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https://www.readbyqxmd.com/read/28454321/the-loss-of-casp4-expression-is-associated-with-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#1
Misako Shibamoto, Hidenari Hirata, Hidetoshi Eguchi, Genta Sawada, Noritaka Sakai, Yoshiaki Kajiyama, Koshi Mimori
Esophageal squamous cell carcinoma (ESCC) has high biological malignant potential among the various digestive tract cancers and is associated with a poor prognosis. To identify novel genes involved in tumor progression, the present study analyzed the genetic and transcriptional alterations in two clinical cohorts, totaling 157 cases of ESCC (78 cases from the discovery set and 79 cases from the validation set). From the discovery set, gene expression and copy number profiles were analyzed using expression arrays and array-comparative genomic hybridization, respectively...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454274/role-of-endoplasmic-reticulum-stress-on-cisplatin-resistance-in-ovarian-carcinoma
#2
Jing Tian, Rong Liu, Quanxin Qu
Endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from apoptosis. The present study examined the effects and mechanism of ERS on cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with Saquinavir were subjected to western blot and reverse transcription-quantitative polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454221/expression-of-inositol-requiring-enzyme-1%C3%AE-is-downregulated-in-colorectal-cancer
#3
Yalin Jiang, Yunfeng Zhou, Yufeng Zheng, Hong Guo, Lei Gao, Pan Chen, Dandan Feng, Ran Qi, Xiaozhen Li, Yongchao Chang, Fong-Fong Chu, Qiang Gao
The endoplasmic reticulum stress inositol-requiring enzyme (IRE) 1α/X-box binding protein (XBP) 1 signaling pathway is involved in the tumorigenesis of breast and prostate cancer. Mucin 2 (MUC2) protects colon tissues from the formation of tumors. In human colorectal cancer (CRC) the role of IRE1α, and its analogue, IRE1β, has yet to be elucidated. In the present study, the expression levels of IRE1α, IRE1β, un-spliced XBP1u, spliced XBP1s and MUC2 in surgically resected cancerous and adjacent non-cancerous tissues from patients with CRC were investigated...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28453961/diabetic-nephropathy-new-insights-into-established-therapeutic-paradigms-and-novel-molecular-targets
#4
REVIEW
Dilip Sharma, Pallab Bhattacharya, Kiran Kalia, Vinod Tiwari
Diabetic nephropathy is one of the most prevalent microvascular complication in patients suffering from diabetes and is reported to be the major cause of renal failure when compared to any other kidney disease. Currently, available therapies provide only symptomatic relief and unable to treat the underlying pathophysiology of diabetic nephropathy. This review will explore new insights into the established therapeutic paradigms targeting oxidative stress, inflammation and endoplasmic reticulum stress with the focus on recent clinical developments...
April 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28453460/endoplasmic-reticulum-stress-regulates-proliferation-migration-and-invasion-of-human-ovarian-cancer-skov3-cells-through-pi3k-akt-mtor-signaling-pathway
#5
Na Yang, Yan-Jun Qu, Yan Cheng, Tian Liang, Mei-Na Zhang, Dan Zhang, Li-Na Dong, Xiao-Wei Wang, Guang-Mei Zhang
OBJECTIVE: The study is to explore the role of tunicamycin-induced endoplasmic reticulum stress (ERS) in human ovarian cancer (OC) SKOV3 cells proliferation, migration and invasion by modulating the activity of PI3K/AKT/mTOR pathway. METHODS: The collected human OC SKOV3 cells were randomly separated into three groups: The control group, the Tun group (treated with tunicamycin to induce ERS) and the CHOP-si group (transfected with CHOP-siRNA before tunicamycin treatment)...
April 21, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28453376/control-of-the-unfolded-protein-response-in-health-and-disease
#6
Dimitrios Doultsinos, Tony Avril, Stéphanie Lhomond, Nicolas Dejeans, Philippe Guédat, Eric Chevet
The unfolded protein response (UPR) is an integrated, adaptive biochemical process that is inextricably linked with cell homeostasis and paramount to maintenance of normal physiological function. Prolonged accumulation of improperly folded proteins in the endoplasmic reticulum (ER) leads to stress. This is the driving stimulus behind the UPR. As such, prolonged ER stress can push the UPR past beneficial functions such as reduced protein production and increased folding and clearance to apoptotic signaling. The UPR is thus contributory to the commencement, maintenance, and exacerbation of a multitude of disease states, making it an attractive global target to tackle conditions sorely in need of novel therapeutic intervention...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28447936/ppp1r15a-mediated-dephosphorylation-of-eif2%C3%AE-is-unaffected-by-sephin1-or-guanabenz
#7
Ana Crespillo-Casado, Joseph E Chambers, Peter M Fischer, Stefan J Marciniak, David Ron
Dephosphorylation of translation initiation factor 2 (eIF2α) terminates signalling in the mammalian integrated stress response (ISR) and has emerged as a promising target for modifying the course of protein misfolding diseases. The [(o-chlorobenzylidene)amino]guanidines (Guanabenz and Sephin1) have been proposed to exert protective effects against misfolding by interfering with eIF2α-P dephosphorylation through selective disruption of a PP1-PPP1R15A holophosphatase complex. Surprisingly, they proved inert in vitro affecting neither stability of the PP1-PPP1R15A complex nor substrate-specific dephosphorylation...
April 27, 2017: ELife
https://www.readbyqxmd.com/read/28447729/effects-of-endoplasmic-reticulum-stress-on-apoptosis-induction-in-radioresistant-macrophages
#8
Hironori Yoshino, Yu Kumai, Ikuo Kashiwakura
Macrophages are important in the host's immune defense against pathogens. However, recent evidence has demonstrated that macrophages are also involved in the development of disease, including cancer. Therefore, it is important to regulate apoptosis in tumor‑related macrophages for effective cancer treatment. In the present study, the effect of endoplasmic reticulum (ER) stress on apoptosis induction was examined in human monocytic cell‑derived macrophages. Radiation therapy in cancer results in irradiating macrophages as well as cancer cells in the tumor microenvironment...
March 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446632/dietary-methionine-restriction-regulates-liver-protein-synthesis-and-gene-expression-independently-of-eukaryotic-initiation-factor-2-phosphorylation-in-mice
#9
Ashley P Pettit, William O Jonsson, Albert R Bargoud, Emily T Mirek, Frederick F Peelor, Yongping Wang, Thomas W Gettys, Scot R Kimball, Benjamin F Miller, Karyn L Hamilton, Ronald C Wek, Tracy G Anthony
Background: The phosphorylation of eukaryotic initiation factor 2 (p-eIF2) during dietary amino acid insufficiency reduces protein synthesis and alters gene expression via the integrated stress response (ISR).Objective: We explored whether a Met-restricted (MR) diet activates the ISR to reduce body fat and regulate protein balance.Methods: Male and female mice aged 3-6 mo with either whole-body deletion of general control nonderepressible 2 (Gcn2) or liver-specific deletion of protein kinase R-like endoplasmic reticulum kinase (Perk) alongside wild-type or floxed control mice were fed an obesogenic diet sufficient in Met (0...
April 26, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28444766/endoplasmic-reticulum-stress-mediates-distinct-impacts-of-sevoflurane-on-different-subfields-of-immature-hippocampus
#10
Gang Zhu, Lei Tao, Ronglin Wang, Ying Xue, Xingqin Wang, Shaosong Yang, Xude Sun, Guodong Gao, Zixu Mao, Qian Yang
Sevoflurane, a typical inhaled anesthetic, is widely used in patients of all ages during surgery. The negative effects, such as inducing cell death and damaging spatial memory, of sevoflurane on neurodevelopment have raised increasing concerns in recent years. However, the molecular mechanism remains unclear. The current study focused on the crucial role of endoplasmic reticulum (ER) stress in sevoflurane-induced hippocampal injury. Three-week-old rats were exposed to sevoflurane or control air for 5h with or without ER stress inhibitor (4-phenylbutyric acid, 4-PBA) injection...
April 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28444413/cerebral-dopamine-neurotrophic-factor-protects-h9c2-cardiomyocytes-from-apoptosis
#11
H Liu, C Yu, H Yu, L Zhong, Y Wang, J Liu, S Zhang, J Sun, L Duan, L Gong, J Yang
BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) has been studied in animal models of Parkinson's disease, where it was shown to repair and protect dopamine neurons. Alongside its neurotrophic activity, it can also localize in the endoplasmic reticulum (ER) acting as an ER stress response (ERSR) protein to maintain ER homeostasis. Since ER stress plays a major role in the development and progression of cardiovascular diseases, we investigated the role of CDNF in cardiomyocytes during ER stress...
April 25, 2017: Herz
https://www.readbyqxmd.com/read/28443461/mir-1202-functions-as-a-tumor-suppressor-in-glioma-cells-by-targeting-rab1a
#12
Yu Quan, Qian Song, Jvbo Wang, Lingyu Zhao, Jian Lv, Shouping Gong
Aberrant expression of microRNAs correlates with the development and progression of human cancers by targeting downstream proteins. MiR-1202 is downregulated in ovarian cancer and clear cell papillary renal cell carcinoma; however, its role in glioma remains unknown. The purpose of this study was to determine the expression and the role of miR-1202 and to elucidate its regulatory mechanism in glioma. We used quantitative real-time polymerase chain reaction to measure miR-1202 expression in both glioma tissues and cell lines...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28442375/implication-of-hyperoxaluria-on-osteopontin-and-er-stress-mediated-apoptosis-in-renal-tissue-of-rats
#13
Rishi Bhardwaj, Ankita Bhardwaj, Chanderdeep Tandon, Devinder K Dhawan, Rakesh Kumar Bijarnia, Tanzeer Kaur
Hyperoxaluria is a stress that leads to calcium oxalate crystal deposition which further causes inflammation and renal cell necroptosis. Many studies have linked osteopontin expression with apoptosis and inflammation but so far its association with apoptosis with regard to hyperoxaluria is undiscovered. Moreover, a recent report has suggested that osteopontin induces endoplasmic reticulum stress and subsequently apoptosis in myocytes. In this study, the impact of hyperoxaluria on the modulation of osteopontin expression and endoplasmic reticulum (ER) stress mediated apoptosis in rats is explored...
April 22, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28442322/in-vitro-and-in-vivo-antitumor-activities-of-t-3764518-a-novel-and-orally-available-small-molecule-stearoyl-coa-desaturase-1-inhibitor
#14
Satoru Nishizawa, Hiroyuki Sumi, Yoshihiko Satoh, Yukiko Yamamoto, Satoshi Kitazawa, Kohei Honda, Hideo Araki, Kazuyo Kakoi, Keisuke Imamura, Masako Sasaki, Ikuo Miyahisa, Yoshinori Satomi, Ryuuichi Nishigaki, Megumi Hirayama, Kazunobu Aoyama, Hironobu Maezaki, Takahito Hara
Most cancer cells are characterized by elevated lipid biosynthesis. The rapid proliferation of cancer cells requires de novo synthesis of fatty acids. Stearoyl-CoA desaturase-1 (SCD1), a key enzyme for lipogenesis, is overexpressed in various types of cancer and plays an important role in cancer cell proliferation. Therefore, it has been studied as a candidate target for cancer therapy. In this study, we demonstrate the pharmacological properties of T-3764518, a novel and orally available small molecule inhibitor of SCD1...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28441457/autophagy-contributes-to-falcarindiol-induced-cell-death-in-breast-cancer-cells-with-enhanced-endoplasmic-reticulum-stress
#15
Tingting Lu, Ming Gu, Yan Zhao, Xinyu Zheng, Chengzhong Xing
Falcarindiol (FAD) is a natural polyyne have been found in many food and dietary plants. It has been found to have various beneficial biological activities. In this study, we demonstrated its anticancer function and mechanism in breast cancer cells. We found that FAD preferentially induces cell death in breast cancer cells. FAD-induced cell death is caspase-dependent. However, FAD induces autophagy to contribute to the cell death. Blocking autophagy by either chemical inhibitors or genetic knockout of autophagy signaling component inhibits FAD-induced cell death...
2017: PloS One
https://www.readbyqxmd.com/read/28440735/nuclear-factor-e2-related-factor-2-knockdown-enhances-glucose-uptake-and-alters-glucose-metabolism-in-aml12-hepatocytes
#16
Xiaoyang Yuan, Huijing Huang, Yi Huang, Jinli Wang, Jinhua Yan, Ling Ding, Cuntai Zhang, Le Zhang
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to induce the expression of a variety of antioxidant and detoxification genes. Recently, increasing evidence has revealed roles for Nrf2 in glucose, lipid, and energy metabolism; however, the exact functions of Nrf2 in hepatocyte biology are largely unclear. In the current study, the transient knockdown of Nrf2 via siRNA transfection enhanced the glucose uptake of fasting AML12 hepatocytes to 325.3 ± 11.1% ( P < 0.05) of that of untransfected control cells...
May 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28440472/human-umbilical-cord-mesenchymal-stem-cells-alleviate-acute-myocarditis-by-modulating-endoplasmic-reticulum-stress-and-extracellular-signal-regulated-1-2-mediated-apoptosis
#17
Changyi Zhang, Guichi Zhou, Chanxin Cai, Jindi Li, Fen Chen, Lichun Xie, Wei Wang, Yonggang Zhang, Xiulan Lai, Lian Ma
Acute myocarditis is a non-ischemic inflammatory disease of the myocardium, and there is currently no standard treatment. Mesenchymal stem cells (MSCs) can alleviate myosin‑induced myocarditis; however, the mechanism has not been clearly elucidated. In the present study, the authors investigated the ability of human umbilical cordMSCs (HuMSCs) to attenuate myocardial injury and dysfunction during the acute phase of experimental myocarditis. Male Lewis rats (aged 8 weeks) were injected with porcine myosin to induce myocarditis...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440344/toxicogenomic-module-associations-with-pathogenesis-a-network-based-approach-to-understanding-drug-toxicity
#18
J J Sutherland, Y W Webster, J A Willy, G H Searfoss, K M Goldstein, A R Irizarry, D G Hall, J L Stevens
Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP')...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440222/dual-leucine-zipper-kinase-dependent-perk-activation-contributes-to-neuronal-degeneration-following-insult
#19
Martin Larhammar, Sarah Huntwork-Rodriguez, Zhiyu Jiang, Hilda Solanoy, Arundhati Sengupta Ghosh, Bei Wang, Joshua S Kaminker, Kevin Huang, Jeffrey Eastham-Anderson, Michael Siu, Zora Modrusan, Madeline M Farley, Marc Tessier-Lavigne, Joseph W Lewcock, Trent A Watkins
The PKR-like endoplasmic reticulum kinase (PERK) arm of the Integrated Stress Response (ISR) is implicated in neurodegenerative disease, although the regulators and consequences of PERK activation following neuronal injury are poorly understood. Here we show that PERK signaling is a component of the mouse MAP kinase neuronal stress response controlled by the Dual Leucine Zipper Kinase (DLK) and contributes to DLK-mediated neurodegeneration. We find that DLK-activating insults ranging from nerve injury to neurotrophin deprivation result in both c-Jun N-terminal Kinase (JNK) signaling and the PERK- and ISR-dependent upregulation of the Activating Transcription Factor 4 (ATF4)...
April 25, 2017: ELife
https://www.readbyqxmd.com/read/28439950/protein-disulfide-isomerase-inhibition-synergistically-enhances-the-efficacy-of-sorafenib-for-hepatocellular-carcinoma
#20
Jae-Kyung Won, Su Jong Yu, Chae Young Hwang, Sung-Hwan Cho, Sang-Min Park, Kwangsoo Kim, Won-Mook Choi, Hyeki Cho, Eun Ju Cho, Jeong-Hoon Lee, Kyung Bun Lee, Yoon Jun Kim, Kyung-Suk Suh, Ja-June Jang, Chung Yong Kim, Jung-Hwan Yoon, Kwang-Hyun Cho
Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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