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https://www.readbyqxmd.com/read/27922075/cancer-associated-fibroblasts-treated-with-cisplatin-facilitates-chemoresistance-of-lung-adenocarcinoma-through-il-11-il-11r-stat3-signaling-pathway
#1
Leilei Tao, Guichun Huang, Rui Wang, Yan Pan, Zhenyue He, Xiaoyuan Chu, Haizhu Song, Longbang Chen
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909731/hypoxia-drives-the-transition-of-human-dermal-fibroblasts-to-a-myofibroblast-like-phenotype-via-the-tgf-%C3%AE-1-smad3-pathway
#2
Bin Zhao, Hao Guan, Jia-Qi Liu, Zhao Zheng, Qin Zhou, Jian Zhang, Lin-Lin Su, Da-Hai Hu
Keloids, partially considered as benign tumors, are characterized by the overgrowth of fibrosis beyond the boundaries of the wound and are regulated mainly by transforming growth factor (TGF)-β1, which induces the transition of fibroblasts to myofibroblasts. Hypoxia is an important driving force in the development of lung and liver fibrosis by activating hypoxia inducible factor-1α and stimulating epithelial‑mesenchymal transition. However, it is unknown whether and hypoxia can influence human dermal scarring...
December 1, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27909724/hsp27-regulates-tgf-%C3%AE-mediated-lung-fibroblast-differentiation-through-the-smad3-and-erk-pathways
#3
Gang Wang, Hao Jiao, Jun-Nian Zheng, Xia Sun
Idiopathic pulmonary fibrosis (IPF) is a chronic lethal interstitial lung disease with unknown etiology. Recent studies have indicated that heat-shock protein 27 (HSP27) contributes to the pathogenesis of IPF through the regulation of epithelial-mesenchymal transition (EMT). However, the expression and role of HSP27 in fibroblasts during pulmonary fibrogenesis has not been investigated to date, at least to the best of our knowledge. In this study, we examined the expression of HSP27 in fibrotic lung tissue and fibroblasts from bleomycin (BLM)-challenged mice and human lung fibroblasts treated with transforming growth factor-β (TGF-β)...
November 28, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27905298/haploinsufficiency-of-the-folliculin-gene-leads-to-impaired-functions-of-lung-fibroblasts-in-patients-with-birt-hogg-dub%C3%A3-syndrome
#4
Yoshito Hoshika, Fumiyuki Takahashi, Shinsaku Togo, Muneaki Hashimoto, Takeshi Nara, Toshiyuki Kobayashi, Fariz Nurwidya, Hideyuki Kataoka, Masatoshi Kurihara, Etsuko Kobayashi, Hiroki Ebana, Mika Kikkawa, Katsutoshi Ando, Koichi Nishino, Okio Hino, Kazuhisa Takahashi, Kuniaki Seyama
Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant inherited disorder caused by germline mutations in the FLCN gene, and characterized by skin fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax, and renal neoplasms. Pulmonary manifestations frequently develop earlier than other organ involvements, prompting a diagnosis of BHDS However, the mechanism of lung cyst formation and pathogenesis of pneumothorax have not yet been clarified. Fibroblasts were isolated from lung tissues obtained from patients with BHDS (n = 12) and lung cancer (n = 10) as controls...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27905295/desensitization-of-idiopathic-pulmonary-fibrosis-fibroblasts-to-alternaria-alternata-extract-mediated-necrotic-cell-death
#5
Jintaek Im, Kyutae Kim, Ji Young Yhee, Scott M O'Grady, Richard S Nho
Alternaria alternata is an allergenic fungus and known to cause an upper respiratory tract infection and asthma in humans with compromised immunity. Although A. alternata's effect on airway epithelial cells has previously been examined, the potential role of A. alternata on lung fibroblast viability is not understood. Since lung fibroblasts derived from patients with idiopathic pulmonary fibrosis (IPF) display a distinct phenotype that is resistant to stress and cell death inducing conditions, the investigation of the role of Alternaria on pathological IPF fibroblasts provides a better understanding of the fibrotic process induced by an allergenic fungus...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27901003/fibroblast-growth-factor-receptor-1-gene-amplification-in-nonsmall-cell-lung-cancer
#6
REVIEW
Jian-Long Miao, Rui-Juan Liu, Jin-Hua Zhou, Shu-Hua Meng
OBJECTIVE: To review the prevalence and prognostic significance of fibroblast growth factor receptor 1 (FGFR1) amplification and to establish an association between FGFR1 amplification and the clinical characteristics of nonsmall cell lung cancer (NSCLC). DATA SOURCES: We searched PubMed for English-language studies published between January 2010 and May 2016. STUDY SELECTION: We included all relevant articles, with no limitation of study design...
2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27895174/human-lung-fibroblasts-present-bacterial-antigens-to-autologous-lung-th-cells
#7
Andrew J Hutton, Marta E Polak, C Mirella Spalluto, Joshua C Wallington, Chris Pickard, Karl J Staples, Jane A Warner, Tom M A Wilkinson
Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4(+) Th cells. During severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating Th cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4(+) T cell Ag-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to IFN-γ...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895126/versican-deficiency-significantly-reduces-lung-inflammatory-response-induced-by-polyinosine-polycytidylic-acid-stimulation
#8
Inkyung Kang, Ingrid A Harten, Mary Y Chang, Kathleen R Braun, Alyssa Sheih, Mary P Nivison, Pamela Y Johnson, Gail Workman, Gernot Kaber, Stephen P Evanko, Christina K Chan, Mervyn J Merrilees, Steven F Ziegler, Michael G Kinsella, Charles W Frevert, Thomas N Wight
Viral infection is an exacerbating factor contributing to chronic airway diseases such as asthma via mechanisms which are still unclear. Polyinosine-polycytidylic acid (poly I:C), a toll-like receptor (TLR) 3 agonist used as a mimetic to study viral infection, has been shown to elicit inflammatory responses in lungs and to exacerbate pulmonary allergic reactions in animal models. Previously, we have shown that poly I:C stimulates lung fibroblasts to accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its binding partner versican, which promotes monocyte adhesion...
November 28, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27894755/dna-damage-induced-by-coal-dust-fly-and-bottom-ash-from-coal-combustion-evaluated-using-the-micronucleus-test-and-comet-assay-in-vitro
#9
Cristina Araujo Matzenbacher, Ana Letícia Hilario Garcia, Marcela Silva Dos Santos, Caroline Cardoso Nicolau, Suziane Premoli, Dione Silva Corrêa, Claudia Telles de Souza, Liana Niekraszewicz, Johnny Ferraz Dias, Tânia Valéria Delgado, Wolfgang Kalkreuth, Ivana Grivicich, Juliana da Silva
Coal mining and combustion generating huge amounts of bottom and fly ash are major causes of environmental pollution and health hazards due to the release of polycyclic aromatic hydrocarbons (PAH) and heavy metals. The Candiota coalfield in Rio Grande do Sul, is one of the largest open-cast coal mines in Brazil. The aim of this study was to evaluate genotoxic and mutagenic effects of coal, bottom ash and fly ash samples from Candiota with the comet assay (alkaline and modified version) and micronucleus test using the lung fibroblast cell line (V79)...
November 22, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27894210/protective-effects-of-lemongrass-essential-oil-against-benzo-a-pyrene-induced-oxidative-stress-and-dna-damage-in-human-embryonic-lung-fibroblast-cells
#10
Jiao Jiang, Henggui Xu, Hetong Wang, Yining Zhang, Ping Ya, Chun Yang, Fasheng Li
Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies had implicated BaP as a causative agent in human cancer, particularly lung cancer.The lemongrass essential oil (LEO) possessed various pharmacological activities, especially the anti-oxidative stress and cancer prevention. In the current study, human embryonic lung fibroblast (HELF) cells were treated with 25 mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability and levels of oxidative stress and DNA damage in the cells were then measured...
November 28, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27893716/hic-5-remodeling-of-the-stromal-matrix-promotes-breast-tumor-progression
#11
G J Goreczny, J L Ouderkirk-Pecone, E C Olson, M Krendel, C E Turner
The remodeling of the stromal extracellular matrix (ECM) has a crucial, but incompletely understood role during tumor progression and metastasis. Hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. To investigate the role of Hic-5 in breast tumor progression in vivo, Hic-5(-/-) mice were generated and crossed with the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic-5(-/-);PyMT mice exhibited increased latency and reduced growth, with fewer lung metastases, as compared with Hic-5(+/-);PyMT mice...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893433/regulation-of-brachyury-by-fibroblast-growth-factor-receptor-1-in-lung-cancer
#12
Yunping Hu, Xin Feng, Akiva Mintz, W Jeffrey Petty, Wesley Hsu
Recent evidence suggests that T-box transcription factor brachyury plays an important role in lung cancer development and progression. However, the mechanisms underlying brachyury-driven cellular processes remain unclear. Here we found that fibroblast growth factor receptor 1/mitogen-activated protein kinase (FGFR1/MAPK) signaling regulated brachyury in lung cancer. Analysis of FGFR1-4 and brachyury expression in human lung tumor tissue and cell lines found that only expression of FGFR1 was positively correlated with brachyury expression...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27891531/origanum-majorana-essential-oil-lacks-mutagenic-activity-in-the-salmonella-microsome-and-micronucleus-assays
#13
Andrea Dos Santos Dantas, Luiz Carlos Klein-Júnior, Miriana S Machado, Temenouga N Guecheva, Luciana D Dos Santos, Régis A Zanette, Fernanda B de Mello, João Antonio Pêgas Henriques, João Roberto Braga de Mello
The present study aimed to investigate the in vitro mutagenic activity of Origanum majorana essential oil. The most abundant compounds identified by GC-MS were γ-terpinene (25.73%), α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). Mutagenicity was evaluated by the Salmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535 Salmonella typhimurium strains, in the absence or in the presence of metabolic activation. Cytotoxicity was detected at concentrations higher than 0...
2016: TheScientificWorldJournal
https://www.readbyqxmd.com/read/27879683/synthesis-and-evaluation-of-new-benzodioxole-based-thiosemicarbazone-derivatives-as-potential-antitumor-agents
#14
Mehlika Dilek Altıntop, Halide Edip Temel, Belgin Sever, Gülşen Akalın Çiftçi, Zafer Asım Kaplancıklı
New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1'-biphenyl]-4-ylmethylene)thiosemicarbazide (5) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells...
November 22, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27878407/low-serum-fibroblast-growth-factor-2-levels-not-accompanied-by-increased-serum-pentraxin-3-levels-in-patients-with-systemic-sclerosis
#15
Ufuk İlgen, Müçteba Enes Yayla, Nurşen Düzgün
There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2 concentrations were compared among SSc, disease control (systemic lupus erythematosus (SLE)), and healthy control groups. We also examined the association of serum levels of PTX3 and FGF2 with disease manifestations. Serum PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n = 66) (p = 1...
November 22, 2016: Clinical Rheumatology
https://www.readbyqxmd.com/read/27878273/pi3k-akt-signaling-is-involved-in-the-pathogenesis-of-bleomycin%C3%A2-induced-pulmonary-fibrosis-via-regulation-of-epithelial%C3%A2-mesenchymal-transition
#16
Xiao-Ling Zhang, Rong-Ge Xing, Liang Chen, Chun-Rong Liu, Zhi-Gang Miao
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by chronic inflammation, fibroblast proliferation and extracellular matrix deposition. However, the molecular and cellular mechanisms underlying the pathogenesis of pulmonary fibrosis remain to be fully elucidated. The contribution of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway in fibrotic processes remains to be investigated. The aim of the present study was to investigate the role of the PI3K/Akt pathway in pulmonary fibrosis...
November 22, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27877129/curcumin-inhibits-transforming-growth-factor-%C3%AE-induced-differentiation-of-mouse-lung-fibroblasts-to-myofibroblasts
#17
Daishun Liu, Ling Gong, Honglan Zhu, Shenglan Pu, Yang Wu, Wei Zhang, Guichuan Huang
Transforming growth factor β (TGF-β) induced differentiation of lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the effect of curcumin on TGF-β induced differentiation of lung fibroblasts to myofibroblasts and explore the underlying mechanism. Mouse lung fibroblasts were cultured and treated with TGF-β2 and curcumin or rosiglitazone. Cell vitality was examined by MTT assay. The secretion of collagen-1 was assessed by ELISA. α smooth muscle actin (α-SMA) was visualized by immunofluorescence technique...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27875573/a-nucleoside-anticancer-drug-1-3-c-ethynyl-%C3%AE-d-ribo-pentofuranosyl-cytosine-induces-depth-dependent-enhancement-of-tumor-cell-death-in-spread-out-bragg-peak-sobp-of-proton-beam
#18
Kenichiro Maeda, Hironobu Yasui, Tohru Yamamori, Taeko Matsuura, Seishin Takao, Motofumi Suzuki, Akira Matsuda, Osamu Inanami, Hiroki Shirato
The effect of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton-induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair...
2016: PloS One
https://www.readbyqxmd.com/read/27872088/h-ras-and-k-ras-oncoproteins-induce-different-tumor-spectra-when-driven-by-the-same-regulatory-sequences
#19
Matthias Drosten, Lucía Simón-Carrasco, Isabel Hernández-Porras, Carmen G Lechuga, María T Blasco, Harrys Kc Jacob, Salvatore Fabbiano, Nicoletta Potenza, Xosé R Bustelo, Carmen Guerra, Mariano Barbacid
Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalency of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-RasG12V oncogene sequences. Germline expression of H-RasG12V or K-RasG12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27870574/evaluation-of-bgj398-a-fibroblast-growth-factor-receptor-1-3-kinase-inhibitor-in-patients-with-advanced-solid-tumors-harboring-genetic-alterations-in-fibroblast-growth-factor-receptors-results-of-a-global-phase-i-dose-escalation-and-dose-expansion-study
#20
Lucia Nogova, Lecia V Sequist, Jose Manuel Perez Garcia, Fabrice Andre, Jean-Pierre Delord, Manuel Hidalgo, Jan H M Schellens, Philippe A Cassier, D Ross Camidge, Martin Schuler, Ulka Vaishampayan, Howard Burris, G Gary Tian, Mario Campone, Zev A Wainberg, Wan-Teck Lim, Patricia LoRusso, Geoffrey I Shapiro, Katie Parker, Xueying Chen, Somesh Choudhury, Francois Ringeisen, Diana Graus-Porta, Dale Porter, Randi Isaacs, Reinhard Buettner, Jürgen Wolf
Purpose This two-part, first-in-human study was initiated in patients with advanced solid tumors harboring genetic alterations in fibroblast growth factor receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3 tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily continuously in 28-day cycles...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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