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Pancreatic cancer and metabolism

Feng Yin, Tommy Anderson, Nishtha Panwar, Kang Zhang, Swee Chuan Tjin, Beng Koon Ng, Ho Sup Yoon, Junle Qu, Ken-Tye Yong
Transition metal dichalcogenides (TMDCs) are categorized as novel two-dimensional (2D) nanomaterials with unique physical and chemical properties, bearing varied applications in medical and materials sciences. However, only a few works report the application of TMDCs for gene therapy in cancer treatment. Here, we engineer a multi-gene delivery system based on functionalized monolayer MoS2 , which can co-deliver HDAC1 and KRAS small interfering RNAs (siRNAs) to Panc-1 cancer cells for combinational cancer therapy...
2018: Nanotheranostics
Jiayu Liu, Nannan Song, Yibing Huang, Yuxin Chen
Irisin, a recently identified myokine that is released from skeletal muscle following exercise, regulates body weight and influences various metabolic diseases such as obesity and diabetes. In this study, human recombinant nonglycosylated P-irisin (expressed in Escherichia coli prokaryote cell system) or glycosylated E-irisin (expressed in Pichia pastoris eukaryote cell system) were compared to examine the role of recombinant irisin against pancreatic cancer (PC) cells lines, MIA PaCa-2 and Panc03.27. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-di phenyltetrazolium bromide] and cell colony formation assays revealed that irisin significantly inhibited the growth of MIA PaCa-2 and Panc03...
October 15, 2018: Scientific Reports
Young-Seon Kim, Yoon-Mi Lee, Taek-In Oh, Dong Hoon Shin, Geon-Hee Kim, Sang-Yeon Kan, Hyeji Kang, Ji Hyung Kim, Byeong Mo Kim, Woo Jong Yim, Ji-Hong Lim
Reduced therapeutic efficacy of sorafenib, a first-generation multikinase inhibitor, is often observed during the treatment of advanced hepatocellular carcinoma (HCC). Emodin is an active component of Chinese herbs, and is effective against leukemia, lung cancer, colon cancer, pancreatic cancer, and HCC; however, the sensitizing effect of emodin on sorafenib-based HCC therapy has not been evaluated. Here, we demonstrate that emodin significantly improved the anti-cancer effect of sorafenib in HCC cells, such as HepG2, Hep3B, Huh7, SK-HEP-1, and PLC/PRF5...
October 12, 2018: International Journal of Molecular Sciences
Sungwoo Hong, Zhenghuan Fang, Hoi-Yun Jung, Jin-Ha Yoon, Soon-Sun Hong, Han-Joo Maeng
To investigate the amino acid transporter-based prodrug anticancer strategy further, several amino acid-conjugated amide gemcitabine prodrugs were synthesized to target amino acid transporters in pancreatic cancer cells. The structures of the synthesized amino acid-conjugated prodrugs were confirmed by ¹H-NMR and LC-MS. The pancreatic cancer cells, AsPC1, BxPC-3, PANC-1 and MIAPaCa-2, appeared to overexpress the amino acid transporter LAT-1 by conventional RT-PCR. Among the six amino acid derivatives of gemcitabine, threonine derivative of gemcitabine (Gem-Thr) was more effective than free gemcitabine in the pancreatic cancer cells, BxPC-3 and MIAPaCa-2, respectively, in terms of anti-cancer effects...
October 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Rui He, Yue Yin, Wenzhen Yin, Yin Li, Jing Zhao, Weizhen Zhang
Roux-en-Y Gastric Bypass Surgery (RYGB) prevents the occurrence of pancreatic cell acinar carcinoma (ACC) in male and female Ngn3-Tsc1-/- mice. Ngn3 directed Cre deletion of Tsc1 gene induced the development of pancreatic ACC. The transgenic mice with sham surgery demonstrated a cancer incidence of 96.7 ± 3.35% and survival rate of 67.0 ± 1.4% at the age of 300 days. Metastasis to liver and kidney was observed in 69.7 ± 9.7% and 44.3 ± 8.01% of these animals, respectively. All animals with RYGB performed at the age of 16 weeks survived free of pancreatic ACC up to the age of 300 days...
October 10, 2018: Nature Communications
Maria R Depaoli, Felix Karsten, Corina T Madreiter-Sokolowski, Christiane Klec, Benjamin Gottschalk, Helmut Bischof, Emrah Eroglu, Markus Waldeck-Weiermair, Thomas Simmen, Wolfgang F Graier, Roland Malli
Reprogramming of metabolic pathways determines cell functions and fate. In our work, we have used organelle-targeted ATP biosensors to evaluate cellular metabolic settings with high resolution in real time. Our data indicate that mitochondria dynamically supply ATP for glucose phosphorylation in a variety of cancer cell types. This hexokinase-dependent process seems to be reversed upon the removal of glucose or other hexose sugars. Our data further verify that mitochondria in cancer cells have increased ATP consumption...
October 9, 2018: Cell Reports
Giovanna Butera, Raffaella Pacchiana, Nidula Mullappilly, Marilena Margiotta, Stefano Bruno, Paola Conti, Chiara Riganti, Massimo Donadelli
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and devastating human malignancies. In about 70% of PDACs the tumor suppressor gene TP53 is mutated generally resulting in conformational changes of mutant p53 (mutp53) proteins, which acquire oncogenic functions triggering aggressiveness of cancers and alteration of energetic metabolism. Here, we demonstrate that mutant p53 prevents the nuclear translocation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) stabilizing its cytoplasmic localization, thus supporting glycolysis of cancer cells and inhibiting cell death mechanisms mediated by nuclear GAPDH...
October 5, 2018: Biochimica et biophysica acta. Molecular cell research
Gauri Lamture, Peter A Crooks, Michael J Borrelli
Preclinical Research & Development Pancreatic cancer is the third leading cause of death in the US with a poor 5-year survival rate of 8.5%. A novel anti-cancer drug, dimethylamino parthenolide (DMAPT), is the water-soluble analog of the natural sesquiterpene lactone, parthenolide. The putative modes of action of DMAPT are inhibition of the Nuclear chain factor kappa-light-chain enhancer of activated B cells (NFκB) pathway and depletion of glutathione levels; the latter causing cancer cells to be more susceptible to oxidative stress-induced cell death...
September 2018: Drug Development Research
Jie Lin, Yan-Jun Wu, Xing Liang, Meng Ji, Hui-Min Ying, Xin-Yu Wang, Xia Sun, Cheng-Hao Shao, Li-Xing Zhan, Yan Zhang
Pancreatic cancer is regarded as the most fatal and aggressive malignancy cancer due to its low 5-year survival rate and poor prognosis. The approaches of early diagnosis and treatment are limited, which makes it urgent to identify the complex mechanism of pancreatic oncogenesis. In this study, we used RNA-seq to investigate the transcriptomic (mRNA and miRNA) profiles of pancreatic cancer in paired tumor and normal pancreatic samples from ten patients. More than 1000 differentially expressed genes were identified, nearly half of which were also found to be differentially expressed in the majority of examined patients...
October 8, 2018: Molecular Carcinogenesis
Vineet Kumar Gupta, Nikita S Sharma, Kousik Kesh, Patricia Dauer, Alice Nomura, Bhuwan Giri, Vikas Dudeja, Santanu Banerjee, Sanjoy Bhattacharya, Ashok Saluja, Sulagna Banerjee
Metabolic rewiring is an integral part of tumor growth. Among metabolic pathways, the Mevalonic-Acid-Pathway (MVAP) plays a key role in maintaining membrane architecture through cholesterol synthesis, thereby affecting invasiveness. In the current study, we show for the first time that CD133Hi pancreatic tumor initiating cells (TIC) have increased expression of MVAP enzymes, cholesterol-content and Caveolin expression. Further, we show that CD133 in these cells is localized in the lipid-rafts (characterized by Cav-1-cholesterol association)...
October 2, 2018: Cancer Letters
M Perusina Lanfranca, J K Thompson, F Bednar, C Halbrook, C Lyssiotis, B Levi, T L Frankel
No abstract text is available yet for this article.
September 28, 2018: Seminars in Cancer Biology
Lenka Michálková, Štěpán Horník, Jan Sýkora, Lucie Habartová, Vladimír Setnička
Metabolic changes induced by pancreatic cancer were investigated by 1H NMR spectroscopy of plasma samples of patients and healthy controls. The acquired data were submitted to multivariate statistical analysis providing clear discrimination between both groups. The most significant differences were found in levels of 3-hydroxybutyrate and lactate. The obtained results (100% sensitivity, 90% specificity) clearly show the potential of 1H NMR spectroscopy in pancreatic cancer diagnosis. Therefore, the NMR-based metabolomics may contribute to the early diagnosis, prevention and/or therapy of diseases in the future...
October 1, 2018: Analyst
Aura D Herrera-Martínez, Sergio Pedraza-Arevalo, Fernando L-López, Manuel D Gahete, María A Gálvez-Moreno, Justo P Castaño, Raúl M Luque
Background: Biguanides and statins have been reported to exert beneficial effects on various cancer types. However, their precise effects and underlying molecular mechanisms are still poorly understood. Materials and Methods: We analyzed the relation between metabolic-syndrome, i.e., presence of type-2 diabetes (T2DM), hyperlipidemia and their treatment, with histological, epidemiological, and prognosis variables in two patient cohorts with neuroendocrine-tumors [NETs: lung-carcinoids (LCs; n=81) and gastro-entero-pancreatic (GEP-NET; n=100)]...
September 27, 2018: Journal of Clinical Endocrinology and Metabolism
Federica Sotgia, Bela Ozsvari, Marco Fiorillo, Ernestina Marianna De Francesco, Gloria Bonuccelli, Michael P Lisanti
Here, we wish to propose a new systematic approach to cancer therapy, based on the targeting of mitochondrial metabolism, especially in cancer stem cells (CSCs). In the future, we envision that anti-mitochondrial therapy would ultimately be practiced as an add-on to more conventional therapy, largely for the prevention of tumor recurrence and cancer metastasis. This mitochondrial based oncology platform would require a panel of FDA-approved therapeutics (e.g. Doxycycline) that can safely be used to inhibit mitochondrial OXPHOS and/or biogenesis in CSCs...
September 26, 2018: Cell Cycle
Rui Kang, Yangchun Xie, Herbert J Zeh, Daniel J Klionsky, Daolin Tang
Mitochondrial quality control is an essential process required to maintain cellular homeostasis and functions. Mutations of PINK1 and PRKN/PARK2 contribute to the risk of Parkinson disease. Our recent findings indicate that depletion of Pink1 and Prkn promotes pancreatic tumorigenesis in KRAS-driven engineered mouse models. Mechanistically, PINK1- and PRKN-mediated autophagic degradation of mitochondrial iron importers (e.g., SLC25A37 and SLC25A28) suppresses pancreatic tumor growth by attenuating mitochondrial iron accumulation, inflammasome activation, HMGB1 release, and subsequent immune checkpoint expression...
September 25, 2018: Autophagy
James Osei-Owusu, Junhua Yang, Maria Del Carmen Vitery, Zhaozhu Qiu
The Volume-Regulated Anion Channel (VRAC) is activated by cell swelling and plays a key role in cell volume regulation. VRAC is ubiquitously expressed in vertebrate cells and also implicated in many other physiological and cellular processes including fluid secretion, glutamate release, membrane potential regulation, cell proliferation, migration, and apoptosis. Although its biophysical properties have been well characterized, the molecular identity of VRAC remained a mystery for almost three decades. The field was transformed by recent discoveries showing that the leucine-rich repeat-containing protein 8A (LRRC8A, also named SWELL1) and its four other homologs form heteromeric VRAC channels...
2018: Current Topics in Membranes
Joseph Zhou, Scott Massey, Darren Story, Lixin Li
Metformin is a biguanide drug that has been used to treat type 2 diabetes mellitus for more than 60 years. The United Kingdom Prospective Diabetic Study (UKPDS) has shown metformin to improve mortality rates in diabetes patients, and recent studies suggest metformin has additional effects in treating cancer, obesity, nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic syndrome. Metformin has also been shown to alleviate weight gain associated with antipsychotic medication...
September 21, 2018: International Journal of Molecular Sciences
Arianna Scuteri, Marianna Monfrini
Diabetes is a worldwide disease which actually includes different disorders related to glucose metabolism. According to different epidemiological studies, patients affected by diabetes present a higher risk to develop both acute and chronic pancreatitis, clinical situations which, in turn, increase the risk to develop pancreatic cancer. Current therapies are able to adjust insulin levels according to blood glucose peak, but they only partly reach the goal to abrogate the consequent inflammatory milieu responsible for diabetes-related diseases...
September 16, 2018: International Journal of Molecular Sciences
Hala Salim Sonbol
The extracellular matrix (ECM) is a meshwork of proteins and carbohydrates that supports many biological structures and processes, from tissue development and elasticity to preserve the structures of entire organs. In each organ, the composition of the ECM is distinct. It is a remarkably active three-dimensional structure that is continuously undergoing remodeling to regulate tissue homeostasis. This review aims to explain the role of ECM proteins in the remodeling process in different types of disease. The hardening of the ECM (desmoplasia), as well as its manipulation, induction, and impairment in regulation of its composition can play a role in several diseases, examples of which are chronic obstructive pulmonary disease, pancreatic ductal adenocarcinoma, spinal cord injury, progression and metastasis of breast cancer, and neurodegenerative condition in the brain such as Alzheimer's disease...
July 2018: Journal of microscopy and ultrastructure
Jin Young Park, H Bas Bueno-de-Mesquita, Pietro Ferrari, Elisabete Weiderpass, Jordi de Batlle, Anne Tjønneland, Cecilie Kyro, Vinciane Rebours, Marie-Christine Boutron-Ruault, Francesca Romana Mancini, Verena Katzke, Tilman Kühn, Heiner Boeing, Antonia Trichopoulou, Carlo La Vecchia, Maria Kritikou, Giovanna Masala, Valeria Pala, Rosario Tumino, Salvatore Panico, Petra H Peeters, Guri Skeie, Susana Merino, Eric J Duell, Miguel Rodríguez-Barranco, Miren Dorronsoro, Maria-Dolores Chirlaque, Eva Ardanaz, Björn Gylling, Jörn Schneede, Ulrika Ericson, Hanna Sternby, Kay-Tee Khaw, Kathryn E Bradbury, Inge Huybrechts, Dagfinn Aune, Paolo Vineis, Nadia Slimani
Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded...
September 4, 2018: International Journal of Cancer. Journal International du Cancer
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