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Epigenetics immune therapy cancer

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https://www.readbyqxmd.com/read/29771197/emerging-insights-into-wnt-%C3%AE-catenin-signaling-in-head-and-neck-cancer
#1
K A Alamoud, M A Kukuruzinska
Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits...
June 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29768164/epigenomic-guided-mass-cytometry-profiling-reveals-disease-specific-features-of-exhausted-cd8-t-cells
#2
Bertram Bengsch, Takuya Ohtani, Omar Khan, Manu Setty, Sasikanth Manne, Shaun O'Brien, Pier Federico Gherardini, Ramin Sedaghat Herati, Alexander C Huang, Kyong-Mi Chang, Evan W Newell, Niels Bovenschen, Dana Pe'er, Steven M Albelda, E John Wherry
Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29735917/cancer-immunotherapy-a-focus-on-the-regulation-of-immune-checkpoints
#3
REVIEW
Tao Shi, Yanyu Ma, Lingfeng Yu, Jiaxuan Jiang, Sunan Shen, Yayi Hou, Tingting Wang
In recent years, the role of cancer immunotherapy has become increasingly important compared to traditional cancer treatments, including surgery, chemotherapy and radiotherapy. Of note, the clinical successes of immune checkpoint blockade, such as PD-1 and CTLA-4, represent a landmark event in cancer immunotherapy development. Therefore, further exploration of how immune checkpoints are regulated in the tumor microenvironment will provide key insights into checkpoint blockade therapy. In this review, we discuss in details about the regulation of immune checkpoints mediated by immune cells, oncolytic viruses, epigenetics, and gut microbiota and mutual regulation by co-expressed checkpoints...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29732386/naturally-occurring-canine-invasive-urothelial-carcinoma-a-model-for-emerging-therapies
#4
REVIEW
Breann C Sommer, Deepika Dhawan, Timothy L Ratliff, Deborah W Knapp
The development of targeted therapies and the resurgence of immunotherapy offer enormous potential to dramatically improve the outlook for patients with invasive urothelial carcinoma (InvUC). Optimization of these therapies, however, is crucial as only a minority of patients achieve dramatic remission, and toxicities are common. With the complexities of the therapies, and the growing list of possible drug combinations to test, highly relevant animal models are needed to assess and select the most promising approaches to carry forward into human trials...
April 26, 2018: Bladder Cancer
https://www.readbyqxmd.com/read/29726727/epigenetic-therapy-and-dermatologic-disease-moving-beyond-ctcl
#5
Joshua S Mervis, Jean S McGee
The epigenetic regulation of gene expression is accomplished primarily through DNA methylation, histone modification, and gene silencing via the action of microRNAs. While previously very difficult to study, the field of epigenetics has been greatly facilitated by recent technological innovations. Alterations in the epigenome and epigenetic machinery are now known to be present in a variety of diseases, most notably cancers. Moreover, evidence has emerged that epigenetic dysregulation plays a causative role in disease pathogenesis...
May 4, 2018: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/29695769/suppression-of-tgf%C3%AE-mediated-conversion-of-endothelial-cells-and-fibroblasts-into-cancer-associated-myo-fibroblasts-via-hdac-inhibition
#6
Dae Joong Kim, James M Dunleavey, Lin Xiao, David W Ollila, Melissa A Troester, Carol A Otey, Wei Li, Thomas H Barker, Andrew C Dudley
BACKGROUND: Cancer-associated fibroblasts (CAFs) support tumour progression and invasion, and they secrete abundant extracellular matrix (ECM) that may shield tumour cells from immune checkpoint or kinase inhibitors. Targeting CAFs using drugs that revert their differentiation, or inhibit their tumour-supportive functions, has been considered as an anti-cancer strategy. METHODS: We have used human and murine cell culture models, atomic force microscopy (AFM), microarray analyses, CAF/tumour cell spheroid co-cultures and transgenic fibroblast reporter mice to study how targeting HDACs using small molecule inhibitors or siRNAs re-directs CAF differentiation and function in vitro and in vivo...
April 26, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29666625/dying-to-be-noticed-epigenetic-regulation-of-immunogenic-cell-death-for-cancer-immunotherapy
#7
REVIEW
Brianne Cruickshank, Michael Giacomantonio, Paola Marcato, Sherri McFarland, Jonathan Pol, Shashi Gujar
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various "hallmarks" of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29625794/the-role-of-epigenetic-therapies-in-colorectal-cancer
#8
REVIEW
Marina Baretti, Nilofer Saba Azad
Although developments in the diagnosis and therapy of colorectal cancer (CRC) have been made in the last decade, much work remains to be done as it remains the second leading cause of cancer death. It is now well established that epigenetic events, together with genetic alterations, are key events in initiation and progression of CRC. Epigenetics refers to heritable alterations in gene expression that do not involve changes in the DNA sequence. These alterations include DNA methylation, histone alterations, chromatin remodelers, and noncoding RNAs...
March 12, 2018: Current Problems in Cancer
https://www.readbyqxmd.com/read/29625051/machine-learning-identifies-stemness-features-associated-with-oncogenic-dedifferentiation
#9
Tathiane M Malta, Artem Sokolov, Andrew J Gentles, Tomasz Burzykowski, Laila Poisson, John N Weinstein, Bożena Kamińska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwińska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, Alex Krasnitz, Andrew K Godwin, Alexander J Lazar, Joshua M Stuart, Katherine A Hoadley, Peter W Laird, Houtan Noushmehr, Maciej Wiznerowicz
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state...
April 5, 2018: Cell
https://www.readbyqxmd.com/read/29575112/the-what-when-and-why-of-human-prostate-cancer-xenografts
#10
REVIEW
W Nathaniel Brennen, John T Isaacs
BACKGROUND: Presently, ∼85 serially transplantable human prostate cancer xenografts spanning the phenotypic, epigenetic, and genetic heterogeneity seen clinically are available in a variety of laboratories throughout the world. If distributed to the prostate cancer research community, these can provide an experimental platform for resolving the specificity versus generalizability of basic cancer biology principles (eg, credentialing of therapeutic molecular targets) and for validating translational approaches for prevention, diagnosis, and therapy...
March 24, 2018: Prostate
https://www.readbyqxmd.com/read/29562193/combination-cancer-therapy-with-immune-checkpoint-blockade-mechanisms-and-strategies
#11
REVIEW
Shetal A Patel, Andy J Minn
The success of immune checkpoint blockade in patients with a wide variety of malignancies has changed the treatment paradigm in oncology. However, combination therapies with immune checkpoint blockade will be needed to overcome resistance and broaden the clinical utility of immunotherapy. Here we discuss a framework for rationally designing combination therapy strategies based on enhancing major discriminatory functions of the immune system that are corrupted by cancer-namely, antigenicity, adjuvanticity, and homeostatic feedback inhibition...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29556394/epigenetic-regulation-of-cancer-progression-by-ezh2-from-biological-insights-to-therapeutic-potential
#12
REVIEW
Lu Gan, Yanan Yang, Qian Li, Yi Feng, Tianshu Liu, Weijian Guo
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells...
2018: Biomarker Research
https://www.readbyqxmd.com/read/29551125/leveraging-epigenetics-to-enhance-the-cellular-response-to-chemotherapies-and-improve-tumor-immunogenicity
#13
Liliya Tyutyunyk-Massey, Syed U Haqqani, Reshma Mandava, Kirubel Kentiba, Mallika Dammalapati, Nga Dao, Joshua Haueis, David Gewirtz, Joseph W Landry
Cancer chemotherapeutic drugs have greatly advanced our ability to successfully treat a variety of human malignancies. The different forms of stress produced by these agents in cancer cells result in both cell autonomous and cell nonautonomous effects. Desirable cell autonomous effects include reduced proliferative potential, cellular senescence, and cell death. More recently recognized cell nonautonomous effects, usually in the form of stimulating an antitumor immune response, have significant roles in therapeutic efficiency for a select number of chemotherapies...
2018: Advances in Cancer Research
https://www.readbyqxmd.com/read/29540357/pulmonary-arterial-hypertension-pathogenesis-and-clinical-management
#14
REVIEW
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/29535070/hdac-inhibitors-as-epigenetic-regulators-for-cancer-immunotherapy
#15
REVIEW
Mariarosaria Conte, Raffaele De Palma, Lucia Altucci
In recent years, anti-tumor immunotherapy has shown promising results, and immune-oncology is now emerging as the fourth major wave in the treatment of tumors after radiotherapy, chemotherapy and molecular targeted therapy. Understanding the impact of the immune system on neoplastic cells is crucial to improve its effectiveness against cancer. The stratification of patients who might benefit from immunotherapy as well as the personalization of medicine have contributed to the discovery of new immunotherapeutic targets and molecules...
March 10, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29503796/epigenetic-therapeutics-and-their-impact-in-immunotherapy-of-lung-cancer
#16
Ju Hwan Cho, Filiz Oezkan, Michael Koenig, Gregory A Otterson, James Gordon Herman, Kai He
Lung cancer is the leading cause of cancer-related death in the United States and worldwide. Novel therapeutic developments are critically necessary to improve outcomes for this disease. Aberrant epigenetic change plays an important role in lung cancer development and progression. Therefore, drugs targeting the epigenome are being investigated in the treatment of lung cancer. Monotherapy of epigenetic therapeutics such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) have so far not shown any apparent benefit while one of the clinical trials with the combinations of DNMTi and HDACi showed a small positive signal for treating lung cancer...
December 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/29487129/biomarkers-of-platinum-resistance-in-ovarian-cancer-what-can-we-use-to-improve-treatment
#17
REVIEW
Belinda van Zyl, Denise Tang, Nikola A Bowden
Ovarian cancer has poor survival rates due to a combination of diagnosis at advanced disease stages and disease recurrence as a result of platinum chemotherapy resistance. High-grade serous ovarian cancer (HGSOC), the most common ovarian cancer subtype, is conventionally treated with surgery and paclitaxel/carboplatin combination chemotherapy. Initial response rates are 60-80%, but eventually the majority of patients become platinum-resistant with subsequent relapses. Extensive research on individual biomarkers of platinum resistance has revealed many potential targets for the development new treatments...
May 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29486673/cellular-plasticity-targeted-therapy-in-head-and-neck-cancers
#18
W Shang, Q Zhang, Y Huang, R Shanti, F Alawi, A Le, C Jiang
Head and neck cancer is one of the most frequent human malignancies worldwide, with a high rate of recurrence and metastasis. Head and neck squamous cell carcinoma (HNSCC) is cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like properties, called cancer stem cells (CSCs). Epithelial-mesenchymal transition, gene mutation, and epigenetic modification are associated with the formation of cellular plasticity of tumor cells in HNSCC, contributing to the acquisition of invasive, recurrent, and metastatic properties and therapeutic resistance...
February 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29471827/nuclear-functions-of-mammalian-micrornas-in-gene-regulation-immunity-and-cancer
#19
REVIEW
Hongyu Liu, Cheng Lei, Qin He, Zou Pan, Desheng Xiao, Yongguang Tao
MicroRNAs (miRNAs) are endogenous non-coding RNAs that contain approximately 22 nucleotides. They serve as key regulators in various biological processes and their dysregulation is implicated in many diseases including cancer and autoimmune disorders. It has been well established that the maturation of miRNAs occurs in the cytoplasm and miRNAs exert post-transcriptional gene silencing (PTGS) via RNA-induced silencing complex (RISC) pathway in the cytoplasm. However, numerous studies reaffirm the existence of mature miRNA in the nucleus, and nucleus-cytoplasm transport mechanism has also been illustrated...
February 22, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29445380/the-role-of-indoleamine-2-3-dioxygenase-in-cancer-development-diagnostics-and-therapy
#20
REVIEW
Lilla Hornyák, Nikoletta Dobos, Gábor Koncz, Zsolt Karányi, Dénes Páll, Zoltán Szabó, Gábor Halmos, Lóránt Székvölgyi
Tumors are composed of abnormally transformed cell types and tissues that differ from normal tissues in their genetic and epigenetic makeup, metabolism, and immunology. Molecular compounds that modulate the immune response against neoplasms offer promising new strategies to combat cancer. Inhibitors targeting the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent therapeutic opportunities to inhibit tumor growth. Herein, we assess the biochemical role of IDO1 in tumor metabolism and immune surveillance, and review current diagnostic and therapeutic approaches that are intended to increase the effectiveness of immunotherapies against highly aggressive and difficult-to-treat IDO-expressing cancers...
2018: Frontiers in Immunology
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