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https://www.readbyqxmd.com/read/27922590/neutrophils-are-essential-in-short-hairpin-rna-of-indoleamine-2-3-dioxygenase-mediated-antitumor-efficiency
#1
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
#2
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)...
November 9, 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
#3
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...
November 22, 2016: 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
#4
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
https://www.readbyqxmd.com/read/27821490/suppression-of-type-i-ifn-signaling-in-tumors-mediates-resistance-to-anti-pd-1-treatment-that-can-be-overcome-by-radiotherapy
#5
Xiaohong Wang, Jonathan E Schoenhals, Ailin Li, David R Valdecanas, Huiping Ye, Fenglin Zhang, Chad Tang, Ming Tang, Chang-Gong Liu, Xiuping Liu, Sunil Krishnan, James P Allison, Padmanee Sharma, Patrick Hwu, Ritsuko Komaki, Willem W Overwijk, Daniel R Gomez, Joe Y Chang, Stephen M Hahn, Maria Angelica Cortez, James W Welsh
Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passaging of Kras-mutated, p53-deficient murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host exposed to repetitive dosing with anti-mouse PD-1 antibodies. PDL1 (CD274) expression did not differ between the resistant and parental tumor cells...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27754528/-clinical-trials-and-licensing-of-monoclonal-antibodies-and-biological-medicines-for-cancer-treatment-in-brazil
#6
Cecilia Ferreira da Silva, Miriam Ventura da Silva, Claudia Garcia Serpa Osorio-de-Castro
Objective To analyze the pathway of clinical trials of monoclonal antibodies and biological medicines for cancer treatment involving Brazilian institutions from 2003 to 2012. Method This retrospective, descriptive study was based on review of two clinical trial registries, ClinicalTrials.gov and the Brazilian registry ReBEC. Phase II or III studies with participation from Brazilian institutions listed in at least one of the registries were included. Following selection of the trials, the pathway of monoclonal antibodies and biological medicines was investigated from the research stage until licensing by the Brazilian Agency for Sanitary Surveillance (Anvisa), Food and Drug Administration (FDA), and European Medicines Agency (EMA)...
March 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
https://www.readbyqxmd.com/read/27752361/immune-modulating-effects-of-bevacizumab-in-metastatic-non-small-cell-lung-cancer-patients
#7
E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27698705/increased-soluble-and-membrane-bound-pd-l1-contributes-to-immune-regulation-and-disease-progression-in-patients-with-tuberculous-pleural-effusion
#8
Xue Pan, Anyuan Zhong, Yufei Xing, Minhua Shi, Bin Qian, Tong Zhou, Yongjing Chen, Xueguang Zhang
Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M)...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27688730/interferon-%C3%AE-reduces-the-gefitinib-sensitivity-of-human-non-small-cell-lung-cancer
#9
Chi Pan, Shanshan Weng, Yin Duan, Ling Ding, Suzhan Zhang, Jianjin Huang
AIM OF THE STUDY: Many studies have shown that interferon-α (IFN-α) enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-α with gefitinib in human non-small cell lung cancer (NSCLC) cell lines (A549, H1299, HCC827) with different EGFR and K-Ras gene statuses. MATERIAL AND METHODS: An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR) and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3)...
2016: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/27687232/mda7-il-24-is-an-anti-viral-factor-that-inhibits-influenza-virus-replication
#10
Rak-Kyun Seong, Young-Ki Choi, Ok Sarah Shin
Melanoma differentiation associated gene-7 (mda-7)/interleukin- 24 (IL-24) is a secreted cytokine, which plays an essential role in tumor suppression. Although its role as a multifunctional protein affecting broad types of cancers is well described, functions of IL-24 in host defense against virus infection are yet to be determined. In this study, we explored the anti-viral effect of recombinant IL-24 treatment during influenza infection. Infection of human lung adenocarcinoma cells (A549) with the influenza A virus up-regulated IL-24 mRNA and protein expression in a time-dependent manner...
October 2016: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/27683114/methylation-of-rad51b-xrcc3-and-other-homologous-recombination-genes-is-associated-with-expression-of-immune-checkpoints-and-an-inflammatory-signature-in-squamous-cell-carcinoma-of-the-head-and-neck-lung-and-cervix
#11
Damian T Rieke, Sebastian Ochsenreither, Konrad Klinghammer, Tanguy Y Seiwert, Frederick Klauschen, Inge Tinhofer, Ulrich Keilholz
Immune checkpoints are emerging treatment targets, but mechanisms underlying checkpoint expression are poorly understood. Since alterations in DNA repair genes have been connected to the efficacy of checkpoint inhibitors, we investigated associations between methylation of DNA repair genes and CTLA4 and CD274 (PD-L1) expression.A list of DNA repair genes (179 genes) was selected from the literature, methylation status and expression of inflammation-associated genes (The Cancer Genome Atlas data) was correlated in head and neck squamous cell carcinoma (HNSCC), cervical and lung squamous cell carcinoma...
September 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27677289/arsenic-trioxide-inhibits-lung-metastasis-of-mouse-colon-cancer-via-reducing-the-infiltration-of-regulatory-t-cells
#12
Lei Wang, Xiang Hu, Yingxin Xu, Zhong Liu
The purpose of this study was to investigate the effects of arsenic trioxide (As2O3) on the infiltration of regulatory T cells (Tregs) in the local lung metastasis of mouse colon cancer in vivo and the regulation of Tregs in cytokine-induced killer cells (CIKs) in vitro. A high Tregs infiltration mouse colon cancer lung metastasis model was established by intravenous injection of CT26 murine colon carcinoma cells. Tumor-bearing mice were randomly divided into three groups: control group, low-dose As2O3 group, and high-dose As2O3 group...
September 27, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27647974/endostatin-enhances-antitumor-effect-of-tumor-antigen-pulsed-dendritic-cell-therapy-in-mouse-xenograft-model-of-lung-carcinoma
#13
Jing Liang, Xiaolin Liu, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li
OBJECTIVE: To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell (DC)-T cell therapy on lung cancer. METHODS: Transplanted Lewis lung cancer (LLC) models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC-T+endostatin group, DC-T group, and phosphate-buffered saline (PBS) control group...
August 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/27636009/heterogeneity-of-grade-3-gastroenteropancreatic-neuroendocrine-carcinomas-new-insights-and-treatment-implications
#14
Nicola Fazio, Massimo Milione
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are currently classified as grade (G) 1, G2 and G3, in accordance with the 2010 WHO classification. G1 and G2 are named neuroendocrine tumors (NETs) whereas G3 neuroendocrine carcinomas (NECs). While advanced G1 and G2 are usually treated with several different therapies, including somatostatin analogs, chemotherapy, interferon, molecular targeted agents, peptide receptor radionuclide therapy (PRRT) and liver-directed treatments, advanced G3 NECs are usually treated with a platinum-etoposide chemotherapy, trusting their clinical homogeneity is similar to that of small cell lung cancer...
August 28, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27603913/cancer-testis-antigens-expression-regulation-tumor-invasion-and-use-in-immunotherapy-of-cancers
#15
Arash Salmaninejad, Mohammad Reza Zamani, Mehrnaz Pourvahedi, Zahra Golchehre, Ali Hosseini Bereshneh, Nima Rezaei
UNLABELLED: Cancer/testis antigens (CTAs) are named based on their expression pattern that is restricted in a number of normal and abnormal tissues. Tumor cells frequently express antigens whose expression is typically restricted to germ cells. Their unique expression pattern is guaranteed by precise epigenetic regulatory mechanisms. Because of their tumor-limited, high immunogenicity, and biased expression, discovery of these molecules provides unprecedented opportunities for further research and clinical development in the field of cancer diagnosis and immunotherapy...
October 2016: Immunological Investigations
https://www.readbyqxmd.com/read/27496222/disrupted-cooperation-between-transcription-factors-across-diverse-cancer-types
#16
Jing Wang, Qi Liu, Jingchun Sun, Yu Shyr
BACKGROUND: Transcription Factors (TFs), essential for many cellular processes, generally work coordinately to induce transcriptional change in response to internal and external signals. Disrupted cooperation between TFs, leading to dysregulation of target genes, contributes to the pathogenesis of many diseases, including cancer. Although the aberrant activation of individual TFs and the functional effects have been widely studied, the perturbation of TF cooperativity in cancer has rarely been explored...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27447482/interleukin-2-reverses-cd8-t-cell-exhaustion-in-clinical-malignant-pleural-effusion-of-lung-cancer
#17
C Y Hu, Y H Zhang, T Wang, L Chen, Z H Gong, Y S Wan, Q J Li, Y S Li, B Zhu
Malignant pleural effusion (MPE) is a poor prognostic sign for cancer patients, whereas the functional condition of MPE CD8(+) T cells is unknown. Intracavitary immunotherapy with interleukin (IL)-2 has been proven effective in controlling MPE. To elucidate the underlying mechanism, 35 lung cancer (LC) patients with MPE and 12 healthy donors were included in this study. For the IL-2 therapy experiments, after draining partial MPE, we treated 14 patients by administrating IL-2 (3 or 5 × 10(6) U in 50 ml saline) into the thoracic cavity...
October 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27443896/current-status-of-immunotherapy-for-non-small-cell-lung-cancer
#18
Martina Imbimbo, Giuseppe Lo Russo, Fiona Blackhall
In the last few years, the introduction of novel immunotherapeutic agents has represented a treatment shift for a subset of patients with non-small-cell lung cancer (NSCLC). Checkpoint inhibitors have been demonstrated to improve survival in advanced stage disease with very good tolerability. This success follows many years of scientific effort to manipulate the human immune system to attack cancer cells. With a variety of approaches ranging from vaccines to administration of interleukin or interferon-γ, the results in NSCLC were unsuccessful, with the view that it is a scarcely immunogenic cancer, unlike melanoma or renal cell carcinoma...
August 3, 2016: Tumori
https://www.readbyqxmd.com/read/27432157/an-fc-small-molecule-conjugate-for-targeted-inhibition-of-the-adenosine-2a-receptor
#19
Po-Yuan Hsiao, Jay Kalin, Im-Hong Sun, Mohammed Amin, Ying-Chun Lo, Meng-Jung Chiang, John Giddens, Polina Sysa-Shah, Kathleen Gabrielson, Lai-Xi Wang, Jonathan Powell, Philip A Cole
The adenosine A2A receptor (A2AR) is expressed in immune cells as well as heart and lung tissue and has been intensively studied as a therapeutic target for multiple disease indications.Inhibitors of the A2AR have the potential for stimulating immune response which could be valuable for cancer immune surveillance and mounting a response against pathogens. One well-established potent and selective small-molecule A2AR antagonist, ZM-241385 (ZM), has a short pharmacokinetic half-life and has the potential for systemic toxicity due to A2AR effects in the brain and the heart...
July 19, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27430156/identifying-the-role-of-wilms-tumor-1-associated-protein-in-cancer-prediction-using-integrative-genomic-analyses
#20
Li-Sheng Wu, Jia-Yi Qian, Minghai Wang, Haiwei Yang
The Wilms tumor suppressor, WT1 was first identified due to its essential role in the normal development of the human genitourinary system. Wilms tumor 1 associated protein (WTAP) was subsequently revealed to interact with WT1 using yeast two-hybrid screening. The present study identified 44 complete WTAP genes in the genomes of vertebrates, including fish, amphibians, birds and mammals. The vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From 1,347 available SNPs in the human WTAP gene, 19 were identified to cause missense mutations...
September 2016: Molecular Medicine Reports
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