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Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

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… In epithelium lacking cytopathic alterations, CpGs remain methylated, whereas, in low-grade lesions or permissive infections, changes in methylation are related to the epithelial differentiation layer, keeping the E2-binding site (E2BS) of the promoter region demethylated. … Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer. Clin. Cancer Res. 23, 7276–7287. 10.1158/1078-0432.ccr-17-1438 Blachon S., Bellanger S., Demeret C., Thierry F. (2005). …

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

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… Interventions targeting either of the enzymes lead to H3K9/H3K27 demethylation and activation of anti-angiogenic gene transcription. JHDM1D specifically demethylates the inhibitory marks of mono-methylation of histone H3K9 and H3K27, countering the epigenetic gene regulation of HMTs. … Some studies have shown that H3K4 demethylation occurs during NHEJ and HR repair processes 126 . KDM5B is a member of the histone demethylase family that can recruit Ku70 and BRCA1 to promote NHEJ and HR repair. …

Keyword Index for Volume 88

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… 1741 cytokines 630, 1207, 1773 cytological techniques 1883 cytology 702 cytology performance 1570 cytoprotection 754 cytoskeleton 1794 cytotoxic medium conditioning 447 Dacarbazine 132, 496 darbepoetin alpha 1851 decision making 1675 delayed reproductive death 548 deletion spectrum 90 demethylation …

CD70-targeted CAR-T/NK therapy: Rationale, advances, and future directions.

Chimeric antigen receptor T and natural killer (CAR-T/NK) cells is a rapidly evolving cellular immunotherapy technology that has made great achievements in the treatment of hematologic diseases. CD70, as a surface antigen expressed on tumor cells in a variety of hematologic malignancies, including acute myeloid leukemia, non-Hodgkin lymphoma, multiple myeloma, etc., and solid tumors such as renal cell carcinoma, osteosarcoma, and glioma, is a potential target for CAR-T/NK cells. Several preclinical studies and clinical trials on CAR-T/NK cells targeting CD70 are currently underway, bringing ne

Fanconi anemia pathway as a prospective target for cancer intervention.

Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of th

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… Aldehydes, which are produced by many metabolic processes such as lipid peroxidation, histone demethylation, and alcohol metabolism, cause the formation of ICLs [ 9 – 12 ]. … Similar resistance has also been found in the subset of cell lines harboring aberrant demethylation of the FANCF gene [ 99 ]. …

Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium.

Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7-8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overvie

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

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… Demethylation of the CpG DNA regions occurs passively or via the Ten-Eleven Translocation (TET) pathway, increasing gene expression ( 23 ). …

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous inves

In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells.

Background & aimThe miR-221/222 cluster is upregulated in malignant plasma cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We previously reported that silencing of miR-221/222 by an antisense oligonucleotide induces anti-MM activity and upregulates canonical miR-221/222 targets. The in vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered directly into MM xenografts. The aim of the present study was to evaluate the anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-22

Short and Long Non-Coding RNAs in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents the most frequent kidney malignancy and remains a major clinical challenge due to its often silent onset, high metastatic potential, and limited responsiveness to conventional chemotherapy. Increasing evidence indicates that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are key regulators of RCC tumorigenesis, progression, and therapy resistance. Rather than providing a purely descriptive overview, this review focuses on emerging mechanistic paradigms through which ncRNAs actively shap

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… Mechanistically, MIR4435-2HG expression was epigenetically upregulated by fumarate through histone demethylation. … migration and invasion by suppressing miR-491-5p, leading to increased MMP-9; knockdown reduces tumor growth | Upregulated | [ 95 ] lncRNA-SERB | Promotes tumor cell invasion enhancing VM formation; increases Erβ expression | Upregulated | [ 96 ] MIR4435-2HG | Upregulated by fumarate through histone demethylation …

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

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… Vitamin C is also involved in the regulation of DNA and histone demethylation, serving as a cofactor for ten-eleven translocation (TET) enzymes, which are involved in DNA demethylation [ 115 ]. …

Therapeutic targeting in pediatric acute myeloid leukemia with aberrant HOX/MEIS1 expression.

Despite advances in the clinical management of childhood acute myeloid leukemia (AML) during the last decades, outcome remains fatal in approximately one third of patients. Primary chemoresistance, relapse and acute and long-term toxicities to conventional myelosuppressive therapies still constitute significant challenges and emphasize the unmet need for effective targeted therapies. Years of scientific efforts have translated into extensive insights on the heterogeneous spectrum of genetics and oncogenic signaling pathways of AML and identified a subset of patients characterized by upregulati

Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.

Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough in cancer immunotherapy, demonstrating impressive clinical outcomes, particularly for hematologic malignancies. However, its broader therapeutic application, especially against solid tumors, remains limited. Key challenges include T cell exhaustion, limited persistence, cytokine-mediated toxicities, and logistical hurdles associated with manufacturing autologous products. Emerging gene editing technologies, such as CRISPR/Cas systems, base editing, and prime editing, offer novel approaches to optimize CAR-T cells, aiming

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… For example, knockout of TET2, involved in DNA demethylation, promotes robust clonal expansion with a durable memory profile 102 . TET2 knockout induces a central memory phenotype, fostering clonal expansion of CAR-Ts. … The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells. Immunity. 2015;42:613–26. doi: 10.1016/j.immuni.2015.03.005. 103. Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA, Reich TJ. et al. …

Next-generation CAR-T therapy for acute myeloid leukemia: bridging innovation with clinical translation.

Acute myeloid leukemia (AML) is a high-risk hematologic malignancy with poor long-term survival and frequent relapse, sustained by leukemic stem cells, antigenic heterogeneity, and an immunosuppressive bone marrow niche. Although chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in B-cell malignancies, its application in AML is restricted by on-target myelotoxicity from antigen overlap with normal progenitors, heterogeneous and dynamic antigen expression, rapid T-cell exhaustion in suppressive microenvironments, limited manufacturing windows with compromised T-cell qual

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

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… The inability to preserve methylation during DNA replication or the separate processes of base excision repair (BER) and nucleotide excision repair (NER) can both result in the demethylation of DNA [ 192 ]. … Demethylation results via the iron-dependent α-ketoglutarate dioxygenase enzyme TET1’s conversion of 5-methylcytosine to 5-hydroxy methylcytosine. …

Evolving treatment strategies for myeloma.

In this article, we will discuss how treatment strategies for myeloma have evolved and outline the challenges now faced following the introduction of a number of novel active agents. In particular, we will focus on how achieving a maximum response and maintaining such responses is becoming a key therapeutic strategy and how novel agents can be used to achieve this in the context of current strategies such as autologous transplantation.

Lactylation in health and disease: physiological or pathological?

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles in different aspects of energy metabolism and signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as a novel posttranslational modification (PTM). Research indicates that Kla is an essential balancing mechanism in a variety of organisms and is involved in many key cellular biological processes through different pathways. Kla is closely related to disease development and represents a potential and important new drug target

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… HIF1α-dependent manner, thereby promoting the lactylation of c-Myc; | PMID: 39277835 IGF2BP3 | unknown | Reprogram serine metabolism and enhance the antioxidant defense system; | PMID: 39450426 ALKBH5 | unknown | Lactylated ALKBH5 binds to interferon-β (IFN-β) messenger RNA (mRNA), leading to its m6A demethylation … Kla increases ALKBH3 expression by demethylating m1A on SP100A, which decreases PML body formation and promotes UM malignancy 156 . These findings offer new perspectives for treating UM. …

Токсичность тяжелых металлов в клиническом и экологическом здравоохранении: источники, механизмы, диагностика и научно обоснованное управление ртутью, свинцом, кадмием и арсеником.

Тяжелые металлы, включая ртуть (Hg), свинец (Pb), кадмий (Cd) и мышьяк (As), по-прежнему остаются значительными глобальными токсинами в силу их экологической стойкости, широкомасштабного антропогенного высвобождения и серьезного биологического воздействия. Этот обзор укрепляет нынешнее понимание их природных и промышленных источников, круговорота окружающей среды, маршрутов воздействия на человека и факторов уязвимости на уровне населения. Она охватывает их токсикокинетику и токсикодинамику, делая акцент на специфических для каждого вида механизмах поглощения, распределения и травмирования, вк

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… Research is also ongoing into catalysts that transform more toxic metal species into forms easier to eliminate, such as organomercury demethylation or arsenic oxidation [ 196 ]. …

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

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… It has been reported that the antitumor effects of emodin on PC growth may be related to the demethylation of tumor suppressor genes 145 , 146 . High expression of HIF-1α in tumor cells supports growth, angiogenesis, and high glycolysis, which is also known as the Warburg effect in tumors 147 . …

CD13 downregulation mediated by ubenimex inhibits autophagy to overcome 5-FU resistance by disturbing the EMP3/FAK/NF-κB pathway in gastric cancer cells.

BackgroundGastric cancer (GC) is one of the most common malignant tumours in China, but the efficacy of chemotherapy on GC is significantly reduced due to the occurrence of drug resistance. Some studies have shown that the expression level of CD13 is associated with tumour resistance, but whether ubenimex, as a CD13 inhibitor, reverses GC drug resistance and the underlying mechanism remain unclear.MethodsHerein, resistance to 5-fluorouracil (5-FU) was reversed in GC by ubenimex, and the underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assays, gene chip analysis, high conte