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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/29684618/everolimus-is-a-new-anti-cancer-molecule-metabolic-side-effects-as-lipid-disorders-and-hyperglycemia
#1
REVIEW
L Morviducci, F Rota, L Rizza, P Di Giacinto, S Ramponi, M R Nardone, C Tubili, A Lenzi, P Zuppi, R Baldelli
In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors (Yao, 2011; Jensenn, 2012). It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1...
April 20, 2018: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29683977/slco1b1-polymorphism-is-a-drug-response-predictive-marker-for-advanced-pancreatic-cancer-patients-treated-with-gemcitabine-s-1-or-gemcitabine-plus-s-1
#2
Yasunori Sato, Hideki Ueno, Tatsuya Ioka, Shinichi Ohkawa, Masafumi Ikeda, Tomotaka Shimamura, Akihito Tsuji, Yoshiaki Tsuchiya, Junji Furuse, Hiroshi Ishii, Ken Furuya, Haruo Iguchi, Yoshihiro Saito, Nahoko Kaniwa, Jun-Ichi Sawada, Hiromi Sakamoto, Akihiro Sekine, Takuji Okusaka, Teruhiko Yoshida
OBJECTIVES: The aim of this study was to evaluate the effects of single-nucleotide polymorphisms (SNPs) on advanced pancreatic cancer risk and overall survival (OS) in a candidate-gene approach. METHODS: Overall, 5438 SNPs in 219 candidate genes encoding several drug-metabolizing enzymes or transporters were analyzed. In the screening study, 3 SNPs were found associated with OS (P ≤ 0.0005). We validated these SNPs as part of the randomized phase 3 study (GEST study)...
April 19, 2018: Pancreas
https://www.readbyqxmd.com/read/29682162/metabolic-alterations-in-a-slow-paced-model-of-pancreatic-cancer-induced-wasting
#3
Elisabeth Wyart, Simone Reano, Myriam Y Hsu, Dario Livio Longo, Mingchuan Li, Emilio Hirsch, Nicoletta Filigheddu, Alessandra Ghigo, Chiara Riganti, Paolo Ettore Porporato
Cancer cachexia is a devastating syndrome occurring in the majority of terminally ill cancer patients. Notably, skeletal muscle atrophy is a consistent feature affecting the quality of life and prognosis. To date, limited therapeutic options are available, and research in the field is hampered by the lack of satisfactory models to study the complexity of wasting in cachexia-inducing tumors, such as pancreatic cancer. Moreover, currently used in vivo models are characterized by an explosive cachexia with a lethal wasting within few days, while pancreatic cancer patients might experience alterations long before the onset of overt wasting...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29670543/phosphoinositide-3-kinase-signaling-pathway-in-pancreatic-ductal-adenocarcinoma-progression-pathogenesis-and-therapeutics
#4
REVIEW
Divya Murthy, Kuldeep S Attri, Pankaj K Singh
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by its sudden manifestation, rapid progression, poor prognosis, and limited therapeutic options. Genetic alterations in key signaling pathways found in early pancreatic lesions are pivotal for the development and progression of pancreatic intraepithelial neoplastic lesions into invasive carcinomas. More than 90% of PDAC tumors harbor driver mutations in K-Ras that activate various downstream effector-signaling pathways, including the phosphoinositide-3-kinase (PI3K) pathway...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29665526/novel-hydrazide-hydrazone-and-amide-substituted-coumarin-derivatives-synthesis-cytotoxicity-screening-microarray-radiolabeling-and-in-vivo-pharmacokinetic-studies
#5
Tamer Nasr, Samir Bondock, Hassan M Rashed, Walid Fayad, Mahmoud Youns, Tamer M Sakr
The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7...
April 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29650943/-a-useful-case-of-photodynamic-diagnosis-of-inferior-vena-cava-invasion-by-pancreatic-head-cancer-using-5-aminolevulinic-acid-5-ala
#6
Toru Mizutani, Yasutoshi Murayama, Hisashi Ikoma, Tomohiro Arita, Toshiyuki Kosuga, Hirotaka Konishi, Ryo Morimura, Atsushi Shiozaki, Yoshiaki Kuriu, Masayoshi Nakanishi, Hitoshi Fujiwara, Kazuma Okamoto, Eigo Otsuji
Curative resection is necessary to survival in pancreatic cancer, however after surgery, pathologic examination sometimes diagnoses the remains of cancer at the resected stump. Therefore, it is necessary to evaluate the stump by intraoperative rapid pathological examination. 5-aminolevulinic acid(5-ALA)is an endogenous natural amino acid and precursor of the heme pathway. 5-ALA is metabolized and accumulated as protoporphyrin IX(Pp IX)that is photosensitive substance. 5-ALA mediated photodynamic diagnosis(PDD)(ALA-PDD)has high diagnostic ability...
March 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29628435/dependence-on-the-pyrimidine-biosynthetic-enzyme-dhodh-is-a-synthetic-lethal-vulnerability-in-mutant-kras-driven-cancers
#7
Malvika Koundinya, Judith Sudhalter, Albane Courjaud, Bruno Lionne, Gaetan Touyer, Luc Bonnet, Isabelle Menguy, Isabelle Schreiber, Christelle Perrault, Stephanie Vougier, Brigitte Benhamou, Bailin Zhang, Timothy He, Qiang Gao, Patricia Gee, Daniel Simard, M Paola Castaldi, Ronald Tomlinson, Stephan Reiling, Matthieu Barrague, Richard Newcombe, Hui Cao, Yanjun Wang, Fangxian Sun, Joshua Murtie, Mark Munson, Eric Yang, David Harper, Monsif Bouaboula, Jack Pollard, Claudine Grepin, Carlos Garcia-Echeverria, Hong Cheng, Francisco Adrian, Christopher Winter, Stuart Licht, Ivan Cornella-Taracido, Rosalia Arrebola, Aaron Morris
Activating KRAS mutations are major oncogenic drivers in multiple tumor types. Synthetic lethal screens have previously been used to identify targets critical for the survival of KRAS mutant cells, but their application to drug discovery has proven challenging, possibly due in part to a failure of monolayer cultures to model tumor biology. Here, we report the results of a high-throughput synthetic lethal screen for small molecules that selectively inhibit the growth of KRAS mutant cell lines in soft agar. Chemoproteomic profiling identifies the target of the most KRAS-selective chemical series as dihydroorotate dehydrogenase (DHODH)...
April 3, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29623758/targeting-altered-cancer-methionine-metabolism-with-recombinant-methioninase-rmetase-overcomes-partial-gemcitabine-resistance-and-regresses-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model-of-pancreatic-cancer
#8
Kei Kawaguchi, Kentaro Miyake, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Thinzar M Lwin, Takashi Higuchi, Tasuku Kiyuna, Masuyo Miyake, Hiromichi Oshiro, Michael Bouvet, Michiaki Unno, Robert M Hoffman
Pancreatic cancer is a recalcitrant disease. Gemcitabine (GEM) is the most widely-used first-line therapy for pancreatic cancer, but most patients eventually fail. Transformative therapy is necessary to significantly improve the outcome of pancreatic cancer patients. Our and other's previous work has demonstrated tumors have an elevated requirement for methionine and are susceptible to methionine restriction. The present study used a patient-derived orthotopic xenograft (PDOX) nude mouse model of pancreatic cancer to determine the efficacy of recombinant methioninase (rMETase) to effect methionine restriction and thereby overcome GEM-resistance...
April 6, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29609556/the-warburg-effect-in-human-pancreatic-cancer-cells-triggers-cachexia-in-athymic-mice-carrying-the-cancer-cells
#9
Feng Wang, Hongyi Liu, Lijuan Hu, Yunfei Liu, Yijie Duan, Rui Cui, Wencong Tian
BACKGROUND: Cancer cachexia is a cancer-induced metabolic disorder and a major cause of cancer-induced death. The constituents of cancer cachexia include an increase in energy expenditure, hepatic gluconeogenesis, fat lipolysis, and skeletal-muscle proteolysis and a decrease in body weight. The aetiology of cancer cachexia is unclear and may involve cancer-cell metabolism and secretion. In this study, we investigated whether the high glycolysis in cancer cells (the Warburg effect) triggers cachexia in athymic mice carrying pancreatic cancer cells...
April 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29609037/%C3%AE-cyano-4-hydroxycinnamate-impairs-pancreatic-cancer-cells-by-stimulating-the-p38-signaling-pathway
#10
Maria Schönrogge, Hagen Kerndl, Xianbin Zhang, Simone Kumstel, Brigitte Vollmar, Dietmar Zechner
Multiple studies are currently targeting dysregulated cancer cell metabolism with distinct combinations of inhibitors. In this study, we evaluated in pancreatic cancer cells metformin, which blocks oxidative phosphorylation, in combination with α-cyano-4-hydroxycinnamate, which has been reported to inhibit the export of lactate from the cytosol. The combination of metformin with α-cyano-4-hydroxycinnamate had a major inhibitory effect on the migration of 6606PDA cells. Monotherapy with α-cyano-4-hydroxycinnamate and especially the combination with metformin also caused significant inhibition of cell proliferation and induced cell death...
March 30, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29587668/knockdown-delta-5-desaturase-in-breast-cancer-cells-that-overexpress-cox-2-results-in-inhibition-of-growth-migration-and-invasion-via-a-dihomo-%C3%AE-linolenic-acid-peroxidation-dependent-mechanism
#11
Yi Xu, Xiaoyu Yang, Tao Wang, Liu Yang, Yu-Ying He, Keith Miskimins, Steven Y Qian
BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible COX form, is a bi-functional membrane-bound enzyme that typically metabolizes arachidonic acid (downstream ω-6 fatty acid) to form 2-series of prostaglandins known to be involved in cancer development. Overexpression of COX-2 has been found in a majority of breast carcinomas, and has also been associated with increased severity and the development of the metastasis. Our lab recently demonstrated that COX-2 can also metabolize dihomo-γ-linolenic acid (DGLA, a precursor of ω-6 arachidonic acid) to produce an anti-cancer byproduct, 8-hydroxyoctanoic acid (8-HOA) that can inhibit growth and migration of colon and pancreatic cancer cells...
March 27, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29575390/metabolome-analysis-for-pancreatic-cancer-risk-in-nested-case-control-study-jphc-study
#12
Takashi Nakagawa, Takashi Kobayashi, Shin Nishiumi, Akihisa Hidaka, Taiki Yamaji, Norie Sawada, Yuichi Hirata, Kodai Yamanaka, Takeshi Azuma, Atsushi Goto, Taichi Shimazu, Manami Inoue, Motoki Iwasaki, Masaru Yoshida, Shoichiro Tsugane
Discovery of the high risk group of pancreatic cancer is important for prevention of pancreatic cancer. This study was conducted in a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30,239 subjects who answered a baseline questionnaire and supplied blood samples. The 12 targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. The odds ratios and their corresponding 95% confidence intervals were calculated using conditional logistic regression models...
March 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/29556128/formulation-characterization-cytotoxicity-and-salmonella-microsome-mutagenicity-ames-studies-of-a-novel-5-fluorouracil-derivative
#13
Çinel Köksal Karayildirim, Mustafa Kotmakçi, Erkan Halay, Kadir Ay, Yücel Başpinar
5-Fluorouracil is one of the first line drugs for the systemic therapy of solid tumors like breast, colorectal, oesophageal, stomach, pancreatic, head and neck. It could be shown that sugars can improve the absorption across cell membranes and can help to bypass some pharmacokinetic problems. Carbohydrates as most common organic molecules are an important issue of plant and animal metabolisms. They are non toxic and have important duties in the body like participating in DNA and RNA synthesis and being responsible for energy production...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29552293/targeting-stearoyl-coa-desaturase-1-to-repress-endometrial-cancer-progression
#14
Weihua Li, Huimin Bai, Shiping Liu, Dongyan Cao, Hongying Wu, Keng Shen, Yanhong Tai, Jiaxin Yang
Stearoyl-CoA desaturase 1 (SCD1) is an established molecular target in many primary tumors including breast, lung, pancreatic, colon and hepatocellular carcinomas. However, its potential role in supporting endometrial cancer growth and progression has not yet been determined. In this study, we evaluated the value of SCD1 as a candidate therapeutic target in human endometrial cancer. Compared with secretory and post-menopausal endometrium, SCD1 was highly expressed in normal endometrium of proliferative phase, endometrial hyperplasia and endometrial carcinoma, while was absent or low expression in non-malignant control stromal cells and adjacent normal endometrium...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29548696/gut-microbiota-and-mtor-signaling-insight-on-a-new-pathophysiological-interaction
#15
REVIEW
Mohamed H Noureldein, Assaad A Eid
The gut microbiota plays a substantial role in regulating the host metabolic and immune functions. Dysbiosis, resulting from disruption of gut microbiota, predisposes many morbid pathologies like obesity and its associated comorbidities, diabetes and inflammatory conditions including some types of cancer. There are numerous proposed signaling pathways through which alterations in gut microbiota and its metabolites can disturb the host's normal physiological functions. Interestingly, many of these processes happen to be controlled by the mammalian target of rapamycin (mTOR)...
March 13, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29545590/on-target-action-of-anti-tropomyosin-drugs-regulates-glucose-metabolism
#16
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29543757/abc-transporters-and-their-role-in-the-neoadjuvant-treatment-of-esophageal-cancer
#17
REVIEW
David Vrana, Viktor Hlavac, Veronika Brynychova, Radka Vaclavikova, Cestmir Neoral, Jiri Vrba, Rene Aujesky, Marcel Matzenauer, Bohuslav Melichar, Pavel Soucek
The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful...
March 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29541401/intra-tumor-l-methionine-level-highly-correlates-with-tumor-size-in-both-pancreatic-cancer-and-melanoma-patient-derived-orthotopic-xenograft-pdox-nude-mouse-models
#18
Kei Kawaguchi, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Bartosz Chemielwski, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Arun S Singh, Mark A Eckardt, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
An excessive requirement for methionine (MET) for growth, termed MET dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by MET restriction such as with recombinant methioninase (rMETase). In the present study, we utilized patient-derived orthotopic xenograft (PDOX) nude mouse models with pancreatic cancer or melanoma to determine the relationship between intra-tumor MET level and tumor size. After the tumors grew to 100 mm3 , the PDOX nude mice were divided into two groups: untreated control and treated with rMETase (100 units, i...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29532765/starch-synthase-iiia-and-starch-branching-enzyme-iib-deficient-mutant-rice-line-ameliorates-pancreatic-insulin-secretion-in-rats-screening-and-evaluating-mutant-rice-lines-with-antidiabetic-functionalities
#19
Yasutake Tanaka, Kiyomi Takahashi, Jun-Ichi Kato, Ai Sawazaki, Taiki Akasaka, Naoko Fujita, Toshihide Kumamaru, Yuhi Saito, Bungo Shirouchi, Masao Sato
Diabetes mellitus is a metabolic disease spreading worldwide that has been reported to worsen the development and progression of other diseases (cancer, vascular diseases and dementia). To establish functional rice lines with anti-postprandial hyperglycaemic effects, we developed mutant rice lines, which lack one or two gene(s) related to starch synthesis, and evaluated their effects. Powder of mutant rice lines or other grains was loaded to rats fasted overnight (oral grain powder loading test). Incremental area under time-concentration curves (iAUC) were calculated with monitored blood glucose levels...
March 13, 2018: British Journal of Nutrition
https://www.readbyqxmd.com/read/29527315/effect-of-exercise-therapy-on-sarcopenia-in-pancreatic-cancer-a-study-protocol-for-a-randomised-controlled-trial
#20
Kazunori Yoh, Hiroki Nishikawa, Hirayuki Enomoto, Noriko Ishii, Yoshinori Iwata, Akio Ishii, Yukihisa Yuri, Yuho Miyamoto, Kunihiro Hasegawa, Chikage Nakano, Ryo Takata, Takashi Nishimura, Nobuhiro Aizawa, Yoshiyuki Sakai, Naoto Ikeda, Tomoyuki Takashima, Hiroko Iijima, Shuhei Nishiguchi
Introduction and purpose: Sarcopenia is defined as a decrease in muscle mass and muscle strength, and it has been demonstrated to be an adverse predictor in numerous types of cancers. Exercise therapy (ET) carries multiple health benefits in several diseases. Despite these clinical benefits, there are limited data available regarding patients with pancreatic cancer (PC) undergoing ET. We aim to prospectively examine the effect of ET on sarcopenia in patients with PC. Methods and analysis: All clinical stages of PC can be included...
2018: BMJ Open Gastroenterology
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