Результаты поиска

Ремонт тканей в центральной нервной системе: эпигенетическое программирование регуляторных Т клеток.

Регулирующие Т клетки хорошо известны своей иммуномодуляционной ролью, но также их регенеративная функция все чаще признается в различных типах тканей, включая скелетные мышцы, легкие и центральную нервную систему (ЦНС). В CNS Tregs, как было показано, поощряют дифференциацию олигодендроцитов в прекурсорных клетках, и их взаимодействие с микроглией поддерживает стимулирующую регенеративную микроокружную среду в мозгу. Подавляющая функция Tregs в значительной степени зависит от эпигенетической сигнатуры, в частности метилации ДНК, определенной сети связанных с Treg генов, включая FOXP3, CTLA4,

Совпадение в полном тексте источника
… In addition to passive DNA demethylation accompanying cell division, DNA demethylation can also be catalyzed by a family of enzymes called ten-eleven translocation (TET), specifically TET1, TET2, and TET3. … This region is primarily regulated by DNA demethylation, which is necessary for stable Foxp3 expression and Treg suppressive function ( 57 ). …

Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.

Epigenetic regulation is a fundamental mechanism controlling gene expression and cellular function, primarily mediated through reversible modifications such as DNA methylation, histone acetylation, and chromatin remodeling. Dysregulation of critical epigenetic enzymes, including histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and bromodomain and extraterminal domain (BET) proteins, has been closely associated with tumor initiation, progression, metastasis, immune evasion, and resistance to conventional therapies. Targeting these epigenetic regulators with small-molecule inhibitor

Совпадение в полном тексте источника
… Once incorporated, they trap DNMT enzymes in covalent adducts, leading to enzyme degradation and passive DNA demethylation during subsequent cell divisions. … However, the specific mechanism by which it induces DNA demethylation and the association between DNA demethylation and apoptosis remain unclear. …

Control of Breast Cancer Pathogenesis by Histone Methylation and the Hairless Histone Demethylase.

Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors, and prognoses. Although traditionally seen as a genetic disease, breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as DNA methyltransferases and histone-modifying enzymes, play essential roles in gene regulation and cancer development. Dysregulation of epigenetic regulator activity has been causally linked with breast cancer pathogenesis. Hairless (HR) encodes a 130-kDa transcription factor that is essential for development and tissue

Oncogenic Roles and Inhibitors of DNMT1, DNMT3A, and DNMT3B in Acute Myeloid Leukaemia.

Epigenetic alteration has been proposed to give rise to numerous classic hallmarks of cancer. Impaired DNA methylation plays a central role in the onset and progression of several types of malignancies, and DNA methylation is mediated by DNA methyltransferases (DNMTs) consisting of DNMT1, DNMT3A, and DNMT3B. DNMTs are frequently implicated in the pathogenesis and aggressiveness of acute myeloid leukaemia (AML) patients. In this review, we describe and discuss the oncogenic roles of DNMT1, DNMT3A, and DNMT3B in AML. The clinical response predictive roles of DNMTs in clinical trials utilising hy

Совпадение в полном тексте источника
… Furthermore, a phase I/II trial of adult R/R AML patients (n = 122) receiving guadecitabine showed that global DNA demethylation was strongly associated with clinical response, and DNMT3B (but not DNMT1 and DNMT3A ) expression contributed >5% in predicting clinical response. … Discovery and characterization of Isofistularin-3, a marine brominated alkaloid, as a new DNA demethylating agent inducing cell cycle arrest and sensitization to TRAIL in cancer cells. Oncotarget. 2016;7:24027–24049. 119. Joshi M, Rajpathak SN, Narwade SC, Deobagkar D. …

Fetal hemoglobin induction during decitabine treatment of elderly patients with high-risk myelodysplastic syndrome or acute myeloid leukemia: a potential dynamic biomarker of outcome.

Hematologic responses to hypomethylating agents are often delayed in patients with myelodysplastic syndrome or acute myeloid leukemia. Fetal hemoglobin is a potential novel bio-marker of response: recently, we demonstrated that a high fetal hemoglobin level prior to decitabine treatment was associated with superior outcome. Here we investigated whether early fetal hemoglobin induction during decitabine treatment also had prognostic value, and studied the potential of decitabine to induce erythroid differentiation and fetal hemoglobin expression in vitro Fetal hemoglobin levels were measured by

Chidamide in Combination With DCAG With or Without Venetoclax for Relapsed/Refractory Acute Myeloid Leukemia.

INTRODUCTION: Currently, there are only a few avaailable treatment options for patients with relapsed and refractory acute myeloid leukemia (R/R AML). METHODS: We conducted a single-center, phase 1 prospective study (ChiCTR2200065634) to evaluate the efficacy and safety of chidamide, demethylating drugs (azacitidine), cytarabine, aclacinomycin, and G-CSF plus venetoclax (CDCAG-VEN) in patients with R/R AML. The previous CDCAG regimen was used as a historical control to compare its efficacy and safety. Thirty and 22 patients received one course of CDCAG with or without a 14-day course of venet

The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BackgroundTumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response.AimsThis review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy.MethodsWe analyzed publications and outlined a comprehensive of overview the re

Совпадение в полном тексте источника
… In conclusion, the expression of CTA gene in ovarian cancer largely depends on abnormal DNA demethylation. Histone modification The posttranscriptional modification of histones is one of the important epigenetic regulatory mechanisms. … Similarly, DNA demethylation and histone acetylation promote the expression of the multiple subtypes of the BORIS family in ovarian cancer cells, 18 indicating that histone modification and DNA methylation can synergically regulate the expression of CTA genes in ovarian cancer. …

Epigenetic Modifiers as Novel Therapeutic Targets and a Systematic Review of Clinical Studies Investigating Epigenetic Inhibitors in Head and Neck Cancer.

The survival rate of head and neck squamous cell carcinoma patients with the current standard of care therapy is suboptimal and is associated with long-term side effects. Novel therapeutics that will improve survival rates while minimizing treatment-related side effects are the focus of active investigation. Epigenetic modifications have been recognized as potential therapeutic targets in various cancer types, including head and neck cancer. This review summarizes the current knowledge on the function of important epigenetic modifiers in head and neck cancer, their clinical implications and di

Совпадение в полном тексте источника
… The role of DNA demethylation through azacytidine has also been investigated in HPV-positive HNSCC [ 15 ]. Azacytidine induced growth inhibition and cell death, reduced the expression of HPV genes, stabilized p53 and induced p53 dependent apoptosis in HPV-positive HNSCC cells. … Currently, there are no biomarkers that have been developed to predict responses to DNA-demethylating agents or histone deacetylase inhibitors. …

H3 histone methylation landscape in male urogenital cancers: from molecular mechanisms to epigenetic biomarkers and therapeutic targets.

During the last decades, male urogenital cancers (including prostate, renal, bladder and testicular cancers) have become one of the most frequently encountered malignancies affecting all ages. While their great variety has promoted the development of various diagnosis, treatment and monitoring strategies, some aspects such as the common involvement of epigenetic mechanisms are still not elucidated. Epigenetic processes have come into the spotlight in the past years as important players in the initiation and progression of tumors, leading to a plethora of studies highlighting their potential as

Histone modifications across cancers: mechanisms, therapy and clinical translation.

Cancer continues to be a major cause of death across the globe, and epigenetic dysregulation, including histone modifications, has been recognized as a major hallmark of cancer development, heterogeneity, and drug resistance. This review seeks to offer an overview of histone modifications in cancer, including the more studied histone modifications such as acetylation and methylation, as well as the less explored histone modifications such as phosphorylation, ubiquitination, and glycosylation. It also examines the role of histone modifications in the dysregulation of the three categories of enz

Совпадение в полном тексте источника
… These agents operate via different mechanisms: DNMT inhibitors integrate into DNA and covalently sequester DNMT enzymes, resulting in DNA demethylation and the reactivation of silenced tumor suppressor genes, whereas HDAC inhibitors impede the removal of acetyl groups, fostering a more accessible chromatin … demethylation and gene re-expression FDA Approved for MDS, AML, CMML, JMML Improved overall survival in MDS and AML; hypomethylating activity Toxicity (myelosuppression); chemical instability; limited efficacy in solid tumors [ 98 ] HDAC Inhibitors (HDACi) Vorinostat, Romidepsin, Panobinostat Block …

The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.

Cancer development and progression are increasingly understood to arise from dynamic interactions between genetic alterations and environmentally driven epigenetic regulation, with dietary exposures representing one of the most biologically influential and modifiable factors. Given the expanding evidence linking nutrition to epigenomic remodeling, a comprehensive synthesis of how specific dietary components influence cancer-relevant epigenetic mechanisms is needed to clarify their preventive and therapeutic relevance. This review brings together mechanistic, epidemiologic, and translational fi

Совпадение в полном тексте источника
… These enzymes are key contributors to DNA demethylation, particularly in hematological malignancies. … These changes are further reinforced by altered Polycomb protein activity and impaired chromatin-remodeling and DNA demethylation pathways, particularly involving SWI/SNF and TET. …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

Совпадение в полном тексте источника
… Regarding delivery systems, progress requires engineering bacterial outer membrane vesicles (OMVs) for CRISPR-Cas9 332 , 333 mediated site-specific DNA demethylation alongside developing soluble ligand-modified lipid nanoparticles 334 , 335 that optimize pharmacokinetic and pharmacodynamic profiles to … DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell. 2015;162:961–973. doi: 10.1016/j.cell.2015.07.056. 34. Maes K., De Smedt E., Lemaire M., De Raeve H., Menu E., Van Valckenborgh E., et al. …

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

Совпадение в полном тексте источника
… TET dioxygenase and thymine DNA glycosylase mediate DNA demethylation and may also contribute to oncogenic progression [ 24 , 25 ]. … LSD inhibitors are capable of inducing global DNA demethylation or inhibiting LSD1-driven H3K4me2 and H3K4me1 demethylation to establish active chromatin structures [ 259 ]. …

Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate

Совпадение в полном тексте источника
… However, this effect of DNA demethylating agents, although capable of restoring genes silenced in cancer is not specific, and may result in the aberrant expression of many non-epithelial genes, affecting positively EMT progression and tumor metastasis [ 169 ]. 6.4. … TET enzymes, TDG and the dynamics of DNA demethylation Nature 2013 502 472 479 10.1038/nature12750 24153300 PMC4046508 53. Kim V.N. Han J. Siomi M.C. Biogenesis of small RNAs in animals Nat. Rev. Mol. Cell Biol. 2009 10 126 139 10.1038/nrm2632 19165215 54. Park S.-M. Gaur A.B. Lengyel E. …

Диабетическая иммунотерапия Адаптация с BCG: Metabolic and Immune Reprogramming.

В настоящем обзоре клеточные и молекулярные механизмы, лежащие в основе мультидозы Bacille Calmette-Guérin (BCG), характеризуются как лечебная иммунная терапия для улучшения глицемии аутоиммунного диабета. Данные BCG чаще всего представляют собой данные клинических испытаний человека за последние годы. 15 годы в паре с механистическими представлениями. БЦЖ как вакцина имеет отличный послужной список в плане безопасности, который за сто лет был достигнут в области профилактики туберкулеза во всем мире, и за 36 Годы, были утверждены УЛХ при более высоких дозах для лечения рака мочевого пузыря. Н

Совпадение в полном тексте источника
… As early as week 8 after BCG exposure, dozens of CpG sites within these genes exhibited significant DNA demethylation compared with baseline. … Because DNA demethylation is expected to increase gene transcription, the study found upregulated mRNA expression of the same Treg signature genes, as measured by mRNAseq [ 28 ]. …

Epigenetic therapy: use of agents targeting deacetylation and methylation in cancer management.

The emergence of epigenetic mechanisms as key regulators of gene expression has led to dramatic advances in understanding cancer biology. Driven by complex layers that include aberrant DNA methylation and histone modification, epigenetic aberrations have emerged as critical processes that disrupt cellular machinery and homeostasis. Recent discoveries have already translated into successful clinical trials and improved patient care, with several agents approved for hematologic disease and others undergoing study. As the field matures, substantial challenges persist that will require resolution.

Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to

Совпадение в полном тексте источника
… Epigenetic drugs, such as DNA demethylating agents and histone deacetylase inhibitors, have shown potential in reversing aberrant epigenetic states, thereby inhibiting cancer progression and metastasis [ 18 ]. However, challenges remain in translating these therapies into clinical settings. … Similarly, the orphan nuclear receptor NR2F1 is epigenetically upregulated in dormancy models across various cancer types, connecting retinoic acid signaling and DNA demethylation to the initiation and sustenance of dormancy [ 152 ]. …

Hypomethylating Chemotherapeutic Agents as Therapy for Myelodysplastic Syndromes and Prevention of Acute Myeloid Leukemia.

Myelodysplastic Syndromes (MDSs) affect the elderly and can progress to Acute Myeloid Leukemia (AML). Epigenetic alterations including DNA methylation and chromatin modification may contribute to the initiation and progression of these malignancies. DNA hypomethylating agents such as decitabine and azacitidine are used as therapeutic treatments and have shown to promote expression of genes involved in tumor suppression, apoptosis, and immune response. Another anti-cancer drug, the proteasome inhibitor bortezomib, is used as a chemotherapeutic treatment for multiple myeloma (MM). Phase III clin

Совпадение в полном тексте источника
… One of the initial studies found decitabine and azacytidine, another cytidine-analog, to induced gene expression via DNA demethylation ( Figure 1 A–C) [ 16 ]. … In vitro experiments demonstrated that continuous drug exposure resulted in a subsequent increase in DNA demethylation and reactivation of silenced genes. …

Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations.

Vitamin C is an antioxidant that may scavenge reactive oxygen species preventing DNA damage and other effects important in cancer transformation. Dietary vitamin C from natural sources is taken with other compounds affecting its bioavailability and biological effects. High pharmacological doses of vitamin C may induce prooxidant effects, detrimental for cancer cells. An oxidized form of vitamin C, dehydroascorbate, is transported through glucose transporters, and cancer cells switch from oxidative phosphorylation to glycolysis in energy production so an excess of vitamin C may limit glucose tr

Совпадение в полном тексте источника
… TETs are involved in active DNA demethylation that is achieved through TET2-mediated oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). … Ascorbic acid enhances Tet-mediated 5-methylcytosine oxidation and promotes DNA demethylation in mammals. Journal of the American Chemical Society. 2013;135(28):10396–10403. doi: 10.1021/ja4028346. 111. Hore T. A., von Meyenn F., Ravichandran M., et al. …

Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.

Cancer immunotherapy is a groundbreaking therapeutic strategy, yet it continues to face significant challenges, including limited overall response rates and treatment resistance. Emerging research has demonstrated the pivotal role of epigenetic modifications in tumor immune evasion, providing a strong rationale for developing "epi-immunotherapy"-an innovative approach that combines epigenetic therapy with immunotherapy. This comprehensive review systematically examines how epigenetic regulation mediates tumor immune escape and the mechanisms involved, including suppression of tumor antigen exp

Совпадение в полном тексте источника
… TET methylcytosine dioxygenases, particularly TET2 and TET3, play essential roles in maintaining Treg functional stability and immune homeostasis through their DNA demethylation activity [ 57 ]. The histone methyltransferase, EZH2, is another critical epigenetic regulator in Treg biology. … Xue F., Liu L., Tao X., and Zhu W., “TET 3 ‐Mediated DNA Demethylation Modification Activates Shp 2 Expression to Promote Endometrial Cancer Progression Through the EGFR/ERK Pathway,” Journal of Gynecologic Oncology 35, no. 5 (2024): e64, 10.3802/jgo.2024.35.e64. 13. Brückmann N. H., Pedersen C. …