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https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#1
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28432480/predictive-value-of-18-f-fdg-pet-ct-for-axillary-lymph-node-metastasis-in-invasive-ductal-breast-cancer
#2
Bong-Il Song, Hae Won Kim, Kyoung Sook Won
BACKGROUND: This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC). METHODS: In this study, 128 IDC patients who underwent pretreatment (18)F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed...
April 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28432278/blood-glucose-concentration-and-risk-of-liver-cancer-systematic-review-and-meta-analysis-of-prospective-studies
#3
Hedong Han, Tianyi Zhang, Zhichao Jin, Honglei Guo, Xin Wei, Yuzhou Liu, Qi Chen, Jia He
The question of whether elevated blood glucose is a risk factor for liver cancer has been intensively studied, yet with inconsistent results. To explore the relationship between blood glucose concentration and risk of liver cancer, we conduct a meta-analysis of prospective studies. Literature search was comprehensively performed using database of PubMed, EMBASE and the Cochrane Library through October 2016. Random-effect models were used to combine the effect estimations. Eight articles containing ten studies with a total of 1975 liver cancer cases were included...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431964/microvillus-specific-protein-tyrosine-phosphatase-sap-1-plays-a-role-in-regulating-the-intestinal-paracellular-transport-of-macromolecules
#4
Shingo Mori, Noriyasu Kamei, Yoji Murata, Kozo Takayama, Takashi Matozaki, Mariko Takeda-Morishita
The stomach cancer associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases, however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed to clarify the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules...
April 18, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28431259/allosteric-regulation-of-metabolism-in-cancer-endogenous-mechanisms-and-considerations-for-drug-design
#5
REVIEW
Jamie A Macpherson, Dimitrios Anastasiou
Alterations in metabolic processes have been linked to various diseases, including cancer. Although gene expression can dictate long-term metabolic adaptation, many metabolic changes found in cancer are associated with altered allosteric properties of the underlying enzymes. Small molecule-protein interactions and intracellular signalling converge to orchestrate these allosteric mechanisms, which, emerging evidence suggests, constitute a promising therapeutic avenue. In this review we focus on glucose and energy metabolism to illustrate the role of allostery in cancer physiology and we discuss approaches to streamline the process of targeting aberrant allosteric pathways with small molecules...
April 18, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28430653/preventive-effects-of-the-sodium-glucose-cotransporter-2-inhibitor-tofogliflozin-on-diethylnitrosamine-induced-liver-tumorigenesis-in-obese-and-diabetic-mice
#6
Koki Obara, Yohei Shirakami, Akinori Maruta, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Hiroyasu Sakai, Takuji Tanaka, Mitsuru Seishima, Masahito Shimizu
Sodium glucose cotransporter 2 inhibitors are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease. In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb obese and diabetic mice. The direct effects of tofogliflozin on human liver cancer cell proliferation were also evaluated. Mice were administered diethylnitrosamine-containing water for 2 weeks and were treated with tofogliflozin throughout the experiment...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429737/the-glutamate-cystine-xct-antiporter-antagonizes-glutamine-metabolism-and-reduces-nutrient-flexibility
#7
Chun-Shik Shin, Prashant Mishra, Jeramie D Watrous, Valerio Carelli, Marilena D'Aurelio, Mohit Jain, David C Chan
As noted by Warburg, many cancer cells depend on the consumption of glucose. We performed a genetic screen to identify factors responsible for glucose addiction and recovered the two subunits of the xCT antiporter (system xc(-)), which plays an antioxidant role by exporting glutamate for cystine. Disruption of the xCT antiporter greatly improves cell viability after glucose withdrawal, because conservation of glutamate enables cells to maintain mitochondrial respiration. In some breast cancer cells, xCT antiporter expression is upregulated through the antioxidant transcription factor Nrf2 and contributes to their requirement for glucose as a carbon source...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429188/18f-fluorodeoxyglucose-uptake-on-positron-emission-tomography-computed-tomography-is-associated-with-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma
#8
Misu Lee, Jeong Yong Jeon, Micheal L Neugent, Jung-Whan Kim, Mijin Yun
Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer mortality worldwide. Several studies have investigated the relationship between (18)F-fluorodeoxyglucose ((18)F-FDG) uptake on positron emission tomography and the prognosis of patients with HCC, although the relationship between (18)F-FDG uptake and expression of EMT-related proteins in these patients remains unclear. We retrospectively enrolled 116 patients with HCC treated by curative surgical resection and who underwent (18)F-FDG positron emission tomography/computed tomography (PET/CT) for preoperative staging...
April 20, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28428083/the-roles-of-subcellularly-located-egfr-in-autophagy
#9
REVIEW
Hongsen Li, Liangkun You, Jiansheng Xie, Hongming Pan, Weidong Han
The epidermal growth factor receptor (EGFR) is a well-studied receptor-tyrosine kinase that serves vital roles in regulation of organ development and cancer progression. EGFR not only exists on the plasma membrane, but also widely expressed in the nucleus, endosomes, and mitochondria. Most recently, several lines of evidences indicated that autophagy is regulated by EGFR in kinase-active and -independent manners. In this review, we summarized recent advances in our understanding of the functions of different subcellularly located EGFR on autophagy...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28427443/benserazide-a-dopadecarboxylase-inhibitor-suppresses-tumor-growth-by-targeting-hexokinase-2
#10
Wei Li, Mengzhu Zheng, Shuangping Wu, Suyu Gao, Mei Yang, Zhimei Li, Qiuxia Min, Weiguang Sun, Lixia Chen, Guangya Xiang, Hua Li
BACKGROUND: Hexokinase (HK) is the rate-limiting enzyme in the first reaction of glycolysis. And Hexokinase 2 (HK2) is most closely related to malignant tumor which expresses at higher level compared with normal cells. HK2 plays a pivotal role in tumor initiation and maintenance, which provides a new target for cancer therapy. METHODS: Structure-based virtual ligand screening was used in hit identification from ZINC Drug Database. Microscale thermophoresis assay was performed to evaluate the binding affinity...
April 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28427230/deguelin-inhibits-non-small-cell-lung-cancer-via-down-regulating-hexokinases-ii-mediated-glycolysis
#11
Wei Li, Feng Gao, Xiaoqian Ma, Ruike Wang, Xin Dong, Wei Wang
Hexokinases II (HK2) is a hub in the regulation of cancer cell glycolysis. Here we reported deguelin, a natural compound which has been studied in various tumor types, has a profound anti-tumor effect on human non-small cell lung cancer (NSCLC) via directly down-regulating of glycolysis. In NSCLC cell lines and primary NSCLC tissue, we found HK2 is overexpressed. Deguelin treatment markedly inhibited anchorage-dependent and independent growth of NSCLC cell lines. We revealed that deguelin exposure impaired glucose metabolism by inhibiting Akt-mediated Hexokinase II expression, overexpression of constitutively activated Akt1 substantially rescued deguelin-induced glycolysis suppression...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427228/mir-29a-regulated-er-positive-breast-cancer-cell-growth-and-invasion-and-is-involved-in-the-insulin-signaling-pathway
#12
Zhi-Hua Li, Qiu-Yun Xiong, Liang Xu, Peng Duan, Qianwen Ou Yang, Ping Zhou, Jian-Hong Tu
Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425973/edim-tktl1-apo10-blood-test-an-innate-immune-system-based-liquid-biopsy-for-the-early-detection-characterization-and-targeted-treatment-of-cancer
#13
REVIEW
Johannes F Coy
Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers...
April 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28425269/evaluation-of-cytotoxic-membrane-and-dna-damaging-effects-of-thymus-revolutus-c%C3%A3-lak-essential-oil-on-different-cancer-cells
#14
Aysun Özkan, Ayşe Erdoğan
BACKGROUND/AIM: In this study, we evaluated Thymus revolutus Célak essential oil and its two main constituents, γ-terpinene and p-cymene, as potential oxidative agents against lung cancer and epidermoid carcinoma cells. MATERIALS AND METHODS: Cell viability assessment was made by CellTiter-Blue1397904493 cell viability and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after treatment with 5-600 μg/mL concentrations of essential oil, γ-terpinene, and p-cymene...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#15
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28424264/identification-of-a-multienzyme-complex-for-glucose-metabolism-in-living-cells
#16
Casey L Kohnhorst, Minjoung Kyoung, Miji Jeon, Danielle L Schmitt, Erin L Kennedy, Julio Ramirez, Syrena M Bracey, Bao Tran Luu, Sarah J Russell, Songon An
Sequential metabolic enzymes in glucose metabolism have long been hypothesized to form multienzyme complexes that regulate glucose flux in living cells. However, it has been challenging to directly observe these complexes and their functional roles in living systems. In this work, we have used wide-field and confocal fluorescence microscopy to investigate the spatial organization of metabolic enzymes participating in glucose metabolism in human cells. We provide compelling evidence that human liver-type phosphofructokinase 1 (PFKL), which catalyzes a bottleneck step of glycolysis, forms various sizes of cytoplasmic clusters in human cancer cells, independent of protein expression levels and of the choice of fluorescent tags...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28423638/her-inhibitor-promotes-braf-mek-inhibitor-induced-redifferentiation-in-papillary-thyroid-cancer-harboring-brafv600e
#17
Lingxiao Cheng, Yuchen Jin, Min Liu, Maomei Ruan, Libo Chen
Redifferentiation therapy with BRAF/MEK inhibitors to facilitate treatment with radioiodine represents a good choice for radioiodine-refractory differentiated thyroid carcinoma, but recent initial clinical outcomes were modest. MAPK rebound caused by BRAF/MEK inhibitors-induced activation of HER2/HER3 is a resistance mechanism, and combination with HER inhibitor to prevent MAPK rebound may sensitize BRAFV600E-mutant thyroid cancer cells to redifferentiation therapy. To evaluate if inhibiting both BRAF/MEK and HER can produce stronger redifferetiation effect, we tested the effects of BRAF/MEK inhibitor dabrafenib/selumetinib alone or in combination with HER inhibitor lapatinib on the expression and function of iodine- and glucose-handling genes in BRAFV600E-positive BCPAP and K1 cells, using BHP 2-7 cells harboring RET/PTC1 rearrangement as control...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423496/mtor-inhibitors-activate-perk-signaling-and-favor-viability-of-gastrointestinal-neuroendocrine-cell-lines
#18
Patricia Freis, Julien Bollard, Justine Lebeau, Patrick Massoma, Joëlle Fauvre, Cécile Vercherat, Thomas Walter, Serge Manié, Colette Roche, Jean-Yves Scoazec, Carole Ferraro-Peyret
mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently activated in cancer cells. The mTOR pathway has been shown to be up-regulated in most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known about the UPR status in neoplastic neuroendocrine cells. However, these hormone-producing cells are likely to present distinctive adaptations of this pathway, as other secretory cells. We therefore analyzed the status of the three axes of UPR and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors (GI-NET) cell lines STC-1 and GluTag...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423351/significance-of-inflammation-based-indices-in-the-prognosis-of-patients-with-non-metastatic-colorectal-cancer
#19
Xiangping Song, Hong Zhu, Qian Pei, Fengbo Tan, Chenglong Li, Zhongyi Zhou, Yuan Zhou, Nanhui Yu, Yuqiang Li, Haiping Pei
Previous studies demonstrated that several inflammation-based hematological indices are closely related to various malignancies, including colorectal cancer (CRC). In this study, the prognostic value of inflammation-based markers, including a combination index termed coNLR-PDW, comprising the preoperative neutrophil-to-lymphocyte ratio (NLR) and the platelet distribution width (PDW), was evaluated in 206 patients with non-metastatic CRC treated with surgery at a single medical center. The association of patient demographics, blood chemistry, and serum biochemical indices with recurrence-free survival (RFS) and overall survival (OS) were examined through univariate and multivariate analysis...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422115/cancer-obesity-and-diabetes-tkis-exert-multiple-effects-on-glucose-homeostasis
#20
Minglin Lin, Junfei Jin
No abstract text is available yet for this article.
May 2017: Nature Reviews. Clinical Oncology
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