DNMT Inhibitors Increase Methylation in the Cancer Genome

In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-cancer therapy (Minkovsky et al., 2015; Ramos M.P. et al., 2015; Bohl et al., 2018). At present, two DNMTi drugs, decitabine and azacytidine, have been approved for treating patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) (Döhner et al., 2017; Bohl et al., 2018), and are also being tested as therapeutic options in multiple solid cancers (Fu et al., 2011; Singal et al., 2015; Lee et al., 2018). However, treatment response rates have remained very low in both solid and hematological cancers patients (Derissen et al., 2013; Nervi et al., 2015; Koch et al., 2018). At the same time, DNMTi treatment incurs considerable side effects (e.g., bleeding, anemia, and joint pain). Attempts are being made to improve treatment efficacy (e.g., by testing combinations of DNMTis with other anticancer agents) and safety (e.g., by stratifying can...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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This article reviews the role of iPSCs in regenerative medicine and examines the possibility of using phospholipids for quality control of iPSCs and differentiated cells. PMID: 31228130 [PubMed - as supplied by publisher]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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Source: Cellular and Molecular Biology Letters - Category: Biochemistry Authors: Tags: Cell Mol Biol Lett Source Type: research
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Source: Cellular and Molecular Biology Letters - Category: Biochemistry Authors: Tags: Cell Mol Biol Lett Source Type: research
Authors: Baer HR, Thomas SP, Pan Z, Tagawa A, Carollo J, Heyn PC Abstract PURPOSE: To understand the relationship of walking speed to self-reported pain, fatigue, and physical function in adults with CP. METHODS: Design: Cross-sectional study. SETTING: Accredited clinical motion analysis laboratory in a regional children's hospital. PARTICIPANTS: 72 ambulatory patients ⩾ 18 years of age, diagnosed with CP, who previously had ⩾ 1 prior instrumented gait analysis at our facility. MAIN OUTCOME MEASURES: PROMIS-57 pain interference/intensity, physical function, and fatigue measures and walking ...
Source: Journal of Pediatric Rehabilitation Medicine - Category: Rehabilitation Tags: J Pediatr Rehabil Med Source Type: research
Authors: Miceli M, Baldi D, Cavaliere C, Soricelli A, Salvatore M, Napoli C Abstract Introduction: Stem cells (ESC, iPSC, MSC) are known to have intrinsic regenerative properties. In the last decades numerous findings have favored the development of innovative therapeutic protocols based on the use of stem cells (Regenerative Medicine/Cell Therapy) for the treatment of numerous diseases including PAD, with promising results in preclinical studies. So far, several clinical studies have shown a general improvement of the patient's clinical outcome, however they possess many critical issues caused by the non-randomize...
Source: Expert Review of Cardiovascular Therapy - Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
Authors: Bewersdorf JP, Stahl M, Zeidan AM Abstract Key paper evaluation: Craddock C, et al. Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia. J Clin Oncol. 2019; 37: 580-8. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, most patients relapse after allo-HSCT and treatment options are limited. Craddock et al. reported recently in the Journal of Clinical Oncology results from a ...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Abstract A cluster of nine mesothelioma cases was observed among 341 registrants' deaths in the US Transuranium and Uranium Registries. Descriptive analysis showed that mesothelioma cases had the highest average cumulative external radiation dose compared with lung cancer, other cancer, and noncancer deaths. Further analysis indicated that the mesothelioma cluster was very different demographically from lung cancer, other cancer, and noncancer deaths. Therefore, an internally matched case-control approach was applied to evaluate the differences in an average cumulative external radiation dose between mesothelioma ...
Source: Health Physics - Category: Physics Authors: Tags: Health Phys Source Type: research
Authors: Banach M, Robert J Abstract Cancers impose a significant health and economic burden. By harnessing the immune system, current immunotherapies have revolutionized the treatment against human cancers and potentially offer a long-term cure. Among others, innate-like T (iT) cells, including natural killer T cells, are promising candidates for immunotherapies. Unlike conventional T cells, iT cells regulate multiple immune processes and express an invariant T cell receptor that is shared among different individuals. However, the conditions that activate the pro- and antitumor functions of iT cells are partially ...
Source: Immunological Investigations - Category: Allergy & Immunology Tags: Immunol Invest Source Type: research
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