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Epigenetics immune response in cancer

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https://www.readbyqxmd.com/read/28324831/primary-and-acquired-resistance-to-pd-1-pd-l1-blockade-in-cancer-treatment
#1
REVIEW
Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous...
March 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#2
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314406/the-role-of-targeted-therapy-in-the-management-of-sinonasal-malignancies
#3
REVIEW
Lawrence Kashat, Christopher H Le, Alexander G Chiu
Cancers develop secondary to genetic and epigenetic changes that provide the cell with a survival advantage that promotes cellular immortality. Malignancy arises when tumors use mechanisms to evade detection and destruction by the immune system. Many malignancies seem to elicit an immune response, yet somehow manage to avoid destruction by the cells of the immune system. Cancers may evade this immune response by numerous mechanisms. Several targeted immune therapies are available that block some of these inhibitory signals and enhance the cell-mediated immune response...
April 2017: Otolaryngologic Clinics of North America
https://www.readbyqxmd.com/read/28220199/-novel-pharmaceutical-treatment-approaches-for-gastric-cancer
#4
F Lordick
This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging...
February 20, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#5
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#6
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28174608/genome-wide-dna-methylation-profile-identified-a-unique-set-of-differentially-methylated-immune-genes-in-oral-squamous-cell-carcinoma-patients-in-india
#7
Baidehi Basu, Joyeeta Chakraborty, Aditi Chandra, Atul Katarkar, Jadav Ritesh Kumar Baldevbhai, Debjit Dhar Chowdhury, Jay Gopal Ray, Keya Chaudhuri, Raghunath Chatterjee
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28154780/human-endogenous-retroviruses-and-cancer
#8
María Gonzalez-Cao, Paola Iduma, Niki Karachaliou, Mariacarmela Santarpia, Julià Blanco, Rafael Rosell
Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2)...
December 2016: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#9
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28124158/pathogenesis-of-gastric-cancer-genetics-and-molecular-classification
#10
Ceu Figueiredo, M Constanza Camargo, Marina Leite, Ezequiel M Fuentes-Pananá, Charles S Rabkin, José C Machado
Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance...
2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#11
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
March 2017: Cell Biology International
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#12
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28018344/adjunct-strategies-for-tuberculosis-vaccines-modulating-key-immune-cell-regulatory-mechanisms-to-potentiate-vaccination
#13
REVIEW
Lakshmi Jayashankar, Richard Hafner
Tuberculosis (TB) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. The only available licensed vaccine, Bacillus Calmette-Guérin, does not confer lifelong protection against active TB. To date, development of an effective vaccine against TB has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. Insights gained over the last several years have revealed multiple mechanisms of immune manipulation by Mycobacterium tuberculosis (Mtb) in infected macrophages and dendritic cells that support disease progression and block development of protective immunity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28000527/epigenetic-regulation-of-immune-checkpoints-another-target-for-cancer-immunotherapy
#14
Mahmoud A Ali, Marwa Matboli, Marwa Tarek, Maged Reda, Kamal M Kamal, Mahmoud Nouh, Ahmed M Ashry, Ahmed Fath El-Bab, Hend A Mesalam, Ayman El-Sayed Shafei, Omar Abdel-Rahman
Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27999745/microrna-155-deficiency-impairs-dendritic-cell-function-in-breast-cancer
#15
Junfeng Wang, Stephen Iwanowycz, Fang Yu, Xuemei Jia, Shuilong Leng, Yuzhen Wang, Wei Li, Shiang Huang, Walden Ai, Daping Fan
In antitumor immunity, dendritic cells (DCs) capture, process, and present tumor antigens to T cells, initiating a tumoricidal response. However, DCs are often dysfunctional due to their exposure to the tumor microenvironment (TME), leading to tumor escape from immune surveillance. Here, a vital role of microRNA-155 (miR-155) in regulating the function of DCs in breast cancer is reported. Host miR-155 deficiency enhanced breast cancer growth in mice, accompanied by reduced DCs in the tumors and draining lymph nodes...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27982729/differential-dna-methylation-and-pm2-5-species-in-a-450k-epigenome-wide-association-study
#16
Lingzhen Dai, Amar Mehta, Irina Mordukhovich, Allan C Just, Jincheng Shen, Lifang Hou, Petros Koutrakis, David Sparrow, Pantel S Vokonas, Andrea A Baccarelli, Joel D Schwartz
Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects...
February 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27923508/surfacing-role-of-probiotics-in-cancer-prophylaxis-and-therapy-a-systematic-review
#17
REVIEW
Subramanyam Dasari, Chandrasekhar Kathera, Avilala Janardhan, Arthala Praveen Kumar, Buddolla Viswanath
Cancers figure among the most important causes of morbidity and mortality worldwide. Cancer and its associated infections are always complicated even when specific cancer regimens are available. It is well proved that Lactobacillus and other probiotic bacteria can modulate-ameliorate specific mechanisms against various infections including cancers. The present systematic review is intended to focus on the 'cellular and molecular mechanisms' of probiotic bacteria in the prevention and treatment of various cancers...
November 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/27903713/-trained-immunity-consequences-for-lymphoid-malignancies
#18
REVIEW
Wendy B C Stevens, Mihai G Netea, Arnon P Kater, Walter J F M van der Velden
In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#19
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27887656/looking-beyond-the-cancer-cell-for-effective-drug-combinations
#20
Jonathan R Dry, Mi Yang, Julio Saez-Rodriguez
Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer's pervasive resistance to treatment. Research efforts to discover effective combination treatments have focused on drugs targeting intracellular processes of the cancer cells and in particular on small molecules that target aberrant kinases. Accordingly, most of the computational methods used to study, predict, and develop drug combinations concentrate on these modes of action and signaling processes within the cancer cell...
November 25, 2016: Genome Medicine
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