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https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#1
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28523294/autophagy-in-aging-and-disease
#2
Mădălina Fîlfan, Raluca Elena Sandu, Alexandra Daniela Zăvăleanu, Andrei GreşiŢă, Daniela Gabriela Glăvan, Denissa Greta Olaru, Aurel Popa-Wagner
Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28522565/integrin-%C3%AE-v%C3%AE-5-inhibition-protects-against-ischemia-reperfusion-induced-lung-injury-in-an-autophagy-dependent-manner
#3
Dan Zhang, Chichi Li, Yuanlin Song, Jian Zhou, Yuping Li, Jing Li, Chunxue Bai
Integrin αvβ5 mediates pulmonary endothelial barrier function and acute lung injury (LI), but its roles in cell apoptosis and autophagy are unclear. Thus, the aims of this study were to investigate the significance of αvβ5 in ischemia/reperfusion (I/R)-induced apoptosis and LI and to explore the relationship between αvβ5 and autophagy. Human pulmonary micro-vascular endothelial cells (HPMVECs) were pretreated with an αvβ5-blocking antibody (ALULA) and challenged with oxygen-glucose deprivation/oxygen-glucose restoration, which mimics I/R; then, cellular autophagy and apoptosis were detected, and cell permeability was assessed...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28515477/cancer-cachexia-associates-with-a-systemic-autophagy-inducing-activity-mimicked-by-cancer-cell-derived-il-6-trans-signaling
#4
Kristine Pettersen, Sonja Andersen, Simone Degen, Valentina Tadini, Joël Grosjean, Shinji Hatakeyama, Almaz N Tesfahun, Siver Moestue, Jana Kim, Unni Nonstad, Pål R Romundstad, Frank Skorpen, Sveinung Sørhaug, Tore Amundsen, Bjørn H Grønberg, Florian Strasser, Nathan Stephens, Dag Hoem, Anders Molven, Stein Kaasa, Kenneth Fearon, Carsten Jacobi, Geir Bjørkøy
The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28510366/hmga2-plays-an-important-role-in-cr-vi-induced-autophagy
#5
Fan Yang, Lian Zhao, Dan Mei, Liping Jiang, Chengyan Geng, Qiujuan Li, Xiaofeng Yao, Yong Liu, Ying Kong, Jun Cao
Cr (VI) is mutagenic and carcinogenic, but the mechanism is unclear. In this study, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-induced autophagy was investigated. Cr (VI) treatment induced formation of autophagosomes, increased expression of LC3II, Atg12-Atg5, Atg4, Atg10, HMGA1 and HMGA2 proteins, and decreased the expression of p62 in A549 cells. Silencing of HMGA2 gene by siRNA blocked Cr (VI)-induced formation of autophagosomes, expression of LC3II, Atg12-Atg5, Atg10 and reduction of p62...
May 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28500633/the-novel-role-of-pyrvinium-in-cancer-therapy
#6
REVIEW
Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Faezeh Ghasemi, Michele Caraglia, Amirhossein Sahebkar
Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryp-tosporidium parvum and Plasmodium falciparum in the 1950 s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer and some hematological malignancies...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498463/mir-138-suppresses-the-proliferation-metastasis-and-autophagy-of-non-small-cell-lung-cancer-by-targeting-sirt1
#7
Zaiting Ye, Bingmu Fang, Jiongwei Pan, Ning Zhang, Jinwei Huang, Congying Xie, Tianzheng Lou, Zhuo Cao
The present study determined the role and mechanism of miR-138 in non-small cell lung cancer (NSCLC). In total, 45 freshly resected clinical NSCLC tissues were collected. The expression of miR-138 in tissues and cell lines were determined by real-time quantitative PCR. miR-138 mimics were transfected into A549 and Calu-3 cells in vitro, and then the effects of miR-138 on lung cancer cell proliferation, cell cycle, invasion and metastasis were investigated by CCK-8 assay, Transwell and flow cytometry, respectively...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498429/sbi0206965-a-novel-inhibitor-of-ulk1-suppresses-non-small-cell-lung-cancer-cell-growth-by-modulating-both-autophagy-and-apoptosis-pathways
#8
Fang Tang, Pengchao Hu, Zetian Yang, Chao Xue, Jun Gong, Shaoxing Sun, Liu Shi, Shimin Zhang, Zhenzhen Li, Chunxu Yang, Junhong Zhang, Conghua Xie
Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients...
May 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495516/7-o-geranylquercetin-induced-autophagy-contributes-to-apoptosis-via-ros-generation-in-human-non-small-cell-lung-cancer-cells
#9
En-Xia Wang, Bo-Yang Zou, Lei Shi, Lin-Ying Du, Yan-Yan Zhu, Ya-Meng Jiang, Xiao-Dong Ma, Xiao-Hui Kang, Chang-Yuan Wang, Yu-Hong Zhen, Li-Dan Sun
AIMS: To investigate the antitumor effects of 7-O-geranylquercetin (GQ), a novel O-alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. MAIN METHODS: Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay...
May 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28493079/tlr2-regulates-allergic-airway-inflammation-and-autophagy-through-pi3k-akt-signaling-pathway
#10
Xuqin Jiang, Lei Fang, Huimei Wu, Xiaodong Mei, Fang He, Peishan Ding, Rongyu Liu
Toll-like receptors (TLRs) are innate pattern recognition receptors that play a critical role in allergic inflammation, yet their contribution to autophagy in asthma remains poorly defined. Here, we investigate the role of Toll-like receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild-type (WT) and TLR2-knockout (TLR2(-/-)) C57BL/6 mice were ovalbumin-sensitized and ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell hyperplasia, and increased mucus production were observed...
May 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28487978/enhanced-circulating-ilc2s-and-mdscs-may-contribute-to-ensure-maintenance-of-th2-predominant-in-patients-with-lung-cancer
#11
Yumin Wu, Yulan Yan, Zhaoliang Su, Qingli Bie, Xiaobo Chen, Prince Amoah Barnie, Qi Guo, Shengjun Wang, Huaxi Xu
Group 2 innate lymphoid cells (ILC2s) were demonstrated to be involved in the initiation and coordination of type 2 T helper cell (Th2) responses. Myeloid‑derived suppressor cells (MDSCs) have received a great deal of attention for their role in creating an immunosuppressive microenvironment in cancer‑bearing hosts. However, the contributions of ILC2s in the occurrence and development of lung cancer, and the association between ILC2s and Th2 or MDSCs in lung cancer remain to be elucidated. In the present study, 36 patients newly diagnosed with lung cancer based on the guidelines of the International Union Against Cancer Tumor Node Metastasis were included...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28476498/molecular-targets-of-chloropicrin-in-human-airway-epithelial-cells
#12
Maija Pesonen, Jaana Rysä, Markus Storvik, Kirsi Rilla, Markku Pasanen, Kirsi Vähäkangas
Chloropicrin is a vaporizing, irritating compound that causes complications in the respiratory system when inhaled. In this study, we examined the effects of exposure to chloropicrin for 24h on ultrastructure and global gene expression in primary human bronchial epithelial cells. The treatment increased the number of round and shrunken cells, which detached from culture plates more readily than the untreated control cells. Transmission electron microscopy revealed some swollen mitochondria and the appearance of autophagy/lysosome type of vacuoles in the treated cells...
May 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28473326/reduced-carboxylesterase-1-is-associated-with-endothelial-injury-in-methamphetamine-induced-pulmonary-arterial-hypertension
#13
Mark E Orcholski, Artyom Khurshudyan, Elya A Shamskhou, Ke Yuan, Ian Y Chen, Sean D Kodani, Christophe Morisseau, Bruce D Hammock, Ellen M Hong, Ludmila Alexandrova, Tero-Pekka Alastalo, Gerald Berry, Roham T Zamanian, Vinicio A de Jesus Perez
Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH) but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. While no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to both internalize and metabolize METH...
May 4, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28471447/microrna-18a-5p-functions-as-an-oncogene-by-directly-targeting-irf2-in-lung-cancer
#14
Chen Liang, Xing Zhang, Hui-Min Wang, Xiao-Min Liu, Xin-Ju Zhang, Bo Zheng, Guang-Ren Qian, Zhong-Liang Ma
Lung cancer is the major form of cancer resulting in cancer-related mortality around the world. MicroRNAs are endogenous small non-coding single-stranded RNAs, which can engage in the regulation of gene expression. In this study, miR-18a-5p significantly upregulated in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines, suggesting an oncogenic function in lung cancer. Additionally, miR-18a-5p can promote carcinogenesis by directly targeting interferon regulatory factor 2 (IRF2). Further experiments indicated that IRF2 can increase cell apoptosis, inhibit cell proliferation and migration ability...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28465453/rational-combination-immunotherapy-understand-the-biology
#15
Howard L Kaufman
Selecting rational treatment combinations remains a major challenge for improving immunotherapy outcomes. In this issue of Cancer Immunology Research, Zhang and colleagues reduced tumors by inhibiting CD47 in a lung carcinoma model, a treatment that inadvertently induced autophagy through inhibition of the Akt/mTOR pathway. By also targeting autophagy, the therapeutic response improved, highlighting the importance of understanding the biology beneath antitumor immunity. Cancer Immunol Res; 5(5); 355-6. ©2017 AACRSee article by Zhang et al...
May 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28464882/differential-regulation-of-muscle-protein-turnover-in-response-to-emphysema-and-acute-pulmonary-inflammation
#16
Judith J M Ceelen, Annemie M W J Schols, Stefan J van Hoof, Chiel C de Theije, Frank Verhaegen, Ramon C J Langen
BACKGROUND: Exacerbations in COPD are often accompanied by pulmonary and systemic inflammation, and associated with increased susceptibility to and prevalence of weight loss and muscle wasting. Muscle mass loss during disease exacerbations may contribute to emphysema-associated muscle atrophy. However, whether pulmonary inflammation in presence of emphysema differentially affects skeletal muscle, including protein synthesis and degradation signaling pathways has not previously been addressed...
May 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28463025/autophagy-enhanced-the-radioresistance-of-non-small-cell-lung-cancer-by-regulating-ros-level-under-hypoxia-condition
#17
Xiaoyan Chen, Ping Wang, Fei Guo, Xiangdong Wang, Juan Wang, Jinping Xu, Dexiao Yuan, Jianghong Zhang, Chunlin Shao
PURPOSE: Tumor resistance towards radiation has been a big obstacle to patient's poor prognosis of lung cancer. It has been reported that hypoxia and autophagy are contributing to this resistance partly. However, there is controversy over whether autophagy plays positive role in cancer therapy or not. We aim to find out the specific mechanism of radiation resistance. MATERIALS AND METHODS: A549 cells were treated with conditioned medium (CM) under 12h hypoxia or normoxia before irradiation...
May 2, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28460464/ppar%C3%AE-activation-by-troglitazone-enhances-human-lung-cancer-cells-to-trail-induced-apoptosis-via-autophagy-flux
#18
Uddin Md Nazim, Ji-Hong Moon, You-Jin Lee, Jae-Won Seol, Sang-Youel Park
Members of the tumor necrosis factor (TNF) transmembrane cytokine superfamily, such as TNFα and Fas ligand (FasL), play crucial roles in inflammation and immunity. TRAIL is a member of this superfamily with the ability to selectively trigger cancer cell death but does not motive cytotoxicity to most normal cells. Troglitazone are used in the cure of type II diabetes to reduce blood glucose levels and improve the sensitivity of an amount of tissues to insulin. In this study, we revealed that troglitazone could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454732/fluvastatin-prevents-lung-adenocarcinoma-bone-metastasis-by-triggering-autophagy
#19
Zuozhang Yang, Zhenyi Su, Judy Park DeWitt, Lin Xie, Yongbin Chen, Xiaojuan Li, Lei Han, Dongqi Li, Junfeng Xia, Ya Zhang, Yihao Yang, Congguo Jin, Jing Zhang, Su Li, Kun Li, Zhiping Zhang, Xin Qu, Zewei He, Yanjin Chen, Yan Shen, Mingyan Ren, Zhongqin Yuan
Bone is one of the most preferred sites of metastasis in lung cancer. Currently, bisphosphonates and denosumab are major agents for controlling tumor-associated skeletal-related events (SREs). However, both bisphosphonates and denosumab significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently prescribed cholesterol-lowering agents, have been reported to inhibit tumor progression and induce autophagy in cancer cells...
April 11, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28454554/impaired-lysosomal-activity-mediated-autophagic-flux-disruption-by-graphite-carbon-nanofibers-induce-apoptosis-in-human-lung-epithelial-cells-through-oxidative-stress-and-energetic-impairment
#20
Sandeep Mittal, Pradeep Kumar Sharma, Ratnakar Tiwari, Raja Gopal Rayavarapu, Jai Shankar, Lalit Kumar Singh Chauhan, Alok Kumar Pandey
BACKGROUND: Graphite carbon nanofibers (GCNF) have emerged as a potential alternative of carbon nanotubes (CNT) for various biomedical applications due to their superior physico-chemical properties. Therefore in-depth understanding of the GCNF induced toxic effects and underlying mechanisms in biological systems is of great interest. Currently, autophagy activation by nanomaterials is recognized as an emerging toxicity mechanism. However, the association of GCNF induced toxicity with this form of cell death is largely unknown...
April 28, 2017: Particle and Fibre Toxicology
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