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Interferon and lung cancer

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https://www.readbyqxmd.com/read/28537924/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#1
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#2
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28492513/an-aaag-rich-oligodeoxynucleotide-rescues-mice-from-bacterial-septic-peritonitis-by-interfering-interferon-regulatory-factor-5
#3
Shuang Gao, Xin Li, Shu Nie, Lei Yang, Liqun Tu, Boqi Dong, Peiyan Zhao, Yangyang Wang, Yongli Yu, Liying Wang, Shucheng Hua
A previous study found that an AAAG-rich Oligodeoxynucleotide (ODN), designated as MS19, could lessen the acute lung inflammatory injury (ALII) in mice infected by influenza viruses. Bioinformatics analysis found that MS19 is consensus with the binding site of interferon regulatory factor 5 (IRF5) in the regulatory elements of pro-inflammatory genes. This study established a septic peritonitis model in Institute of Cancer Research (ICR) mice infected with Escherichia coli (E. coli), and found that MS19 prolonged the survival of the mice and down-regulated the expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28487385/immune-related-gene-expression-profiling-after-pd-1-blockade-in-non-small-cell-lung-carcinoma-head-and-neck-squamous-cell-carcinoma-and-melanoma
#4
Aleix Prat, Alejandro Navarro, Laia Paré, Noemí Reguart, Patricia Galvan, Tomás Pascual, Alex Martínez, Paolo Nuciforo, Laura Comerma, Llucia Alos, Nuria Pardo, Susana Cedrés, Cheng Fan, Joel S Parker, Lydia Gaba, Ivan Victoria, Nuria Viñolas, Ana Vivancos, Ana Arance, Enriqueta Felip
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor speciments from 65 patients with melanoma, lung non-squamous, squamous cell lung or head and neck cancers who were treated with the approved PD1 targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS)...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28471447/microrna-18a-5p-functions-as-an-oncogene-by-directly-targeting-irf2-in-lung-cancer
#5
Chen Liang, Xing Zhang, Hui-Min Wang, Xiao-Min Liu, Xin-Ju Zhang, Bo Zheng, Guang-Ren Qian, Zhong-Liang Ma
Lung cancer is the major form of cancer resulting in cancer-related mortality around the world. MicroRNAs are endogenous small non-coding single-stranded RNAs, which can engage in the regulation of gene expression. In this study, miR-18a-5p significantly upregulated in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines, suggesting an oncogenic function in lung cancer. Additionally, miR-18a-5p can promote carcinogenesis by directly targeting interferon regulatory factor 2 (IRF2). Further experiments indicated that IRF2 can increase cell apoptosis, inhibit cell proliferation and migration ability...
May 4, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28466543/mutation-patterns-in-genes-encoding-interferon-signaling-and-antigen-presentation-a-pan-cancer-survey-with-implications-for-the-use-of-immune-checkpoint-inhibitors
#6
Jan Budczies, Michael Bockmayr, Frederick Klauschen, Volker Endris, Stefan Fröhling, Peter Schirmacher, Carsten Denkert, Albrecht Stenzinger
Blockade of immune checkpoints has become a powerful tool in cancer medicine, which is effective across various solid cancer types and hematologic malignancies. While immunohistochemical detection of PD-L1 expression in tumor cells, immune cells, or both has been introduced as predictive biomarker in several clinical trials, shortcomings and limitations of this approach were quickly recognized. As a single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer, various genetic determinants of therapy success, including microsatellite instability, mutational burden, and PD-L1 amplification, are being investigated...
May 2, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28414566/the-changed-proportion-of-cd45ra-cd45ro-t-cells-in-chronic-hepatitis-c-patients-during-pegylated-interferon-%C3%AE-with-ribavirin-therapy
#7
Jung-Lung Hsiao, Wang-Sheng Ko, Chia-Ju Shih, Ya-Ling Chiou
Infection with the hepatitis C virus (HCV) may progress toward chronic hepatitis, liver cirrhosis, and liver cancer. A therapy for patients with chronic HCV infection is the combination of pegylated interferon-α with ribavirin, which increases the rate of sustained virological response (SVR) to 56%. However, a practical biomarker to predict SVR is lacking. T cells expressing the CD45RA isoform are considered naive, and antigenic stimulation converts them to CD45RO(+). CD45RO(+) T cells exhibit immediate response and high lymphokine production, leading to the maintenance and upregulation of immune reactions...
April 17, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28375674/the-inflammatory-cxc-chemokines-gro%C3%AE-high-ip-10-low-and-mig-low-in-tumor-microenvironment-can-be-used-as-new-indicators-for-non-small-cell-lung-cancer-progression
#8
Ya Cao, Haitao Huang, Zhenxin Wang, Guangbo Zhang
AIMS: To investigate the clinical significance of tumor tissue-infiltrating chemokines expression in non-small cell lung cancer (NSCLC) microenvironment. MATERIALS AND METHODS: Fresh tissue samples were acquired from 50 patients with NSCLC after operation. Then, we quantified the total protein with the BCA Protein Assay Kit and tested 13 chemotactic factors in paired samples including tumor tissues, tumor adjacent tissues, and normal tissues with the CBA Kit. RESULTS: We found that the chemokine CC subfamily of MCP-1, MIP-1α, MIP-1β, and MIP-3α and the chemokine CXC subfamily of IL-8, GROα, IP-10, and MIG expressions in tumor tissues were significantly higher than those in tumor-adjacent tissues and normal tissues...
April 4, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#9
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28303311/-immunotherapy-of-cancer-with-checkpoint-inhibitors-not-only-in-malignant-melanoma
#10
A Neubauer
The newest weapon in cancer therapy is checkpoint inhibition, which is the result of basic immunology research. The success of this therapy is based on the fact that upon light microscopy, many solid tumors harbor lymphocytic cells infiltrating the tumor (TILs), and in many solid tumors, the presence of these TILs are prognostic. Ipilimumab was the first monoclonal antibody developed against a target present on T cells after becoming activated, CTLA-4. In malignant melanoma, ipilimumab showed its beneficial effect as compared to a placebo peptide...
March 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28286532/efficacy-of-juzentaihoto-for-tumor-immunotherapy-in-b16-melanoma-metastasis-model
#11
Shintaro Ishikawa, Takako Ishikawa, Chiaki Tezuka, Kazuhito Asano, Masataka Sunagawa, Tadashi Hisamitsu
Introduction. Medical care for Japanese cancer patients includes Western and Kampo medicines, and treatments with juzentaihoto (JTT) reportedly prevent cancer metastasis and recurrence. In this study, we examined the effects of JTT on natural killer (NK) cell activity and metastasis in combined treatments with anti-PD-1 antibody in a mouse model of melanoma metastasis. Methods. C57BL/6 male mice were intravenously injected with B16 melanoma cells (B16 cell) and were given chow containing 3% JTT. In subsequent in vivo experiments, we assessed serum cytokine levels and tumor colony formation in the lungs...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28260924/impact-of-gefitinib-in-early-stage-treatment-on-circulating-cytokines-and-lymphocytes-for-patients-with-advanced-non-small-cell-lung-cancer
#12
Jin Sheng, Wenfeng Fang, Xia Liu, Shan Xing, Jianhua Zhan, Yuxiang Ma, Yan Huang, Ningning Zhou, Hongyun Zhao, Li Zhang
OBJECTIVES: The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance. PATIENTS AND METHODS: Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28242811/deubiquitinase-usp18-loss-mislocalizes-and-destabilizes-kras-in-lung-cancer
#13
Lisa Maria Mustachio, Yun Lu, Laura J Tafe, Vincent Memoli, Jaime Rodriguez-Canales, Barbara Mino, Pamela Andrea Villalobos, Ignacio Wistuba, Hiroyuki Katayama, Samir M Hanash, Jason Roszik, Masanori Kawakami, Kwang-Jin Cho, John F Hancock, Fadzai Chinyengetere, Shanhu Hu, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
KRAS is frequently mutated in lung cancers and is associated with aggressive biology and chemotherapy resistance. Therefore, innovative approaches are needed to treat these lung cancers. Prior work implicated the IFN-stimulated gene 15 (ISG15) deubiquitinase (DUB) USP18 as having antineoplastic activity by regulating lung cancer growth and oncoprotein stability. This study demonstrates that USP18 affects the stability of the KRAS oncoprotein. Interestingly, loss of USP18 reduced KRAS expression, and engineered gain of USP18 expression increased KRAS protein levels in lung cancer cells...
February 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#14
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
May 2017: Biomaterials
https://www.readbyqxmd.com/read/28228217/-t-peptide-enhances-the-killing-effects-of-cisplatinum-on-lung-cancer
#15
Hongyi Zhang, Minghui Liu, Ying Li, Yongwen Li, Song Xu, Zhenhua Pan, Mingbiao Li, Haiyang Fan, Hongyu Liu, Jun Chen
BACKGROUND: T peptide is extensively used in anti-tumor treatment. The aims of this study were to investigate whether T peptide enhances cisplatinum efficiency while reducing its side effects and to identify its effective mechanisms. METHODS: (1) Human macrophage U937 cells were treated with T peptide and/or cisplatinum. The levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) of each group were detected by enzyme-linked immunosorbent assay (ELISA); (2) Xenograft mouse models of human lung cancer were treated with T peptide and/or cisplatinum once every five days for three times...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28223169/igf1-igf1r-stat3-signaling-inducible-ifitm2-promotes-gastric-cancer-growth-and-metastasis
#16
Li Xu, Rui Zhou, Lezhong Yuan, Shiqing Wang, Xiaoyin Li, Huanrong Ma, Minyu Zhou, Changqie Pan, Jingwen Zhang, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#17
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28184177/human-basonuclin-2-up-regulates-a-cascade-set-of-interferon-stimulated-genes-with-anti-cancerous-properties-in-a-lung-cancer-model
#18
Egon Urgard, Anu Reigo, Eva Reinmaa, Ana Rebane, Andres Metspalu
BACKGROUND: Human basonuclin 2 (BNC2) acts as a tumor suppressor in multiple cancers in an as yet unidentified manner. The role and expression of the BNC2 gene in lung cancer has not yet been investigated. METHODS: BNC2 expression was studied in the A549 and BEAS-2B cell lines, as well as in lung cancer tissue. Illumina array analysis and a viability assay were used to study the effects of transient transfection of BNC2 in A549 cells. Ingenuity pathway analysis and g:Profiler were applied to identify affected pathways and networks...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28166197/chemerin-has-a-protective-role-in-hepatocellular-carcinoma-by-inhibiting-the-expression-of-il-6-and-gm-csf-and-mdsc-accumulation
#19
Y Lin, X Yang, W Liu, B Li, W Yin, Y Shi, R He
Hepatocellular carcinoma (HCC) is linked to inflammation and immunosuppression. Chemerin is highly expressed in the liver and implicated in the regulation of inflammation. However, the role of chemerin in HCC remains unclear. In this study, we aimed to investigate whether chemerin is able to influence HCC progression by regulating tumor-associated inflammation. Here we demonstrated that chemerin significantly decreased in blood and tumor tissues of HCC patients, and tumor chemerin levels were inversely associated with the prognosis...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28109085/silencing-of-interferon-induced-transmembrane-protein-1-ifitm1-inhibits-proliferation-migration-and-invasion-in-lung-cancer-cells
#20
Bing Jin, Hua Jin, Jing Wang
Interferon-induced transmembrane protein 1 (IFITM1), a 17-kDa membrane protein, is largely known as a player in many cellular functions. Recently, there have been studies showing overexpression of IFITM1 in cancers and a positive correlation of IFITM1 overexpression with tumor progression. However, it is poorly understood what role IFITM1 plays in lung cancer. In this study, we presented evidence that IFITM1 was highly expressed in lung cancer tissues and cell lines. IFITM1 silencing inhibited lung cancer cell proliferation, migration and invasion <em>in vitro</em>...
January 20, 2017: Oncology Research
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