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Interferon and lung cancer

Liang Yi, Dan Sun, Qian Han, Zhonghui Liu, Zeng Zeng, Yanping Wu, Xiaoyu Chai, Xinmin Liu
Immunotherapy is considered one of the most promising treatments for lung cancer. The cell signalling molecules melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I protein (RIG‑I) are essential receptors that recognise intracellular pathogen-associated nucleic acids, whereas interferon regulatory factor 3 (IRF3) controls the expression of innate immunity-associated genes in macrophages. However, the innate immune response to polyinosinic:polycytidylic acid [Poly(I:C)] in lung cancer remains to be elucidated...
March 5, 2018: International Journal of Oncology
Michael S Broder, Beilei Cai, Eunice Chang, Maureen P Neary, Elya Papoyan, Al B Benson Iii
OBJECTIVE: The aim of this study was to describe real-world lung neuroendocrine tumor (NET) treatment patterns. METHODS: This study examined cytotoxic chemotherapy (CC), somatostatin analogues (SSA), targeted therapy (TT), interferon, and liver-directed therapies in 2 US claims databases. Patients ≥18 years with ≥1 inpatient or ≥2 outpatient claims for lung NET, initiating pharmacologic treatment between July 1, 2009, and June 30, 2014, were identified and followed until the end of enrollment or study end, whichever occurred first...
March 6, 2018: Oncology
Çiğdem Damla Deniz, Mehmet Gürbilek, Mehmet Koç
Background/aim: This study aimed to investigate the effect of chemoradiotherapy (CRT) on interferon-gamma (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), which are critical markers of the clinical radiation response of patients with locally advanced non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). Materials and methods: Thirty patients who were treated with CRT and 20 healthy controls were prospectively evaluated. Circulating levels of cytokines were measured by enzyme-linked immunosorbent assay procedure...
February 23, 2018: Turkish Journal of Medical Sciences
Sean Pitroda, Melinda Stack, Gene-Fu Liu, Sui-Sui Song, Lucy Chen, Hua Liang, Akash D Parekh, Xiaona Huang, Paul B Roach, Mitchell C Posner, Ralph R Weichselbaum, Nikolai N Khodarev
Lung cancer is the leading cause of cancer deaths worldwide. Approximately 85% of all lung cancers are non-small-cell histology (NSCLC). Modern treatment strategies for NSCLC target driver oncogenes and immune checkpoints. However, less than fifteen percent of patients survive beyond five years. Here, we investigated the effects of SAR302503 (SAR), a selective JAK2 inhibitor, on NSCLC cell lines and tumors. We show that SAR is cytotoxic to NSCLC cells which exhibit resistance to genotoxic therapies, such as ionizing radiation, cisplatin, and etoposide...
February 21, 2018: Molecular Cancer Therapeutics
Xiaolin Liu, Weiwei Nie, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li, Jing Liang
Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-17, interferon (IFN)-γ and hypoxia inducible factor (HIF)-1α, following endostatin therapy...
February 2018: Oncology Letters
Theresa Relation, Tai Yi, Adam J Guess, Krista La Perle, Satoru Otsuru, Suheyla Hasgur, Massimo Dominici, Christopher Breuer, Edwin M Horwitz
Neuroblastoma, the most common extracranial solid tumor in childhood, remains a therapeutic challenge. However, one promising patient treatment strategy is the delivery of anti-tumor therapeutic agents via mesenchymal stromal cell (MSC) therapy. MSCs have been safely utilized to treat genetic bone diseases such as osteogenesis imperfecta, cardiovascular diseases, autoimmune diseases, and cancer. The pro-inflammatory cytokine interferon-gamma (IFNγ) has been shown to decrease tumor proliferation by altering the tumor microenvironment (TME)...
February 12, 2018: Stem Cells
Qi Lai, Haiyong Wang, Angui Li, Yinhui Xu, Liang Tang, Qiang Chen, Chunfang Zhang, Yang Gao, Jianfei Song, Zhenzong Du
IFN-γ-induced PD-L1 expression represents the existence of tumor-specific T cells, which predicts high-response rate to anti-PD-1/L1 therapy, but loss-of-function of IFN signals (e.g., JAK mutation) induces adaptive immune resistance in patients with low-response rate. Interferon regulatory factors (IRF) are frequently epigenetic silenced in carcinogenesis, while the role of methylation in anti-PD-1/L1 therapy remains unclear. We here investigated the methylation status of IFN-γ related genes IRF1/8 and IFN-α/β-related genes IRF3/7 in lung cancer tissues and found that only highly methylated IRF1 and 7 negatively correlated to cd274 (coding PD-L1) expression, similar to JAK mutation...
February 9, 2018: Oncogene
Naoko Kumagai-Takei, Shoko Yamamoto, Suni Lee, Megumi Maeda, Hidenori Masuzzaki, Nagisa Sada, Min Yu, Kei Yoshitome, Yasumitsu Nishimura, Takemi Otsuki
Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity...
February 8, 2018: International Journal of Molecular Sciences
Keith D Eaton, Perrin E Romine, Gary E Goodman, Mark D Thornquist, Matt J Barnett, Effie W Petersdorf
INTRODUCTION: Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aim to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for developing lung cancer. METHODS: Using a nested case-control study design, 625 cases and 625 well-matched controls were selected from participants in the CARET study, a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon γ, IL-10, IL-1α, IL-1β, IL-2, IL-4R, IL-4, IL-6, PTGS2 (COX-2), TGF-β1, and TNFα) was evaluated...
February 2, 2018: Journal of Thoracic Oncology
Niki Karachaliou, Maria Gonzalez-Cao, Guillermo Crespo, Ana Drozdowskyj, Erika Aldeguer, Ana Gimenez-Capitan, Cristina Teixido, Miguel Angel Molina-Vila, Santiago Viteri, Maria De Los Llanos Gil, Salvador Martin Algarra, Elisabeth Perez-Ruiz, Ivan Marquez-Rodas, Delvys Rodriguez-Abreu, Remedios Blanco, Teresa Puertolas, Maria Angeles Royo, Rafael Rosell
Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR...
2018: Therapeutic Advances in Medical Oncology
Lang Yoo, A-Rum Yoon, Chae-Ok Yun, Kwang Chul Chung
The carboxyl terminus of Hsp70-interacting protein (CHIP) acts as a ubiquitin E3 ligase and a link between the chaperones Hsp70/90 and the proteasome system, playing a vital role in maintaining protein homeostasis. CHIP regulates a number of proteins involved in a myriad of physiological and pathological processes, but the underlying mechanism of action via posttranslational modification has not been extensively explored. In this study, we investigated a novel modulatory mode of CHIP and its effect on CHIP enzymatic activity...
January 24, 2018: Cell Death & Disease
Nicoletta Caronni, Francesca Simoncello, Francesca Stafetta, Corrado Guarnaccia, Juan Sebastian Ruiz-Moreno, Bastian Opitz, Thierry Galli, Veronique Proux-Gillardeaux, Federica Benvenuti
Restoring antigen presentation for efficient and durable activation of tumor-specific CD8+ T cell responses is pivotal to immunotherapy, yet the mechanisms that cause subversion of dendritic cells (DC) functions are not entirely understood, limiting the development of targeted approaches. In this study, we show that bone fide DC resident in lung tumor tissues or DC exposed to factors derived from whole lung tumors become refractory to endosomal and cytosolic sensor stimulation and fail to secrete IL-12 and IFN-I...
January 23, 2018: Cancer Research
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma...
January 10, 2018: Cancer Letters
Yuan-Hua Xu, Zheng-Li Li, Sheng-Feng Qiu
Interferon γ (IFN-γ), a multifunctional cytokine, was upregulated in the resected gastric cancer tissue. However, whether IFN-γ is involved in the regulation of gastric cancer has not been well elucidated. Herein, we aimed to investigate the effects and mechanism of IFN-γ on gastric cancer. In this study, we found a vital role of IFN-γ in enhancing proliferation, inhibiting apoptosis, and promoting cell migration and invasion in gastric cancer cells SGC-7901 and MGC-803. Additionally, IFN-γ activated nuclear factor κB (NF-κB) signaling pathway by upregulating the phosphorylation expression of p65 and IκBα, and induced the expression of integrin β3 in vitro...
January 4, 2018: Translational Oncology
W Chung, Y Jung, K Lee, J Park, S Sheen, K Park
SETTING: A tertiary care academic medical centre. OBJECTIVE: To evaluate the clinical usefulness of C-X-C motif chemokine receptor 3 (CXCR3) ligands in tuberculous pleural effusion (TPE). DESIGN: We recruited 336 patients with pleural effusion due to various causes. Concentrations of interferon-gamma (IFN-γ) and the CXCR3 ligands CXCL9 and CXCL11 were determined using enzyme immunoassays; adenosine deaminase (ADA) activity was measured in pleural fluid and serum...
December 1, 2017: International Journal of Tuberculosis and Lung Disease
Hsu-Ching Huang, Wei-Juin Su, Chi-Lu Chiang, Jia-Yih Feng, Hsin-Yi Huang, Ching-Hsiung Lin, Sheng-Hao Lin, Ching-Yuan Cheng, Chao-Hua Chiu
OBJECTIVES: IFN-γ takes part in immunologic responses to cancer and its interactions with chemotherapy have also been described. Our previous study had showed an association between phytohemagglutinin (PHA)-stimulated IFN-γ (PSIG) response and overall survival in patients with advanced non-small-cell lung cancer (NSCLC). Here, we aimed to evaluate the correlation between PSIG and chemotherapy responses. MATERIALS AND METHODS: From January 2011 to August 2012, 340 newly diagnosed patients with lung cancer were enrolled in a prospective latent tuberculosis observational study...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Baiba Kurena, Elisabeth Müller, Panagiotis F Christopoulos, Ingvild Bjellmo Johnsen, Branislava Stankovic, Inger Øynebråten, Alexandre Corthay, Anna Zajakina
Cytokine gene delivery by viral vectors is a promising novel strategy for cancer immunotherapy. Semliki Forest virus (SFV) has many advantages as a delivery vector, including the ability to (i) induce p53-independent killing of tumor cells via apoptosis, (ii) elicit a type-I interferon (IFN) response, and (iii) express high levels of the transgene. SFV vectors encoding cytokines such as interleukin (IL)-12 have shown promising therapeutic responses in experimental tumor models. Here, we developed two new recombinant SFV vectors encoding either murine tumor necrosis factor-α (TNF-α) or murine interferon-γ (IFN-γ), two cytokines with documented immunostimulatory and antitumor activity...
2017: Frontiers in Immunology
Jian-Jun Jin, Yuan-Hua Liu, Ji-Ming Si, Ran Ni, Jing Wang
MicroRNAs are small endogenous non-coding RNAs, which can frequently emerge as regulators in many cancer types. MiR-1290 was found to be abnormally elevated in non small cell lung cancer (NSCLC). However, the underlying molecular mechanism still needs to be investigated. Here, we demonstrated that miR-1290 expression levels were remarkably upregulated in NSCLC tissues compared to adjacent normal tissues. Higher miR-1290 expression levels positively associated with lymph node metastasis and advanced tumor stage...
December 21, 2017: International Journal of Biochemistry & Cell Biology
Ayako Miyazawa, Satoru Ito, Shuichi Asano, Ichidai Tanaka, Mitsuo Sato, Masashi Kondo, Yoshinori Hasegawa
Expression of programmed death-ligand 1 (PD-L1) in tumor cells such as lung cancer cells plays an important role in mechanisms underlying evasion of an immune check point system. Lung cancer tissue with increased deposition of extracellular matrix is much stiffer than normal lung tissue. There is emerging evidence that the matrix stiffness of cancer tissue affects the phenotypes and properties of cancer cells. Nevertheless, the effects of substrate rigidity on expression of PD-L1 in lung cancer cells remain elusive...
December 21, 2017: Biochemical and Biophysical Research Communications
Xiaoqiang Xiao, Yingjie Cao, Haoyu Chen
Butyrate inhibits growth of lung cancer. However, the molecular mechanism is still unclear. Here we profiled miRNAs that responded to sodium butyrate(NaB) stimulation in A549 cells, a non-small cell lung cancer cell line, using microarray. We found 33 up-regulated microRNAs and 22 down-regulated microRNAs (log2 ≥1.5 folds, P-value <0.05). The expression of miR-3935, miR-574-3p, and miR-494-3p was confirmed by realtime qPCR. Then,we explored their potential targets of miR-3935 and miR-494-3p using long noncoding RNA(LncRNA) microarray...
April 2018: Journal of Cellular Biochemistry
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