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Pancreatic cancer and metabolism

Duguang Li, Xiaowei Qian, Peng Xu, Xiaodong Wang, Zhennan Li, Jianjun Qian, Jie Yao
Drug resistance is a major problem in the treatment of pancreatic cancer (PC). Long noncoding (lnc)RNAs modulate a variety of cellular processes. This study was carried out to identify lncRNAs that are differentially expressed in drug-resistant PC by next-generation RNA sequencing. We identified 205 differentially expressed lncRNAs (DELs) and 847 differentially expressed mRNAs (DEMs) in a comparison of gemcitabine-resistant and -sensitive SW1990 human PC cells. The expression levels of 12 randomly selected lncRNAs were confirmed by quantitative real-time PCR...
August 16, 2018: DNA and Cell Biology
Steven H Woolf, Derek A Chapman, Jeanine M Buchanich, Kendra J Bobby, Emily B Zimmerman, Sarah M Blackburn
OBJECTIVE: To systematically compare midlife mortality patterns in the United States across racial and ethnic groups during 1999-2016, documenting causes of death and their relative contribution to excess deaths. DESIGN: Trend analysis of US vital statistics among racial and ethnic groups. SETTING: United States, 1999-2016. POPULATION: US adults aged 25-64 years (midlife). MAIN OUTCOME MEASURES: Absolute changes in mortality measured as average year-to-year change during 1999-2016 and 2012-16; excess deaths attributable to increasing mortality; and relative changes in mortality measured as relative difference between mortality in 1999 versus 2016 and the nadir year versus 2016, and the slope of modeled mortality trends for 1999-2016 and for intervals between joinpoints...
August 15, 2018: BMJ: British Medical Journal
Biplab Giri, Sananda Dey, Tanaya Das, Mrinmoy Sarkar, Jhimli Banerjee, Sandeep Kumar Dash
Chronic exposure of glucose rich environment creates several physiological and pathophysiological changes. There are several pathways by which hyperglycemia exacerbate its toxic effect on cells, tissues and organ systems. Hyperglycemia can induce oxidative stress, upsurge polyol pathway, activate protein kinase C (PKC), enhance hexosamine biosynthetic pathway (HBP), promote the formation of advanced glycation end-products (AGEs) and finally alters gene expressions. Prolonged hyperglycemic condition leads to severe diabetic condition by damaging the pancreatic β-cell and inducing insulin resistance...
August 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yahui Kong, Chih-Heng Hsieh, Laura C Alonso
The CDKN2A/B genomic locus is associated with risk of human cancers and metabolic disease. Although the locus contains several important protein-coding genes, studies suggest disease roles for a lesser-known antisense lncRNA encoded at this locus, called ANRIL . ANRIL is a complex gene containing at least 21 exons in simians, with many reported linear and circular isoforms. Like other genes, abundance of ANRIL is regulated by epigenetics, classic transcription regulation, splicing, and post-transcriptional influences such as RNA stability and microRNAs...
2018: Frontiers in Endocrinology
Manendra Babu Lankadasari, Jayasekharan S Aparna, Sabira Mohammed, Shirley James, Kazunori Aoki, Valsalakumari S Binu, Sindhu Nair, Kuzhuvelil B Harikumar
Rationale: Pancreatic cancer is associated with poor prognosis with a 5-year survival rate of less than 6%. Approximately 90% of pancreatic cancer patients harbor somatic mutations in the KRAS gene. Multiple lines of evidence suggest a persistent activation of STAT3 in KRAS-driven oncogenesis contributing to desmoplasia and gemcitabine resistance. Sphingosine 1-phosphate receptor 1 (S1PR1) is an integral component of tumor progression and maintains an activated state of STAT3. FTY720 is an approved drug for multiple sclerosis and acts as a functional antagonist for S1PR1...
2018: Theranostics
Sophie Turpin, Marjorie Perron, Stéphanie Vairy, Sébastien Bénali, Amélie Damphousse
Pancreatic neoplasm is very rare in the pediatric population. Malignant tumors represent less than 0.2% of pediatric cancer-related mortality. Pancreas lesions can be from exocrine or endocrine origin or present themselves as cystic masses. Clinical, biological, and radiological findings usually are sufficient to establish diagnosis, but in some cases, they may be misleading. We present the case of a young patient presenting a pancreatic mass where anatomical and metabolic characteristics of the lesion were discordant to the final diagnosis...
August 4, 2018: Clinical Nuclear Medicine
Yuanjie Pang, Christiana Kartsonaki, Iain Turnbull, Yu Guo, Ling Yang, Zheng Bian, Yiping Chen, Iona Y Millwood, Fiona Bragg, Weiwei Gong, Qinai Xu, Quan Kang, Junshi Chen, Liming Li, Michael V Holmes, Zhengming Chen
BACKGROUND: Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults. METHODS AND FINDINGS: The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded...
August 2018: PLoS Medicine
Li-Chun Lin, Tzu-Ting Kuo, Hsin-Yi Chang, Wen-Shan Liu, Shih-Min Hsia, Tsui-Chin Huang
Marine sponges are known to produce numerous bioactive secondary metabolites as defense strategies to avoid predation. Manzamine A is a sponge-derived β-carboline-fused pentacyclic alkaloid with various bioactivities, including recently reported anticancer activity on pancreatic cancer. However, its cytotoxicity and mode of action against other tumors remain unclear. In this study, we exhibit that manzamine A reduced cell proliferation in several colorectal cancer (CRC) cell lines. To further investigate the manzamine A triggered molecular regulation, we analyzed the gene expression with microarray and revealed that pathways including cell cycle, DNA repair, mRNA metabolism, and apoptosis were dysregulated...
July 29, 2018: Marine Drugs
Enrica Saponara, Michele Visentin, Francesco Baschieri, Gitta Seleznik, Paola Martinelli, Irene Esposito, Johanna Buschmann, Rong Chen, Rossella Parrotta, Nathalie Borgeaud, Marta Bombardo, Ermanno Malagola, Amedeo Caflisch, Hesso Farhan, Rolf Graf, Sabrina Sonda
Pancreatic ductal adenocarcinoma (PDAC), the primary cause of pancreatic cancer mortality, is poorly responsive to currently available interventions. Identifying new targets that drive PDAC formation and progression is critical to develop alternative therapeutic strategies to treat this lethal malignancy. Using genetic and pharmacologic approaches, we investigated in vivo and in vitro whether uptake of the monoamine serotonin is required for PDAC development. We demonstrated that pancreatic acinar cells have the ability to readily take up serotonin in a transport-mediated manner...
July 30, 2018: Journal of Pathology
Bin Yan, Zhengdong Jiang, Liang Cheng, Ke Chen, Cancan Zhou, Liankang Sun, Weikun Qian, Jie Li, Junyu Cao, Qinhong Xu, Qingyong Ma, Jianjun Lei
Pancreatic stellate cells (PSCs), a pivotal component of the tumor microenvironment, contribute to tumor growth and metastasis. PSC-derived factors are essential for triggering the generation and maintenance of cancer stem cells (CSCs). However, the mechanisms by which paracrine signals regulate CSC-like properties such as glycolytic metabolism have not been fully elucidated. Here, we report that two pancreatic cancer cell lines, Panc-1 and MiaPaCa-2, reacted differently when treated with hepatocyte growth factor (HGF) secreted from PSCs...
July 26, 2018: Experimental Cell Research
Dominick G A Burton, Richard G A Faragher
Cellular senescence is now considered as a major mechanism in the development and progression of various diseases and this may include metabolic diseases such as obesity and type-2 diabetes. The presence of obesity and diabetes is a major risk factor in the development of additional health conditions, such as cardiovascular disease, kidney disease and cancer. Since senescent cells can drive disease development, obesity and diabetes can potentially create an environment that accelerates cell senescence within other tissues of the body...
July 27, 2018: Biogerontology
Stephen Bigelsen
Despite new and exciting research and renewed optimism about future therapy, current statistics of survival from pancreatic cancer remains dismal. Patients seeking alternative or complementary treatments should be warned to avoid the hype and instead look to real science. A variety of relatively safe and inexpensive treatment options that have shown success in preclinical models and/or retrospective studies are currently available. Patients require their physicians to provide therapeutic guidance and assistance in obtaining and administrating these various therapies...
2018: Cancer Management and Research
Chris E Forsmark
PURPOSE OF REVIEW: Recent studies have documented that many patients with pancreatic exocrine insufficiency (EPI) are not identified and are not treated with appropriate dosages of pancreatic enzyme replacement therapy. This review will summarize the approach to diagnosis, treatment, and monitoring for treatment effect and complications in patients with exocrine insufficiency. RECENT FINDINGS: While chronic pancreatitis is the most commonly identified cause of EPI, pancreatic cancer and pancreatic surgery are increasingly important...
July 19, 2018: Current Treatment Options in Gastroenterology
Musalula Sinkala, Nicola Mulder, Darren Patrick Martin
Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcomes to show that the three major pancreatic cancer subtypes each display distinctive aberrations in cell signaling and metabolic pathways...
June 26, 2018: Oncotarget
Michelle J Schmahl, Daniel P Regan, Adam C Rivers, William C Joesten, Michael A Kennedy
Pancreatic cancer is the third leading cause of cancer deaths in the United States with more than 53,000 expected to be diagnosed with the disease in 2018. The median survival time after diagnosis is four to six months. The poor survival statistics are due in part to the fact that pancreatic cancer is typically asymptomatic until it reaches advanced stages of the disease. Although surgical resection provides the best chance of survival, pancreatic cancer is rarely detected when surgery is still possible due, in part, to lack of effective biomarkers for early detection...
2018: PloS One
Yuchen Tang, Zixiang Zhang, Yaocheng Tang, Xinyu Chen, Jian Zhou
Pancreatic ductal adenocarcinoma (PDAC) is one of the most complicated and fatally pathogenic human malignancies. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of PDAC. The aim of the present study was to identify the key genes and signaling pathways associated with PDAC using bioinformatics analysis. Four transcriptome microarray datasets (GSE15471, GSE55643, GSE62165 and GSE91035) were acquired from Gene Expression Omnibus datasets, which included 226 PDAC samples and 65 normal pancreatic tissue samples...
August 2018: Oncology Letters
Chaoran Chen, Zhenxing Xie, Yingbin Shen, Shu Fang Xia
It is widely accepted that thyroid hormones (THs), secreted from the thyroid, play important roles in energy metabolism. It is also known that THs also alter the functioning of other endocrine glands; however, their effects on pancreatic function have not yet been reviewed. One of the main functions of the pancreas is insulin secretion, which is altered in diabetes. Diabetes, therefore, could be related to thyroid dysfunction. Earlier research on this subject focused on TH regulation of pancreas function (such as insulin secretion) or on insulin function through TH-mediated increase of energy metabolism...
2018: International Journal of Endocrinology
Kozo Noguchi, Masamitsu Konno, Jun Koseki, Naohiro Nishida, Koichi Kawamoto, Daisaku Yamada, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Daisuke Sakai, Toshihiro Kudo, Taroh Satoh, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Hideshi Ishii
The expression levels of one-carbon metabolic enzymes were investigated and observed to be correlated with clinicopathological parameters in patients with pancreatic cancer. Mitochondrial one-carbon metabolism comprises a network of biological reactions that integrate nutrient status with nucleotide synthesis, amino acid metabolism, antioxidant reduced nicotinamide adenine dinucleotide phosphate production and epigenetic methylation processes. Previous studies have reported that the hyper-activation of mitochondrial one-carbon metabolism serves a significant role in malignant cancer phenotypes...
August 2018: Oncology Letters
David Y Hui
The group 1B phospholipase A2 (PLA2G1B) is a secreted phospholipase that catalyzes the hydrolytic removal of the sn-2 fatty acyl moiety from phospholipids. This enzyme is synthesized most abundantly in the pancreas and is also expressed in the lung. The first part of this review article focuses on the role of pancreatic-derived PLA2G1B in mediating lipid absorption and discusses how the PLA2G1B-derived metabolic product contributes to cardiometabolic diseases, including obesity, hyperinsulinemia, hyperlipidemia, and atherosclerosis...
July 9, 2018: Biochimica et Biophysica Acta
Rui Ju, Kailun Fei, Siang Li, Chen Chen, Lei Zhu, Juan Li, Dechang Zhang, Lei Guo, Caiying Ye
The anti-cancer and anti-inflammatory effects of carboxyamidotriazole (CAI) have been demonstrated in several studies, but the underlying mechanisms remain to be elucidated. This study showed that CAI caused metabolic reprogramming of pancreatic cancer cells. The inhibition of mitochondrial oxidative metabolism by CAI led to increased glutamine-dependent reductive carboxylation and enhanced glycolytic metabolism. The presence of environmental substances that affect cellular metabolism, such as glutamine and pyruvate, attenuated the anti-cancer efficacy of CAI...
July 12, 2018: Journal of Pharmacology and Experimental Therapeutics
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