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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/29445052/increase-in-breath-hydrogen-concentration-was-correlated-with-the-main-pancreatic-duct-stenosis
#1
Daisuke Sakai, Yoshiki Hirooka, Hiroki Kawashima, Eizaburo Ohno, Takuya Ishikawa, Hiroki Suhara, Tomoaki Takeyama, Toshinari Koya, Hiroyuki Tanaka, Tadashi Iida, Ryo Nishio, Hirotaka Suzuki, Kota Uetsuki, Masanobu Matsushita, Takeshi Yamamura, Kazuhiro Furukawa, Kohei Funasaka, Masanao Nakamura, Ryoji Miyahara, Osamu Watanabe, Masatoshi Ishigami, Akihiro Tsuruta, Woosuck Shin, Hidemi Goto
Hydrogen is produced from unabsorbed carbohydrates in the intestine through degradation and metabolism by hydrogenase of intestinal bacteria. The hydrogen is then partially diffused into blood flow and released and detected in exhaled breath. Pancreatic juice production is decreased in patients with reduced pancreatic exocrine function, including those with pancreatic cancer, thus decreasing digestion and absorption of nutrients including carbohydrates, which may increase undigested carbohydrates in the intestine and increase breath hydrogen concentration (BHC)...
February 15, 2018: Journal of Breath Research
https://www.readbyqxmd.com/read/29436682/fatostatin-suppresses-growth-and-enhances-apoptosis-by-blocking-srebp-regulated-metabolic-pathways-in-endometrial-carcinoma
#2
Shuhong Gao, Zhengzheng Shi, Xin Li, Wenzhi Li, Yiling Wang, Zhiming Liu, Jie Jiang
Fatostatin, a chemical inhibitor of the sterol regulatory element‑binding protein (SREBP) pathway, has been reported to possess high antitumor activity against prostate and pancreatic cancer. The main aim of the present study was to investigate the effects and mechanism of fatostatin in endometrial carcinoma (EC). In the present study, we determined that fatostatin inhibited EC cell viability and colony formation capacity, decreased the invasive and migratory capacities of EC cells, induced EC cell cycle arrest at the G2/M phase and stimulated caspase‑mediated apoptosis of EC cells...
February 13, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29420223/oxidative-phosphorylation-as-an-emerging-target-in-cancer-therapy
#3
Thomas M Ashton, W Gillies McKenna, Leoni A Kunz-Schughart, Geoff S Higgins
Cancer cells have upregulated glycolysis compared to normal cells, which has led many to the assumption that oxidative phosphorylation (OXPHOS) is downregulated in all cancers.  However, recent studies have shown that OXPHOS can be also upregulated in certain cancers, including leukemias, lymphomas, pancreatic ductal adenocarcinoma, high OXPHOS subtype melanoma and endometrial carcinoma, and that this can occur even in the face of active glycolysis.  OXPHOS inhibitors could therefore be used to target cancer subtypes in which OXPHOS is upregulated, and to alleviate therapeutically adverse tumor hypoxia...
February 2, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29397631/development-of-epidermal-growth-factor-receptor-targeted-therapy-in-pancreatic-cancer
#4
Liu Qing, Wang Qing
The epidermal growth factor receptor (EGFR) family are a series of important cancer therapeutic targets involved in cancer biology. These genes play an important role in tumor biological characteristics including angiogenesis, cell survival, invasion and glucose metabolism. In recent years, progresses have been achieved upon the cellular and molecular biological characteristics of EGFR and its role in cancer development based on the study of tumor specimens and experimental animal model. EGFR(HER1/ErbB) is overexpressed in over sixty percent of triple-negative breast cancers and occurs in pancreatic, bladder, lung and head-and-neck cancers...
February 1, 2018: Minerva Chirurgica
https://www.readbyqxmd.com/read/29393429/notch-signaling-molecule-is-involved-in-the-invasion-of-miapaca2-cells-induced-by-cocl2-via-regulating-epithelial%C3%A2-mesenchymal-transition
#5
Ding-Wei Chen, Hong Wang, Ya-Fang Bao, Kun Xie
Pancreatic cancer exhibits a high mortality rate resulting from metastasis and there is currently no effective treatment strategy. Hypoxia serves an important role in cancer cells, where cellular metabolic rate is high. The underlying mechanisms that trigger hypoxia and the invasion of pancreatic cancer cells remain unknown. Investigation of the importance of hypoxia in the invasion of pancreatic cancer cells for potential, novel treatment strategies is of primary concern. Cell Counting Kit‑8 assay, invasion assay, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate invasion and epithelial mesenchymal transition (EMT) and the expression of Notch1 in MiaPaCa2 cells treated with cobalt II chloride (CoCl2)...
January 26, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29393401/pyruvate-kinase-type-m2-contributes-to-the-development-of-pancreatic-ductal-adenocarcinoma-by-regulating-the-production-of-metabolites-and-reactive-oxygen-species
#6
Misa Yokoyama, Nobuhiro Tanuma, Rie Shibuya, Takeharu Shiroki, Makoto Abue, Kuniharu Yamamoto, Koh Miura, Kazunori Yamaguchi, Ikuro Sato, Keiichi Tamai, Kennichi Satoh
The majority of cancer cells maintain a high glycolytic activity and an increased lactate production, even in a well oxygenated environment. This phenomenon is known as the Warburg effect. Previous studies have revealed that various types of cancer selectively express the pyruvate kinase M2 isoform (PKM2), and that PKM2 plays a pivotal role in the Warburg effect. Although elevated PKM2 levels have been observed in pancreatic cancer and other types of cancer, little is known about the biological function of PKM2...
January 30, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29384525/mtor-inhibitor-based-combination-therapies-for-pancreatic-cancer
#7
Zonera Hassan, Christian Schneeweis, Matthias Wirth, Christian Veltkamp, Zahra Dantes, Benedikt Feuerecker, Güralp O Ceyhan, Shirley K Knauer, Wilko Weichert, Roland M Schmid, Roland Stauber, Alexander Arlt, Oliver H Krämer, Roland Rad, Maximilian Reichert, Dieter Saur, Günter Schneider
BACKGROUND: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. METHODS: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance...
January 2, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29374159/the-responsively-decreased-pkm2-facilitates-the-survival-of-pancreatic-cancer-cells-in-hypoglucose
#8
Xiang Li, Shichang Deng, Mingliang Liu, Yan Jin, Shuai Zhu, Shijiang Deng, Jingyuan Chen, Chi He, Qi Qin, Chunyou Wang, Gang Zhao
Cancer cells predominantly produce energy at a high rate of glycolysis even in aerobic environment. It is termed as Warburg effect and is necessary for the tumorigenesis. Studies showed pyruvate kinase M2 (PKM2), a key regulator of the Warburg effect, is overexpressed and involved in numerous cancers. However, the expression and function of PKM2 in pancreatic cancer (PC) remain undefined. Our results showed that PKM2 is overexpressed in the PC tissue compared to the peritumoral tissue. Unexpected, the downregulation of PKM2 did not affect the proliferation, invasion, and chemoresistance of PC cells...
January 26, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29373514/the-ever-evolving-concept-of-the-cancer-stem-cell-in-pancreatic-cancer
#9
REVIEW
Sandra Valle, Laura Martin-Hijano, Sonia Alcalá, Marta Alonso-Nocelo, Bruno Sainz
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is the 4th most frequent cause of cancer-related death worldwide, primarily due to the inherent chemoresistant nature and metastatic capacity of this tumor. The latter is believed to be mainly due to the existence of a subpopulation of highly plastic "stem"-like cells within the tumor, known as cancer stem cells (CSCs), which have been shown to have unique metabolic, autophagic, invasive, and chemoresistance properties that allow them to continuously self-renew and escape chemo-therapeutic elimination...
January 26, 2018: Cancers
https://www.readbyqxmd.com/read/29370702/discovery-and-preclinical-development-of-iiim-290-an-orally-active-potent-cyclin-dependent-kinase-inhibitor
#10
Sandip B Bharate, Vikas Kumar, Shreyans K Jain, Mubashir Javeed Mintoo, Santosh Kumar Guru, Vijay K Nuthakki, Mohit Sharma, Sonali S Bharate, Sumit G Gandhi, Dilip Manikrao Mondhe, Shashi Bhushan, Ram A Vishwakarma
Rohitukine (1), a chromone alkaloid isolated from Indian medicinal plant Dysoxylum binectariferum has inspired the discovery of flavopiridol and riviciclib, both of which are bioavailable only via IV route. With the objective to address oral bioavailability issue of this scaffold, four series of rohitukine derivatives were prepared and screened for Cdk inhibition and cellular antiproliferative activity. The 2,6-dichloro-styryl derivative IIIM-290 (11d) showed strong inhibition of Cdk-9/T1 (IC50 1.9 nM) kinase and Molt-4/MIAPaCa-2 cell growth (GI50 < 1...
January 25, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29367463/mutant-p53r270h-drives-altered-metabolism-and-increased-invasion-in-pancreatic-ductal-adenocarcinoma
#11
Heather K Schofield, Jörg Zeller, Carlos Espinoza, Christopher J Halbrook, Annachiara Del Vecchio, Brian Magnuson, Tania Fabo, Ayse Ece Cali Daylan, Ilya Kovalenko, Ho-Joon Lee, Wei Yan, Ying Feng, Saadia A Karim, Daniel M Kremer, Chandan Kumar-Sinha, Costas A Lyssiotis, Mats Ljungman, Jennifer P Morton, Stefanie Galbán, Eric R Fearon, Marina Pasca di Magliano
Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29358341/temporal-effects-of-combined-birinapant-and-paclitaxel-on-pancreatic-cancer-cells-investigated-via-large-scale-ion-current-based-quantitative-proteomics-ionstar
#12
Xue Wang, Jin Niu, Jun Li, Xiaomeng Shen, Shichen Shen, Robert M Straubinger, Jun Qu
Despite decades of effort, pancreatic adenocarcinoma (PDAC) remains an intractable clinical challenge. An insufficient understanding of mechanisms underlying tumor cell responses to chemotherapy contributes significantly to the lack of effective treatment regimens. Here, paclitaxel, a first-line chemotherapeutic agent, was observed to interact synergistically with birinapant, a Second Mitochondrial-derived Activator of Caspases mimetic. Therefore, we investigated molecular-level drug interaction mechanisms using comprehensive, reproducible, and well-controlled ion-current-based MS1 quantification (IonStar)...
January 22, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29352139/mitochondrial-glutamine-metabolism-via-got2-supports-pancreatic-cancer-growth-through-senescence-inhibition
#13
Seungyeon Yang, Sunsook Hwang, Minjoong Kim, Sung Bin Seo, Jeong-Hwa Lee, Seung Min Jeong
Cellular senescence, which leads to a cell cycle arrest of damaged or dysfunctional cells, is an important mechanism to restrain the malignant progression of cancer cells. Because metabolic changes underlie many cell-fate decisions, it has been suggested that cell metabolism might play key roles in senescence pathways. Here, we show that mitochondrial glutamine metabolism regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells. Glutamine deprivation or inhibition of mitochondrial aspartate transaminase (GOT2) results in a profound induction of senescence and a suppression of PDAC growth...
January 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#14
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29337110/muc16-c-terminal-induced-secretion-of-tumor-derived-il-6-contributes-to-tumor-associated-treg-enrichment-in-pancreatic-cancer
#15
Kun Fan, Chao Yang, Zhiyao Fan, Qiuyi Huang, Yiyin Zhang, He Cheng, Kaizhou Jin, Yu Lu, Zhengshi Wang, Guopei Luo, Xianjun Yu, Chen Liu
Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an important serum marker for pancreatic cancer diagnosis and treatment. High serum CA125 is related to metabolic tumor burden and poor prognosis. The circulating Treg subset is another independent prognostic factor for pancreatic cancer. Our unpublished data indicated that the circulating Treg proportion might be related to the serum CA125 level. However, the potential relationship and underlying mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear...
January 11, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29335522/pyruvate-kinase-m2-promotes-pancreatic-ductal-adenocarcinoma-invasion-and-metastasis-through-phosphorylation-and-stabilization-of-pak2-protein
#16
Tsu-Yao Cheng, Yi-Chieh Yang, Hsiu-Po Wang, Yu-Wen Tien, Chia-Tung Shun, Hsin-Yi Huang, Michael Hsiao, Kuo-Tai Hua
Pyruvate kinase muscle isozymes (PKMs) have crucial roles in regulating metabolic changes during carcinogenesis. A switch from PKM1 to PKM2 isoform was thought to lead to aerobic glycolysis promoting carcinogenesis, and was considered as one of the cancer signatures. However, recent evidence has argued against the existence of PKM isoform switch and related metabolic effects during cancer progression. We compared the effects of PKM1 and PKM2 in cell invasiveness and metastasis of pancreatic ductal adenocarcinoma (PDAC)...
January 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29331423/thymidylate-synthase-prompts-metastatic-progression-through-the-dtmp-associated-emt-process-in-pancreatic-ductal-adenocarcinoma
#17
Muxing Kang, Wen Zheng, Qing Chen, Wenjie Qin, Pengping Li, Shifei Huang, Yizhao Zhou, Lantian Wang, Haolei Cai, Wenjie Lu, Biao Jiang, Qingqu Guo, Jian Chen, Dylan Wan, Jianyu Rao, Yulian Wu
As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has been shown to be an effective therapy for human cancers. However, the genuine effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We systemically assessed the prognostic value and whether TS associated with malignant progression in PDA. Protein and mRNA expression level of TS were evaluated in en bloc PDA samples, the prognostic effect of TS expressed in cytoplasm or cytonuclear was determined separately in the first time...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330807/evaluation-of-macrophage-polarization-in-pancreatic-cancer-microenvironment-under-hypoxia
#18
Kuldeep S Attri, Kamiya Mehla, Pankaj K Singh
Hypoxic microenvironment found in pancreatic ductal adenocarcinoma and other solid tumors is central to physiological and metabolic alterations of immune cells that significantly impact tumor growth dynamics. Hypoxic adaptations in the immune cells are primarily mediated by the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which regulates cellular metabolism by modulating glycolysis and other interconnected metabolic pathways. HIF-1α plays distinct roles in M1 and M2 macrophage polarization, which, in turn, regulates tumor cell immune escape and growth...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330794/hypoxia-mediated-in-vivo-tumor-glucose-uptake-measurement-and-analysis
#19
Surendra K Shukla, Scott E Mulder, Pankaj K Singh
Most solid tumors are hypoxic in nature due to the limited supply of oxygen to internal tissues. Hypoxia plays an important role in metabolic adaptations of tumors that contribute significantly to cancer pathogenesis. Among the several metabolic alterations induced by hypoxia, hypoxia-mediated increased glucose uptake serves as the hallmark of metabolic reprogramming. Hypoxia-mediated stabilization of hypoxia-inducible factor-1 alpha (HIF-1α) transcription factor leads to altered expression of several glycolytic genes and glucose transporters, which results in increased glucose uptake by tumor cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330793/hypoxia-induced-metabolomic-alterations-in-pancreatic-cancer-cells
#20
Venugopal Gunda, Sushil Kumar, Aneesha Dasgupta, Pankaj K Singh
Hypoxic conditions in the pancreatic tumor microenvironment lead to the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which acts as the master regulator of cancer cell metabolism. HIF-1α-mediated metabolic reprogramming results in large-scale metabolite perturbations. Characterization of the metabolic intermediates and the corresponding metabolic pathways altered by HIF-1α would facilitate the identification of therapeutic targets for hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other solid tumors...
2018: Methods in Molecular Biology
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