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Cancer immunity cycle

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https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#1
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29145241/the-prognostic-value-of-the-serum-neuron-specific-enolase-and-lactate-dehydrogenase-in-small-cell-lung-cancer-patients-receiving-first-line-platinum-based-chemotherapy
#2
Xiaofan Liu, Weiming Zhang, Wen Yin, Yang Xiao, Changzhi Zhou, Yi Hu, Shuang Geng
The aim of this study was to investigate the associations of serum levels of neuron-specific enolase (NSE), pro-gastrin releasing peptide (ProGRP), and lactate dehydrogenase (LDH) with clinical response and survival in small cell lung cancer (SCLC) patients receiving first-line platinum-based chemotherapy.One hundred thirty-six patients with SCLC were recruited in this study. All the patients received first-line platinum-based chemotherapy. Clinical efficacy was assessed according to Response Evaluation Criteria in Solid Tumors v1...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29143726/recent-advances-in-vesicular-stomatitis-virus-based-oncolytic-virotherapy-a-5-year-update
#3
Sébastien A Felt, Valery Z Grdzelishvili
Oncolytic virus (OV) therapy is an anti-cancer approach that uses viruses that preferentially infect, replicate in and kill cancer cells. Vesicular stomatitis virus (VSV, a rhabdovirus) is an OV that is currently being tested in the USA in several phase I clinical trials against different malignancies. Several factors make VSV a promising OV: lack of pre-existing human immunity against VSV, a small and easy to manipulate genome, cytoplasmic replication without risk of host cell transformation, independence of cell cycle and rapid growth to high titres in a broad range of cell lines facilitating large-scale virus production...
November 16, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29143272/preliminary-results-of-immune-modulating-antibody-mdv9300-pidilizumab-treatment-in-children-with-diffuse-intrinsic-pontine-glioma
#4
Iris Fried, Alex Lossos, Tal Ben Ami, Rina Dvir, Helen Toledano, Myriam Weil Ben Arush, Sergei Postovski, Abed Abu Kuidar, Michal Yalon, Michael Weintraub, Mony Benifla
Diffuse intrinsic pontine glioma (DIPG) is an incurable disease with a median overall survival of 10 months. Immune modulating antibodies have recently emerged as a highly promising treatment modality in multiple cancer types. We present results from the first study to evaluate the immune modulating antibody MDV9300 (pidilizumab) in pediatric patients with DIPG. All patients aged 3 years and older, diagnosed with DIPG between February 2014 and June 2015 in Israel, were offered to participate in the study...
November 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29137231/an-oral-keratinocyte-life-cycle-model-identifies-novel-host-genome-regulation-by-human-papillomavirus-16-relevant-to-hpv-positive-head-and-neck-cancer
#5
Michael R Evans, Claire D James, Oonagh Loughran, Tara J Nulton, Xu Wang, Molly L Bristol, Brad Windle, Iain M Morgan
Many aspects of the HPV life cycle have been characterized in cervical cell lines (W12, CIN612) and in HPV immortalized primary foreskin keratinocytes. There is now an epidemic of HPV positive oropharyngeal cancers (HPV16 is responsible for 80-90% of these); therefore increased understanding of the HPV16 life cycle in oral keratinocytes is a priority. To date there have been limited reports characterizing the HPV16 life cycle in oral keratinocytes. Using TERT immortalized "normal" oral keratinocytes (NOKs) we generated clonal cell lines maintaining the HPV16 genome as an episome, NOKs+HPV16...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#6
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132393/interferon-%C3%AE-inducible-protein-16-ifi16-is-required-for-the-maintenance-of-epstein-barr-virus-latency
#7
Gina Pisano, Arunava Roy, Mairaj Ahmed Ansari, Binod Kumar, Leela Chikoti, Bala Chandran
BACKGROUND: Epstein-Barr virus (EBV) exhibits both lytic and latent (Lat. I, II, and III) phases in an infected individual. It's during the latent phase of EBV that all EBV-associated cancers, including Burkitt's lymphoma, nasopharyngeal carcinoma and lymphoproliferative disease arise. Interferon-γ-inducible protein 16 (IFI16) is a well-established innate immune sensor and viral transcriptional regulator involved in response to invading DNA viruses. During latency, IFI16 remains in the nucleus, in part bound to the EBV genome; however, neither its role in EBV lytic cycle or latency has been established...
November 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/29127120/primary-and-acquired-resistance-to-immune-checkpoint-inhibitors-in-metastatic-melanoma
#8
Tuba N Gide, James S Wilmott, Richard A Scolyer, Georgina V Long
Immune checkpoint inhibitors have revolutionized the treatment of advanced stage metastatic melanoma patients, as well as patients with many other solid cancers, yielding long lasting responses and improved survival. However, a subset of patients who initially respond to immunotherapy, later relapse and develop therapy resistance (termed acquired resistance), while others do not respond at all (termed primary resistance). Primary and acquired resistance are key clinical barriers to further improving outcomes of patients with metastatic melanoma and the known mechanisms underlying them involve various components of the cancer immune cycle, and interactions between multiple signalling molecules and pathways...
November 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29126306/the-future-of-radiobiology
#9
David G Kirsch, Max Diehn, Aparna H Kesarwala, Amit Maity, Meredith A Morgan, Julie K Schwarz, Robert Bristow, Sandra Demaria, Iris Eke, Robert J Griffin, Daphne Haas-Kogan, Geoff S Higgins, Alec C Kimmelman, Randall J Kimple, Isabelle M Lombaert, Li Ma, Brian Marples, Frank Pajonk, Catherine C Park, Dörthe Schaue, Eric J Bernhard
Innovation and progress in radiation oncology depend on discovery and insights realized through research in radiation biology. Radiobiology research has led to fundamental scientific insights, from the discovery of stem/progenitor cells to the definition of signal transduction pathways activated by ionizing radiation that are now recognized as integral to the DNA damage response (DDR). Radiobiological discoveries are guiding clinical trials that test radiation therapy combined with inhibitors of the DDR kinases DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and immune or cell cycle checkpoint inhibitors...
November 3, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29124478/the-role-of-rna-binding-protein-tristetraprolin-in-cancer-and-immunity
#10
REVIEW
Jian Guo, Huiheng Qu, Ye Chen, Jiazeng Xia
RNA-binding protein tristetraprolin (TTP) plays a fundamental role in various physiological and pathological processes including differentiation, reprogramming, metabolism, proliferation, pluripotency, tumorigenesis and immunity. Due to its ability to bind and target ARE-containing mRNAs for rapid degradation, TTP down-regulates the expression of a mass of critical genes, thereby functioning as cancer suppressor gene. The loss of TTP has been reported in several human cancers and is relevant to poor prognosis...
November 9, 2017: Medical Oncology
https://www.readbyqxmd.com/read/29123948/no-patient-left-behind-the-promise-of-immune-priming-with-epigenetic-agents
#11
REVIEW
Corey A Carter, Bryan T Oronsky, Joseph Roswarski, Arnold L Oronsky, Neil Oronsky, Jan Scicinski, Harry Lybeck, Michelle M Kim, Michelle Lybeck, Tony R Reid
Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as a component of an integrated strategy to boost anticancer T cell effector function in relation to a tumor immunosuppression cycle and, finally, makes the case that the success of this no-patient-left-behind strategy critically depends on the toxicity profile of the epigenetic agent(s)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29119048/elucidating-immunometabolic-targets-in-glioblastoma
#12
REVIEW
Pooja Agarwal, Michael J Pajor, David M Anson, Maheedhara R Guda, Collin M Labak, Andrew J Tsung, Kiran K Velpula
Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29118924/effects-of-targeted-cd97-immune-epitopes-small-interference-rna-on-cellular-biological-behaviors-in-mda-mb231-malignant-breast-cancer-cell-line
#13
Hua Tian, Yang Chen, Jian-Gang Zhao, Da-Ren Liu, Wei-Hua Gong, Li Chen, Yu-Lian Wu, Jian-An Wang
Two CD97 immune epitopes, CD97(EGF) (epidermal growth factor domain) and CD97(Stalk) (stalk domain), have different distribution patterns in malignant epidermal tumors. However, little is known about the effect of CD97(EGF) and CD97(Stalk) immune epitopes in breast cancer metastasis. To explore the effects on cell proliferation, infiltration, apoptosis, and the cell cycle, we used small interfering RNA (siRNA) against CD97(EGF) and CD97(Stalk) immune epitopes to knock down CD97 in MDA-MB231 breast cancer cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118756/th17-cell-and-epithelial-cell-crosstalk-during-inflammatory-bowel-disease-and-carcinogenesis
#14
REVIEW
Jan Kempski, Leonie Brockmann, Nicola Gagliani, Samuel Huber
The intestine is colonized by hundreds of different species of commensal bacteria, viruses, and fungi. Therefore, the intestinal immune system is constantly being challenged by foreign antigens. The immune system, the commensal microbiota, and the intestinal epithelial surface have to maintain a tight balance to guarantee defense against potential pathogens and to prevent chronic inflammatory conditions at the same time. Failure of these mechanisms can lead to a vicious cycle in which a perpetual tissue damage/repair process results in a pathological reorganization of the normal mucosal surface...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29113340/analgecine-enhances-the-anti-tumor-response-of-radiotherapy-by-increasing-apoptosis-and-cell-cycle-arrest-in-non-small-cell-lung-cancer
#15
Xue Chen, Xibing Zhuang, Qi Zhang, Youjun Luo, Sujuan Yuan, Tiankui Qiao
We investigated whether Analgecine treatment enhanced the antitumor response of radiotherapy in non-small cell lung cancer (NSCLC) cells. Lewis lung carcinoma (LLC) xenograft mice treated with Analgecine plus irradiation showed reduced tumor growth and increased survival. Tumor cell apoptosis was enhanced by Analgecine, based on TUNEL assays. It also increased plasma levels of pro-inflammatory cytokines (IL-6, IL-12, and IFN-γ) and decreased anti-inflammatory cytokines (TGFβ and IL-10), suggesting an enhanced immune response...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111351/chemoprevention-with-isothiocyanates-from-bench-to-bedside
#16
Carsten Gründemann, Roman Huber
Isothiocyanates (ITCs) are naturally occurring hydrolization products from glucosinolates (GLSs) in brassicaceae and in epidemiological studies their intake has been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity, c.) cyclin-mediated cell cycle arrest and d...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29108332/whether-low-dose-metronomic-oral-cyclophosphamide-improves-the-response-to-docetaxel-in-first-line-treatment-of-non-triple-negative-metastatic-breast-cancer
#17
Jian Zhang, Leiping Wang, Zhonghua Wang, Biyun Wang, Jun Cao, Fangfang Lv, Sheng Zhang, Zhimin Shao, Xichun Hu
Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. We initiated the single-center, randomized, open-label, phase II study to determine whether the addition of metronomic cyclophosphamide to docetaxel (T) (w/o trastuzumab) improves overall response rate (ORR) as first-line treatment among patients with non-triple-negative metastatic breast cancer (MBC). Eligible patients with previously untreated non-triple-negative MBC were randomly assigned (1:1) to receive 3-weekly cycles of Metro-TC (T 75mg/m(2), d1 plus oral cyclophosphamide 50 mg daily) or T alone...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29101066/regulation-and-biological-roles-of-the-multifaceted-mirna-23b-mir23b
#18
REVIEW
Wei Wang, Yuji Wang, Weijun Liu, Andre J van Wijnen
MicroRNAs (miRNAs) are important short endogenous non-coding RNAs that have critical biological roles by acting as post-transcriptional regulators of gene expression. Chromosomal region 9q22.32 encodes the miR-23b/27b/24-1 cluster and produces miR-23b, which is a pleiotropic modulator in many developmental processes and pathological conditions. Expression of miR-23b is actively suppressed and induced in response to many different stimuli. We discuss the biological functions and transcriptional regulation of this multifaceted miRNA in different tumor types, during development, upon viral infection, as well as in various clinical disorders, immune responses, as well as cardiovascular and thyroid functions...
October 31, 2017: Gene
https://www.readbyqxmd.com/read/29101064/development-of-a-highly-sensitive-in-vitro-system-to-detect-and-discriminate-between-vitamin-d-receptor-agonists-and-antagonists-based-on-split-luciferase-technique
#19
Hiroki Mano, Shinichi Ikushiro, Nozomi Saito, Atsushi Kittaka, Toshiyuki Sakaki
Split-luciferase techniques are widely used to detect protein-protein interaction and bioactive small molecules including some hormones and vitamins. Previously, we successfully expressed chimeric proteins of luciferase and the ligand binding domain (LBD) of the vitamin D receptor (VDR), LucC-LBD-LucN in COS-7 cells. The LucC-LBD-LucN biosensor was named split-luciferase vitamin D biosensor (SLDB). This biosensor can detect and discriminate between VDR agonists and antagonists in mammalian cells. In this study, we established an in vitro screening system for VDR ligands using the SLDB proteins expressed in Escherichia coli (E...
October 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29097422/intratumoral-cd8-t-cell-apoptosis-is-a-major-component-of-t-cell-dysfunction-and-impedes-anti-tumor-immunity
#20
Brendan L Horton, Jason B Williams, Alexandra Cabanov, Stefani Spranger, Thomas F Gajewski
Subsets of human tumors are infiltrated with tumor antigen-specific CD8(+) T cells (TILs) despite tumor progression. These TILs are thought to be inactivated by the immunosuppressive tumor microenvironment, through the engagement of inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific CD8+ TILs are not functionally inert, but are undergoing activation in situ. Here, we show that antigen-specific CD8(+) TIL are actively proliferating, yet also undergo high rates of apoptosis, leading to a vicious cycle of activation and death that limits immune efficacy...
November 2, 2017: Cancer Immunology Research
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