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https://www.readbyqxmd.com/read/29328793/novel-molecular-and-phenotypic-insights-into-congenital-lung-malformations
#1
Daniel T Swarr, William H Peranteau, Jennifer Pogoriler, David B Frank, N Scott Adzick, Holly L Hedrick, Mike Morley, Su Zhou, Edward E Morrisey
RATIONALE: Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects as they are often surgically resected. OBJECTIVES: To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions. METHODS: Clinical data, and lung tissue for DNA, RNA, and histology were obtained from 58 infants undergoing surgical resection of a congenital lung lesion...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29328495/fucoidan-downregulates-insulin-like-growth-factor-i-receptor-levels-in-ht-29-human-colon-cancer-cells
#2
In-Hye Kim, Taek-Jeong Nam
Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated anticancer activity in lung, breast, liver and colon cells. The insulin-like growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways. The aim of the present study was to investigate whether fucoidan downregulates the IGF-IR signaling pathway in HT-29 human colon cancer cells...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328421/antitumor-activity-of-curcumin-by-modulation-of-apoptosis-and-autophagy-in-human-lung-cancer-a549-cells-through-inhibiting-pi3k-akt-mtor-pathway
#3
Furong Liu, Song Gao, Yuxuan Yang, Xiaodan Zhao, Yameng Fan, Wenxia Ma, Danrong Yang, Aimin Yang, Yan Yu
Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin‑induced multiple PCDs on human non‑small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co‑culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti‑proliferation effect of different stimulus was measured by MTT assay...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326439/lung-fibroblasts-promote-metastatic-colonization-through-upregulation-of-stearoyl-coa-desaturase-1-in-tumor-cells
#4
Guanghua Liu, Shi Feng, Lin Jia, Chunying Wang, Yan Fu, Yongzhang Luo
As a rate-limiting step in metastasis, metastatic colonization requires survival signals from supportive stroma. However, the mechanisms driving this process are incompletely understood. Here, we showed that the proliferation of B16F10 cells was promoted when cocultured with lung fibroblasts. Meanwhile, co-injection of B16F10 tumor cells with mouse lung fibroblasts significantly increased lung metastasis. Based on GEO database, we identified stearoyl-CoA desaturase 1 (SCD1) as a novel factor promoting metastatic colonization...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29321644/cox-2-induces-oncogenic-micro-rna-mir655-in-human-breast-cancer
#5
Mousumi Majumder, Leanna Dunn, Ling Liu, Asma Hasan, Krista Vincent, Muriel Brackstone, David Hess, Peeyush K Lala
We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA miR655 in human breast cancer cells by activation of EP4. MiR655 expression positively correlated with COX-2 in genetically disparate breast cancer cell lines and increased in all cell lines when grown as spheroids, implicating its link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid formation and Epithelial to Masenchymal transition (EMT)...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320511/application-of-a-phenotypic-drug-discovery-strategy-to-identify-biological-and-chemical-starting-points-for-inhibition-of-tslp-production-in-lung-epithelial-cells
#6
Adelina Orellana, Vicente García-González, Rosa López, Sonia Pascual-Guiral, Estrella Lozoya, Julia Díaz, Daniel Casals, Antolín Barrena, Stephane Paris, Miriam Andrés, Victor Segarra, Dolors Vilella, Rajneesh Malhotra, Paul Eastwood, Anna Planagumà, Montserrat Miralpeix, Arsenio Nueda
Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung epithelium in response to external insult. Considered as a master switch in T helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role in allergic diseases including asthma. The aim of this study was to use a phenotypic approach to identify new biological and chemical starting points for inhibition of TSLP production in human bronchial epithelial cells (NHBE), with the objective of reducing Th2-mediated airway inflammation...
2018: PloS One
https://www.readbyqxmd.com/read/29315773/mir-451-selectively-increases-sensitivity-to-cisplatin-in-ercc1-high-non-small-cell-lung-cancer-cells
#7
Kaihua Liu, Hong Tian, Yong Zhang, Hao Zhao, Kai Ma
Lung cancer is the leading cause of cancer-related death throughout the world and cisplatin chemoresistance is one of the major hindrances of efficiency in this malignancy therapy. It has been reported that miR-451, a tumor suppressor, is involved in sensitivity of cancer cells to cisplatin. However, the role of miR-451 in chemosensitivity of lung cancer cells and the underlying mechanism still remains to be not fully illuminated. We first assessed the expression of ERCC1 and miR-451 in six NSCLS cell lines and NHBE cells by qRT-PCR...
January 6, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29299135/acquired-resistance-to-pi3k-mtor-inhibition-is-associated-with-mitochondrial-dna-mutation-and-glycolysis
#8
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235. Monoclonal cells with stable and increased resistance to BEZ235 were obtained after 8 months treatment. These AQR clones showed class-specific resistance to PI3K/mTOR inhibitors, reduced G1 cell cycle arrest and impedance of migration following PI3K/mTOR inhibition, reduced PTEN expression and increased Akt and S6RP phosphorylation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298996/the-phosphatidylinositide-3-kinase-pi3k-signaling-pathway-is-a-determinant-of-zileuton-response-in-adults-with-asthma
#9
Amber Dahlin, Weiliang Qiu, Augusto A Litonjua, John J Lima, Mayumi Tamari, Michiaki Kubo, Charles G Irvin, Stephen P Peters, Ann C Wu, Scott T Weiss, Kelan G Tantisira
Variable responsiveness to zileuton, a leukotriene antagonist used to treat asthma, may be due in part to genetic variation. While individual SNPs were previously associated with zileuton-related lung function changes, specific quantitative trait loci (QTLs) and biological pathways that may contribute have not been identified. In this study, we investigated the hypothesis that genetic variation within biological pathways is associated with zileuton response. We performed an integrative QTL mapping and pathway enrichment study to investigate data from a GWAS of zileuton response, in addition to mRNA expression profiles and leukotriene production data from lymphoblastoid cell lines (LCLs) (derived from asthmatics) that were treated with zileuton or ethanol (control)...
January 3, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29298657/coumarin-derivatives-as-anticancer-agents-for-lung-cancer-therapy-a-review
#10
Manvendra Kumar, Ramit Singla, Jyoti Dandriyal, Vikas Jaitak
In worldwide lung cancer shares 14% among the newly diagnosed cancer cases. Currently, the numbers of drugs that are in clinical practice are having a high prevalence of side effect and multidrug resistance. Researchers have made an attempt to expand a suitable anticancer drug that has no MDR and side effect. Coumarin scaffold became an attractive subject due to their broad spectrum of pharmacological activities. Coumarin derivatives extensively explored for anticancer activities as it possesses minimum side effect along with multi-drug reversal activity...
December 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29297621/amnion-epithelial-cell-derived-exosomes-restrict-lung-injury-and-enhance-endogenous-lung-repair
#11
Jean L Tan, Sin N Lau, Bryan Leaw, Hong P T Nguyen, Lois A Salamonsen, Mohamed I Saad, Siow T Chan, Dandan Zhu, Mirja Krause, Carla Kim, William Sievert, Euan M Wallace, Rebecca Lim
Idiopathic pulmonary fibrosis (IPF) is characterized by chronic inflammation, severe scarring, and stem cell senescence. Stem cell-based therapies modulate inflammatory and fibrogenic pathways by release of soluble factors. Stem cell-derived extracellular vesicles should be explored as a potential therapy for IPF. Human amnion epithelial cell-derived exosomes (hAEC Exo) were isolated and compared against human lung fibroblasts exosomes. hAEC Exo were assessed as a potential therapy for lung fibrosis. Exosomes were isolated and evaluated for their protein and miRNA cargo...
January 3, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29296237/march8-is-associated-with-poor-prognosis-in-non-small-cell-lung-cancers-patients
#12
Jiye Fan, Liying Tian, Manli Li, Shu-Hong Huang, Jing Zhang, Baohua Zhao
MARCH8 belongs to a family of membrane-associated RING-CH (MARCH) ubiquitin ligases. The functions of MARCH8 have been thoroughly investigated but its mechanism of action remains unknown. In this study, we detected the expression of MARCH8 protein in NSCLC samples and identified MARCH8 mRNA expression through a TCGA database. In addition, we analyzed the correlation between MARCH8 and the clinical characteristics of NSCLC patients and their prognosis.(www.kmplot.com). The roles of MARCH8 in proliferation, migration, and metastasis were further explored through ectopic expression analysis and western blot analysis; its mechanism of expressionwas also explored...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296234/the-pyrazolyl-urea-gege3-inhibits-tumor-angiogenesis-and-reveals-dystrophia-myotonica-protein-kinase-dmpk-1-as-a-novel-angiogenesis-target
#13
Elda Meta, Beat A Imhof, Patricia Ropraz, Richard J Fish, Chiara Brullo, Olga Bruno, Adama Sidibé
The limitation of targeting VEGF/VEGFR2 signalling to stop angiogenesis in cancer therapy has been blamed on re-activation of alternative receptor tyrosine kinases by compensatory angiogenic factors. Targeting MAPK and PI3K signaling pathways in endothelial cells may be an alternative or complementary approach. Herein we aimed to evaluate the antitumor and antiangiogenic potential of a novel pyrazolyl-urea kinase inhibitor, GeGe3, and to identify its kinase targets. We found GeGe3 to inhibit the proliferation of HUVEC and endothelial tube formation...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295962/rational-approaches-for-combination-therapy-strategies-targeting-the-map-kinase-pathway-in-solid-tumors
#14
Anthony W Tolcher, Wei Peng, Emiliano Calvo
Molecular characterization of oncogenic mutations within genes in the MAPK and PI3K/AKT/mTOR pathways has led to the rational development of targeted therapies. Combining BRAF and MEK inhibitors to target two steps in the MAPK pathway (vertical inhibition) is now standard of care in advanced-stage melanoma harboring BRAF V600 mutation. Encouraging results have been seen in several tumor types with the same mutation, including BRAF V600-mutant non-small cell lung cancer. Yet similar results in other tumors, such as colorectal cancer, have not been observed, highlighting the unique nature of different tumors...
January 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29290965/combination-treatment-of-rad001-and-bez235-exhibits-synergistic-antitumor-activity-via-down-regulation-of-p-4e-bp1-mcl-1-in-small-cell-lung-cancer
#15
Bo Hong, Huogang Wang, Ke Deng, Wei Wang, Haiming Dai, Vivian Wai Yan Lui, Wenchu Lin
Small cell lung cancer (SCLC) is a highly malignant cancer with few targeted therapies. In the study, by mining the Cancer Cell Line Encyclopedia (CCLE) database, we found that PI3K/AKT/mTOR pathway was aberrant in 92% of SCLC cell lines. Moreover, we found that the phosphorylation level of 4E-BP1 was significantly correlated with SCLC sensitivity to RAD001 (mTOR inhibitor) and BEZ235 (PI3K/mTOR dual inhibitor). Combination of RAD001 and BEZ235 synergistically inhibited the growth of SCLC cells, which was accompanied by enhanced induction of cell cycle arrest and apoptosis...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288364/mirna-signature-predicts-the-response-of-patients-with-advanced-lung-adenocarcinoma-to-platinum-based-treatment
#16
Xiaoyue Xu, Shaorong Yu, Wenbo Sun, Xiaobing Qin, Yan Chen, Leilei Zhou, Rui Lou, Shuchen Dong, Bo Shen, Jianzhong Wu, Jialan Zang, Haixia Cao, Meiqi Shi, Qin Zhang, Jifeng Feng
BACKGROUND: Accumulating literature proved that miRNAs can regulate the sensitivity of platinum and act as a promising candidate to predict the response of patients with lung adenocarcinoma to chemotherapy. However, most studies on miRNAs were restricted to in vitro experiments. This study aimed to evaluate whether miRNAs alone or in combination (miRNA signature) can act as predictive biomarkers of platinum-based chemotherapy in patients with lung adenocarcinoma. METHODS: Eight miRNAs that most probably predict the efficacy of platinum were screened in 111 tumor tissues of lung adenocarcinoma...
December 29, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29286212/knockdown-of-cpeb4-expression-suppresses-cell-migration-and-invasion-via-akt-pathway-in-non-small-cell-lung-cancer
#17
Jing Hu, LiBin Zhang, Qiang Chen, Jie Lin, ShaoBo Wang, Ri Liu, WenJing Zhang, Kun Miao, Tao Shou
Cytoplasmic polyadenylation element binding protein 4 (CPEB4) could be an important regulator in variety of cancers. However, the biological function and the underlying molecular mechanism of CPEB4 in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the metastasis role of CPEB4 in NSCLC cells, we knocked down CPEB4 using siRNA. Transwell migration assay and cell invasion assay on Matrigel were presented, and cell migration was also determined by scratch-healing assay. ROS generation were determined by fluorescence probe DCFH2-DA...
December 29, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29285119/trichosanthin-enhances-the-antitumor-effect-of-gemcitabine-in-non-small-cell-lung-cancer-via-inhibition-of-the-pi3k-akt-pathway
#18
Naren Tuya, Yadi Wang, Lanmei Tong, Weishi Gao, Rong Yu, Liying Xue
Gemcitabine (GEMZ) is the first-line therapy used against non-small cell lung cancer (NSCLC), and studies have focused on investigating the potential effects of agents combined with GEMZ to enhance the anticancer efficacy in NSCLC. Previous studies have reported that trichosanthin (TCS) has various physiological and pharmacological effects, including anti-human influenza virus enzymes, inhibition of protein synthesis and antitumor activity. The purpose of the present study was to investigate if TCS enhanced the antitumor effects of GEMZ in NSCLC...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29281903/assessment-of-fgfr1-overexpression-and-over-activity-in-lung-cancer-cells-a-toolkit-for-anti-fgfr1-drug-screening
#19
Penghui Hu, Hongjie Chen, Eileen McGowan, Nina Ren, Ming Xu, Yiguang Lin
Lung cancer, mainly caused by smoking, is one of the most prevalent diseases in China resulting in high mortality rates. The increasing incidence of chronic disease due to lung cancer places a huge burden on the welfare and cost to the Chinese society. Amplification of the fibroblast growth factor receptor 1 (FGFR1) is associated with high incidence and mortality in lung cancer patients. FGFR1 signaling is implicated in oncogenic traits such as proliferation, cell survival, angiogenesis and migration. Targeting the FGFR1 and its ligand basic FGF (bFGF) is a key step forward in developing new therapies for this crippling disease...
December 27, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29277178/-clinical-significance-and-mechanism-of-pi3k-p110%C3%AE-overexpression%C3%A2-in-non-small-cell-lung-cancer
#20
Yan Xiong, Linlin Qu, Dong Li, Ying Wang, Ting Li
BACKGROUND: Phosphatidylinositide 3-kinases (PI3K) pathway is one of the most important pathway in cells, which plays an important role in proliferation, growth, differentiation and mobility of cells. The aberrant activation of PI3K pathway was exsited in 50%-70% cases of non-small cell lung cancer (NSCLC). As the key point in PI3K pathway, expression of PI3K plays a critical role in activity of the pathway, which is closely related with the initiation and development of NSCLC, furthermore with the response of tumor to target treatment...
December 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
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