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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
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...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28228217/-t-peptide-enhances-the-killing-effects-of-cisplatinum-on-lung-cancer
#2
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
#3
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 18, 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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28101568/puerarin-inhibits-m2-polarization-and-metastasis-of-tumor-associated-macrophages-from-nsclc-xenograft-model-via-inactivating-mek-erk-1-2-pathway
#8
Honggang Kang, Jing Zhang, Baozhong Wang, Meirong Liu, Jun Zhao, Mengxiang Yang, Yingxue Li
Non-small cell lung carcinoma (NSCLC) metastasis is responsible for most of cancer-related mortality. The tumor associated macrophages (TAMs) are known to be crucial cells in lung cancer and are usually divided into two antagonistic types, M1 and M2. Puerarin has a wide spectrum of pharmacological properties. The present study explores puerarin on macrophage polarization and metastasis of NSCLC. The results demonstrated that puerarin inhibited tumor growth and tumor volumes in NSCLC xenograft model, increased M1 markers [CD197+, inducible nitric oxide synthase (iNOS)+, CD40+)] and reduced M2 markers (CD206+, Arg-1+ and CD163+)...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28059079/trim14-is-a-putative-tumor-suppressor-and-regulator-of-innate-immune-response-in-non-small-cell-lung-cancer
#9
Josephine Hai, Chang-Qi Zhu, Tao Wang, Shawna L Organ, Frances A Shepherd, Ming-Sound Tsao
Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28051153/the-metastasis-suppressor-rarres3-as-an-endogenous-inhibitor-of-the-immunoproteasome-expression-in-breast-cancer-cells
#10
Alison M Anderson, Murugan Kalimutho, Sarah Harten, Devathri M Nanayakkara, Kum Kum Khanna, Mark A Ragan
In breast cancer metastasis, the dynamic continuum involving pro- and anti-inflammatory regulators can become compromised. Over 600 genes have been implicated in metastasis to bone, lung or brain but how these genes might contribute to perturbation of immune function is poorly understood. To gain insight, we adopted a gene co-expression network approach that draws on the functional parallels between naturally occurring bone marrow-derived mesenchymal stem cells (BM-MSCs) and cancer stem cells (CSCs). Our network analyses indicate a key role for metastasis suppressor RARRES3, including potential to regulate the immunoproteasome (IP), a specialized proteasome induced under inflammatory conditions...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039262/potential-predictive-value-of-tp53-and-kras-mutation-status-for-response-to-pd-1-blockade-immunotherapy-in-lung-adenocarcinoma
#11
Zhong-Yi Dong, Wenzhao Zhong, Xu-Chao Zhang, Jian Su, Zhi Xie, Si-Yang Liu, Hai-Yan Tu, Hua-Jun Chen, Yue-Li Sun, Qing Zhou, Jinji Yang, Xuening Yang, Jia-Xin Lin, Honghong Yan, Hao-Ran Zhai, Li-Xu Yan, Ri-Qiang Liao, Si-Pei Wu, Yi-Long Wu
PURPOSE: Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which subtype patients will be responsive to checkpoint blockade are not fully understood. EXPERIMENTAL DESIGN: We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic and clinical data from cohorts of lung adenocarcinoma public (Discovery Set) and internal (Validation Set) database and immunotherapeutic patients...
December 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28002583/association-between-il18-607c-a-and-137g-c-polymorphisms-and-susceptibility-to-non-small-cell-lung-cancer-in-a-chinese-population
#12
W Y Gan, H M Li, Y G Zhang, C M Li, Y Wang
Lung cancer is one of the main causes of cancer-related mortality in males and females worldwide. A pleiotropic effect has been observed in the interleukin 18 gene (IL18); its effects include the activation of natural killer cell cytotoxicity and the promotion of the Th1 immune response through the alteration of the expression of interferon-γ and TNF-α in humans. IL18 is therefore involved in the elimination of tumor cells in the human body. We recruited 357 patients with non-small cell lung cancer (NSCLC) and 414 controls to evaluate the correlation between two genetic variations (IL18-607C/A and IL18-137G/C) and the pathogenesis of NSCLC...
December 19, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27998891/inflammatory-cytokines-and-lung-cancer-risk-in-3-prospective-studies
#13
Darren R Brenner, Anouar Fanidi, Kjell Grankvist, David C Muller, Paul Brennan, Jonas Manjer, Graham Byrnes, Allison Hodge, Gianluca Severi, Graham G Giles, Mikael Johansson, Mattias Johansson
To further investigate the role of inflammation in lung carcinogenesis, we evaluated associations between proinflammatory cytokines and lung cancer risk. We conducted a case-control study nested within 3 prospective cohort studies-the Melbourne Collaborative Cohort Study (1990-1994), the Malmö Diet and Cancer Study (1991-1996), and the Northern Sweden Health and Disease Study (initiated in 1985)-involving 807 incident lung cancer cases and 807 smoking-matched controls. Conditional logistic regression models adjusting for serum cotinine concentrations were used to estimate odds ratios for lung cancer risk associated with concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12, interferon γ, tumor necrosis factor α, and granulocyte-macrophage colony-stimulating factor...
January 15, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/27993599/cd73-specific-sirna-loaded-chitosan-lactate-nanoparticles-potentiate-the-antitumor-effect-of-a-dendritic-cell-vaccine-in-4t1-breast-cancer-bearing-mice
#14
Farhad Jadidi-Niaragh, Fatemeh Atyabi, Ali Rastegari, Nasim Kheshtchin, Samaneh Arab, Hadi Hassannia, Maryam Ajami, Zahra Mirsanei, Sima Habibi, Farimah Masoumi, Farshid Noorbakhsh, Fazel Shokri, Jamshid Hadjati
The efficacy of conventional anti-tumor immunotherapeutic approaches is markedly affected by the immunosuppressive microenvironment of tumor. Since adenosine is one of the main orchestra leaders in immunosuppression symphony of tumor, targeting its producing molecules such as CD73 can help to achieve a better clinical outcome following conventional cancer immunotherapeutic approaches. In the present study, we evaluated the efficacy of CD73-specific siRNA-loaded chitosan-lactate nanoparticles (ChLa NPs) in combination with tumor lysate pulsed dendritic cells (DCs) vaccine in treatment of 4T1 (murine derived) breast cancer bearing mice...
December 18, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27990285/non-small-cell-lung-cancer-is-characterised-by-a-distinct-inflammatory-signature-in-serum-compared-with-chronic-obstructive-pulmonary-disease
#15
Hanne Astrid Eide, Ann Rita Halvorsen, Vandana Sandhu, Anne Fåne, Janna Berg, Vilde Drageset Haakensen, Elin H Kure, Odd Terje Brustugun, Cecilie Essholt Kiserud, Jon Amund Kyte, Åslaug Helland
Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27980214/the-isg15-specific-protease-usp18-regulates-stability-of-pten
#16
Lisa Maria Mustachio, Masanori Kawakami, Yun Lu, Jaime Rodriguez-Canales, Barbara Mino, Carmen Behrens, Ignacio Wistuba, Neus Bota-Rabassedas, Jun Yu, J Jack Lee, Jason Roszik, Lin Zheng, Xi Liu, Sarah J Freemantle, Ethan Dmitrovsky
The ubiquitin-like modifier interferon-stimulated gene 15 (ISG15) is implicated in both oncogenic and tumor suppressive programs. Yet, few ISGylation substrates are known and functionally validated in cancer biology. We previously found specific oncoproteins were substrates of ISGylation and were stabilized by the ISG15-specific deubiquitinase (DUB) ubiquitin specific peptidase 18 (USP18). Using reverse-phase protein arrays (RPPAs), this study reports that engineered loss of the DUB USP18 destabilized the tumor suppressor protein phosphatase and tensin homologue (PTEN) in both murine and human lung cancer cell lines...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#17
Kuan-Ting Liu, Yao-Hua Liu, Hsin-Liang Liu, Inn-Wen Chong, Meng-Chi Yen, Po-Lin Kuo
Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear...
December 6, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27889479/ido1-is-an-integral-mediator-of-inflammatory-neovascularization
#18
Arpita Mondal, Courtney Smith, James B DuHadaway, Erika Sutanto-Ward, George C Prendergast, Arturo Bravo-Nuevo, Alexander J Muller
The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been well documented and genetic studies in mice have clearly established the significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of IDO1, the inflammatory cytokine IFNγ (interferon-γ), is a key mediator of immune-based tumor suppression. One means by which IFNγ can exert an anti-cancer effect is by decreasing tumor neovascularization. We speculated that IDO1 might contribute to cancer promotion by countering this anti-neovascular effect of IFNγ, possibly through IDO1-potentiated elevation of the pro-tumorigenic inflammatory cytokine IL6 (interleukin-6)...
December 2016: EBioMedicine
https://www.readbyqxmd.com/read/27878235/accelerated-cell-cycle-progression-of-human-regulatory-t%C3%A2-cell-like-cell-line-caused-by-continuous-exposure-to-asbestos-fibers
#19
Suni Lee, Hidenori Matsuzaki, Megumi Maeda, Shoko Yamamoto, Naoko Kumagai-Takei, Tamayo Hatayama, Miho Ikeda, Kei Yoshitome, Yasumitsu Nishimura, Takemi Otsuki
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of immune cells cause reduction of antitumor immunity, the decrease of natural killer cell killing activity with reduction of NKp46 activating receptor expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3 chemokine receptor expression and production of interferon-γ production in CD4+ T cells were reported using cell line models, freshly isolated peripheral blood immune cells from health donors as well as asbestos exposed patients such as pleural plaque and mesothelioma...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27835886/elevated-serum-granulocyte-macrophage-colony-stimulating-factor-levels-during-radiotherapy-predict-favorable-outcomes-in-lung-and-esophageal-cancer
#20
Guodong Deng, Pingping Hu, Jingxin Zhang, Qiqi Liu, Ning Liang, Jian Xie, Lili Qiao, Hui Luo, Deguo Xu, Fengjun Liu, Xinshuang Yu, Zhen Liu, Yajuan Lv, Jiandong Zhang
The combination of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiotherapy (RT) has been demonstrated to strengthen the antitumor immune response. We hypothesized that the variation of GM-CSF during RT was correlated with cancer prognosis. We measured serum levels of GM-CSF and interferon-γ (IFN-γ) before and during RT in 126 unresectable lung and esophageal cancer patients and performed survival analyses. Upregulated GM-CSF levels during RT correlated with longer overall survival (OS) and progression-free survival (PFS)...
November 8, 2016: Oncotarget
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