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https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#1
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28644965/3-4-dihydroxybenzalacetone-attenuates-lipopolysaccharide-induced-inflammation-in-acute-lung-injury-via-down-regulation-of-mmp-2-and-mmp-9-activities-through-suppressing-ros-mediated-mapk-and-pi3k-akt-signaling-pathways
#2
Wei Chao, Jeng-Shyan Deng, Shyh-Shyun Huang, Pei-Ying Li, Yu-Chia Liang, Guan-Jhong Huang
3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)-induced acute lung injuries in mice. Pretreatment with DBL significantly improved LPS-induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and the activities of matrix metalloproteinase (MMP)-2 and -9 in the bronchoalveolar lavage fluid...
June 20, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28644386/capsaicin-induces-autophagy-and-apoptosis-in-human-nasopharyngeal-carcinoma-cells-by-downregulating-the-pi3k-akt-mtor-pathway
#3
Yu-Tsai Lin, Hung-Chen Wang, Yi-Chiang Hsu, Chung-Lung Cho, Ming-Yu Yang, Chih-Yen Chien
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28642632/mcl-plays-an-anti-inflammatory-role-in-mycobacterium-tuberculosis-induced-immune-response-by-inhibiting-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#4
Qingwen Zhang, Xinru Jiang, Weigang He, Kailin Wei, Jinxia Sun, Xiangyang Qin, Yuejuan Zheng, Xin Jiang
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28642450/cbp501-inhibits-egf-dependent-cell-migration-invasion-and-epithelial-to-mesenchymal-transition-of-non-small-cell-lung-cancer-cells-by-blocking-kras-to-calmodulin-binding
#5
Naoya Saito, Naoki Mine, Donald W Kufe, Daniel D Von Hoff, Takumi Kawabe
The anti-cancer agent CBP501 binds to calmodulin (CaM). Recent studies showed that migration and metastasis are inhibited by several CaM antagonists. However, there is no available evidence that CBP501 has similar effects. Here we found that CBP501 inhibits migration of non-small cell lung cancer (NSCLC) cells in vitro, even in the presence of migration inducing factors such as WNT, IL-6, and several growth factors. CBP501 also inhibited epidermal growth factor (EGF) enhanced invasion and the epithelial-to-mesenchymal transition (EMT), and this inhibition was accompanied by (i) suppression of Akt and ERK1/2 phosphorylation, and (ii) suppression of expression of transcription factor Zeb1 and the mesenchymal marker Vimentin...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642170/lncrna-dancr-promotes-tumor-progression-and-cancer-stemness-features-in-osteosarcoma-by-upregulating-axl-via-mir-33a-5p-inhibition
#6
Nian Jiang, Xuedi Wang, Xianbiao Xie, Yan Liao, Ni Liu, Junfeng Liu, Nabo Miao, Jingnan Shen, Tingsheng Peng
lncRNAs regulate the initiation and progression of osteosarcoma, although the mechanism by which this occurs remains unknown. The present study shows that over-expression of the lncRNA DANCR increased osteosarcoma cell proliferation, migration, and invasion in vitro, as well as promoted xenograft tumor growth and lung metastasis in vivo. Mechanistically, DANCR promoted osteosarcoma progression by mediating cancer stem cells (CSC) features. Moreover, pull-down assays and luciferase reporter assays indicated that DANCR upregulated expression of the receptor tyrosine kinase AXL by competitively binding to miR-33a-5p...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28642129/fucoxanthin-inhibits-profibrotic-protein-expression-in-vitro-and-attenuates-bleomycin-induced-lung-fibrosis-in-vivo
#7
Sun Young Ma, Won Sun Park, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Won-Kyo Jung, Sae Gwang Park, Su-Kil Seo, Sung Jae Park, Il Yong Han, Yung Hyun Choi, Il-Whan Choi
Pulmonary fibrosis, a potentially fatal disease, results from acute and chronic interstitial lung diseases. Fucoxanthin (Fx), a carotenoid found in brown seaweed, shows a wide range of pharmacological activities. In this study, we investigated the antifibrotic effects of fucoxanthin and their underlying molecular mechanisms in transforming growth factor-beta1 (TGF-β1)-stimulated human pulmonary fibroblasts (HPFs). Thus, the effects of Fx on TGF-β1-induced expression of fibrotic factors, such as alpha-smooth muscle actin (α-SMA), type 1 collagen, fibronectin, and interleukin-6 (IL-6), in HPFs were investigated...
June 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28638955/lipopolysaccharide-induced-ccn1-production-enhances-interleukin-6-secretion-in-bronchial-epithelial-cells
#8
Lin Shi, Nian Dong, Dongxiang Ji, Xiaomin Huang, Zhaojian Ying, Xiangdong Wang, Chengshui Chen
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells...
June 21, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28629998/aloe-emodin-ae-nanoparticles-suppresses-proliferation-and-induces-apoptosis-in-human-lung-squamous-carcinoma-via-ros-generation-in-vitro-and-in-vivo
#9
Yuan-Yuan Wu, Jing-Hua Zhang, Jing-Hua Gao, Yong-Sheng Li
Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629514/erythropoietin-mediated-regulation-of-central-respiratory-command
#10
Tommy Seaborn, Céline Caravagna
Erythropoietin (Epo) is a cytokine expressed throughout the body, including in the central nervous system where it can act as a breathing modulator in the central respiratory network. In vitro, Epo allows maintaining the activity of respiratory neurons during acute hypoxia, resulting in inhibition of the hypoxia-induced rhythm depression. In vivo, Epo action on the central respiratory command results in enhancement of the acute hypoxic ventilatory response, allowing a better oxygenation of the body by improvement of gases exchanges in the lungs...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28625629/a-phase-ib-trial-of-continuous-once-daily-oral-afatinib-plus-sirolimus-in-patients-with-epidermal-growth-factor-receptor-mutation-positive-non-small-cell-lung-cancer-and-or-disease-progression-following-prior-erlotinib-or-gefitinib
#11
Teresa Moran, Ramón Palmero, Mariano Provencio, Amelia Insa, Margarita Majem, Noemí Reguart, Joaquim Bosch-Barrera, Dolores Isla, Enric Carcereny Costa, Chooi Lee, Marta Puig, Sandrine Kraemer, David Schnell, Rafael Rosell
OBJECTIVES: Dysregulation of the downstream PI3K/AKT/mTOR signaling pathway is a proposed mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We investigated safety and antitumor activity of afatinib plus sirolimus as a potential combination to reverse acquired resistance to EGFR-TKIs in a phase IB trial in patients with EGFR mutation-positive non-small-cell lung cancer (EGFR mut NSCLC) and/or disease progression following prior erlotinib/gefitinib...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28620690/acquired-resistance-to-erlotinib-in-egfr-mutation-positive-lung-adenocarcinoma-among-hispanics-clicap
#12
Andrés F Cardona, Oscar Arrieta, Martín Ignacio Zapata, Leonardo Rojas, Beatriz Wills, Noemí Reguart, Niki Karachaliou, Hernán Carranza, Carlos Vargas, Jorge Otero, Pilar Archila, Claudio Martín, Luis Corrales, Mauricio Cuello, Carlos Ortiz, Luis E Pino, Rafael Rosell, Zyanya Lucia Zatarain-Barrón
BACKGROUND: Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE: The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS: EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015...
June 15, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28617535/research-on-the-protective-effects-of-antioxidants-on-metabolic-syndrome-induced-by-thyroid-dysfunction
#13
Y Chen, Z Zhou, X-X Li, T Wang
OBJECTIVE: This paper researches on the protective effects of antioxidants on metabolic syndrome induced by thyroid dysfunction. While the role of Lipoic acid (LA), Resveratrol (R) and Quercetin (Q) are recognized, the mechanisms for their ameliorative effects are partially understood. Therefore, the objective of this study was to determine the prevalence of MS among university workers and to examine the relationship with thyroid function and mechanisms for protective effects of LA, Resveratrol and Quercetin on the heart, kidneys and lungs...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28615126/unveiling-the-participation-of-avian-kinin-ornithokinin-and-its-receptors-in-the-chicken-inflammatory-response
#14
Rodrigo Guabiraba, Damien Garrido, Geoffrey Bailleul, Angélina Trotereau, Mélanie Pinaud, Anne-Christine Lalmanach, Nathalie K Chanteloup, Catherine Schouler
Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28609459/het0016-decreases-lung-metastasis-from-breast-cancer-in-immune-competent-mouse-model
#15
Thaiz F Borin, Adarsh Shankar, Kartik Angara, Mohammad H Rashid, Meenu Jain, Asm Iskander, Roxan Ara, Iryna Lebedyeva, Hasan Korkaya, Bhagelu R Achyut, Ali S Arbab
Distant metastasis is the primary cause of death in the majority of the cancer types. Recently, much importance has been given to tumor microenvironment (TME) in the development of invasive malignant tumors, as well as the metastasis potential. The ability of tumor cells to modulate TME and to escape immune-mediated attack by releasing immunosuppressive cytokines has become a hallmark of breast cancer. Our study shows the effect of IV formulation of HET0016 (HPßCD-HET0016) a selective inhibitor of 20-HETE synthesis, administered intravenously in immune-competent in vivo mouse model of murine breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28608828/kaempherol-and-luteolin-decrease-claudin-2-expression-mediated-by-inhibition-of-stat3-in-lung-adenocarcinoma-a549-cells
#16
Hiroyuki Sonoki, Asami Tanimae, Satoshi Endo, Toshiyuki Matsunaga, Takumi Furuta, Kenji Ichihara, Akira Ikari
Claudin-2 is highly expressed in human lung adenocarcinoma tissues and may be a novel target for cancer chemotherapy because knockdown of claudin-2 decreases cell proliferation. We found that flavonoids including kaempferol, chrysin, and luteolin concentration-dependently decrease claudin-2 expression in lung adenocarcinoma A549 cells. Claudin-2 expression is up-regulated by mitogen-activated protein kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK)/c-Fos and phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor-κB (NF-κB) pathways, but these activities were not inhibited by kaempferol, chrysin, and luteolin...
June 13, 2017: Nutrients
https://www.readbyqxmd.com/read/28606154/microrna-1296-inhibits-metastasis-and-epithelial-mesenchymal-transition-of-hepatocellular-carcinoma-by-targeting-srpk1-mediated-pi3k-akt-pathway
#17
Qiuran Xu, Xin Liu, Zhikui Liu, Zhenyu Zhou, Yufeng Wang, Jianfeng Tu, Lijie Li, Hangxing Bao, Liu Yang, Kangsheng Tu
BACKGROUND: Increasing evidences demonstrate that miRNAs contribute to development and progression of hepatocellular carcinoma (HCC). Underexpression of miR-1296 is recently reported to promote growth and metastasis of human cancers. However, the expression and role of miR-1296 in HCC remain unknown. METHODS: The levels of miR-1296 in HCC tissues and cells were detected by qRT-PCR. Immunoblotting and immunofluorescence were used for detection of epithelial-to-mesenchymal transition (EMT) progression in HCC cells...
June 12, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28597653/overexpression-of-atp-binding-cassette-subfamily-g-member-2-confers-resistance-to-phosphatidylinositol-3-kinase-inhibitor-pf-4989216-in-cancer-cells
#18
Chung-Pu Wu, Megumi Murakami, Sung-Han Hsiao, An-Wei Chou, Yan-Qing Li, Yang-Hui Huang, Tai-Ho Hung, Suresh V Ambudkar
Deregulated activation of phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently found in human cancers, which plays a key role in promoting cancer proliferation and resistance to anticancer therapies. Therefore, developing inhibitors targeting key components of the PI3K/Akt/mTOR signaling pathway has great clinical significance. PF-4989216 is a novel, orally available small-molecule drug that was developed to selectively inhibit the PI3K/Akt/mTOR signaling pathway and subsequent cancer cell proliferation...
June 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28596475/enhanced-efficacy-of-akt-and-fak-kinase-combined-inhibition-in-squamous-cell-lung-carcinomas-with-stable-reduction-in-pten
#19
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...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28595637/exosome-mir-371b-5p-promotes-proliferation-of-lung-alveolar-progenitor-type-ii-cells-by-using-pten-to-orchestrate-the-pi3k-akt-signaling
#20
Yuan Quan, Zhaohua Wang, Ling Gong, Xinmiao Peng, Melissa A Richard, Junlan Zhang, Myriam Fornage, Joseph L Alcorn, Dachun Wang
BACKGROUND: Pathways directing endogenous stem/progenitor cells to restore normal architecture and function of damaged/diseased lungs remain underexplored. Published data have revealed that alveolar progenitor type II cell (ATIIC)-derived signaling promotes re-epithelialization of injured alveoli, yet the underlying mechanism is unknown. Here we aim to define the role of ATIIC-derived exosome miRNA signaling in controlling ATIIC-specific proliferation or differentiation in response to injury...
June 8, 2017: Stem Cell Research & Therapy
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