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Philipp E. Scherer  (Scherer PE) 2 Articles
Metabolic risk/Epidemiology
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Obesity, Diabetes, and Increased Cancer Progression
Dae-Seok Kim, Philipp E. Scherer
Diabetes Metab J. 2021;45(6):799-812.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0077
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Rates of obesity and diabetes have increased significantly over the past decades and the prevalence is expected to continue to rise further in the coming years. Many observations suggest that obesity and diabetes are associated with an increased risk of developing several types of cancers, including liver, pancreatic, endometrial, colorectal, and post-menopausal breast cancer. The path towards developing obesity and diabetes is affected by multiple factors, including adipokines, inflammatory cytokines, growth hormones, insulin resistance, and hyperlipidemia. The metabolic abnormalities associated with changes in the levels of these factors in obesity and diabetes have the potential to significantly contribute to the development and progression of cancer through the regulation of distinct signaling pathways. Here, we highlight the cellular and molecular pathways that constitute the links between obesity, diabetes, cancer risk and mortality. This includes a description of the existing evidence supporting the obesity-driven morphological and functional alternations of cancer cells and adipocytes through complex interactions within the tumor microenvironment.

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Hyperglycemia as a Risk Factor for Cancer Progression
Tae Young Ryu, Jiyoung Park, Philipp E. Scherer
Diabetes Metab J. 2014;38(5):330-336.   Published online October 17, 2014
DOI: https://doi.org/10.4093/dmj.2014.38.5.330
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AbstractAbstract PDFPubReader   

As the prevalence of diabetes mellitus is substantially increasing worldwide, associated diseases such as renal failure, cardiovascular diseases, fatty liver, and cancers have also increased. A number of cancers such as pancreatic, liver, breast, and female reproductive cancers have shown an increased prevalence and a higher mortality rate in diabetic patients compared to healthy subjects. Thus, this suggests an association between diabetes, especially type 2 diabetes and cancer incidence and progression. Recent studies have suggested that hyperinsulinemia, chronic inflammation and hyperglycemia, all frequently seen in diabetics, may lead to increased tumor growth; the underlying molecular mechanisms of this association are not fully understood. In particular, chronic hyperglycemic episodes could serve as a direct or indirect mediator of the increase in tumor cell growth. Here, we will discuss our current understanding how hyperglycemia and cancer risk may be linked, and what the implications are for the treatment of diabetic cancer patients.

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    Stefanie de Groot, Hanno Pijl, Ayoub Charehbili, Saskia van de Ven, Vincent T. H. B. M. Smit, Elma Meershoek-Klein Kranenbarg, Joan B. Heijns, Laurence J. C. van Warmerdam, Lonneke W. Kessels, M. Wouter Dercksen, Manon J. A. E. Pepels, Hanneke W. M. van L
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  • Efficacy of Complementary Therapies in the Quality of Life of Breast Cancer Survivors
    Sahar Zaidi, Showket Hussain, Shalini Verma, Zubia Veqar, Asiya Khan, Sheeraz Un Nazir, Neha Singh, Jamal Ali Moiz, Pranay Tanwar, Anurag Srivastava, G. K. Rath, Ravi Mehrotra
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    Jeremy C. Borniger, William H. Walker II, Surbhi, Kathryn M. Emmer, Ning Zhang, Abigail A. Zalenski, Stevie L. Muscarella, Julie A. Fitzgerald, Alexandra N. Smith, Cornelius J. Braam, Tial TinKai, Ulysses J. Magalang, Maryam B. Lustberg, Randy J. Nelson,
    Cell Metabolism.2018; 28(1): 118.     CrossRef
  • Model-based in silico analysis of the PI3K/Akt pathway: the elucidation of cross-talk between diabetes and breast cancer
    Sammia Rehman, Ayesha Obaid, Anam Naz, Amjad Ali, Shahzina Kanwal, Jamil Ahmad
    PeerJ.2018; 6: e5917.     CrossRef
  • Inhibitory Effect of Anoectochilus formosanus Extract on Hyperglycemia-Related PD-L1 Expression and Cancer Proliferation
    Yih Ho, Yan-Fang Chen, Li-Hsuan Wang, Kuang-Yang Hsu, Yu-Tang Chin, Yu-Chen S. H. Yang, Shwu-Huey Wang, Yi-Ru Chen, Ya-Jung Shih, Leroy F. Liu, Kuan Wang, Jacqueline Whang-Peng, Heng-Yuan Tang, Hung-Yun Lin, Hsuan-Liang Liu, Shwu-Jiuan Lin
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    Mohammad Imran Khan, Suvasmita Rath, Vaqar Mustafa Adhami, Hasan Mukhtar
    Seminars in Cancer Biology.2018; 49: 75.     CrossRef
  • Metformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female mice
    Roxanne Weiss, Elizabeth Fernandez, Yuhong Liu, Randy Strong, Adam B. Salmon
    Aging.2018; 10(3): 386.     CrossRef
  • High glucose induces epithelial‑mesenchymal transition and results in the migration and invasion of colorectal cancer cells
    Jiayan Wu, Jiayi Chen, Yang Xi, Fuyan Wang, Hongcun Sha, Lin Luo, Yabin Zhu, Xiaoming Hong, Shizhong Bu
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    Yu-Hsiang Lee, Chien-Hsuan Yeh
    In Vitro Cellular & Developmental Biology - Animal.2018; 54(2): 120.     CrossRef
  • Methylglyoxal-derived stress: An emerging biological factor involved in the onset and progression of cancer
    Akeila Bellahcène, Marie-Julie Nokin, Vincent Castronovo, Casper Schalkwijk
    Seminars in Cancer Biology.2018; 49: 64.     CrossRef
  • Extracellular matrix glycation and receptor for advanced glycation end-products activation: a missing piece in the puzzle of the association between diabetes and cancer
    Armando Rojas, Carolina Añazco, Ileana González, Paulina Araya
    Carcinogenesis.2018; 39(4): 515.     CrossRef
  • Good glycaemic control is associated with a better prognosis in breast cancer patients with type 2 diabetes mellitus
    Yen-Lin Chang, Wayne Huey-Herng Sheu, Shih-Yi Lin, Wen-Shyong Liou
    Clinical and Experimental Medicine.2018; 18(3): 383.     CrossRef
  • High glucose contributes to the proliferation and migration of non-small-cell lung cancer cells via GAS5-TRIB3 axis
    Cheng-Zhi Ding, Xu-Feng Guo, Guo-Lei Wang, Hong-Tao Wang, Guang-Hui Xu, Yuan-Yuan Liu, Zhen-Jiang Wu, Yu-Hang Chen, Jiao Wang, Wen-Guang Wang
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  • Challenges and perspectives in the treatment of diabetes associated breast cancer
    Samson Mathews Samuel, Elizabeth Varghese, Sharon Varghese, Dietrich Büsselberg
    Cancer Treatment Reviews.2018; 70: 98.     CrossRef
  • Linking type 2 diabetes and gynecological cancer: an introductory overview
    Emanuela Anastasi, Tiziana Filardi, Sara Tartaglione, Andrea Lenzi, Antonio Angeloni, Susanna Morano
    Clinical Chemistry and Laboratory Medicine (CCLM).2018; 56(9): 1413.     CrossRef
  • Hyperglycaemia and Survival in Solid Tumours: A Systematic Review and Meta-analysis
    R. Barua, A.J. Templeton, B. Seruga, A. Ocana, E. Amir, J.-L. Ethier
    Clinical Oncology.2018; 30(4): 215.     CrossRef
  • Hepatocellular carcinoma-associated hypercholesterolemia: involvement of proprotein-convertase-subtilisin-kexin type-9 (PCSK9)
    Dipti Athavale, Surbhi Chouhan, Vimal Pandey, Shyamananda Singh Mayengbam, Snahlata Singh, Manoj Kumar Bhat
    Cancer & Metabolism.2018;[Epub]     CrossRef
  • An insight on the association of glycation with hepatocellular carcinoma
    Nasimudeen R. Jabir, Saheem Ahmad, Shams Tabrez
    Seminars in Cancer Biology.2018; 49: 56.     CrossRef
  • Risk score system for the prediction of hepatocellular carcinoma in patients with type 2 diabetes: Taiwan Diabetes Study
    Tsai-Chung Li, Chia-Ing Li, Chiu-Shong Liu, Wen-Yuan Lin, Chih-Hsueh Lin, Sing-Yu Yang, Cheng-Chieh Lin
    Seminars in Oncology.2018; 45(5-6): 264.     CrossRef
  • RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer—a Review
    Gowri Palanissami, Solomon F. D. Paul
    Hormones and Cancer.2018; 9(5): 295.     CrossRef
  • Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation
    Catharina Bartmann, Sudha R. Janaki Raman, Jessica Flöter, Almut Schulze, Katrin Bahlke, Jana Willingstorfer, Maria Strunz, Achim Wöckel, Rainer J. Klement, Michaela Kapp, Cholpon S. Djuzenova, Christoph Otto, Ulrike Kämmerer
    Cancer & Metabolism.2018;[Epub]     CrossRef
  • Obesity, Diabetes and Gastrointestinal Malignancy: The role of Metformin and other Anti-diabetic Therapy
    McFarlane Samy I
    Global Journal of Obesity, Diabetes and Metabolic Syndrome.2018; : 008.     CrossRef
  • Pretreatment glycemic control status is an independent prognostic factor for cervical cancer patients receiving neoadjuvant chemotherapy for locally advanced disease
    Jing Li, Ni-ya Ning, Qun-xian Rao, Rong Chen, Li-juan Wang, Zhong-qiu Lin
    BMC Cancer.2017;[Epub]     CrossRef
  • Differences in risk factors of malignancy between men and women with type 2 diabetes: A retrospective case-control study
    Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak
    Oncotarget.2017; 8(40): 66940.     CrossRef
  • Beta-glucans and cancer: The influence of inflammation and gut peptide
    Sara Baldassano, Giulia Accardi, Sonya Vasto
    European Journal of Medicinal Chemistry.2017; 142: 486.     CrossRef
  • Enemies or weapons in hands: investigational anti-diabetic drug glibenclamide and cancer risk
    Rui Gao, Tao Yang, Wei Xu
    Expert Opinion on Investigational Drugs.2017; 26(7): 853.     CrossRef
  • Hyperglycemia triggers HIPK2 protein degradation
    Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D’Orazi
    Oncotarget.2017; 8(1): 1190.     CrossRef
  • Monitoring p53 by MDM2 and MDMX is required for endocrine pancreas development and function in a spatio-temporal manner
    Yiwei Zhang, Shelya X. Zeng, Qian Hao, Hua Lu
    Developmental Biology.2017; 423(1): 34.     CrossRef
  • Modulation of Mammary Stromal Cell Lactate Dynamics by Ambient Glucose and Epithelial Factors
    Nicolas Tobar, Omar Porras, Patricio C. Smith, L. Felipe Barros, Jorge Martínez
    Journal of Cellular Physiology.2017; 232(1): 136.     CrossRef
  • Energy metabolism in glioblastoma stem cells: PPARα a metabolic adaptor to intratumoral microenvironment
    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
    Oncotarget.2017; 8(65): 108430.     CrossRef
  • Hyperglycemia is Associated with Poor Survival in Primary Central Nervous System Lymphoma Patients
    Ayumi Debata, Koichi Yoshida, Kenta Ujifuku, Haruna Yasui, Kensaku Kamada, Daisuke Niino, Takayuki Matsuo
    Tumori Journal.2017; 103(3): 272.     CrossRef
  • Micronucleus, cell-free DNA, and plasma glycan composition in the newborns of healthy and diabetic mothers
    Aleksandra Fucic, Vedrana Guszak, Toma Keser, Jasenka Wagner, Emilja Juretić, Davor Plavec, Ranko Stojković, Olga Gornik, Gordan Lauc
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis.2017; 815: 6.     CrossRef
  • Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway
    A Vasconcelos-dos-Santos, H F B R Loponte, N R Mantuano, I A Oliveira, I F de Paula, L K Teixeira, J C M de-Freitas-Junior, K C Gondim, N Heise, R Mohana-Borges, J A Morgado-Díaz, W B Dias, A R Todeschini
    Oncogenesis.2017; 6(3): e306.     CrossRef
  • Associations between prediagnostic blood glucose levels, diabetes, and glioma
    Judith Schwartzbaum, Michael Edlinger, Victoria Zigmont, Pär Stattin, Grzegorz A. Rempala, Gabriele Nagel, Niklas Hammar, Hanno Ulmer, Bernhard Föger, Göran Walldius, Jonas Manjer, Håkan Malmström, Maria Feychting
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  • Gestational diabetes mellitus may be associated with increased risk of breast cancer
    Yong-Moon Mark Park, Katie M O'Brien, Shanshan Zhao, Clarice R Weinberg, Donna D Baird, Dale P Sandler
    British Journal of Cancer.2017; 116(7): 960.     CrossRef
  • The transcription factor carbohydrate-response element-binding protein (ChREBP): A possible link between metabolic disease and cancer
    Katsumi Iizuka
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2017; 1863(2): 474.     CrossRef
  • The essential role of YAP O-GlcNAcylation in high-glucose-stimulated liver tumorigenesis
    Xiao Zhang, Yongxia Qiao, Qi Wu, Yan Chen, Shaowu Zou, Xiangfan Liu, Guoqing Zhu, Yinghui Zhao, Yuxin Chen, Yongchun Yu, Qiuhui Pan, Jiayi Wang, Fenyong Sun
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  • Anthocyanins from Purple Corn Ameliorated Tumor Necrosis Factor‐α‐Induced Inflammation and Insulin Resistance in 3T3‐L1 Adipocytes via Activation of Insulin Signaling and Enhanced GLUT4 Translocation
    Diego Luna‐Vital, Matthew Weiss, Elvira Gonzalez de Mejia
    Molecular Nutrition & Food Research.2017;[Epub]     CrossRef
  • Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan
    Sören Twarock, Christina Reichert, Ulrike Peters, Daniel J. Gorski, Katharina Röck, Jens W. Fischer
    International Journal of Cancer.2017; 141(4): 791.     CrossRef
  • Das Karzinom in der Polarität zwischen Stoffwechsel- und Nerven-Sinnes-System – Konsequenzen für die Therapie
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    Der Merkurstab.2017; 70(3): 221.     CrossRef
  • Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment
    Michaela A. Onstad, Rosemarie E. Schmandt, Karen H. Lu
    Journal of Clinical Oncology.2016; 34(35): 4225.     CrossRef
  • Mechanisms through which diabetes mellitus influences renal cell carcinoma development and treatment: A review of the literature
    Dominika Labochka, Barbara Moszczuk, Wojciech Kukwa, Cezary Szczylik, Anna M. Czarnecka
    International Journal of Molecular Medicine.2016; 38(6): 1887.     CrossRef
  • Cancer Risk in Patients With Empyema
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    Medicine.2016; 95(9): e2934.     CrossRef
  • High Glucose Stimulates Tumorigenesis in Hepatocellular Carcinoma Cells Through AGER-Dependent O-GlcNAcylation of c-Jun
    Yongxia Qiao, Xiao Zhang, Yue Zhang, Yulan Wang, Yanfeng Xu, Xiangfan Liu, Fenyong Sun, Jiayi Wang
    Diabetes.2016; 65(3): 619.     CrossRef
  • Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories
    Rhonda Arthur, Henrik Møller, Hans Garmo, Lars Holmberg, Pår Stattin, Håkan Malmstrom, Mats Lambe, Niklas Hammar, Göran Walldius, David Robinson, Ingmar Jungner, Mieke Van Hemelrijck
    Cancer Medicine.2016; 5(6): 1307.     CrossRef
  • Risk factors for cancer development in type 2 diabetes: A retrospective case-control study
    Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak
    BMC Cancer.2016;[Epub]     CrossRef
  • High-fat Western diet–induced obesity contributes to increased tumor growth in mouse models of human colon cancer
    Ann Marie O'Neill, Christine M. Burrington, Erin A. Gillaspie, Darin T. Lynch, Melissa J. Horsman, Michael W. Greene
    Nutrition Research.2016; 36(12): 1325.     CrossRef
  • Diabetes Pharmacotherapies and Bladder Cancer: A Medicare Epidemiologic Study
    Todd A. Mackenzie, Rebecca Zaha, Jeremy Smith, Margaret R. Karagas, Nancy E. Morden
    Diabetes Therapy.2016; 7(1): 61.     CrossRef
  • Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway
    Lishan Wang, Ying-Ying Bai, Yang Yang, Fangfang Hu, Yonghui Wang, Zeqian Yu, Zhangjun Cheng, Jiahua Zhou
    Oncotarget.2016; 7(25): 38539.     CrossRef
  • Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis
    Hongwei Liu, Zhixiong Liu, Bing Jiang, Xiping Ding, Lei Huo, Xin Wan, Jinfang Liu, Zhenyun Xia
    Molecular Neurobiology.2016; 53(3): 1654.     CrossRef
  • Impact of Hyperglycemia on Outcomes among Patients Receiving Neoadjuvant Chemotherapy for Bulky Early Stage Cervical Cancer
    Jing Li, Miao-fang Wu, Huai-wu Lu, Bing-zhong Zhang, Li-juan Wang, Zhong-qiu Lin, Xing Xie
    PLOS ONE.2016; 11(11): e0166612.     CrossRef
  • Obesity, Inflammation, and Cancer
    Tuo Deng, Christopher J. Lyon, Stephen Bergin, Michael A. Caligiuri, Willa A. Hsueh
    Annual Review of Pathology: Mechanisms of Disease.2016; 11(1): 421.     CrossRef
  • Hyperglycemia, tumorigenesis, and chronic inflammation
    Shu-Chun Chang, Wei-Chung Vivian Yang
    Critical Reviews in Oncology/Hematology.2016; 108: 146.     CrossRef
  • Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis
    Marie-Julie Nokin, Florence Durieux, Paul Peixoto, Barbara Chiavarina, Olivier Peulen, Arnaud Blomme, Andrei Turtoi, Brunella Costanza, Nicolas Smargiasso, Dominique Baiwir, Jean L Scheijen, Casper G Schalkwijk, Justine Leenders, Pascal De Tullio, Elettra
    eLife.2016;[Epub]     CrossRef
  • ZnCl2 sustains the adriamycin-induced cell death inhibited by high glucose
    A Garufi, D Trisciuoglio, M Cirone, G D'Orazi
    Cell Death & Disease.2016; 7(6): e2280.     CrossRef
  • Controlling Malglycemia in Patients Undergoing Treatment for Cancer
    Susan Storey, Veronica Brady, Ashley Leak Bryant, Ellen Davis, Marilyn Hammer, Denise Hershey, Jill Olausson, Jane Seley
    Clinical Journal of Oncology Nursing.2016; 20(1): 92.     CrossRef
  • Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer
    Jessica K. Paulus, Christina D. Williams, Furha I. Cossor, Michael J. Kelley, Robert E. Martell
    Cancer Epidemiology, Biomarkers & Prevention.2016; 25(10): 1418.     CrossRef
  • Thymic emigration patterns in patients with type 2 diabetes treated with metformin
    Grzegorz Dworacki, Olzhas Urazayev, Yerbol Bekmukhambetov, Saule Iskakova, Bartosz A. Frycz, Paweł P. Jagodziński, Marzena Dworacka
    Immunology.2015; 146(3): 456.     CrossRef
  • Resveratrol in the treatment of pancreatic cancer
    Qinhong Xu, Liang Zong, Xin Chen, Zhengdong Jiang, Ligang Nan, Jiahui Li, Wanxing Duan, Jianjun Lei, Lun Zhang, Jiguang Ma, Xuqi Li, Zheng Wang, Zheng Wu, Qingyong Ma, Zhenhua Ma
    Annals of the New York Academy of Sciences.2015; 1348(1): 10.     CrossRef
  • Effect of hyperglycemia on hepatocellular carcinoma development in diabetes
    Yasuhiro Niwa, Kota Ishikawa, Masatoshi Ishigami, Takashi Honda, Koichi Achiwa, Takako Izumoto, Ryuya Maekawa, Kaori Hosokawa, Atsushi Iida, Yusuke Seino, Yoji Hamada, Hidemi Goto, Yutaka Oiso, Hiroshi Arima, Shin Tsunekawa
    Biochemical and Biophysical Research Communications.2015; 463(3): 344.     CrossRef
  • The insulin-like growth factor I system: Physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome
    Jun Ren, Piero Anversa
    Biochemical Pharmacology.2015; 93(4): 409.     CrossRef
  • Diabetes and risk of cancer
    Toshiya Atsumi
    Diabetology International.2015; 6(3): 190.     CrossRef
  • The influencing factors associated with glycemic control among adult diabetes patients
    Kisook Kim
    Journal of the Korea Academia-Industrial cooperation Society.2015; 16(5): 3284.     CrossRef
  • Reply to “Preoperative Evaluation of Pancreatic Adenocarcinoma”
    Siva P. Raman
    American Journal of Roentgenology.2015; 205(2): W226.     CrossRef
Diabetes Metab J : Diabetes & Metabolism Journal
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