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https://www.readbyqxmd.com/read/28336809/lectin-galactoside-binding-soluble-3-binding-protein-promotes-17-n-allylamino-17-demethoxygeldanamycin-resistance-through-pi3k-akt-pathway-in-lung-cancer-cell-line
#1
Jong Kyu Woo, Jeong-Eun Jang, Ju-Hee Kang, Je Kyung Seong, Yeo Sung Yoon, Hyoung-Chin Kim, Sang-Jin Lee, Seun Hyun Oh
Heat shock protein 90 (HSP90) stabilizing oncoproteins has been an attractive target in cancer therapy. 17-N-Allylamino-17-demethoxygeldanamycin (17-AAG), HSP90 inhibitor, was tested in phase II/III clinical trials, but due to lack of efficacy, clinical evaluation of 17-AAG has achieved limited success which led to resistance to 17-AAG. However, the mechanism of 17-AAG resistance has not clearly been identified. Here, we identified LGALS3BP (Lectin, galactoside-binding, soluble, 3 binding protein), a secretory glycoprotein, as a 17-AAG resistance factor...
March 23, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28327179/pterostilbene-prevents-akt-erk-axis-mediated-polymerization-of-surface-fibronectin-on-suspended-lung-cancer-cells-independently-of-apoptosis-and-suppresses-metastasis
#2
Ying-Jan Wang, Jing-Fang Lin, Li-Hsin Cheng, Wen-Tsan Chang, Ying-Hsien Kao, Ming-Min Chang, Bour-Jr Wang, Hung-Chi Cheng
BACKGROUND: Polymeric fibronectin (polyFN) assembled on suspended breast cancer cells is required for metastasis. Conceivably, drugs that target such polyFN may fight against cancer metastasis. While stilbene analogs trigger pro-apoptotic effect on attached cancer cells, whether they prevent polyFN assembly and metastasis of suspended cancer cells via an apoptosis-independent manner remains unexplored. METHODS: We depleted suspended Lewis lung carcinoma (LLC) cells of polyFN by silencing the endogenous FN expression or pterostilbene (PS) to examine whether metastasis of lung cancer cells could thus be suppressed...
March 21, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28301605/ocf-can-repress-tumor-metastasis-by-inhibiting-epithelial-mesenchymal-transition-involved-in-pten-pi3k-akt-pathway-in-lung-cancer-cells
#3
Ye Yang, Shuang Qiu, Lei Qian, Yuan Tian, Yingna Chen, Lei Bi, Weiping Chen
A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28300833/pi3k-akt-mediated-upregulation-of-wdr5-promotes-colorectal-cancer-metastasis-by-directly-targeting-znf407
#4
Xin Tan, Shuai Chen, Jiangxue Wu, Jiaxin Lin, Changchuan Pan, Xiaofang Ying, Zhizhong Pan, Lin Qiu, Ranyi Liu, Rong Geng, Wenlin Huang
Colorectal cancer (CRC) is the third most common cause of cancer deaths, and has a high rate of liver and lung metastasis. Unfortunately, distant metastasis is the main barrier for advanced CRC therapy and leads to a very low survival rate. In this study, we identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for CRC patients. We demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28295876/a-vicious-partnership-between-akt-and-phlda3-to-facilitate-neuroendocrine-tumors
#5
Masahiro Takikawa, Rieko Ohki
Neuroendocrine tumors (NETs) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of NETs. It has been shown that the mTOR inhibitor everolimus can improve the progression-free survival of pancreatic NET (PanNET) patients, suggesting that inhibition of the PI3K-Akt-mTOR pathway may suppress the progression of PanNETs. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP3 ...
March 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28293189/investigation-into-the-role-of-pi3k-and-jak3-kinase-inhibitors-in-murine-models-of-asthma
#6
Akshaya D Wagh, Manoranjan Sharma, Jogeshwar Mahapatra, Abhijeet Chatterjee, Mukul Jain, Veeranjaneyulu Addepalli
Asthma is a clinical disorder commonly characterized by chronic eosinophilic inflammation, remodeling and hyper responsiveness of the airways. However, the kinases like Phosphoinositide 3 kinase (PI3K) and Janus kinase 3 (JAK3) are involved in mast cell proliferation, activation, recruitment, migration, and prolonged survival of inflammatory cells. The present study was designed to evaluate the in-vivo comparative effects of two kinase inhibitors on airway inflammation and airway remodeling in acute and chronic models of asthma...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28293123/pembrolizumab-in-the-treatment-of-metastatic-non-small-cell-lung-cancer-patient-selection-and-perspectives
#7
REVIEW
Ashwin Somasundaram, Timothy F Burns
Lung cancer is the leading killer of both men and women in the US, and the 5-year survival remains poor. However, the approval of checkpoint blockade immunotherapy has shifted the treatment paradigm and provides hope for improved survival. The ability of non-small-cell lung cancer (NSCLC) to evade the host immune system can be overcome by agents such as pembrolizumab (MK-3475/lambrolizumab), which is a monoclonal antibody targeting the programmed death 1 (PD-1) receptor. In early studies, treatment with pembrolizumab led to dramatic and durable responses in select patients (PD-L1+ tumors)...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28292510/corrigendum-to-pi3k-inhibition-augments-the-therapeutic-efficacy-of-a-3a-aza-cyclopenta-%C3%AE-indene-derivative-in-lung-cancer-cells-translational-oncology-7-2014-256-266-e5
#8
Kumar Sanjiv, Chi-Wei Chen, Rajesh Kakadiya, Satishkumar Tala, Sharda Suman, Ming-Hsi Wu, Yen-Hui Chen, Tsann-Long Su, Te-Chang Lee
No abstract text is available yet for this article.
April 2017: Translational Oncology
https://www.readbyqxmd.com/read/28285180/noninvasive-bioluminescence-imaging-of-akt-kinase-activity-in-subcutaneous-and-orthotopic-nsclc-xenografts-correlation-of-akt-activity-with-tumor-growth-kinetics
#9
Karina Suchowski, Thomas Pöschinger, Alnawaz Rehemtulla, Michael Stürzl, Werner Scheuer
Aberrant signaling through the AKT kinase mediates oncogenic phenotypes including cell proliferation, survival, and therapeutic resistance. Here, we utilize a bioluminescence reporter for AKT kinase activity (BAR) to noninvasively assess the therapeutic efficacy of the EGFR inhibitor erlotinib in KRAS-mutated lung cancer therapy. A549 non-small cell lung cancer cell line, engineered to express BAR, enabled the evaluation of compounds targeting the EGFR/PI3K/AKT pathway in vitro as well as in mouse models. We found that erlotinib treatment of resistant A549 subcutaneous and orthotopic xenografts resulted in significant AKT inhibition as determined by an 8- to 13-fold (P < ...
March 9, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28283413/solasodine-inhibits-invasion-of-human-lung-cancer-cell-through-downregulation-of-mir-21-and-mmps-expression
#10
Kun-Hung Shen, Jui-Hsiang Hung, Chia-Wei Chang, Yu-Ting Weng, Ming-Jiuan Wu, Pin-Shern Chen
Solasodine, a naturally occurring aglycone of glycoalkaloid in eggplant (Solanum melongena), was found to inhibit proliferation in various tumor cells. However, the effect of solasodine on cancer cell metastasis remains unclear. This study investigates the suppression mechanism of solasodine on motility of human lung cancer cell A549 in vitro. Results show that solasodine reduces viability of A549 cells. Treatment with non-toxic doses of solasodine suppresses markedly cell invasion. Solasodine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2), MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN), but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2...
March 7, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28282799/celecoxib-erlotinib-combination-treatment-enhances-radiosensitivity-in-a549-human-lung-cancer-cell
#11
Jian Sun, Ning-Bo Liu, Hong-Qing Zhuang, Lun-Jun Zhao, Zhi-Yong Yuan, Ping Wang
BACKGROUND: Radiosensitivity by blocking the epidermal growth factor receptor and cyclooxygenase-2 pathways with erlotinib and celecoxib in A549 human lung cancer cell was investigated. METHODS: MTT assays were used to detect the antitumor effects of erlotinib and celecoxib in A549 cells. Colony formation assays were used to evaluate the antitumor effects. Flow cytometry analysis was used to assess the cell cycle and cell apoptosis, and western blotting analysis was performed to evaluate the expression of AKT and phosphorylated AKT...
March 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28280736/microrna-related-polymorphisms-in-pi3k-akt-mtor-pathway-genes-are-predictive-of-limited-disease-small-cell-lung-cancer-treatment-outcomes
#12
Wei Jiang, Wenjue Zhang, Lihong Wu, Lipin Liu, Yu Men, Jingbo Wang, Jun Liang, Zhouguang Hui, Zongmei Zhou, Nan Bi, Luhua Wang
The phosphoinositide-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in cancer progression and treatment, including that of small cell lung cancer (SCLC), a disease with traditionally poor prognosis. Given the regulatory role of microRNA (miRNA) in gene expression, we examined the association of single nucleotide polymorphisms (SNPs) at miRNA-binding sites of genes in the mTOR pathway with the prognosis of patients with limited-disease SCLC. A retrospective study was conducted of 146 patients with limited-disease SCLC treated with chemoradiotherapy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28276313/inhibition-of-mmp-2-expression-enhances-the-anti-tumor-effect-of-sorafenib-in-hepatocellular-carcinoma-by-suppressing-pi3k-akt-mtor-pathway
#13
Wenliang Tan, Sicong Zhu, Jun Cao, Lei Zhang, Wenda Li, Kairui Liu, Jinyi Zhong, Changzhen Shang, Yajin Chen
Sorafenib has been globally approved as the standard treatment for patients with advanced Hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited due to tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the anti-tumor efficiency. Here we demonstrated that expression of MMP-2 positively correlated with the migration ability of HCC cells. Cells with higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells)...
March 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/28273403/pten-pi3k-akt-regulates-macrophage-polarization-in-emphysematous-mice
#14
JunJuan Lu, LiHua Xie, Chun Liu, Qiang Zhang, ShengHua Sun
Macrophages play an important role in the pathogenesis of COPD. Macrophage polarization toward the M2 phenotype has been observed in the lung tissues of COPD patients and cigarette smokers. The molecular basis of this process remains unclear, and it has not been completely illuminated in animal models of emphysema. In our study we combined cigarette smoke(CS) exposure with intraperitoneal injection of cigarette smoke extract (CSE) to build an emphysema model. We found by immunohistochemical staining and flow cytometry that the expression level of CD206 and the ratio of M2 to M1 macrophages was increased in emphysematous mice...
March 8, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28272712/the-expression-and-function-of-mirna-106-in-pediatric-osteosarcoma
#15
M Xu, Y-Y Zhang, H-F Wang, G-S Yang
OBJECTIVE: This study is to investigate the expression and biological function of miRNA-106b in osteosarcoma. PATIENTS AND METHODS: Freshly resected osteosarcoma tissues and the corresponding para-carcinoma tissues were collected from 54 patients. Then miR-106b level in the carcinoma tissues was detected by real-time PCR. To test the function of miR-106b, osteosarcoma cell line U2-OS was transfected with miR-106b inhibitor in vitro. Then, the proliferation, cell cycle, invasion and metastasis of U2-OS cells were detected by CCK-8 assay, flow cytometry, and transwell respectively...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28263743/deficiency-of-psgl-1-accelerates-bleomycin-blm-induced-lung-fibrosis-and-inflammation-in-mice-through-activating-pi3k-akt
#16
Xiang Han, Shu-Ming Wang
Pulmonary fibrosis is a disease characterized by unremitting fibrosis accumulation in the lung, causing respiratory failure eventually. Presently, the immunological mechanism underlying pulmonary fibrosis still remains unclear. P-selectin glycoprotein ligand-1 (Psgl-1) is a leukocyte ligand that regulates recruitment and activation of multiple cell types, which is associated with phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway activation. In the present study, we attempted to clarify the AKT activation induced by Psgl-1 knockout in mice with bleomycin (BLM)-induced pulmonary fibrosis...
March 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28259980/genistein-decreases-a549-cell-viability-via-inhibition-of-the-pi3k-akt-hif%C3%A2-1%C3%AE-vegf-and-nf%C3%A2-%C3%AE%C2%BAb-cox%C3%A2-2-signaling-pathways
#17
Juan Zhang, Hongzheng Su, Qingfeng Li, Jing Li, Qianfeng Zhao
Genistein is an important chemopreventive agent against atherosclerosis and cancer. However, whether genistein is effective in the treatment of lung cancer, and its underlying mechanism, remains to be determined. The present study demonstrated that genistein treatment of A549 lung cancer cells decreased viability in a dose‑ and time‑dependent manner, and induced apoptosis. Additionally, A549 cells exhibited significantly increased reactive oxygen species formation and cytochrome‑c leakage, and activated caspase‑3, B‑cell lymphoma 2‑associated X protein and apoptosis inducing factor expression levels, which are involved in the mitochondrial apoptosis pathway...
February 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258976/congenital-pulmonary-lymphangiectasia
#18
Shi-Min Yuan
Congenital pulmonary lymphangiectasia (CPL) is a rare but fatal disease, usually having an onset from the first few hours to days after birth. Inconsistent nomenclatures were used for CPL in the past decades. Patients often present with intractable respiratory failure, hydrops fetalis and even sudden death. The etiologies of CPL remain unclear. Previous hypotheses suggested that CPL might be caused by conditions preventing normal regression of the lymphatics after the 18th-20th week of gestation. Up-to-date biological studies on lymphatic development, lymphatic valve formation and occurrence of hydrops fetalis revealed possible causative relations with mutations of genes of the vascular endothelial growth factor receptor (VEGFR), RAS/MAPK, PI3K/AKT and NF-κB signaling pathways...
March 4, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28257996/linking-of-mpges-1-and-inos-activates-stem-like-phenotype-in-egfr-driven-epithelial-tumor-cells
#19
Erika Terzuoli, Federica Finetti, Filomena Costanza, Antonio Giachetti, Marina Ziche, Sandra Donnini
Inflammatory prostaglandin E-2 (PGE-2) favors cancer progression in epithelial tumors characterized by persistent oncogene input. However, its effects on tumor cell stemness are poorly understood at molecular level. Here we describe two epithelial tumor cells A431 and A459, originating from human lung and skin tumors, in which epithelial growth factor (EGF) induces sequential up-regulation of mPGES-1 and iNOS enzymes, producing an inflammatory intracellular milieu. We demonstrated that concerted action of EGF, mPGES-1 and iNOS causes sharp changes in cell phenotype demonstrated by acquisition of stem-cell features and activation of the epithelial-mesenchymal transition (EMT)...
March 1, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28250891/hydrogen-sulfide-prevents-formation-of-reactive-oxygen-species-through-pi3k-akt-signaling-and-limits-ventilator-induced-lung-injury
#20
Sashko Georgiev Spassov, Rosa Donus, Paul Mikael Ihle, Helen Engelstaedter, Alexander Hoetzel, Simone Faller
The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S...
2017: Oxidative Medicine and Cellular Longevity
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