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https://www.readbyqxmd.com/read/27905509/the-er-stress-regulator-bip-mediates-cadmium-induced-autophagy-and-neuronal-senescence
#1
Tao Wang, Yan Yuan, Hui Zou, Jinlong Yang, Shiwen Zhao, Yonggang Ma, Yi Wang, Jianchun Bian, Xuezhong Liu, Jianhong Gu, Zongping Liu, Jiaqiao Zhu
Autophagy is protective in cadmium (Cd)-induced oxidative damage. Endoplasmic reticulum (ER) stress has been shown to induce autophagy in a process requiring the unfolded protein response signalling pathways. Cd treatment significantly increased senescence in neuronal cells, which was aggravated by 3-MA or silencing of Atg5 and abolished by rapamycin. Cd increased expression of ER stress regulators Bip, chop, eIf2α, and ATF4, and activated autophagy as evidenced by upregulated LC3. Moreover, the ER stress inhibitor mithramycin inhibited the expression of ER stress protein chaperone Bip and blocked autophagic flux...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905110/distinct-molecular-landscapes-between-endometrioid-and-non-endometrioid-uterine-carcinomas
#2
Nathaniel L Jones, Joanne Xiu, Sudeshna Chatterjee-Paer, Alexandre Buckley de Meritens, William M Burke, Ana I Tergas, Jason D Wright, June Y Hou
Endometrial carcinoma (EC) is traditionally characterized as endometrioid and non-endometrioid based on histo-pathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27905104/biomarkers-of-folate-and-vitamin-b12-and-breast-cancer-risk-report-from-the-epic-cohort
#3
M Matejcic, J de Batlle, C Ricci, C Biessy, F Perrier, I Huybrechts, E Weiderpass, Boutron-Mc Ruault, C Cadeau, M His, D G Cox, H Boeing, R T Fortner, R Kaaks, P Lagiou, A Trichopoulou, V Benetou, R Tumino, S Panico, S Sieri, D Palli, F Ricceri, H B Bueno-de-Mesquita, G Skeie, P Amiano, M J Sánchez, M D Chirlaque, A Barricarte, J R Quirós, G Buckland, C H van Gils, P H Peeters, T J Key, E Riboli, B Gylling, A Zeleniuch-Jacquotte, M J Gunter, I Romieu, V Chajès
Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin...
December 1, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27904764/mir-193b-directly-targets-stmn1-and-inhibits-the-malignant-phenotype-in-colorectal-cancer
#4
Feng Guo, Yang Luo, Yi-Fei Mu, Shao-Lan Qin, Yang Qi, Yi-Er Qiu, Ming Zhong
Accumulating evidence suggests that aberrantly expressed microRNAs (miRNAs) contribute to the initiation and progression of human cancers. However, the underlying function of miR-193b in colorectal cancer (CRC) remains largely unexplored. Herein, we demonstrate that miR-193b is significantly down-regulated in CRC tissues compared with their normal counterparts. Kaplan-Meier analysis revealed that decreased miR-193b expression was closely associated with the shorter overall survival of patients with CRC. Through gain-and loss-of-function studies, we showed that miR-193b significantly suppressed CRC cell proliferation and invasion...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27904691/implantation-of-placenta-derived-mesenchymal-stem-cells-accelerates-murine-dermal-wound-closure-through-immunomodulation
#5
Haifeng Wang, Lianyu Chen, Yang Liu, Bangzhen Luo, Nanzi Xie, Tao Tan, Lige Song, Pei Erli, Ming Luo
BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904686/fisetin-a-dietary-phytochemical-overcomes-erlotinib-resistance-of-lung-adenocarcinoma-cells-through-inhibition-of-mapk-and-akt-pathways
#6
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904664/tauroursodeoxycholic-acid-inhibits-endoplasmic-reticulum-stress-blocks-mitochondrial-permeability-transition-pore-opening-and-suppresses-reperfusion-injury-through-gsk-3%C3%A3-in-cardiac-h9c2-cells
#7
Yuxi Xie, Yonggui He, Zhiliang Cai, Jianhang Cai, Mengyao Xi, Yidong Zhang, Jinkun Xi
This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H2O2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904477/axon-injury-induced-endoplasmic-reticulum-stress-and-neurodegeneration
#8
REVIEW
Yang Hu
Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904144/causes-and-consequences-of-endoplasmic-reticulum-stress-in-rheumatic-disease
#9
REVIEW
Fatemeh Navid, Robert A Colbert
Rheumatic diseases represent a heterogeneous group of inflammatory conditions, many of which involve chronic activation of both innate and adaptive immune responses by multiple genetic and environmental factors. These immune responses involve the secretion of excessive amounts of cytokines and other signalling mediators by activated immune cells. The endoplasmic reticulum (ER) is the cellular organelle that directs the folding, processing and trafficking of membrane-bound and secreted proteins, including many key components of the immune response...
December 1, 2016: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#10
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27903677/combined-inhibition-of-both-p110%C3%AE-and-p110%C3%AE-isoforms-of-phosphatidylinositol-3-kinase-is-required-for-sustained-therapeutic-effect-in-pten-deficient-er-breast-cancer
#11
Sarah R Hosford, Lloye M Dillon, Stephanie J Bouley, Rachele Rosati, Wei Yang, Vivian S Chen, Eugene Demidenko, Rocco P Morra, Todd W Miller
PURPOSE: Determine the roles of the phosphatidylinositol 3-kinase (PI3K) isoforms p110α and p110β in PTEN-deficient, estrogen receptor α (ER)-positive breast cancer, and the therapeutic potential of isoform-selective inhibitors. EXPERIMENTAL DESIGN: Anti-estrogen-sensitive and -resistant PTEN-deficient, ER+ human breast cancer cell lines, and mice bearing anti-estrogen-resistant xenografts were treated with the anti-estrogen fulvestrant, the p110α inhibitor BYL719, the p110β inhibitor GSK2636771, or combinations...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27903609/protein-sorting-at-the-er-golgi-interface
#12
REVIEW
Natalia Gomez-Navarro, Elizabeth Miller
Protein traffic is of critical importance for normal cellular physiology. In eukaryotes, spherical transport vesicles move proteins and lipids from one internal membrane-bound compartment to another within the secretory pathway. The process of directing each individual protein to a specific destination (known as protein sorting) is a crucial event that is intrinsically linked to vesicle biogenesis. In this review, we summarize the principles of cargo sorting by the vesicle traffic machinery and consider the diverse mechanisms by which cargo proteins are selected and captured into different transport vesicles...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903287/high-content-imaging-quantification-of-multiple-in-vitro-human-neurogenesis-events-after-neurotoxin-exposure
#13
Xian Wu, Anirban Majumder, Robin Webb, Steven L Stice
BACKGROUND: Our objective was to test neural active compounds in a human developmental neurotoxicity (DNT) model that represents neural tube stages of vulnerability. Previously we showed that 14 days in vitro (DIV 14) was sufficient to generate cryopreserved neuronal cells for post thaw neurite recovery assays. However, short exposure and assessment may not detect toxicants that affect an early neurogenesis continuum, from a mitotic human neural progenitor (hNP) cell population through the course of neurite outgrowth in differentiating neurons...
December 1, 2016: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27903276/accurate-prediction-of-response-to-endocrine-therapy-in-breast-cancer-patients-current-and-future-biomarkers
#14
REVIEW
Cigdem Selli, J Michael Dixon, Andrew H Sims
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27903259/differential-variation-patterns-between-hubs-and-bottlenecks-in-human-protein-protein-interaction-networks
#15
Erli Pang, Yu Hao, Ying Sun, Kui Lin
BACKGROUND: The identification, description and understanding of protein-protein networks are important in cell biology and medicine, especially for the study of system biology where the focus concerns the interaction of biomolecules. Hubs and bottlenecks refer to the important proteins of a protein interaction network. Until now, very little attention has been paid to differentiate these two protein groups. RESULTS: By integrating human protein-protein interaction networks and human genome-wide variations across populations, we described the differences between hubs and bottlenecks in this study...
December 1, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27903184/microinvasive-tumor-endoresection-in-combination-with-ocular-stereotactic-radiosurgery
#16
Oleg A Sinyavskiy, Roman L Troyanovsky, Pavel I Ivanov, Alexandr S Golovin, Andrey V Tibilov, Svetlana N Solonina, Anna M Astapenko, Irina S Zubatkina
OBJECTIVE The use of Gamma Knife radiosurgery (GKRS) as monotherapy in the treatment of uveal melanoma (UM) allows clinicians to achieve high local tumor control with low recurrence but does not prevent secondary enucleation due to glaucoma in cases of large tumors. The authors analyzed indications for tumor endoresection (ER), the time interval between irradiation and surgery, and the features and results of performing ER for UM after GKRS. METHODS Thirty-seven patients between 28 and 78 years of age (16 male and 11 female patients) with UM underwent GKRS with a dose of 70 to 80 Gy that was applied to the center of the tumor with complete immobilization of the eye during the procedure...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27902969/rac1-gtp-ase-signals-wnt-beta-catenin-pathway-mediated-integrin-directed-metastasis-associated-tumor-cell-phenotypes-in-triple-negative-breast-cancers
#17
Pradip De, Jennifer H Carlson, Tyler Jepperson, Scooter Willis, Brian Leyland-Jones, Nandini Dey
The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015)...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902959/kaempferol-a-phytoestrogen-suppressed-triclosan-induced-epithelial-mesenchymal-transition-and-metastatic-related-behaviors-of-mcf-7-breast-cancer-cells
#18
Geum-A Lee, Kyung-Chul Choi, Kyung-A Hwang
As a phytoestrogen, kaempferol is known to play a chemopreventive role inhibiting carcinogenesis and cancer progression. In this study, the influences of triclosan, an anti-bacterial agent recently known for an endocrine disrupting chemical (EDC), and kaempferol on breast cancer progression were examined by measuring their effects on epithelial-mesenchymal transition (EMT) and metastatic-related behaviors of MCF-7 breast cancer cells. Morphological changes of MCF-7 cells were observed, and a wound-healing assay was performed after the treatment of triclosan and kaempferol...
November 22, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27902804/hierarchical-map-of-orthologous-genomic-regions-reconstructed-from-two-closely-related-genomes-cucumber-case-study
#19
Huifen Cao, Erli Pang, Kui Lin
Accurate identification of orthologous genomic regions (OGRs) between two closely related genomes is crucial for the reliable detection of genomic changes, which range from small-scale changes (e.g., single nucleotide or small nucleotides) to large-scale structural changes. Although diverse OGRs inferred at different levels have been successfully applied to address various biological questions, a limited number of studies have simultaneously integrated OGRs from different levels. Here, we report on a new approach to construct a hierarchical map of OGRs...
November 2016: Plant Genome
https://www.readbyqxmd.com/read/27902770/mitochondrial-targeted-decyl-triphenylphosphonium-enhances-2-deoxy-d-glucose-mediated-oxidative-stress-and-clonogenic-killing-of-multiple-myeloma-cells
#20
Jeanine Schibler, Ann M Tomanek-Chalkley, Jessica L Reedy, Fenghuang Zhan, Douglas R Spitz, Michael K Schultz, Apollina Goel
Therapeutic advances have markedly prolonged overall survival in multiple myeloma (MM) but the disease currently remains incurable. In a panel of MM cell lines (MM.1S, OPM-2, H929, and U266), using CD138 immunophenotyping, side population staining, and stem cell-related gene expression, we demonstrate the presence of stem-like tumor cells. Hypoxic culture conditions further increased CD138low stem-like cells with upregulated expression of OCT4 and NANOG. Compared to MM cells, these stem-like cells maintained lower steady-state pro-oxidant levels with increased uptake of the fluorescent deoxyglucose analog...
2016: PloS One
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