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https://www.readbyqxmd.com/read/29161592/tumor-suppressor-inactivation-of-gdf11-occurs-by-precursor-sequestration-in-triple-negative-breast-cancer
#1
Sameer S Bajikar, Chun-Chao Wang, Michael A Borten, Elizabeth J Pereira, Kristen A Atkins, Kevin A Janes
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161089/protein-folding-and-the-challenges-of-maintaining-endoplasmic-reticulum-proteostasis-in-idiopathic-pulmonary-fibrosis
#2
Freddy Romero, Ross Summer
Alveolar epithelial type II (AEII) cells are "professional" secretory cells that synthesize and secrete massive quantities of proteins to produce pulmonary surfactant and maintain airway immune defenses. To facilitate this high level of protein synthesis, AEII cells are equipped with an elaborate endoplasmic reticulum (ER) structure and possess an abundance of the machinery needed to fold, assemble, and secrete proteins. However, conditions that suddenly increase the quantity of new proteins entering the ER or that impede the capacity of the ER to fold proteins can cause misfolded or unfolded proteins to accumulate in the ER lumen, also called ER stress...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29161077/mitochondrial-dysfunction-in-pulmonary-fibrosis
#3
Sunad Rangarajan, Karen Bernard, Victor J Thannickal
The aging of the human population has resulted in an unprecedented increase in the incidence and prevalence of age-related diseases, including those of the lung. Idiopathic pulmonary fibrosis is a disease of aging, and is characterized by a progressive decline in lung function and high mortality. Recent studies suggest that mitochondrial dysfunction, which can accompany aging phenotypes, may contribute to the pathogenesis of idiopathic pulmonary fibrosis. In this review, we explore current evidence for mitochondrial dysfunction in alveolar epithelial cells, fibroblasts, and immune cells that participate in the fibrotic process...
November 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29160746/nucleic-acid-therapies-for-cystic-fibrosis
#4
Shruti Sasaki, Shuling Guo
Nucleic acid therapeutics are an established class of drugs that enable specific targeting of a gene of interest. This diverse family of drugs includes antisense oligonucleotides, siRNAs, and mRNA replacement therapies, which can elicit both gene repression and activation, primarily at the RNA level. Recent advances in medicinal chemistry have increased drug potency and enhanced delivery and distribution to a broad array of tissue and cell types. A key advantage of nucleic acid therapeutics is in their application to monogenic diseases...
November 21, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29159900/p100-functions-as-a-metastasis-activator-and-is-targeted-by-tumor-suppressing-microrna-320a-in-lung-cancer
#5
Aimin Xing, Li Pan, Jingzhen Gao
BACKGROUND: Lung cancer is among the most frequently diagnosed types of cancer worldwide, with high morbidity and mortality. Metastasis accounts for the deadliest and most poorly understood feature of lung cancer. Herein, we demonstrate that SND1 (also known as p100) acts as a candidate metastasis activator and is targeted by microRNA-320a (miR-320a) in lung cancer cells. METHODS: p100 expression in lung cancer cell lines and tissues was determined by quantitative real time-PCR and Western blot...
November 21, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/29158824/dioscin-exerts-protective-effects-against-crystalline-silica-induced-pulmonary-fibrosis-in-mice
#6
Chao Li, Yiping Lu, Sitong Du, Siyi Li, Yiting Zhang, Fangwei Liu, Ying Chen, Dong Weng, Jie Chen
Inhalation of crystalline silica particles leads to pulmonary fibrosis, eventually resulting in respiratory failure and death. There are few effective drugs that can delay the progression of this disease; thus, patients with silicosis are usually only offered supportive care. Dioscin, a steroidal saponin, exhibits many biological activities and health benefits including its protective effects against hepatic fibrosis. However, the effect of dioscin on silicosis is unknown. METHODS: We employed experimental mouse mode of silicosis...
2017: Theranostics
https://www.readbyqxmd.com/read/29158503/kr%C3%A3-pple-like-factor-4-attenuates-lung-fibrosis-via-inhibiting-epithelial-mesenchymal-transition
#7
Lianjun Lin, Qian Han, Yan Xiong, Ting Li, Zhonghui Liu, Huiying Xu, Yanping Wu, Nanping Wang, Xinmin Liu
Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29156750/somatic-mutations-in-cdh1-and-ctnnb1-in-primary-carcinomas-at-13-anatomic-sites
#8
Evan L Busch, Jason L Hornick, Renato Umeton, Adem Albayrak, Neal I Lindeman, Laura E MacConaill, Elizabeth P Garcia, Matthew Ducar, Timothy R Rebbeck
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156351/benzamide-porphyrins-with-directly-conjugated-and-distal-pyridyl-or-pyridinium-groups-substituted-to-the-porphyrin-macrocycles-study-of-the-photosensitising-abilities-as-inducers-of-apoptosis-in-cancer-cells-under-photodynamic-conditions
#9
Devashish Sengupta, Zeaul Hoque Mazumdar, Avinaba Mukherjee, Debdulal Sharma, Amit Kumar Halder, Samita Basu, Tarun Jha
Amphiphilic porphyrin photosensitisers (PSs) having combinations of directly substituted pyridyl group(s) at the meso-position of a porphyrin macrocycle, and/or indirectly linked pyridyl groups as benzamide derivatives are reported. The compounds 5,10,15,20-tetrakis-(4-pyridylbenzamide)porphyrin (A.2), 5,10,15,20-tetra[N-(pyridine-4-yl)benzamidium] porphyrin (A.3), 5-mono-(4-pyridyl)-10,15,20-tris-(4-pyridylbenzamide)porphyrin (B.2) and 5-mono-(4-methylpyridinium)-10,15,20-tris-(4-pyridiniumbenzamide)porphyrin (B...
November 13, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29155131/human-lung-epithelial-cell-cultures-for-analysis-of-inhaled-toxicants-lessons-learned-and-future-directions
#10
REVIEW
Pieter S Hiemstra, Gwendolynn Grootaers, Anne M van der Does, Cyrille A M Krul, Ingeborg M Kooter
The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review...
November 15, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29154949/a-novel-microscopy-based-assay-identifies-extended-synaptotagmin-1-esyt1-as-a-positive-regulator-of-anoctamin-1-traffic
#11
Joana R Lérias, Madalena C Pinto, Hugo M Botelho, Nikhil T Awatade, Margarida C Quaresma, Iris A L Silva, Podchanart Wanitchakool, Rainer Schreiber, Rainer Pepperkok, Karl Kunzelmann, Margarida D Amaral
An attractive possibility to treat Cystic Fibrosis (CF), a severe condition caused by dysfunctional CFTR, an epithelial anion channel, is through the activation of alternative (non-CFTR) anion channels. Anoctamin 1 (ANO1) was demonstrated to be a Ca(2+)-activated chloride channel (CaCC) and thus of high potential to replace CFTR. Despite that ANO1 is expressed in human lung CF tissue, it is present at the cell surface at very low levels. In addition, little is known about regulation of ANO1 traffic, namely which factors promote its plasma membrane (PM) localization...
November 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154202/polymorphisms-in-inflammasome-genes-and-risk-of-asthma-in-brazilian-children
#12
Vinicius Nunes Cordeiro Leal, Isabel Rugue Genov, Márcia C Mallozi, Dirceu Solé, Alessandra Pontillo
Considering its role in inflammation and recently described "alternative" roles in epithelial homeostasis and Th1/Th2 balance, we hypothesize that inflammasome genetics could contribute to the development of asthma. Selected functional polymorphisms in inflammasome genes are evaluated in a cohort of asthmatic children and their families. Gain-of-function NLRP1 variants rs11651270, rs12150220 and rs2670660 resulted significantly associated to asthma in trios (TDT) analysis; and rs11651270 and rs2670660 also with asthma severity and total IgE level in asthmatic children...
November 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29152741/neat1-acts-as-an-inducer-of-cancer-stem-cell-like-phenotypes-in-nsclc-by-inhibiting-egcg-upregulated-ctr1
#13
Pan Jiang, Aochang Chen, Xiaoyue Wu, Ming Zhou, Ijaz Ul Haq, Zahula Mariyam, Qing Feng
Long non-coding RNAs (lncRNAs) play significant roles in the pathogenesis of various cancers, including lung cancer. In this study, we aimed to investigate the biological function of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in cancer stem cells (CSCs). CSCs have been suggested as the main cause of tumor metastasis, tumor recurrence and chemotherapy resistance. The copper transporter 1 (CTR1) has been the focus of many recent studies because of its correlation with cisplatin (CDDP) resistance. So far, the mechanism of how NEAT1 regulates CSCs in NSCLC remains unknown...
November 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#14
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29151973/roles-of-micrornas-in-the-resistance-to-platinum-based-chemotherapy-in-the-non-small-cell-lung-cancer
#15
REVIEW
Hongjing Zang, Jianlun Peng, Weiyuan Wang, Songqing Fan
Platinum-based adjuvant chemotherapy improves survival among patients with lung tumors, in particular non-small cell lung cancer (NSCLC). But the predicament of drug resistance in NSCLC patients is frustrating us. The profiles of microRNAs are different between platinum chemotherapy resistant and sensitive NSCLC cells. Researches regarding microRNAs and their targets, in platinum drug resistant cases, illuminate novel ideals for platinum-based chemotherapy for NSCLC patients. Therefore, in this review we will focus on three aspects: Epithelial-mesenchymal transition (EMT), cell proliferation and apoptosis, and the roles of microRNAs in cisplatin (CDDP) and carboplatin (CBP) resistance...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150939/mir-34b-5p-inhibition-attenuates-lung-inflammation-and-apoptosis-in-an-lps-induced-acute-lung-injury-mouse-model-by-targeting-progranulin
#16
Wang Xie, Qingchun Lu, Kailing Wang, Jingjing Lu, Xia Gu, Dongyi Zhu, Fanglei Liu, Zhongliang Guo
BACKGROUND: Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS-induced ALI. Here, we have investigated the potential roles of PGRN-targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. METHODS: LPS-induced lung injury and the protective roles of PGRN in ALI were first confirmed...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29148232/disulfiram-combined-with-copper-inhibits-metastasis-and-epithelial-mesenchymal-transition-in-hepatocellular-carcinoma-through-the-nf-%C3%AE%C2%BAb-and-tgf-%C3%AE-pathways
#17
Yi Li, Li-Hui Wang, Hao-Tian Zhang, Ya-Ting Wang, Shuai Liu, Wen-Long Zhou, Xiang-Zhong Yuan, Tian-Yang Li, Chun-Fu Wu, Jing-Yu Yang
Late-stage hepatocellular carcinoma (HCC) usually has a low survival rate because of the high risk of metastases and the lack of an effective cure. Disulfiram (DSF) has copper (Cu)-dependent anticancer properties in vitro and in vivo. The present work aims to explore the anti-metastasis effects and molecular mechanisms of DSF/Cu on HCC cells both in vitro and in vivo. The results showed that DSF inhibited the proliferation, migration and invasion of HCC cells. Cu improved the anti-metastatic activity of DSF, while Cu alone had no effect...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29148109/notch-signaling-controls-transdifferentiation-of-pulmonary-neuroendocrine-cells-in-response-to-lung-injury
#18
Erica Yao, Chuwen Lin, Qingzhe Wu, Kuan Zhang, Hai Song, Pao-Tien Chuang
Production of an appropriate number of distinct cell types in precise locations during embryonic development is critical for proper tissue function. Homeostatic renewal or repair of damaged tissues in adults also requires cell expansion and transdifferentiation to replenish lost cells. However, the responses of diverse cell types to tissue injury are not fully elucidated. Moreover, the molecular mechanisms underlying transdifferentiation remain poorly understood. This knowledge is essential for harnessing the regenerative potential of individual cell types...
November 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/29146889/exhaled-markers-of-anti-oxidant-activity-and-oxidative-stress-in-stable-cystic-fibrosis-patients-with-moderate-lung-disease
#19
Lucia Spicuzza, Giuseppe Fabio Parisi, Lucia Tardino, Nicola Ciancio, Raffaella Nenna, Fabio Midulla, Salvatore Leonardi
The sustained imbalance between oxidant and antioxidant species contributes to lung damage in patients with cystic fibrosis (CF). Glutathione (GSH) is an important component of the antioxidant defense in the airways epithelial lining fluid and its transportation out of the cells may be altered in CF. The aim of this study was to assess the oxidants/anti-oxidants balance in the airways of patients with CF. We measured the concentrations of GSH, the total antioxidant capacity and the concentration of 8-iso-prostaglandin F2α (8-isoprostane), a marker of oxidative stress, in the exhaled breath condensate of 17 non-smoking patients with CF, in stable phase, and in 17 age-matched healthy subjects...
November 17, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/29146575/lumacaftor-vx-809-restores-the-ability-of-cf-macrophages-to-phagocytose-and-kill-pseudomonas-aeruginosa
#20
Roxanna Barnaby, Katja Koeppen, Amanda Nymon, Thomas H Hampton, Brent Berwin, Alix Ashare, Bruce Stanton
Cystic Fibrosis (CF), the most common lethal genetic disease in Caucasians, is characterized by chronic bacterial lung infection and excessive inflammation, which leads to progressive loss of lung function, and premature death. Although ivacaftor (VX-770) and the combination of ivacaftor and lumacaftor (VX-809) improve lung function in CF patients with the Gly551Asp and del508Phe mutation, respectively, the effects of these drugs on the function of human CF macrophages are unknown. Thus, studies were conducted to examine the effects of lumacaftor alone and in combination with ivacaftor (i...
November 16, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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