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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

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… On the genetic side, there is a correlation between TGCT and mutations in genes such as KITLG and KRAS, as well as risk loci that contain genes responsible for DNA damage repair, microtubule assembly and telomerase function ( Litchfield et al., 2015 ; Ding et al., 2019 ; de Vries et al., 2020 ). …

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics canc

Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia.

In the past decade, novel targeted therapy approaches, such as BTK inhibitors and Bcl2 blockers, and innovative treatments that regulate the immune response against cancer cells, such as monoclonal antibodies, CAR-T cell therapy, and immunomodulatory molecules, have been established to provide support for the treatment of patients. However, drug resistance development and relapse are still major challenges in CLL treatment. Several studies revealed that non-coding RNAs have a main role in the development and progression of CLL. Specifically, microRNAs (miRs) and tRNA-derived small-RNAs (tsRNAs

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… Role of miR-15a/miR-16-1 and the TP53 axis in regulating telomerase expression in chronic lymphocytic leukemia. Haematologica. 2017;102:e253–e256. doi: 10.3324/haematol.2016.157669. 114. Pekarsky Y., Balatti V., Croce C.M. BCL2 and miR-15/16: From gene discovery to treatment. …

Circadian clock and cancer.

Circadian rhythms play a critical role in regulating physiological and behavioral processes, such as the sleep-wake cycle, hormone secretion, and metabolism. These rhythms are controlled by endogenous biological clocks, which are synchronized with environmental cues, primarily the light-dark cycle. Notably, disruption or reprogramming of circadian rhythms is closely associated with cancer initiation, progression, and treatment response. At the molecular level, the dysregulation of core clock genes can disturb normal cellular rhythms, leading to aberrant cell proliferation, impaired DNA repair,

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… , tongue squamous cell carcinoma [262] , and osteosarcoma [263] , BMAL1 induces G2/M arrest and apoptosis by directly repressing CDK5 transcription, activating the p53-p21 pathway and proapoptotic proteins Bcl-2-associated X protein (BAX)/B-cell lymphoma 2 (BCL-2), or recruiting EZH2 to repress the telomerase …

Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants.

Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porok

Регулирование питания иммунной системы кишечного мозга происходит на протяжении всей жизни.

Иммунная ось кишечника объединяет микробные, иммунные и нейронные сигналы для регулирования нейроразвития, гомеостаза и подверженности болезням. Раннее питание, в частности молочные олигозакариды, формирует благотворный микробиотический состав, повышает гиппокампальную пластичность, способствует антивоспалительной микроглианской поляризации и поощряет иммунную терпимость. Микробиота - метаболиты гута, включая короткоцепные жирные кислоты, производные триптофана и вторичные желчные кислоты, регулируют микроглиатическое созревание, функцию астроцита, дифференциацию клеток Т, производство нейротр

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… Impaired T cell survival and function with age is directly associated with loss of telomerase activity, accumulation of DNA damage, and shifts in cellular metabolism towards reduced production of lactate and ATP. 127 These metabolic shifts further favor pro-inflammatory T cell subsets (e.g., Th17 or …

Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions.

Malignant tumors constitute a major global public health burden. Chronic psychological stress (CPS) manifests as sustained dysregulation arising from prolonged adaptive responses to chronic endogenous and exogenous stimuli. Clinical evidence indicates that CPS markedly influences cancer progression, with most oncology patients developing detectable stress-related psychological disorders during disease management. This review synthesizes recent advances in understanding CPS-mediated oncogenic mechanisms and evaluates current intervention approaches. Mechanistically, CPS compromises immune surve

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… NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells. Redox Biol. 2016;8:91–97. 76. Wen P, Sun Z, Gou F, Wang J, Fan Q, Zhao D, Yang L. Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders. …

Organic Nanoparticles in Progressing Cardiovascular Disease Treatment and Diagnosis.

Cardiovascular diseases (CVDs), the world's most prominent cause of mortality, continue to be challenging conditions for patients, physicians, and researchers alike. CVDs comprise a wide range of illnesses affecting the heart, blood vessels, and the blood that flows through and between them. Advances in nanomedicine, a discipline focused on improving patient outcomes through revolutionary treatments, imaging agents, and ex vivo diagnostics, have created enthusiasm for overcoming limitations in CVDs' therapeutic and diagnostic landscapes. Nanomedicine can be involved in clinical purposes for CV

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… Telomerase mRNA reverses senescence in progeria cells. J. Am. Coll. Cardiol. 2017;70:804–805. doi: 10.1016/j.jacc.2017.06.017. 57. Chanda P.K., Sukhovershin R., Cooke J.P. mRNA-enhanced cell therapy and cardiovascular regeneration. Cells. 2021;10:187. doi: 10.3390/cells10010187. 58. …

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, u

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… Melatonin has also been reported to suppress telomerase activity in breast cancer cells, thus contributing to cell death by preventing their genomic stability [ 106 ]. …

Applications of nanotechnologies for miRNA-based cancer therapeutics: current advances and future perspectives.

MicroRNAs (miRNAs) are short (18-25 nt), non-coding, widely conserved RNA molecules responsible for regulating gene expression via sequence-specific post-transcriptional mechanisms. Since the human miRNA transcriptome regulates the expression of a number of tumor suppressors and oncogenes, its dysregulation is associated with the clinical onset of different types of cancer. Despite the fact that numerous therapeutic approaches have been designed in recent years to treat cancer, the complexity of the disease manifested by each patient has prevented the development of a highly effective disease

Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.

This review introduces a paradigm-shifting concept of Dual Distinct Immunotherapy (DDI), which strategically integrates two distinct immunotherapeutic modalities to overcome the limitations of current monotherapies and dual immune checkpoint inhibitor (ICI) combinations. The concept of DDI extends beyond traditional ICI combinations to encompass various innovative pairings: ICIs with oncolytic viruses (OVs), adoptive cell therapies (CAR-T/TIL), cancer vaccines, or cytokine therapies. These combinations demonstrate unique synergistic mechanisms and enhanced therapeutic potential through multi-f

Double jeopardy: how BRCA2, TP53, and DNMT3A redefine the link between infertility and cancer risk.

BackgroundGermline mutations in genes governing DNA repair, cell cycle regulation, and epigenetic modification are now recognized as common etiological factors for both cancer predisposition and reproductive dysfunction. This reveals a profound intersection between reproductive biology and oncogenesis.MethodA systematic narrative review was conducted. The literature search spanned PubMed/MEDLINE, Scopus, and Web of Science using keywords and MeSH terms related to infertility phenotypes, cancer predisposition syndromes, and shared molecular mechanisms (e.g., DNA repair, epigenetics).OutcomesThe

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… DKC1 and telomere biology: linking ovarian aging to epithelial cancers The DKC1 gene encodes dyskerin, a pseudouridine synthase essential for telomerase RNA stabilization and telomere maintenance ( Garus AAutexier and Autexier, 2021 ). …

Phytochemicals as Chemo-Preventive Agents and Signaling Molecule Modulators: Current Role in Cancer Therapeutics and Inflammation.

Cancer is one of the deadliest non communicable diseases. Numerous anticancer medications have been developed to target the molecular pathways driving cancer. However, there has been no discernible increase in the overall survival rate in cancer patients. Therefore, innovative chemo-preventive techniques and agents are required to supplement standard cancer treatments and boost their efficacy. Fruits and vegetables should be tapped into as a source of compounds that can serve as cancer therapy. Phytochemicals play an important role as sources of new medication in cancer treatment. Some synthet

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… Interestingly, patients on ginger supplements had lower levels of MIB-1 and telomerase reverse transcriptase expression [ 270 ]. The inflammatory cytokine MIB-1 was upregulated in the gastrointestinal mucosa of guinea pigs in a study that mimicked mucosal inflammation [ 271 ]. …

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes.

Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials eva

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… TERT promoter | 1 | Telomerase reverse transcriptase promoter (TERT) is used to attenuate virus replication. Interferon-gamma (IFN-ɣ) | 1 | IFN-ɣ is a cytokine molecule with pronounced cytostatic, pro-apoptotic and immune-stimulating effects. …

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

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… NF-kB signaling molecules have been identified in the pathogenesis of MM [ 123 ]; overactive molecules in this pathway promote the growth of MM cells via expression of growth-promoting cytokines like IL-6, cell-cycle regulators that decrease cells’ sensitivity to cycle arrest, anti-apoptotic molecules, telomerase …

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the su

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… glutathione reductase; GSH, glutathione; GSH-Px, glutathione peroxidase; GSK3β, glycogen synthase kinase 3 β; GST, glutathione S-transferase; HER2, human epidermal growth factor receptor 2; HER3, human epidermal growth factor receptor 3; HIF-1α, hypoxia-inducible factor 1-α; HK2, hexokinase 2; hTERT, human telomerase …

Development and Clinical Translation of Approved Gene Therapy Products for Genetic Disorders.

The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understanding of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indicati

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… As an evolutionarily-conserved protein, SMN is encoded by SMN1 and SMN2 genes and is critical for transcriptional regulation, telomerase regeneration and cellular trafficking of motoneurons ( Singh et al., 2009 ). …

Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.

Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, serve as pivotal metabolites within the tumor microenvironment (TME), playing essential roles in modulating tumor progression. Although the biological functions and mechanisms of SCFAs in the TME show some overlap, each SCFA also exerts some distinct regulatory effects on tumors and TME. Notably, even a single SCFA may exhibit pleiotropic effects across different cancer types or under varying conditions within the same malignancy. Consequently, according to the different metabolic microenvironment of patients, precis

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… Butyrate-containing structured lipids act on HDAC4, HDAC6, DNA damage and telomerase activity during promotion of experimental hepatocarcinogenesis. Carcinogenesis. 2021;42:1026–36. doi: 10.1093/carcin/bgab039. 117. Zhang K, Ji X, Song Z, Song W, Huang Q, Yu T. et al. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… Furthermore, DNA hypomethylation can result in the activation of specific key genes involved in tumorigenesis; for example, the TERT gene encoding telomerase reverse transcriptase upon promoter methylation increases transcription and protein expression. …

Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy

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… Telomerase activation is observed in over 90% of HCC patients and is closely related to HCC. 177 C‐terminally truncated middle surface protein of hepatitis B virus (MHBst) and wild‐type/truncated HBx proteins activate the transcripts promoter of TERT in HBV‐associated HCC. 178 Many signaling pathways …