader, under evaluation in a phase III clinical trial for castration-resistant prostate cancer (CRPC). The A/B steroid ring (Δ(5),3β-hydroxyl) structure of galeterone is identical to that of cholesterol, which makes endogenous steroids with the same structure (e.g., dehydroepiandrosterone and pregnenolone) substrates for the enzyme 3β-hydroxysteroid dehydrogenase (3βHSD). We found that galeterone is metabolized by 3βHSD to Δ(4)-galeterone (D4G), which is further converted by steroid-5α-reductase (SRD5A) to 3-keto-5α-galeterone (5αG), 3α-OH-5α-galeterone, and 3β-OH-5α-galeterone; in vivo it is also converted to the three corresponding 5β-reduced metabolites...
June 19, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28648284/common-molecular-subtypes-among-asian-hepatocellular-carcinoma-and-cholangiocarcinoma
#20
Jittiporn Chaisaingmongkol, Anuradha Budhu, Hien Dang, Siritida Rabibhadana, Benjarath Pupacdi, So Mee Kwon, Marshonna Forgues, Yotsawat Pomyen, Vajarabhongsa Bhudhisawasdi, Nirush Lertprasertsuke, Anon Chotirosniramit, Chawalit Pairojkul, Chirayu U Auewarakul, Thaniya Sricharunrat, Kannika Phornphutkul, Suleeporn Sangrajrang, Maggie Cam, Ping He, Stephen M Hewitt, Kris Ylaya, Xiaolin Wu, Jesper B Andersen, Snorri S Thorgeirsson, Joshua J Waterfall, Yuelin J Zhu, Jennifer Walling, Holly S Stevenson, Daniel Edelman, Paul S Meltzer, Christopher A Loffredo, Natsuko Hama, Tatsuhiro Shibata, Robert H Wiltrout, Curtis C Harris, Chulabhorn Mahidol, Mathuros Ruchirawat, Xin W Wang
Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integration of genomics, transcriptomics, and metabolomics. While ICC and HCC share recurrently mutated genes, including TP53, ARID1A, and ARID2, mitotic checkpoint anomalies distinguish the C1 subtype with key drivers PLK1 and ECT2, whereas the C2 subtype is linked to obesity, T cell infiltration, and bile acid metabolism...
June 6, 2017: Cancer Cell
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