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Management of Myeloproliferative Neoplasms: An Integrative Approach.

Myeloproliferative neoplasms (MPNs) are chronic blood cancers characterized by overproduction of blood cells, leading to increased thrombotic and ischemic risk. Patients frequently experience symptoms including fatigue, abdominal discomfort, and complications from thrombotic events, which significantly impact the quality of life (QoL). Many patients inquire about complementary and integrative medicine (CIM) approaches, including nutritional interventions and supplements, creating opportunities for healthcare providers to engage in meaningful discussions guided by the principle of safety. This

Идентификация и каталог регуляторов вирусной транскрипции заболеваний человека.

Вирусные геномы кодируют регуляторы вирусной транскрипции (vTRs), которые манипулируют экспрессией гена хоста, чтобы облегчить воспроизведение и избежать иммунной обнаружения. Тем не менее их роль в нераковых болезнях по-прежнему в значительной степени недооценивается. Здесь мы представили 268 новых кандидатов в VTR из 14 из 20 вирусных семей, которые мы расследовали. Мы картировали связующие профили генома VTR и определили их потенциальные цели человека, которые были обогащены иммунно-посредованными путями, нейродегенеративными расстройствами и раком. На основе анализа предпочтений VTR, имеющ

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidan

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… Epigenomics of Leukemia: From Mechanisms to Therapeutic Applications. Epigenomics (2011) 3:581–609. doi: 10.2217/epi.11.73 87. Abaza Y, Kantarjian H, Alwash Y, Borthakur G, Champlin R, Kadia T, et al. …

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

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… The mammalian epigenome . Cell. 2007 ; 128 ( 4 ): 669 - 681 . 17320505 10.1016/j.cell.2007.01.033 24. Chi P , Allis CD , Wang GG . Covalent histone modifications—miswritten, misinterpreted and mis-erased in human cancers . … Epigenomics. 2012 ; 4 ( 6 ): 675 - 683 . 23244312 10.2217/epi.12.64 140. Liu L , Kimball S , Liu H , Holowatyj A , Yang ZQ . Genetic alterations of histone lysine methyltransferases and their significance in breast cancer . …

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.

Multiple sclerosis (MS) is an immune-mediated central nervous system disease with mapped genetic risk loci but unresolved cross-layer regulatory mechanisms. We harmonised 30 primary public MS datasets spanning bulk transcriptomics (552 samples, 367 MS/185 healthy control [HC]), DNA methylation arrays (475 samples, 244 MS/231 HC) with sorted-cell whole-genome bisulfite sequencing (WGBS) assessment, single-cell RNA sequencing (RNA-seq; 517,533 cells from 81 donors), and cerebrospinal fluid (CSF) and brain white-matter proteomes, and UK Biobank Pharma Proteomics Project (UK Biobank-PPP) plasma pr

Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders.

Within the context of precision medicine, the scientific community is giving particular attention to early diagnosis and intervention, guided by non-invasive methodologies. Liquid biopsy (LBx) is a recent laboratory approach consisting of a non-invasive blood draw, which allows the detection of information about potential prognostic factors, or markers to be used for diagnostic purposes; it might also allow the clinician to establish a treatment regimen and predict a patient's response. Since the discovery of circulating tumor cells (CTCs) in the nineteenth century, the possibility of integrat

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… Epigenomics | Genetic tests NOS | NCT04264767 | Characterization of Methylation Patterns in Cancer and Non-Cancer cfDNA | Characterization of methylation patterns that will discriminate cancer and normal samples and the origin of cancer. ctDNA | Genetic tests NOS | NCT01772771 | Molecular Testing for … Epigenomics. 2019;11:35–51. doi: 10.2217/epi-2018-0123. 202. Wu R., Guo S., Cai J., Huang X., Yang J., Wery J.-P., Li H.Q.-x. Biomarker Predictive Ibrutinib Response Using Profiled ABC-DLBCL Patient Derived Xenografts. Blood. 2015;126:2759. doi: 10.1182/blood.V126.23.2759.2759. 203. …

Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.

Among the well-established alterations contributing to prostate cancer (PCa) pathogenesis, epigenetics is an important player in its development and aggressive disease state. Moreover, since no curative therapies are available for advanced stage disease, there is an urgent need for novel therapeutic strategies targeting this subset of patients. Thus, we aimed to evaluate the combined antineoplastic effects of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid in several prostate cell lines. The effect of these drugs was assessed in four PCa

Exploiting artificial intelligence in precision oncology: an updated comprehensive review.

Precision oncology considers the genetic makeup of both the tumor and the cancer patient, medical history, clinical metadata, lifestyle and environmental factors. Thus, adoption of precision cancer medicine mandates sophisticated integrative analysis. Being a master in sorting and solving the puzzle pieces, artificial intelligence (AI)-powered frameworks emerged to fill the gap via executing multimodal analysis and generating meaningful outputs. Herein, we systematically discussed the opportunities and challenges of exploiting AI-assisted models in preclinical cancer research and in clinical o

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… AI-driven algorithms have been integrated into NGS technologies including genomics, epigenomics, variant calling, transcriptomics, proteomics and single-cell sequencing [ 9 ]. … Tcgar N Genomic and epigenomic landscapes of adult De novo acute myeloid leukemia N Engl J Med 2013 368 2059 74 10.1056/NEJMoa1301689 23634996 PMC3767041 Tcgar N. Genomic and epigenomic landscapes of adult De novo acute myeloid leukemia. …

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.

The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by reg

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

Cytotoxicity of bendamustine, alone and in combination with novel agents, toward adult T-cell leukemia cells.

Adult T-cell leukemia/lymphoma (ATL) develops from the infection of T cells with human T lymphotropic virus type 1 (HTLV-1). There are an estimated 5-20 million HTLV-1 carriers worldwide and the patients are frequently observed in subtropical Africa, the Caribbean, Middle East, South America, and South West Japan. The prognosis of ATL remains dismal due to rapid acquired resistance to treatment with cytotoxic chemotherapeutic agents. In particular, the development of novel therapies for relapsed or refractory (R/R) ATL is an unmet need. Previous clinical trials revealed that bendamustine (BDM)

Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.

Second primary cancers (SPCs) pose an increasingly significant clinical challenge for survivors of hematologic malignancies, attributed to improved therapeutic outcomes and prolonged survival. The development of SPCs is influenced by a complex interplay of treatment-related factors, genetic susceptibility, immune dysregulation, and microenvironmental remodeling. This narrative review summarizes the epidemiological patterns of SPCs in survivors of hematologic malignancies and discusses the underlying biological mechanisms, including therapy-induced genomic instability, clonal hematopoiesis, inf

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… modalities. 103 , 120 , 121 While ctDNA assays are well established in solid tumors, their utility in detecting molecular residual disease and early relapse in survivors of hematologic malignancies remains an active area of research. 121 , 122 Recent advances in multi-omics technologies-including genomics, epigenomics … The ageing epigenome and its rejuvenation . Nat Rev Mol Cell Bio . 2020 ; 21 ( 3 ): 137 – 150 . doi: 10.1038/s41580-019-0204-5 . 32020082 119. Duffy MJ , Crown J . Circulating tumor DNA as a biomarker for monitoring patients with solid cancers: comparison with standard protein biomarkers . …

Venous thromboembolism in China: epidemiology, management strategies, and future directions.

Venous thromboembolism (VTE) is one of the leading causes of unexpected death among hospitalized patients. It is also a preventable condition, and its incidence can be substantially reduced through active and effective prophylaxis. In recent years, the burden of VTE in China has continued to increase, driven by population aging, a rising prevalence of malignancy, a growing volume of complex surgery, and advances in imaging and laboratory testing. At present, the clinical management paradigm for VTE in China has gradually evolved from the traditional acute event-centered 'diagnosis-treatment' p

Одиссей моноколональных гаммопатий: сосредоточен на прекурсорах и переходе от MGUS и SMM к нескольким Myeloma, с кратким обзором новых терапевтических стратегий.

Моноклональные гаммопатии охватывают континуум от моноклональной гаммопатии неопределенного значения (MMUS) и заморозки нескольких миелом (SMM) до открытой множественной миеломы (MM). Эта постепенная клональная эволюция обусловлена первичными цитогенетическими повреждениями, вторичными геномными явлениями и эпигенетической реконструкцией в допустимой микроокружающей среде костного мозга. Традиционные биомаркеры (коэффициенты сыворотки М-протеина и свободных световых цепей) обеспечивают полезную, но неполную прогнозную информацию, поскольку они не отражают пространственной неоднородности или вр

HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease.

Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cell

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… Future research should focus on cell-type-specific epigenomic profiling, development of isoform-selective HDACi, and integration of environmental epigenetics to uncover novel therapeutic avenues and improve disease-modifying strategies in neurodegeneration. 6. … Unlocking the epigenetic symphony: Histone acetylation’s impact on neurobehavioral change in neurodegenerative disorders Epigenomics 2024 16 331 358 10.2217/epi-2023-0428 38321930 PMC10910622 94. Yeh H.H. Young D. Gelovani J.G. Robinson A. Davidson Y. Herholz K. Mann D.M. …

Combination therapy with novel agents for acute myeloid leukaemia: Insights into treatment of a heterogenous disease.

The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation-targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A-rearranged AML. With so many new drugs approved, the number of potential combinator

Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives.

Histone deacetylase inhibitors (HDACis) are a significant category of pharmaceuticals that have developed in the past two decades to treat multiple myeloma. Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. The efficacy of this group of drugs is attributed to the disruption of many processes involved in tumor growth through the inhibition of histone deacetylase, and this mode of action leads to significant anti-multiple myeloma (MM) activity. In

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… Epigenomics. 2023;15:1195–1203. doi: 10.2217/epi-2023-0373. 20. Patel P, Wahan SK, Vishakha S, Kurmi BD, Gupta GD, Rajak H, Asati V. Recent progress in histone deacetylase (HDAC) 1 inhibitors as anticancer agent. … Epigenomics. 2016;8(2):251–269. doi: 10.2217/epi.15.106. 23. Liu L, Dong L, Bourguet E, Fairlie DP. Targeting class IIa HDACs: insights from phenotypes and inhibitors. Curr Med Chem. 2021;28(42):8628–8672. doi: 10.2174/0929867328666210629160647. 24. Kee HJ, Kim I, Jeong MH. …

Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy.

The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As T cells age, especially within the tumor microenvironment, they undergo significant metabolic shifts that may hinder their proliferation and functionality. This manuscript reviews how metabolic alterations contribute to T cell senescence in cancer and discusses potential therapeutic strategies aimed at reversing these metabolic changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, and lipid metabolism adjustments that co

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… Epigenomics. 2017;9:429–45. 24. Lanna A, Henson SM, Escors D, Akbar AN. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat Immunol. 2014;15:965–72. 25. … Environmental epigenomics, imprinting and disease susceptibility. Epigenetics. 2006;1:1–6. 108. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–28. 109. Stubbington MJT, Lonnberg T, Proserpio V, Clare S, Speak AO, Dougan G, et al. …

The role of piRNAs in predicting and prognosing in cancer: a focus on piRNA-823 (a systematic review and meta-analysis).

IntroductionThis article examines the potential of using liquid biopsy with piRNAs to study cancer survival outcomes. While previous studies have explored the relationship between piRNA expression and cancer patient outcomes, a comprehensive investigation is still lacking. To address this gap, we conducted a systematic review and meta-analysis of existing literature.MethodsWe searched major online databases up to February 2024 to identify articles reporting on the role of piRNA in cancer patient survival outcomes. Our meta-analysis used a random-effects model to pool hazard ratios with 95% con

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… Nutritional epigenomics. 14: Academic Press; 2019. p. 37–47. 17. O'Donnell KA Boeke JD Mighty Piwis defend the germline against genome intruders Cell 2007 129 1 37 44 10.1016/j.cell.2007.03.028 17418784 PMC4122227 18. … Assumpção CB Calcagno DQ Araújo TMT dos Santos Batista SE dos Santos Ribeiro ÂKC Riggins GJ The role of piRNA and its potential clinical implications in cancer Epigenomics 2015 7 6 975 984 10.2217/epi.15.37 25929784 PMC4750480 63. …