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Cancer immunity cycle

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https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#1
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28088513/an-immunogram-for-the-cancer-immunity-cycle-towards-personalized-immunotherapy-of-lung-cancer
#2
Takahiro Karasaki, Kazuhiro Nagayama, Hideki Kuwano, Jun-Ichi Nitadori, Masaaki Sato, Masaki Anraku, Akihiro Hosoi, Hirokazu Matsushita, Yasuyuki Morishita, Kosuke Kashiwabara, Masaki Takazawa, Osamu Ohara, Kazuhiro Kakimi, Jun Nakajima
INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle using next-generation sequencing. METHODS: Whole-exome sequencing and RNA-Seq was performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28072766/the-impact-of-body-composition-parameters-on-ipilimumab-toxicity-and-survival-in-patients-with-metastatic-melanoma
#3
Louise E Daly, Derek G Power, Áine O'Reilly, Paul Donnellan, Samantha J Cushen, Kathleen O'Sullivan, Maria Twomey, David P Woodlock, Henry P Redmond, Aoife M Ryan
BACKGROUND: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established. METHODS: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi...
January 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28072716/pneumonitis-in-cancer-patients-receiving-anti-pd-1-and-radiotherapies-three-case-reports
#4
Chieh-Sheng Lu, Jin-Hwang Liu
INTRODUCTION: In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28067913/impaired-h3k36-methylation-defines-a-subset-of-head-and-neck-squamous-cell-carcinomas
#5
Simon Papillon-Cavanagh, Chao Lu, Tenzin Gayden, Leonie G Mikael, Denise Bechet, Christina Karamboulas, Laurie Ailles, Jason Karamchandani, Dylan M Marchione, Benjamin A Garcia, Ilan Weinreb, David Goldstein, Peter W Lewis, Octavia Maria Dancu, Sandeep Dhaliwal, William Stecho, Christopher J Howlett, Joe S Mymryk, John W Barrett, Anthony C Nichols, C David Allis, Jacek Majewski, Nada Jabado
Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) are deadly and common cancers. Recent genomic studies implicate multiple genetic pathways, including cell signaling, cell cycle and immune evasion, in their development. Here we analyze public data sets and uncover a previously unappreciated role of epigenome deregulation in the genesis of 13% of HPV-negative HNSCCs. Specifically, we identify novel recurrent mutations encoding p.Lys36Met (K36M) alterations in multiple H3 histone genes...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28067383/the-functional-consequences-and-prognostic-value-of-dosage-sensitivity-in-ovarian-cancer
#6
Zichuang Yan, Yongjing Liu, Yunzhen Wei, Ning Zhao, Qiang Zhang, Cheng Wu, Zhiqiang Chang, Yan Xu
Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression...
January 9, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28067164/curcumin-and-lung-cancer-the-role-of-micrornas
#7
Diana Lelli, Claudio Pedone, Muhammed Majeed, Amirhosssein Sahebkar
BACKGROUND: Lung cancer is one of the most common types of cancer worldwide and is characterized by a poor prognosis, related both to late diagnosis and lack of effective treatments. In the last years, microRNAs (miRNAs) have been demonstrated to have an important role in tumor microenvironment and immune regulation. These RNAs can be categorized into tumor-suppressor genes, such as let-7 family and miR-34, and oncogenes such as miR-221 and miR-222. Curcumin is a bioactive polyphenol that is documented to have promising anti-cancer activity, and to be well tolerated in humans...
January 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28062796/integrated-cellular-and-plasma-proteomics-of-contrasting-b-cell-cancers-reveals-common-unique-and-systemic-signatures
#8
Harvey E Johnston, Matthew J Carter, Kerry L Cox, Melanie Dunscombe, Antigoni Manousopoulou, Paul A Townsend, Spiro D Garbis, Mark S Cragg
Approximately 800,000 leukaemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukaemia (CLL), are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumour, frequently affecting children, whilst CLL typically presents as an indolent, slow-progressing leukaemia affecting the elderly. The B-cell-specific over-expression of the myc and tcl1 oncogenes in mice induce spontaneous malignancies modelling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labelling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumours...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28061765/mir-663a-regulates-growth-of-colon-cancer-cells-after-administration-of-antimicrobial-peptides-by-targeting-cxcr4-p21-pathway
#9
Kengo Kuroda, Tomokazu Fukuda, Marija Krstic-Demonacos, Constantinos Demonacos, Kazuhiko Okumura, Hiroshi Isogai, Miwa Hayashi, Kazuki Saito, Emiko Isogai
BACKGROUND: Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown. METHODS: miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs...
January 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28061481/b7-h4-promotes-tumor-growth-and-metastatic-progression-in-lung-cancer-by-impacting-cell-proliferation-and-survival
#10
Xiuqin Zhang, Liming Cai, Guangbo Zhang, Yu Shen, Jianan Huang
Aberrant expression of B7-H4 occurs across a broad spectrum of human cancers. The aim of this study was to investigate the key role of B7-H4 during tumorigenesis and metastasis of human lung cancer. Our data showed that the shRNA-mediated disruption of B7-H4 markedly inhibited tumor cell proliferation, invasion and migration, increased cell apoptosis and arrested cell cycle at G0/G1. These changes were accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28045548/vitamin-d-reduces-colitis-and-inflammation-associated-colorectal-cancer-in-mice-independent-of-nod2
#11
Ihsan Elimrani, Jamie Koenekoop, Serge Dionne, Valerie Marcil, Edgar Delvin, Emile Levy, Ernest G Seidman
Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2(-/-) mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates...
January 3, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28043914/bay-1143269-a-novel-mnk1-inhibitor-targets-oncogenic-protein-expression-and-shows-potent-anti-tumor-activity
#12
Susann Santag, Franziska Siegel, Antje M Wengner, Claudia Lange, Ulf Bömer, Knut Eis, Florian Pühler, Philip Lienau, Linda Bergemann, Martin Michels, Franz von Nussbaum, Dominik Mumberg, Kirstin Petersen
The initiation of mRNA translation has received increasing attention as an attractive target for cancer treatment in the recent years. The oncogenic eukaryotic translation initiation factor 4E (eIF4E) is the major substrate of MAP kinase-interacting kinase 1 (MNK1), and it is located at the junction of the cancer-associated PI3K and MAPK pathways. The fact that MNK1 is linked to cell transformation and tumorigenesis renders the kinase a promising target for cancer therapy. We identified a novel small molecule MNK1 inhibitor, BAY 1143269, by high-throughput screening and lead optimization...
December 31, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28042949/recombinant-parvoviruses-armed-to-deliver-cxcl4l1-and-cxcl10-are-impaired-in-their-antiangiogenic-and-antitumoral-effects-in-a-kaposi-sarcoma-tumor-model-due-to-the-chemokines-interference-with-the-virus-cycle
#13
Christiane Dinsart, Kalliopi Pervolaraki, Alexandra Stroh-Dege, Muriel Lavie, Isabelle Ronsse, Jean Rommelaere, Jo Van Damme, Katrien Van Raemdonck, Sofie Struyf
Application of oncolytic viruses is a valuable option to broaden the armament of anti-cancer therapies as these combine specific cytotoxic effects and immune-stimulating properties. The self-replicating H-1 parvovirus (H-1PV) is a prototypical oncolytic virus that besides targeting tumor cells also infects endothelial cells, thus combining oncolytic and angiostatic traits. To increase its therapeutic value, H-1PV can be armed with cytokines or chemokines to enhance the immunological response. Some chemokines, more specifically the CXCR3 ligands CXCL4L1 and CXCL10 combine immune-stimulating properties with angiostatic activity...
January 2, 2017: Human Gene Therapy
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
#14
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/28036243/comparative-analysis-of-22-epstein-barr-virus-genomes-from-diseased-and-healthy-individuals
#15
Lu Zhou, Jian-Ning Chen, Xin-Min Qiu, Yu-Hang Pan, Zhi-Gang Zhang, Chun-Kui Shao
Epstein-Barr virus (EBV) infects most of the world's population and is causally associated with several human cancers, but little is known about how EBV genetic variations ¬might influence EBV-associated diseases and their geographical patterns. In the present study, 22 EBV whole-genome sequences from diseased and healthy individuals were analysed to explore EBV sequence variations at the whole-genome level. We found that the 22 EBV genomes were generally highly similar to each other at the genome level. However, varying degrees of genetic diversity were detected across the entire genome, especially in the latent genes...
December 30, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/28019039/integration-of-gene-expression-and-methylation-to-unravel-biological-networks-in-glioblastoma-patients
#16
Francesco Gadaleta, Kyrylo Bessonov, Kristel Van Steen
The vast amount of heterogeneous omics data, encompassing a broad range of biomolecular information, requires novel methods of analysis, including those that integrate the available levels of information. In this work, we describe Regression2Net, a computational approach that is able to integrate gene expression and genomic or methylation data in two steps. First, penalized regressions are used to build Expression-Expression (EEnet) and Expression-Genomic or Expression-Methylation (EMnet) networks. Second, network theory is used to highlight important communities of genes...
December 26, 2016: Genetic Epidemiology
https://www.readbyqxmd.com/read/28017892/metronomic-chemotherapy-a-potent-macerator-of-cancer-by-inducing-angiogenesis-suppression-and-antitumor-immune-activation
#17
Eirini Biziota, Leonidas Mavroeidis, Eleftheria Hatzimichael, Periklis Pappas
Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels...
December 23, 2016: Cancer Letters
https://www.readbyqxmd.com/read/28013168/integrated-analysis-identifies-molecular-signatures-and-specific-prognostic-factors-for-different-gastric-cancer-subtypes
#18
Li Min, Yu Zhao, Shengtao Zhu, Xintao Qiu, Rui Cheng, Jie Xing, Linlin Shao, Shuilong Guo, Shutian Zhang
BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed. METHODS: GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured...
December 22, 2016: Translational Oncology
https://www.readbyqxmd.com/read/28012777/sequential-administration-of-a-mva-based-muc1-cancer-vaccine-and-the-tlr9-ligand-litenimod-li28-improves-local-immune-defense-against-tumors
#19
Emmanuelle Schaedler, Christelle Remy-Ziller, Julie Hortelano, Nadine Kehrer, Marie-Christine Claudepierre, Tanja Gatard, Christopher Jakobs, Xavier Préville, Antoine F Carpentier, Karola Rittner
TG4010 is an immunotherapeutic vaccine based on Modified Vaccinia virus Ankara (MVA) encoding the human tumor-associated antigen MUC1 and human IL-2. In combination with first-line standard of care chemotherapy in advanced metastatic non-small-cell lung cancer (NSCLC), repeated subcutaneous injection of TG4010 improved progression-free survival in phase 2b clinical trials. In preclinical tumor models, MVATG9931, the research version of TG4010, conferred antigen-specific responses against the weak antigen human MUC1...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/28008156/genomic-binding-of-pax8-pparg-fusion-protein-regulates-cancer-related-pathways-and-alters-the-immune-landscape-of-thyroid-cancer
#20
Yanxiao Zhang, Jingcheng Yu, Vladimir Grachtchouk, Tingting Qin, Carey N Lumeng, Maureen A Sartor, Ronald J Koenig
PAX8-PPARG fusion protein (PPFP) results from a t(2;3)(q13;p25) chromosomal translocation, is found in 30% of follicular thyroid carcinomas, and demonstrates oncogenic capacity in transgenic mice. A PPARG ligand, pioglitazone, is highly therapeutic in mice with PPFP thyroid cancer. However, only limited data exist to characterize the binding sites and oncogenic function of PPFP, or to explain the observed therapeutic effect of pioglitazone. Here we used our previously characterized transgenic mouse model of PPFP follicular thyroid carcinoma to identify PPFP binding sites in vivo using ChIP-seq, and to distinguish genes and pathways regulated directly or indirectly by PPFP with and without pioglitazone treatment via integration with RNA-seq data...
December 20, 2016: Oncotarget
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