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https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#1
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28538182/targeting-metabolic-reprogramming-by-influenza-infection-for-therapeutic-intervention
#2
Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28534966/microrna-92a-promotes-epithelial-mesenchymal-transition-through-activation-of-pten-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer-metastasis
#3
Chaojing Lu, Zhengxiang Shan, Jiang Hong, Lixin Yang
MicroRNAs (miRNAs) have important roles in various cancers, including non-small cell lung cancer (NSCLC). Although several miRNAs have reported to be involved in the development of NSCLC, understanding the regulatory roles of other miRNAs in NSCLC is essential. Therefore, the aim of the current study was to explore the roles and mechanisms of screened miRNAs in NSCLC. First, the differentially expressed miRNAs that were screened based on GSE29248 microarray data retrieved from Gene Expression Omnibus (GEO)...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28529576/increased-mir31hg-lncrna-expression-increases-gefitinib-resistance-in-non-small-cell-lung-cancer-cell-lines-through-the-egfr-pi3k-akt-signaling-pathway
#4
Bing Wang, Hong Jiang, Limin Wang, Xueqin Chen, Kan Wu, Shirong Zhang, Shenglin Ma, Bing Xia
The aim of the present study was to gain insight into the molecular mechanism of gefitinib resistance in non-small cell lung cancer (NSCLC), and demonstrate whether long noncoding RNA (lncRNA) expression signatures differ between gefitinib-sensitive PC9 and gefitinib-resistant PC9 (PC9-R) cell lines. PC9 and PC9-R cells were treated with gefitinib and, after 48 h, proliferation and apoptosis were analyzed using a Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Microarray expression profiling of lncRNAs was undertaken in both PC9 and PC9-R cells, and the expression profiles were verified by reverse transcription quantitative-polymerase chain reaction...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28522751/targeting-fbw7-as-a-strategy-to-overcome-resistance-to-targeted-therapy-in-non-small-cell-lung-cancer
#5
Mingxiang Ye, Yong Zhang, Xinxin Zhang, Jian-Bin Zhang, Pengyu Jing, Liang Cao, Nan Li, Xia Li, Libo Yao, Jian Zhang, Jian Zhang
Inhibition of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non-small cell lung cancer (NSCLC) patients with distinct clinicopathological features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/Erk-independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of anti-apoptotic protein MCL-1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522564/decreased-phosphatase-pten-amplifies-pi3k-signaling-and-enhances-pro-inflammatory-cytokine-release-in-copd
#6
Satoru Yanagisawa, Jonathan R Baker, Chaitanya Vuppusetty, Peter Fenwick, Louise E Donnelly, Kazuhiro Ito, Peter J Barnes
The phosphatidylinositol 3-kinase (PI3K) pathway is activated in chronic obstructive pulmonary disease (COPD), but the regulatory mechanisms for this pathway are yet to be elucidated. Our aim was to determine the expression and role of phosphatase and tensin homolog deleted from chromosome 10 (PTEN), a negative regulator of the PI3K pathway, in COPD. PTEN expression and activity were measured in the peripheral lung of COPD patients compared to smoking and non-smoking controls. The direct influence of cigarette smoke extract (CSE) on PTEN expression was assessed using primary lung epithelial cells and a cell line (BEAS-2B) in the presence or absence of L-buthionine-sulfoximine (BSO) to deplete intracellular glutathione...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28522562/estrogen-and-cigarette-sidestream-smoke-particulate-matter-exhibit-er%C3%AE-dependent-tumor-promoting-effects-in-lung-adenocarcinoma-cells
#7
Lun-Cheng Kuo, Li-Chuan Cheng, Chia-Huei Lee, Chun-Ju Lin, Pei-Yu Chen, Lih-Ann Li
Estrogen and secondhand smoke are key risk factors for nonsmoking female lung cancer patients, who frequently have lung adenocarcinoma and show tumor ERα expression. We speculated that estrogen and secondhand smoke might cause harmful effects via ERα signaling. Our results showed that 17β-estradiol (E2), the primary form of endogenous estrogen, exacerbated proliferation, migration, and granzyme B resistance of lung adenocarcinoma cells in an ERα-dependent manner. Cigarette sidestream smoke particulate matter (CSSP), the major component of secondhand smoke, could activate ERα activity dose dependently in human lung adenocarcinoma cells...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28521397/regulation-of-angiogenic-factors-by-the-pi3k-akt-pathway-in-a549-lung-cancer-cells-under-hypoxic-conditions
#8
Youbang Xie, Yali Qi, Yanmiao Zhang, Jiayi Chen, Tianyi Wu, Yuhai Gu
The aim of the present study was to investigate the influence of hypoxia and PI3K inhibition on angiogenic factors in A549 lung cancer cells. A549 cells were treated with the PI3K inhibitor LY294002 under normoxic and hypoxic conditions. Untreated cells were used as the control group and those treated by the inhibitor, as the suppression group. The cells were further divided based on normoxic or hypoxic conditions and named: Normoxic control group, normoxic suppression group, hypoxic control group and hypoxic suppression group...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514532/the-dickkopf1-ckap4-axis-creates-a-novel-signaling-pathway-and-may-represent-a-molecular-target-for-cancer-therapy
#9
REVIEW
Akira Kikuchi, Katsumi Fumoto, Hirokazu Kimura
Dickkopf 1 (DKK1) is a secretory protein and antagonizes oncogenic Wnt signaling by binding to the Wnt co-receptor low-density lipoprotein receptor-related proteins 6 (LRP6). DKK1 is also suggested to regulate its own signaling to associate with tumor aggressiveness. However, the underlying mechanism by which DKK1 promotes cancer cell proliferation has remained to be clarified for a long time. It has been recently found that cytoskeleton-associated protein 4 (CKAP4), which was originally reported as an endoplasmic reticulum membrane protein, acts as a novel DKK1 receptor...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28513565/epidermal-growth-factor-receptor-cell-proliferation-signaling-pathways
#10
REVIEW
Ping Wee, Zhixiang Wang
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation...
May 17, 2017: Cancers
https://www.readbyqxmd.com/read/28512260/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#11
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28503373/analysis-of-genomic-variation-in-lung-adenocarcinoma-patients-revealed-the-critical-role-of-pi3k-complex
#12
Zhao Min Deng, Lin Liu, Wen Hai Qiu, Yong Qun Zhang, Hong Yan Zhong, Ping Liao, Yun Hong Wu
BACKGROUND: Molecularly targeted therapies improved survival status of some patients with lung adenocarcinoma, which accounts for 40% of all lung cancers, and in-depth study of gene alterations is important for the personalized treatment. METHODS: The legacy archive data of clinical information and genomic variations under the project TCGA Lung Adenocarcinoma were downloaded from the GDC Data Portal using R package TCGAbiolinks. The significantly aberrant copy number variants segments were figured out using GAIA...
2017: PeerJ
https://www.readbyqxmd.com/read/28493830/ing5-knockdown-enhances-migration-and-invasion-of-lung-cancer-cells-by-inducing-emt-via-egfr-pi3k-akt-and-il-6-stat3-signaling-pathways
#13
Xin-Li Liu, Xu-Tao Zhang, Jin Meng, Hong-Fei Zhang, Yong Zhao, Chen Li, Yang Sun, Qi-Bing Mei, Feng Zhang, Tao Zhang
ING5 belongs to the Inhibitor of Growth (ING) candidate tumor suppressor family, whose functions have been involved in the regulation of chromatin remodeling, cell cycle progression, proliferation and apoptosis. Our previous study has shown that ING5 overexpression inhibits lung cancer aggressiveness via suppressing epithelial to mesenchymal transition (EMT). However, the mechanisms remain largely unknown. In the current study, by Phospho-Kinase array and western blot, we have defined significantly upregulated EGFR/PI3K/Akt and IL-6/STAT3 oncogenic signaling pathways in ING5 knockdown A549 cells, which could be downregulated by ING5 overexpression...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28493079/tlr2-regulates-allergic-airway-inflammation-and-autophagy-through-pi3k-akt-signaling-pathway
#14
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/28489822/traf2-and-otud7b-govern-a-ubiquitin-dependent-switch-that-regulates-mtorc2-signalling
#15
Bin Wang, Zuliang Jie, Donghyun Joo, Alban Ordureau, Pengda Liu, Wenjian Gan, Jianping Guo, Jinfang Zhang, Brian J North, Xiangpeng Dai, Xuhong Cheng, Xiuwu Bian, Lingqiang Zhang, J Wade Harper, Shao-Cong Sun, Wenyi Wei
The mechanistic target of rapamycin (mTOR) has a key role in the integration of various physiological stimuli to regulate several cell growth and metabolic pathways. mTOR primarily functions as a catalytic subunit in two structurally related but functionally distinct multi-component kinase complexes, mTOR complex 1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated with a variety of human diseases, including metabolic disorders and cancer. Thus, both mTORC1 and mTORC2 kinase activity is tightly controlled in cells...
May 10, 2017: Nature
https://www.readbyqxmd.com/read/28485480/shikonin-inhibited-migration-and-invasion-of-human-lung-cancer-cells-via-suppression-of-c-met-mediated-epithelial-to-mesenchymal-transition
#16
Yei-San Hsieh, Chiung-Ho Liao, Wan-Shen Chen, Jih-Tung Pai, Meng-Shih Weng
Epithelial-to-mesenchymal transition (EMT) is a major process to regulate cell migration and invasion. Inhibition of epidermal growth factor receptor (EGFR)-mediated EMT by tyrosine kinase inhibitors (TKIs) is a strategy to prevent lung cancer invasion. However, drug resistance is emerged and accelerated invasion through other signaling bypassing EGFR after TKIs therapy. c-Met signaling pathway is highly activated in EGFR-mutated lung cancer cells. Targeting c-Met signaling pathway may be a strategy to suppress EGFR-independent migration and invasion for lung cancer therapy...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28477368/highly-expressed-long-non-coding-rna-crnde-promotes-cell-proliferation-through-pi3k-akt-signaling-in-non-small-cell-lung-carcinoma
#17
Xiao-Xiong Liu, Han-Peng Xiong, Jiu-Sheng Huang, Kai Qi, Jian-Jun Xu
Recently, numerous studies revealed that long non-coding RNAs (lncRNAs) play complex roles in various lung diseases, while the colorectal neoplasia differentially expressed (CRNDE) functions in non-small cell lung carcinomas (NSCLC) remain largely unknown. In the present study, we investigated the role and mechanism of CRNDE in the progression of NSCLC. The mRNA level of CRNDE in NSCLC patients and cells was detected by qRT-PCR. The influence of CRNDE silencing or over-expression on NSCLC cell proliferation and growth were assessed by MTT and flow cytometry, respectively...
May 6, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28470144/dkk3-overexpression-increases-malignant-properties-of-head-and-neck-squamous-cell-carcinoma-cells
#18
Naoki Katase, Shin-Ichiro Nishimatsu, Akira Yamauchi, Masahiro Yamamura, Kumiko Terada, Masumi Itadani, Naoko Okada, Nur Mohammad Monsur Hassan, Hitoshi Nagatsuka, Tohru Ikeda, Tsutomu Nohno, Shuichi Fujita
DKK3, a member of dickkopf WNT signaling pathway inhibitor family, is believed to be a tumor suppressor, because of itsreduced expression in cancer cells. However, our previous studies have revealed that DKK3 expression is predominantly observed in head and neck, and oral squamous cell carcinoma (HNSCC/OSCC). Interestingly, HNSCC/OSCC patients with DKK3 expression showed high metastasis rate and poorer survival, and siRNA-mediated knockdown of DKK3 in HNSCC-derived cancer cell lines resulted in reduced cellular migration and invasion...
May 4, 2017: Oncology Research
https://www.readbyqxmd.com/read/28468627/the-omega-3-polyunsaturated-fatty-acid-docosahexaenoic-acid-inhibits-proliferation-and-progression-of-non-small-cell-lung-cancer-cells-through-the-reactive-oxygen-species-mediated-inactivation-of-the-pi3k-akt-pathway
#19
Yuanqin Yin, Chengguang Sui, Fandong Meng, Ping Ma, Youhong Jiang
BACKGROUND: Docosahexaenoic acid(DHA) inhibits tumor growth and progression in various cancers, including lung cancer. However, the mechanisms involved remain unclear. The aim of this study was to identify the mechanism of DHA in inhibiting progression of non-small cell lung cancer (NSCLC) in vitro. METHODS: The proliferation of A549 was tested by MTT, and cell apoptosis was analysed using flow cytometer. The migration and invasion were examined respectively by wound healing assay and Transwell invasion assay...
May 3, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28467921/molecular-mechanisms-underlying-cardiac-adaptation-to-exercise
#20
REVIEW
Rick B Vega, John P Konhilas, Daniel P Kelly, Leslie A Leinwand
Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart, and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long-term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension...
May 2, 2017: Cell Metabolism
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