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pancreatic cancer metabolism

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https://www.readbyqxmd.com/read/28322141/lessons-learned-from-gemcitabine-impact-of-therapeutic-carrier-systems-and-gemcitabine-s-drug-conjugates-on-cancer-therapy
#1
Sathish Dyawanapelly, Animesh Kumar, Manish K Chourasia
Currently, drug delivery systems have a high impact in cancer therapy and are receiving more attention than conventional cancer treatment modalities. Compared with current cancer therapies, gemcitabine (2', 2'-difluoro-2'-deoxycytidine) has been proven to be an effective chemotherapeutic agent against pancreatic, colon, bladder, breast, ovarian, non-small-cell lung, and head and neck cancers in combination with other anticancer agents. To improve the safety and efficacy of cytotoxic drugs, several drug delivery systems have been explored...
2017: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/28316954/molecular-pathways-controlling-autophagy-in-pancreatic-cancer
#2
REVIEW
Maria New, Tim Van Acker, Jaclyn S Long, Jun-Ichi Sakamaki, Kevin M Ryan, Sharon A Tooze
Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types where the 5-year survival rate shows no improvement. Despite conflicting evidence, the majority of data points to an essential role for autophagy in PDAC growth and survival, in particular constitutively activated autophagy, can provide crucial fuel to PDAC tumor cells in their nutrient-deprived environment. Autophagy, which is required for cell homeostasis, can both suppress and promote tumorigenesis and tumor survival in a context-dependent manner...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28315906/nineteen-cases-with-synchronous-multiple-primary-cancers-studied-by-18-f-fdg-pet-ct
#3
Lifang Pang, Guobing Liu, Hongcheng Shi, Pengcheng Hu, Beilei Li, Dengfeng Cheng
OBJECTIVE: To evaluate the value of fluorine -18-fuoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in evaluating synchronous multiple primary cancers (SMPC). METHODS: Nineteen patients with pathologically-confirmed SMPC were collected. Clinical and (18)F-FDG PET/CT characteristics of these patients were reviewed and analyzed. Maximum standardized uptake value, (SUVmax) of all lesions was measured and difference (Δ)SUVmax between the SUV of two primary tumors in each patient was calculated as: [(the larger SUVmax - the smaller SUVmax)/ the larger SUVmax]×100%...
March 20, 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28303855/expression-and-prognostic-value-of-indoleamine-2-3-dioxygenase-in-pancreatic-cancer
#4
Tao Zhang, Xiang-Long Tan, Yong Xu, Zi-Zheng Wang, Chao-Hui Xiao, Rong Liu
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. METHODS: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ)...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28296649/a-nomogram-to-predict-5-fluorouracil-toxicity-when-pharmacogenomics-meets-the-patient
#5
Andrea Botticelli, Concetta E Onesti, Lidia Strigari, Mario Occhipinti, Francesca R Di Pietro, Bruna Cerbelli, Antonella Petremolo, Elisabetta Anselmi, Serena Macrini, Michela Roberto, Rosa Falcone, Luana Lionetto, Marina Borro, Annalisa Milano, Giovanna Gentile, Maurizio Simmaco, Paolo Marchetti, Federica Mazzuca
Fluoropyrimidines combined with other agents are commonly used for gastrointestinal cancer treatment. Considering that severe toxicities occur in 30% of patients, we aimed to structure a nomogram to predict toxicity, based on metabolic parameter and patients' characteristics. We retrospectively enrolled patients affected by gastrointestinal tract cancers. Pretreatment 5-fluorouracil (5-FU) degradation rate and DPYD, TSER, MTHFR A1298T, and C677T gene polymorphisms were characterized. Data on toxicities were collected according to CTCAE v3...
March 14, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28292435/obstacles-posed-by-the-tumor-microenvironment-to-t%C3%A2-cell-activity-a-case-for-synergistic-therapies
#6
REVIEW
Kristin G Anderson, Ingunn M Stromnes, Philip D Greenberg
T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28283939/high-dose-of-radioactive-iodine-per-se-has-no-effect-on-glucose-metabolism-in-thyroidectomized-rats
#7
Roghaieh Samadi, Mahboubeh Ghanbari, Babak Shafiei, Sevda Gheibi, Fereidoun Azizi, Asghar Ghasemi
PURPOSE: Thyroid concentrates radioactive iodine by sodium-iodide symporter; this is used for treating hyperthyroidism and thyroid cancer. Pancreas expresses NIS and radioactive iodine uptake may damage pancreatic beta-cells and predispose patients to type 2 diabetes. The aim of this study was to determine whether radioactive iodine is associated with glucose metabolism in thyroidectomized rats. METHODS: Forty male Wistar rats were divided into four groups (n = 10/each); control, thyroidectomized, thyroidectomized-treated with 131-I (TX+I), and thyroidectomized-treated with 131-I and L-thyroxine (TX+I+T4)...
March 10, 2017: Endocrine
https://www.readbyqxmd.com/read/28282719/pharmacogenetics-and-personalized-medicine-in-pancreatic-cancer
#8
Ali Hosseini Bereshneh, Fatemeh Morshedi, Mahsa Hematyar, Arastoo Kaki, Masoud Garshasbi
 Pancreatic cancer (PC) is a progressive, fatal disease with a high degree of malignancy. More than 40000 peoplediefrom this cancer annually in the United States. As a multifactorial condition, PC has a complex nature, and there are several genes and signalingpathwaysimplicated in PC pathogenesis and progression. There are diffèrent mutations in master genesincludingtumorsuppressors and oncogenesthat lead to Pancreaticintraepithelialneoplasia (PanIN) whichis the mostcommon non-invasive precursorlesion of pancreatic cancer...
March 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28281169/complications-of-chronic-pancreatitis
#9
REVIEW
Mitchell L Ramsey, Darwin L Conwell, Phil A Hart
Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.
March 9, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28280617/identifying-prognostic-intratumor-heterogeneity-using-pre-and-post-radiotherapy-18f-fdg-pet-images-for-pancreatic-cancer-patients
#10
Yong Yue, Arsen Osipov, Benedick Fraass, Howard Sandler, Xiao Zhang, Nicholas Nissen, Andrew Hendifar, Richard Tuli
BACKGROUND: To stratify risks of pancreatic adenocarcinoma (PA) patients using pre- and post-radiotherapy (RT) PET/CT images, and to assess the prognostic value of texture variations in predicting therapy response of patients. METHODS: Twenty-six PA patients treated with RT from 2011-2013 with pre- and post-treatment 18F-FDG-PET/CT scans were identified. Tumor locoregional texture was calculated using 3D kernel-based approach, and texture variations were identified by fitting discrepancies of texture maps of pre- and post-treatment images...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28275007/gene-expression-profiling-of-patient-derived-pancreatic-cancer-xenografts-predicts-sensitivity-to-the-bet-bromodomain-inhibitor-jq1-implications-for-individualized-medicine-efforts
#11
Benjamin Bian, Martin Bigonnet, Odile Gayet, Celine Loncle, Aurélie Maignan, Marine Gilabert, Vincent Moutardier, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Mehdi Ouaissi, Veronique Secq, Flora Poizat, Rémy Nicolle, Yuna Blum, Laetitia Marisa, Marion Rubis, Jean-Luc Raoul, James E Bradner, Jun Qi, Gwen Lomberk, Raul Urrutia, Andres Saul, Nelson Dusetti, Juan Iovanna
c-MYC controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient-derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state, and a shorter survival time compared to the MYC-low subgroup...
March 8, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28272344/nutritional-and-metabolic-derangements-in-pancreatic-cancer-and-pancreatic-resection
#12
REVIEW
Taylor M Gilliland, Nicole Villafane-Ferriol, Kevin P Shah, Rohan M Shah, Hop S Tran Cao, Nader N Massarweh, Eric J Silberfein, Eugene A Choi, Cary Hsu, Amy L McElhany, Omar Barakat, William Fisher, George Van Buren
Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions...
March 7, 2017: Nutrients
https://www.readbyqxmd.com/read/28263222/mtor-and-cardiovascular-diseases-diabetes-mellitus
#13
Bruno Vergès
The mammalian targets of rapamycin (mTOR) inhibitors are potent immunosuppressors used for prevention of acute rejection following transplantation and have been more recently used as anticancer drugs. mTOR inhibitors have a significant impact on glucose metabolism and induce frequently diabetes. mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors (CNI) but high when used in combination with CNI (from 11...
March 4, 2017: Transplantation
https://www.readbyqxmd.com/read/28260082/cancer-associated-fibroblasts-enhance-pancreatic-cancer-cell-invasion-by-remodeling-the-metabolic-conversion-mechanism
#14
Tao Shan, Shuo Chen, Xi Chen, Wan Run Lin, Wei Li, Jiancang Ma, Tao Wu, Xijuan Cui, Hong Ji, Yiming Li, Ya'an Kang
We investigated the mechanism of cancer-associated fibroblasts (CAFs) in promoting the invasion and metastasis of pancreatic cancer cells in a non-vascular manner. We verified the original generation of isolated cultured CAFs and normal fibroblasts (NFs) based on the expression of α-SMA and vimentin, and we examined the cell glycolysis level through glucose consumption and lactate production experiments. The mRNA and protein expression of CAF glycolytic enzymes, lactate dehydrogenase and pyruvate kinase m2, were examined by RT-PCR and western blotting, respectively...
February 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259298/the-cornerstone-k-ras-mutation-in-pancreatic-adenocarcinoma-from-cell-signaling-network-target-genes-biological-processes-to-therapeutic-targeting
#15
REVIEW
Nicolas Jonckheere, Romain Vasseur, Isabelle Van Seuningen
RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28256041/metabolic-characterization-of-invaded-cells-of-the-pancreatic-cancer-cell-line-panc-1
#16
Mayumi Fujita, Kaori Imadome, Takashi Imai
We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC-1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC-1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC-1 cells, metabolome analysis of the invaded PANC-1 compared with the whole cultured PANC-1 was performed using CE-TOFMS, and concentrations of 110 metabolites were measured...
March 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28252525/comparative-characteristics-of-quantitative-indexes-for-18f-fdg-uptake-and-metabolic-volume-in-sequentially-obtained-pet-mri-and-pet-ct
#17
Soo Jin Lee, Jin Chul Paeng, Jin Mo Goo, Jeong Min Lee, Gi Jeong Cheon, Dong Soo Lee, June-Key Chung, Keon Wook Kang
PURPOSE: The purpose of this study was to compare quantitative indexes for fluorine-18 fluorodeoxyglucose uptake and metabolic volume between PET/MRI and PET/CT. PATIENTS AND METHODS: Sixty-six patients with solid tumors (32 with lung cancer and 34 with pancreatic cancer) who underwent sequential fluorine-18 fluorodeoxyglucose PET/MRI and PET/CT were retrospectively enrolled. On PET images, maximum and peak standardized uptake values (SUVmax and SUVpeak, respectively), and maximum tumor-to-liver ratio (TLRmax) were measured...
April 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#18
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro Enrizues-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander Ra Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche-construction adaptive strategies that remained stable in culture: (1) Invasive cells that produce an acidic environment via upregulated aerobic glycolysis, and (2) Non-invasive cells that were angiogenic and metabolically near-normal...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28241470/pancreatic-exocrine-insufficiency-in-pancreatic-cancer
#19
REVIEW
Miroslav Vujasinovic, Roberto Valente, Marco Del Chiaro, Johan Permert, J-Matthias Löhr
Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion...
February 23, 2017: Nutrients
https://www.readbyqxmd.com/read/28239030/metabolic-profiling-of-gemcitabine-and-paclitaxel-treated-immortalized-human-pancreatic-cell-lines-with-k-ras-g12d
#20
Akiko Todaka, Rina Umehara, Keiko Sasaki, Masakuni Serizawa, Kenichi Urakami, Masatoshi Kusuhara, Ken Yamaguchi, Hirofumi Yasui
The mechanisms of action of gemcitabine (GEM) and paclitaxel (PTX) have been well investigated, and shown to be the inhibition of DNA polymerase and polymerization of tubulin, respectively. Meanwhile, genomic research has revealed that mutations in the K-RAS oncogene occur in over 90% of pancreatic cancer. Oncogenic alteration rewires alternative metabolic pathways to satisfy the demands of growth. The K-RAS oncogene also has been shown to upregulate glycolysis and glutaminolysis. However, it is still unclear whether K-RAS independently plays a central role in controlling tumor metabolism...
2017: Biomedical Research
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