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https://www.readbyqxmd.com/read/28334946/mutations-affecting-the-transmembrane-domain-of-the-ldl-receptor-impact-of-charged-residues-on-the-membrane-insertion
#1
Thea Bismo Strøm, Jon K Laerdahl, Trond P Leren
Familial hypercholesterolemia (FH) is caused by mutations in the low density lipoprotein receptor (LDLR) gene. To study the impact of mutations affecting the hydrophobic transmembrane domain of the LDLR, each of the 22 amino acids of the transmembrane domain was individually mutated to arginine. The more centrally in the transmembrane domain an arginine was located, the lower amounts of the 120 kDa precursor LDLR in the endoplasmic reticulum were observed. This led to lower amounts of the 160 kDa mature LDLR on the cell surface...
February 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334878/high-expression-of-ire1-in-lung-adenocarcinoma-is-associated-with-a-lower-rate-of-recurrence
#2
Toshio Sakatani, Keita Maemura, Noriko Hiyama, Yosuke Amano, Kousuke Watanabe, Hidenori Kage, Masashi Fukayama, Jun Nakajima, Yutaka Yatomi, Takahide Nagase, Daiya Takai
Objective: Recent reports have shown that endoplasmic reticulum stress is associated with cancer. However, the impacts of endoplasmic reticulum stress on the prognosis of lung cancer are unknown. Therefore, in this study, we sought to reveal the relationship between the expression of endoplasmic reticulum stress-related genes (endoplasmic reticulum oxidoreductase 1L, protein kinase RNA-like endoplasmic reticulum kinase, activating transcription factor 6 and inositol-requiring kinase 1) and the outcome of lung adenocarcinoma...
March 17, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28334754/rate-of-renal-function-decline-race-and-referral-to-nephrology-in-a-large-cohort-of-primary-care-patients
#3
Farrukh M Koraishy, Denise Hooks-Anderson, Joanne Salas, Jeffrey F Scherrer
Introduction.: Late nephrology referral is associated with adverse outcomes especially among minorities. Research on the association of the rate of chronic kidney disease (CKD) progression with nephrology referral in white versus black patients is lacking. Objectives.: Compute the odds of nephrology referral in primary care and their associations with race and the rate of CKD progression. Methods.: Electronic health record data were obtained from 2170 patients in primary care clinics in the Saint Louis metropolitan area with at least two estimated glomerular filtration rate (eGFR) values over a 7-year observation period...
February 21, 2017: Family Practice
https://www.readbyqxmd.com/read/28334634/e3-ubiquitin-ligase-cbl-b-prevents-tumor-metastasis-by-maintaining-the-epithelial-phenotype-in-multiple-drug-resistant-gastric-and-breast-cancer-cells
#4
Ling Xu, Ye Zhang, Xiujuan Qu, Xiaofang Che, Tianshu Guo, Ying Cai, Aodi Li, Danni Li, Ce Li, Ti Wen, Yibo Fan, Kezuo Hou, Yanju Ma, Xuejun Hu, Yunpeng Liu
Multiple drug resistance (MDR) and metastasis are two major factors that contribute to the failure of cancer treatment. However, the relationship between MDR and metastasis has not been characterized. Additionally, the role of the E3 ubiquitin ligase Cbl-b in metastasis of MDR gastric and breast cancer is not well known. In the present study, we found that MDR gastric and breast cancer cells possess a typical mesenchymal phenotype and enhanced cell migration capacity. Additionally, Cbl-b is poorly expressed in MDR gastric and breast cancer cells...
March 20, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28334495/elbasvir-grazoprevir-does-not-worsen-renal-function-in-patients-with-hepatitis-c-virus-infection-and-pre-existing-renal-disease
#5
K Rajender Reddy, David Roth, Annette Bruchfeld, Peggy Hwang, Barbara Haber, Michael N Robertson, Eliav Barr, Wayne Greaves
AIM: Treatment options have been limited for patients with hepatitis C virus (HCV) infection and chronic kidney disease stage 4/5 (CKD 4/5). The aim of this analysis was to evaluate the impact of elbasvir/grazoprevir on estimated glomerular filtration rate (eGFR) in patients with CKD stage 3 enrolled in phase II/III clinical trials. METHODS: We conducted a retrospective integrated analysis of patients with CKD 3 enrolled in the EBR/GZR phase II/III clinical trials...
March 23, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28334319/erbb4-acts-as-a-suppressor-in-the-development-of-hepatocellular-carcinoma
#6
Yao Liu, Liming Song, Hengli Ni, Lina Sun, Weijuan Jiao, Lin Chen, Qun Zhou, Tong Shen, Hongxia Cui, Tianming Gao, Jianming Li
ERBB4, one member of the epidermal growth factor receptor (EGFR) family, plays a key role in physiological and pathological processes. Recently, we identified that ERBB4 played a protective role from chronic hepatitis B virus infection. However, the role of ERBB4 in hepatocellular carcinoma (HCC) is still unclear. Here, we explore the role of ERBB4 in the development of HCC using in vitro models, in vivo animal models and clinical samples of HCC. Liver-specific ERBB4 knockout alleles and full ERBB4 except heart knockout mice were used in this study...
March 14, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28333951/prognostic-value-of-plasma-egfr-ctdna-in-nsclc-patients-treated-with-egfr-tkis
#7
Chengjuan Zhang, Bing Wei, Peng Li, Ke Yang, Zhizhong Wang, Jie Ma, Yongjun Guo
OBJECTIVE: Epidermal growth factor receptor (EGFR) specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC). However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients. METHODS: A total of forty-five (45) NSCLC patients who received EGFR-TKI therapy were enrolled...
2017: PloS One
https://www.readbyqxmd.com/read/28332624/effects-of-icotinib-with-and-without-radiation-therapy-on-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-brain-metastases
#8
Yun Fan, Yanjun Xu, Lei Gong, Luo Fang, Hongyang Lu, Jing Qin, Na Han, Fajun Xie, Guoqin Qiu, Zhiyu Huang
EGFR-TKIs and radiation therapy (RT) are the principal treatment for patients with brain metastases (BM) and EGFR mutant NSCLC. However, the optimal use of brain RT for patients with asymptomatic BM remains undefined. A total of 152 patients were identified. 58 patients were excluded. Of the remaining 97 patients, 56 patients received upfront RT followed by icotinib, including WBRT or SRS. 41 patients received icotinib therapy alone. The mOS from diagnosis of BM was 27.0 months for the whole cohort (95% CI, 23...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332606/lumican-effectively-regulates-the-estrogen-receptors-associated-functional-properties-of-breast-cancer-cells-expression-of-matrix-effectors-and-epithelial-to-mesenchymal-transition
#9
Konstantina Karamanou, Marco Franchi, Zoi Piperigkou, Corinne Perreau, Francois-Xavier Maquart, Demitrios H Vynios, Stéphane Brézillon
Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332584/akt-targeting-as-a-strategy-to-boost-chemotherapy-efficacy-in-non-small-cell-lung-cancer-through-metabolism-suppression
#10
Marion Le Grand, Raphael Berges, Eddy Pasquier, Marie-Pierre Montero, Laurence Borge, Alice Carrier, Sophie Vasseur, Veronique Bourgarel, Duje Buric, Nicolas André, Diane Braguer, Manon Carré
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332475/association-of-urinary-uromodulin-with-kidney%C3%A2-function-decline-and-mortality-the%C3%A2-health-abc-study%C3%A2
#11
Pranav S Garimella, Ronit Katz, Joachim H Ix, Linda F Fried, Stephen B Kritchevsky, Prasad Devarajan, Michael R Bennett, Chirag R Parikh, Michael G Shlipak, Tamara B Harris, Orlando M Gutiérrez, Mark J Sarnak
BACKGROUND: Urine uromodulin (uUMOD) is a protein secreted by the kidney tubule. Recent studies have suggested that higher uUMOD may be associated with improved kidney and mortality outcomes. METHODS: Using a case-cohort design, we evaluated the association between baseline uUMOD levels and ≥ 30% estimated glomerular filtration rate (eGFR) decline, incident chronic kidney disease (CKD), rapid kidney function decline, and mortality using standard and modified Cox proportional hazards regression...
March 23, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28332473/correlation-analysis-of-renal-ultrasound-elastography-and-clinical-and-pathological-changes-in-patients-with-chronic-kidney-disease%C3%A2
#12
Lingyan Peng, Tingting Zhong, Qiuling Fan, Yanjun Liu, Xuemei Wang, Lining Wang
OBJECTIVE: To analyze the correlations of renal tissue elastography with clinical biochemical indicators and pathological changes in patients with chronic kidney disease (CKD) as well as to explore the potential for renal tissue elastography as a new, noninvasive method for the dynamic monitoring of renal disease progression, efficacy assessment, and prognosis evaluation. METHODS: Patients admitted to the Department of Nephrology of the First Affiliated Hospital of China Medical University from August 2014 to January 2015 who had undergone renal biopsies were selected...
March 23, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28332137/correction-of-dilutional-anemia-induces-renal-dysfunction-in-diabetic-patients-undergoing-coronary-artery-bypass-grafting-a-consequence-of-microcirculatory-alterations
#13
Güçlü Aykut, Meltem Kilercik, Cem Arıtürk, Halim Ulugöl, Uğur Aksu, Türkan Kudsioğlu, Nazan Atalan, Nihan Yapıcı, Hasan Karabulut, Fevzi Toraman
BACKGROUND: In this study we aimed to evaluate the effects of dilutional anemia resulting from cardiopulmonary bypass (CPB) and its correction with red blood cell (RBC) transfusion on tissue oxygenation and renal function in diabetic patients undergoing coronary artery bypass grafting (CABG). METHOD: 70 diabetic patients who underwent elective CABG and whose hematocrit values had been between 24-28% at any time during CBP were prospectively randomized and equally allocated to two groups: patients who received RBC during CPB (group I, n = 35) vs...
March 22, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#14
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28332017/the-relationship-between-the-renal-reabsorption-of-cysteine-and-the-lowered-urinary-ph-in-diabetics
#15
Susumu Ogawa, Junko Takiguchi, Manami Shimizu, Kazuhiro Nako, Masashi Okamura, Yoshitaka Kinouchi, Sadayoshi Ito
BACKGROUND/AIMS: In diabetic patients, reduced urinary pH (UpH) is a predictive factor for cardiorenal-vascular disorders. Synthesis of glutathione, an anti-oxidative stress substance, is induced to counteract renal oxidative stress. UpH declines as glutamate is consumed, as does the synthesis of ammonia from glutamate. Glutathione is synthesized from glutamate and cysteine; however, in diabetes, the relationship between lowered UpH and the roles of renal amino acids is unknown. We, therefore, examined the relationship between amino-acid kinetics, UpH, and renal function...
March 22, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28331934/microarray-analysis-of-differential-gene-expression-profile-between-human-fetal-and-adult-heart
#16
Zhimin Geng, Jue Wang, Lulu Pan, Ming Li, Jitai Zhang, Xueli Cai, Maoping Chu
Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes...
March 22, 2017: Pediatric Cardiology
https://www.readbyqxmd.com/read/28331001/quantitative-tyrosine-phosphoproteomics-of-egfr-tyrosine-kinase-inhibitor-treated-lung-adenocarcinoma-cells-reveals-potential-novel-biomarkers-of-therapeutic-response
#17
Xu Zhang, Tapan Maity, Manoj K Kashyap, Mukesh Bansal, Abhilash Venugopalan, Sahib Singh, Shivangi Awasthi, Arivusudar Marimuthu, Harrys Kishore Charles Jacob, Natalya Belkina, Stephanie Pitts, Constance M Cultraro, Shaojian Gao, Fatos Kirkali, Romi Biswas, Raghothama Chaerkady, Andrea Califano, Akhilesh Pandey, Udayan Guha
Mutations in the Epidermal growth factor receptor (EGFR) kinase domain, such as the L858R missense mutation and deletions spanning the conserved sequence 747LREA750, are sensitive to tyrosine kinase inhibitors (TKIs). The gatekeeper site residue mutation, T790M accounts for around 60% of acquired resistance to EGFR TKIs. The first generation EGFR TKIs, erlotinib and gefitinib, and the second generation inhibitor, afatinib are FDA approved for initial treatment of EGFR mutated lung adenocarcinoma. The predominant biomarker of EGFR TKI responsiveness is the presence of EGFR TKI-sensitizing mutations...
March 22, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28330951/hypoxia-induced-proliferation-of-hela-cells-depends-on-epidermal-growth-factor-receptor-mediated-arginase-ii-induction
#18
Bhuvana A Setty, Natasha Pillay Smiley, Caitlyn M Pool, Yi Jin, Yusen Liu, Leif D Nelin
Solid tumors can often be hypoxic in regions, and cancer cells can respond to hypoxia with an increase in proliferation and a decrease in apoptosis, leading to a net increase in viable cell numbers. We have recently found that in an osteosarcoma cell line, hypoxia-induced proliferation depends on arginase II induction. Epidermal growth factor receptor (EGFR) has been shown to mediate the hypoxia-induced cellular proliferation in some cancer cell lines. We hypothesized that hypoxia-induced proliferation of HeLa cells would depend on arginase II induction and that this induction of arginase II would occur through EGFR activation...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28329858/cystatin-c-and-the-risk-of-frailty-and-mortality-in-older-men
#19
Allyson Hart, Terri L Blackwell, Misti L Paudel, Brent C Taylor, Eric S Orwoll, Peggy M Cawthon, Kristine E Ensrud
Background: This study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men. Methods: Prospective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead...
November 9, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28329158/kidney-function-estimated-from-cystatin-c-but-not-creatinine-is-related-to-objective-tests-of-physical-performance-in-community-dwelling-older-adults
#20
Mark Canney, Donal J Sexton, Matthew Dl O'Connell, Rose Anne Kenny, Mark A Little, Conall M O'Seaghdha
Background: The burden of chronic kidney disease is highest among older adults but the significance of a diminished level of kidney function in this heterogeneous population is poorly understood. We sought to examine the relationship between estimated glomerular filtration rate (eGFR) and objective physical performance in older adults. Methods: Cross-sectional analysis of 4,562 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years...
March 10, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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