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Xuebin Yang, Yongjun Liu, Haresh Mani, Jeffrey Olson, Gary Clawson, Carla Caruso, Richard Bruggeman, John M Varlotto, Dani S Zander, Negar Rassaei
A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study...
July 13, 2016: Pathology Oncology Research: POR
Saki Yokokura, Nobuhiro Kanaji, Akira Tadokoro, Shigeyuki Yokokura, Norimitsu Kadowaki, Shuji Bandoh
PURPOSE OF THE STUDY: Confluence-dependent resistance (CDR) is a phenomenon in which the efficacy of anti-cancer agents decreases when cell density increases. CDR in lung cancer has never been reported. The purpose of this study is to investigate if CDR can occur in NSCLC cells and to find a role for transforming growth factor (TGF)-β as a mechanism of CDR. MATERIALS AND METHODS: Non-small cell lung cancer (NSCLC) cell lines A549 and H2228 were exposed to cisplatin in a variety of cell density conditions...
May 2016: Experimental Lung Research
Mariacarmela Santarpia, María González-Cao, Santiago Viteri, Niki Karachaliou, Giuseppe Altavilla, Rafael Rosell
A deeper understanding of the key role of the immune system in regulating tumor growth and progression has led to the development of a number of immunotherapies, including cancer vaccines and immune checkpoint inhibitors. Immune checkpoint inhibitors target molecular pathways involved in immunosuppression, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway, with the goal to enhance the host's own immune anticancer response...
December 2015: Translational Lung Cancer Research
K O'Leary, A Shia, F Cavicchioli, V Haley, A Comino, M Merlano, F Mauri, K Walter, M Lackner, M B Wischnewsky, T Crook, C Lo Nigro, P Schmid
BACKGROUND: The transforming growth factor-beta (TGF- β) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF-β accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. METHODS: Methylation microarray and RNA sequencing were carried out on lung cancer cell lines...
September 15, 2015: British Journal of Cancer
Min-Chao Duan, Wei Han, Pei-Wen Jin, Yu-Ping Wei, Qiu Wei, Liang-Ming Zhang, Jun-Chen Li
The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction...
December 2015: Inflammation
Guillaume Desnoyers, Laura D Frost, Lynn Courteau, Michael L Wall, Stephen M Lewis
UNLABELLED: The eIF3e protein is a component of the multisubunit eIF3 complex, which is essential for cap-dependent translation initiation. Decreased eIF3e expression is often observed in breast and lung cancer and has been shown to induce epithelial-to-mesenchymal transition (EMT) in breast epithelial cells by an unknown mechanism. Here, we study the effect of decreased eIF3e expression in lung epithelial cells by creating stable clones of lung epithelial cells (A549) that express an eIF3e-targeting shRNA...
October 2015: Molecular Cancer Research: MCR
Shisuo Du, Sophie Bouquet, Chen-Hao Lo, Ilenia Pellicciotta, Shiva Bolourchi, Renate Parry, Mary Helen Barcellos-Hoff
PURPOSE: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non-small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. METHODS AND MATERIALS: TGF-β-mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure...
January 1, 2015: International Journal of Radiation Oncology, Biology, Physics
Bao-Hong Fu, Zhan-Zhao Fu, Wei Meng, Tao Gu, Xiao-Dong Sun, Zhi Zhang
We examined the levels of platelet vascular endothelial growth factor (VEGF(PLT)) and serum level of transforming growth factor beta 1 (TGF-β1) in non-small cell lung cancer (NSCLC) patients before and after chemotherapy to assess their clinical value as biomarkers. A total of 115 subjects were recruited at the First Hospital of Qinhuangdao between July 2012 and October 2013, including 65 NSCLC patients receiving chemotherapy (NSCLC group) and 50 healthy controls (control group). All NSCLC patients received gemcitabine plus cisplatin (GP regimen) for a total of two courses...
August 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
K Jakubowska, W Naumnik, W Niklińska, E Chyczewska
Lung cancer is associated with poor prognosis. The aim of this study was to evaluate the clinical usefulness of HMGB-1 (high-mobility group protein B1) and TGF-β (transforming growth factor beta) in patients with advanced non-small cell lung cancer (NSCLC). We studied 45 patients with NSCLC prior to chemotherapy, 23 patients with Besnier-Boeck-Schaumann (BBS) disease (sarcoidosis), and 15 healthy volunteers. HMGB-1 and TGF-β levels were measured in serum and BALF samples using ELISA method. A higher serum HMGB-1 and TGF-β levels were in NSCLC patients compared with the other groups...
2015: Advances in Experimental Medicine and Biology
Zhong-Liang Ma, Pin-Pin Hou, Yan-Li Li, De-Tao Wang, Tian-Wei Yuan, Jia-Li Wei, Bo-Tao Zhao, Jia-Tao Lou, Xin-Tai Zhao, Yan Jin, You-Xin Jin
MicroRNAs (MiRNAs) are small non-coding RNA molecules which act as important regulators of post-transcriptional gene expression by binding 3'-untranslated region (3'-UTR) of target messenger RNA (mRNA). In this study, we analyzed miRNA-34a (miR-34a) as a tumor suppressor in non-small cell lung cancer (NSCLC) H1299 cell line. The expression level of miR-34a in four different NSCLC cell lines, H1299, A549, SPCA-1, and HCC827, was significantly lower than that in the non-tumorigenic bronchial epithelium cell line BEAS-2B...
April 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
J Jacob Wamsley, Manish Kumar, David F Allison, Sheena H Clift, Caitlyn M Holzknecht, Szymon J Szymura, Stephen A Hoang, Xiaojiang Xu, Christopher A Moskaluk, David R Jones, Stefan Bekiranov, Marty W Mayo
Soluble growth factors and cytokines within the tumor microenvironment aid in the induction of the epithelial-to-mesenchymal transition (EMT). Although EMT promotes the development of cancer-initiating cells (CIC), cellular mechanisms by which cancer cells maintain mesenchymal phenotypes remain poorly understood. Work presented here indicates that induction of EMT stimulates non-small cell lung cancer (NSCLC) to secrete soluble factors that function in an autocrine fashion. Using gene expression profiling of all annotated and predicted secreted gene products, we find that NF-κB activity is required to upregulate INHBA/Activin, a morphogen in the TGFβ superfamily...
January 15, 2015: Cancer Research
Wei Wang, Xinyu Wu, Yu Tian
The molecular regulation of growth of non-small cell lung cancer (NSCLC) has not been fully clarified. In NSCLC, we detected significantly higher levels of activating protein-4 (AP4), significantly lower levels of p21, and significantly lower levels of phosphorylated SMAD2 as an indicator of activated transforming growth factor β (TGFβ) receptor signaling, compared to the adjacent normal lung tissue. Moreover, a strong negative correlation was detected between AP4 and p21 levels. Since p21 is a potent cell-cycle inhibitor, we were thus promoted to examine the relationships among AP4, TGFβ receptor signaling, and cell growth in NSCLC...
January 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Tianli Cheng, Chengping Hu, Huaping Yang, Liming Cao, Jian An
Altered expression of miRNAs contributes to development and progression of non-small cell lung cancer (NSCLC), while transforming growth factor-β (TGF-β) promotes NSCLC cell epithelial-mesenchymal transition. This study aimed to investigate the effects of TGF-β-induced miR‑143 expression in regulation of NSCLC cell viability, invasion capacity in vitro, and xenograft formation and growth in nude mice. NSCLC A549 cells treated with TGF-β were subjected to miRNA microarray analysis and miR‑143 was selected for further study of tumor cell viability, wound healing, invasion capacity in vitro, and tumor growth in nude mice...
November 2014: International Journal of Oncology
Maurizio Risolino, Nadia Mandia, Francescopaolo Iavarone, Leila Dardaei, Elena Longobardi, Serena Fernandez, Francesco Talotta, Fabrizio Bianchi, Federica Pisati, Lorenzo Spaggiari, Patrick N Harter, Michel Mittelbronn, Dorothea Schulte, Mariarosaria Incoronato, Pier Paolo Di Fiore, Francesco Blasi, Pasquale Verde
Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (Prep1) is a ubiquitous homeoprotein involved in early development, genomic stability, insulin sensitivity, and hematopoiesis. Previously we have shown that Prep1 is a haploinsufficient tumor suppressor that inhibits neoplastic transformation by competing with myeloid ecotropic integration site 1 for binding to the common heterodimeric partner Pbx1. Epithelial-mesenchymal transition (EMT) is controlled by complex networks of proinvasive transcription factors responsive to paracrine factors such as TGF-β...
September 9, 2014: Proceedings of the National Academy of Sciences of the United States of America
L Liu, X Chen, Y Wang, Z Qu, Q Lu, J Zhao, X Yan, H Zhang, Y Zhou
The Notch signaling pathway plays an important role in the bone metastasis microenvironment. Although recent evidence suggests that Notch signaling contributes to bone metastasis in breast and prostate cancer, its role and possible mechanisms in non-small cell lung cancer (NSCLC) bone metastasis are not yet clear. Here, we show that Notch3 is overexpressed in NSCLC bone metastases. The inhibition of Notch3 by small interfering RNA transfection decreased the invasion ability of NSCLC cells and transforming growth factor (TGF)-induced interleukin (IL)-6 and parathyroid hormone-related protein (pTHrP) expression in vitro...
September 2014: Cancer Gene Therapy
Elizabeth Salvo, Saray Garasa, Javier Dotor, Xabier Morales, Rafael Peláez, Peter Altevogt, Ana Rouzaut
BACKGROUND: Transforming Growth Factor beta (TGF-β) acts as a tumor suppressor early in carcinogenesis but turns into tumor promoter in later disease stages. In fact, TGF-β is a known inducer of integrin expression by tumor cells which contributes to cancer metastatic spread and TGF-β inhibition has been shown to attenuate metastasis in mouse models. However, carcinoma cells often become refractory to TGF-β-mediated growth inhibition. Therefore identifying patients that may benefit from anti-TGF-β therapy requires careful selection...
2014: Molecular Cancer
Xinying Xue, Xin Wang, Yuxia Liu, Guigen Teng, Yong Wang, Xuefeng Zang, Kaifei Wang, Jinghui Zhang, Yali Xu, Jianxin Wang, Lei Pan
A post-transcriptional pathway by which TGF-β modulates expression of specific proteins, Disabled-2 (Dab2) and Interleukin-like EMT Inducer (ILEI), inherent to epithelial to mesenchymal transition (EMT) in murine epithelial cells through Akt2-mediated phosphorylation of poly r(C) binding protein (PCBP1), has been previously elucidated. The aims of the current study were to determine if the same mechanism is operative in the non-small cell lung cancer (NSCLC) cell line, A549, and to delineate the underlying mechanism...
August 2014: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Zeyong Jiang, Jun Yin, Wenfan Fu, Yijun Mo, Youguang Pan, Lu Dai, Haoda Huang, Siwen Li, Jian Zhao
MicroRNAs (miRNAs) have been proven to play crucial roles in cancer, including tumor chemotherapy resistance and metastasis of non-small-cell lung cancer (NSCLC). TGFβ signal pathway abnormality is widely found in cancer and correlates with tumor proliferation, apoptosis and metastasis. Here, miR-17, 20a, 20b were detected down-regulated in A549/DDP cells (cisplatin resistance) compared with A549 cells (cisplatin sensitive). Over-expression of miR-17, 20a, 20b can not only decrease cisplatin-resistant but also reduce migration by inhibiting epithelial-to-mesenchymal transition (EMT) in A549/DDP cells...
2014: PloS One
C Eberlein, C Rooney, S J Ross, M Farren, H M Weir, S T Barry
Fibroblasts in the tumour stroma (cancer-associated fibroblasts) influence tumour progression and response to therapeutics; little is known about the mechanisms through which the tumour cell co-opts a normal fibroblast. To study the activation of fibroblasts by tumour cells, a panel of non-small cell lung cancer (NSCLC) cell lines and normal human dermal fibroblasts were co-cultured. A subset of the NSCLC cells induced an activated cancer-associated fibroblast-like fibroblast phenotype defined by induction of fibroblast α-smooth muscle actin expression...
February 5, 2015: Oncogene
Qian Qian, Xiangguang Shi, Zhe Lei, Lei Zhan, Reng-Yun Liu, Jun Zhao, Binghua Yang, Zeyi Liu, Hong-Tao Zhang
Decorin (DCN) has been suggested to display an anti-metastatic role by antagonizing bioactive TGF-β in advanced human cancers. However, the epigenetic mechanisms by which defective expression of DCN causes cancer metastasis remain unclear. We focused on non-small cell lung cancer (NSCLC) cell lines with low metastatic potential (95C) and high metastatic potential (95D), which share a similar genetic background. Quantitative PCR and clonal bisulfite sequencing indicated that the methylation levels of the +58CpG site in the DCN 5'-UTR region was significantly higher in 95D cells with low expression of DCN mRNA compared to 95C cells with high expression of DCN mRNA...
March 2014: International Journal of Oncology
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