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https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#1
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28915708/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
#2
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903339/ing5-knockdown-enhances-migration-and-invasion-of-lung-cancer-cells-by-inducing-emt-via-egfr-pi3k-akt-and-il-6-stat3-signaling-pathways
#3
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903329/fractalkine-cx3cl1-induced-intercellular-adhesion-molecule-1-dependent-tumor-metastasis-through-the-cx3cr1-pi3k-akt-nf-%C3%AE%C2%BAb-pathway-in-human-osteosarcoma
#4
Ju-Fang Liu, Ya-Ting Tsao, Chun-Han Hou
Osteosarcoma is the most common primary bone tumor in children and teens. The exact molecular mechanism underlying osteosarcoma progression still remains unclear. The CX3CL1/fractalkine has been implicated in various tumors but not in osteosarcoma. This study is the first to show that fractalkine promotes osteosarcoma metastasis by promoting cell migration. Fractalkine expression was higher in osteosarcoma cell lines than in normal osteoblasts. Fractalkine induced cell migration by upregulating intercellular adhesion molecule-1 (ICAM-1) expression via CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901474/inhibition-of-mir-23a-increases-the-sensitivity-of-lung-cancer-stem-cells-to-erlotinib-through-pten-pi3k-akt-pathway
#5
Zhijun Han, Xiaoyun Zhou, Shanqing Li, Yingzhi Qin, Yeye Chen, Hongsheng Liu
Epidermal growth factor receptor-targeted tyrosine kinase inhibitors (EGFR-TKIs) have become first-line drugs used for non-small cell lung cancer (NSCLC) treatment. However, drug resistance to EGFR-TKIs will be developed inevitably due to the repeated use of these drugs. In the present study, we isolated cancer stem cells (CSCs) from the PC9 NSCLC cell line. We then observed that the PC9 CSCs showed significant resistance to erlotinib compared with the PC9 non-CSCs. Erlotinib failed to suppress the phosphorylation of PI3K and AKT in PC9 CSCs, although the EGFR was inhibited sufficiently...
September 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28901419/microrna%C3%A2-21-increases-cell-viability-and-suppresses-cellular-apoptosis-in-non%C3%A2-small-cell-lung-cancer-by-regulating-the-pi3k-akt-signaling-pathway
#6
Tao Wang, Zhenyu Cai, Guolin Hong, Gangsen Zheng, Yu Huang, Shun Zhang, Jinhua Dai
MicroRNA (miRNA/miR), a type of non‑coding RNA molecule, is able to inhibit the expression of target genes at multiple stagess. There are 800‑1,000 known miRNAs in the human genome, which serve important roles in cell proliferation, differentiation, apoptosis and migration. Previous studies have demonstrated that the expression of miR‑21 is upregulated in numerous types of malignant tumor, and that miR‑21 participates in the occurrence and development of tumors via complex regulatory mechanisms. The present study aimed to investigate the association between miR‑21 expression, cell viability and apoptosis in a lung cancer cell line, and to elucidate the potential mechanisms...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901268/nrg1-erbb-lost-in-translation-a-new-paradigm-for-lung-cancer
#7
Domenico Trombetta, Antonio Rossi, Federico Pio Fabrizio, A Sparaneo, Paolo Graziano, Vito Michele Fazio, Lucia Anna Muscarella
The ErbB network of receptor tyrosine kinases represents one of the best examples of how the understanding of molecular basis of tumor pathogenesis can give a significant improvement for patients treatment, suggesting new therapeutic options to overcome acquired treatment resistance. This amazing bridge between growth factor receptors and cancer has been consolidated during the last decades through the identification of many driver mutations in the gene key of the RTKs network. Unexpected molecular lesions of the NRG1 gene followed by an aberrant ErbB signaling were recently described as a new molecular features of non-small cell lung cancer, but it has been also sporadically reported in other tumors...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28901260/vdac1-mediated-anticancer-activity-of-gallic-acid-in-human-lung-adenocarcinoma-a549-cells
#8
Aikebaier Maimaiti, Amier Aili, Hureshitanmu Kuerban, Xuejun Li
Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied...
September 11, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28900482/study-on-inhibitory-effect-of-maimendong-decoction-and-weijing-decoction-combination-with-cisplatin-on-nci-a549-xenograft-in-nude-mice-and-its-mechanism
#9
Fei Xiong, Miao Jiang, Meijuan Chen, Xiaoxia Wang, Shiping Zhang, Jing Zhou, Ke Li, Yan Sheng, Lian Yin, Yuping Tang, Lihong Ye, Mianhua Wu, Haian Fu, Xu Zhang
MaiMenDong Decoction and WeiJing Decoction (Jin formula) is a traditional Chinese medication that consists of 8 medicinal plants, which recorded in the classical TCM literature Jin Kui Yao Lue and has been utilized in the treatment of lung diseases for hundreds of years in China. The present study aimed to determine the anti-tumor activity and the underlying mechanisms of Jin formula combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC). Xenograft model of NCI-A549 was established in Balb/c nude mice...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900284/mir-503-modulates-epithelial-mesenchymal-transition-in-silica-induced-pulmonary-fibrosis-by-targeting-pi3k-p85-and-is-sponged-by-lncrna-malat1
#10
Weiwen Yan, Qiuyun Wu, Wenxi Yao, Yan Li, Yi Liu, Jiali Yuan, Ruhui Han, Jingjin Yang, Xiaoming Ji, Chunhui Ni
Silicosis is a kind of chronic, progressive and incurable lung fibrotic diseases with largely unknown and complex pathogenesis and molecular mechanisms. Mounting evidence suggests that microRNAs (miRNAs, miRs) are involved in the pathogenesis of silicosis. Our previous study based on miRNA microarray had shown that the expression levels of miR-503 were down-regulated in mouse lung tissues of silica-induced pulmonary fibrosis. Here, we validated the decreased expression of miR-503 in the fibrotic mouse lung tissues, human bronchial epithelial cells (HBE) and human lung adenocarcinoma A549 cells which were exposed to silica...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886261/syndecan-2-attenuates-radiation-induced-pulmonary-fibrosis-and-inhibits-fibroblast-activation-by-regulating-pi3k-akt-rock-pathway-via-cd148
#11
Konstantin Tsoyi, Sarah G Chu, Nasly G Patino-Jaramillo, Julie Wilder, Julian Villalba, Melanie Doyle-Eisele, Jacob McDonald, Xiaoli Liu, Souheil El-Chemaly, Mark A Perrella, Ivan O Rosas
RATIONALE: Radiation-induced pulmonary fibrosis is a severe complication of patients treated with thoracic irradiation. We have previously shown that syndecan-2 reduces fibrosis by exerting alveolar epithelial cytoprotective effects. Here, we investigate whether syndecan-2 attenuates radiation-induced pulmonary fibrosis by inhibiting fibroblast activation. METHODS: C57BL/6 wild type (WT) mice and transgenic (TG) mice that overexpress human syndecan-2 in alveolar macrophages were exposed to 14 Gy whole thoracic radiation...
September 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28885267/bcl-2-and-bcl-xl-mediate-resistance-to-receptor-tyrosine-kinase-targeted-therapy-in-lung-and-gastric-cancer
#12
Junfei Jin, Ying Xiong, Bo Cen
Promising clinical efficacy has been observed with receptor tyrosine kinase inhibitors (TKIs) particularly in lung and gastric cancers with mutations or amplifications in the targeted receptor tyrosine kinases (RTKs). However, the efficacy and the duration of the response to these inhibitors are limited by the emergence of drug resistance. Here, we report treatment of RTK-dependent lung and gastric cancer cell lines with TKIs increased protein levels of Bcl-2 and Bcl-xL. The combination of the Bcl-2 and Bcl-xL inhibitor ABT-263 and TKIs was superior to TKIs alone in reducing cell viability and capacity of resistant colony formation...
September 6, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28883791/proteasome-inhibitor-ysy01a-abrogates-constitutive-stat3-signaling-via-down-regulation-of-gp130-and-jak2-in-human-a549-lung-cancer-cells
#13
Wei Huang, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li, Jingrong Cui
Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28881794/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#14
Andrea Cavazzoni, Silvia La Monica, Roberta Alfieri, Andrea Ravelli, Nele Van Der Steen, Rocco Sciarrillo, Denise Madeddu, Costanza Anna Maria Lagrasta, Federico Quaini, Mara Bonelli, Claudia Fumarola, Daniele Cretella, Graziana Digiacomo, Marcello Tiseo, Godefridus J Peters, Andrea Ardizzoni, Pier Giorgio Petronini, Elisa Giovannetti
Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#15
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28871449/arhgef39-promotes-gastric-cancer-cell-proliferation-and-migration-via-akt-signaling-pathway
#16
Haixiao Wang, Miaomiao Li, Xiaobao Tao, Yan Qian, Linfang Chen, Guoquan Tao
Dbl-family guanine nucleotide exchange factors (GEFs) can activate RhoGTPases by facilitating the exchange of GDP for GTP, the aberrant expression of which has been implicated in tumorigenicity and metastasis of human cancers. ARHGEF39, as a member of Dbl-family GEFs, was reported to be a potential oncogene in human hepatocellular carcinoma previously. However, the role of ARHGEF39 in gastric cancer (GC) remains unclear so far. In the current study, we demonstrated that ARHGEF39 expression was significantly upregulated in GC tissues compared with paired adjacent normal tissues by quantitative real-time PCR analysis...
September 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28869936/synergistic-effect-of-baicalin-and-adriamycin-in-resistant-hl-60-adm-leukaemia-cells
#17
Jing Zheng, Tetsuya Asakawa, Yingyu Chen, Zhihong Zheng, Buyuan Chen, Minhui Lin, Tingbo Liu, Jianda Hu
BACKGROUND/AIMS: The present study was designed to investigate the expression of multidrug resistance (MDR)-related genes, verify the synergistic effects of baicalin and Adriamycin (ADM) and investigate the related mechanisms in ADM-resistant leukaemic HL-60/ADM cells. METHODS: We used a HL-60/ADM cell line. Cytotoxicity and flow cytometry assays were employed to verify the cytotoxic effects of baicalin. Real-time polymerase chain reaction and Western blotting assays were used to assess the expression of MDR-related genes and the changes in gene expression (both MDR-related and PI3K/Akt pathway-related) induced by administration of baicalin...
August 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28866730/egfr-targeted-therapies-in-the-post-genomic-era
#18
Mary Jue Xu, Daniel E Johnson, Jennifer R Grandis
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials...
September 2, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28860768/the-effects-of-collagen-rich-extracellular-matrix-on-the-intracellular-delivery-of-glycol-chitosan-nanoparticles-in-human-lung-fibroblasts
#19
Ji Young Yhee, Hong Yeol Yoon, Hyunjoon Kim, Sangmin Jeon, Polla Hergert, Jintaek Im, Jayanth Panyam, Kwangmeyung Kim, Richard Seonghun Nho
Recent progress in nanomedicine has shown a strong possibility of targeted therapy for obstinate chronic lung diseases including idiopathic pulmonary fibrosis (IPF). IPF is a fatal lung disease characterized by persistent fibrotic fibroblasts in response to type I collagen-rich extracellular matrix. As a pathological microenvironment is important in understanding the biological behavior of nanoparticles, in vitro cellular uptake of glycol chitosan nanoparticles (CNPs) in human lung fibroblasts was comparatively studied in the presence or absence of type I collagen matrix...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28856747/anticancer-effects-of-a-korean-herbal-medicine-formula-h9-via-ampk-and-her2-pi3k-akt-signaling-in-breast-cancer-cells
#20
Ju-Hee Lee, Young Hoon Son, Young-Won Kwon, Sung Yun Park, Byung-Soo Koo, Seung Hyun Jung
An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung-tang, a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non-small-cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis...
August 30, 2017: Phytotherapy Research: PTR
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