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Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.

Cancer remains a major global health challenge, with therapeutic resistance significantly limiting treatment success. Traditional approaches, including surgery, chemotherapy, and radiotherapy, often encounter barriers such as metastasis and adverse effects on healthy tissues. The Warburg effect, which describes cancer cells’ reliance on glucose fermentation despite oxygen availability, has prompted investigations into alternative metabolic interventions. The ketogenic diet (KD), characterized by high fat intake and low carbohydrate intake, induces a metabolic shift that may selectively disadva

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… An illustrative example is the demethylation of the ABCB1 transporter gene, which reduces chemotherapy drug retention within cancer cells, resulting in multiple drug resistance [ 18 ]. … The transformation of cells during cancer development involves epigenetic changes dependent on various metabolites: acetyl-CoA (acetylation), NAD (deacetylation), SAM (methylation), α-ketoglutarate (demethylation), and UDP-GlcNAc (glycosylation). …

Complementary and alternative medicine (CAM) supplements in cancer outpatients: analyses of usage and of interaction risks with cancer treatment.

PurposeThe aim of our study was to analyze the use of complementary and alternative medicine (CAM) supplements, identify possible predictors, and analyze and compile potential interactions of CAM supplements with conventional cancer therapy.MethodsWe included outpatient cancer patients treated at a German university hospital in March or April 2020. Information was obtained from questionnaires and patient records. CAM-drug interactions were identified based on literature research for each active ingredient of the supplements consumed by the patients.Results37.4% of a total of 115 patients consu

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… (Accessed 15 Apr 2021) Al-Jenoobi FI Al-Thukair AA Abbas FA Ansari MJ Alkharfy KM Al-Mohizea AM Al-Suwayeh SA Jamil S Effect of black seed on dextromethorphan O- and N-demethylation in human liver microsomes and healthy human subjects Drug Metab Lett 2010 4 1 51 55 10.2174/187231210790980435 20201775 … Al-Jenoobi FI, Al-Thukair AA, Abbas FA, Ansari MJ, Alkharfy KM, Al-Mohizea AM, Al-Suwayeh SA, Jamil S (2010) Effect of black seed on dextromethorphan O- and N-demethylation in human liver microsomes and healthy human subjects. …

T-Regulatory Cells In Tumor Progression And Therapy.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic ef

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… Epigenetic regulation of these CNS, mainly demethylation, is important for Foxp3 expression during Treg differentiation. 46 – 53 Thus, genetic and epigenetic factors regulate the Foxp3 level thereby play an important role in Treg levels and activity. … Frequency of circulating Tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially Treg-depleting agents . Clin Cancer Res . 2011 ; 17 : 841 – 848 . doi: 10.1158/1078-0432.CCR-10-2227 21177412 67. Gabler C , Blank N , Hieronymus T , et al. …

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

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… Active DNA demethylation occurs mainly at enhancers and gene bodies. The first step of this process is the conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Genome-wide 5hmC profiling of tumor PC has been recently performed. … Misregulation of histone demethylase KDM3A, which demethylates H3K9me1/2, is also involved in MM. It is upregulated in MM cells under hypoxia and its knockdown has anti-MM effect [ 219 , 230 , 231 ]. …

Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research.

T lymphocytes (T cells) are essential components of the adaptive immune system that play a vital role in identifying and eliminating infected and tumor cells. In tumor immunotherapy, T cells have emerged as a promising therapeutic strategy due to their high specificity, potent cytotoxic capability, long-lasting immune memory, and adaptability within immunotherapeutic approaches. However, tumors can evade the immune system by depleting T cells through various mechanisms, such as inhibitory receptor signaling, metabolic exhaustion, and physical barriers within the tumor microenvironment. This re

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… For example, DNA demethylation of the promoter regions of immunosuppressive receptor genes, such as PD-1 and TIM-3, in depleted T cells results in the upregulation of their expression [ 44 ]. …

Протеин тиросин фосфатаза-рецептор типа каппа (ПТПРК) вернулся к рассмотрению: развивающееся понимание структуры, функций и патологии.

Protein Tyrosine Phosphataze Type Cappa (PTPRK) — мембранная тиросина фосфатаза, кодируемая часто удаляемой областью хромосомы 6q, которая играет ключевую роль в регулировании сигнала, сцепления и иммунной реакции клеток. Структурно PTPRK включает внеклеточную область, связанную с сцеплением клеток, область трансмембрана и две внутриклеточные каталитические области, ответственные за фосфатазу. В частности, PTPRK подвергается протеолитическому декольте с помощью Furin и ADAM10, в результате чего образуется внеклеточная подгруппа E и подгруппа P. Дальнейшая обработка с помощью β-Secretasa выпуск

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… STAT3 activation can be regulated through various post-translational mechanisms, including phosphorylation/dephosphorylation of serine or tyrosine residues [ 46 ], acetylation [ 47 ], or demethylation [ 48 ]. …

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

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… Histone modifications such as acetylation, deacetylation, methylation, and demethylation, permit the unwrapping of DNA and loosening of the nucleosome structure, in order to enable access of transcription factors to their target genes and initiate the transcriptional process ( Figure 1 ) [ 15 ]. …

Oral formulation of bendamustine hydrochloride for patients with advanced solid tumors; a phase 1 study.

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of orally-administered bendamustine in Japanese patients with advanced solid tumors. The optimal dosing schedule, safety, pharmacokinetics, and preliminary antitumor effects were also evaluated. A multicenter, open-label trial with a standard 3 + 3 design and dose escalation by dose-limiting toxicity (DLT) was conducted. The treatment schedules were once daily for 7, 14, and 21 days every 3 weeks as one cycle. The total dose per cycle was increased from 175 to 840 mg/m2. Eighteen patients were enrolled in this study. DLT o

Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia.

Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoi

Миксобактериальная реакция на воздействие метильясмоната свидетельствует о вкладе в набор микропрепараторов на заводы.

Химические обмены между растениями и микробами в пределах ризобиомы имеют решающее значение для развития общинной структуры. Такие летучие корневые экюды, как фитохормоновый метилжасмонат (MeJA), способствуют принятию различных мер реагирования в связи со стрессом на растения, и они были причастны к тому, чтобы играть определенную роль в поддержании микробных сообществ. Миксобактерия является компетентным хищником растительных патогенов и, как правило, считается полезной для ризобиомов. Хотя было предложено использовать миксобактерию растений для защиты от патогенов, не известно о каких-либо с

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… While the transcription of the FrzCD homolog from A. sp., WP_073562522.1 , was not impacted by MeJA exposure ( Supplementary Material ), FrzCD is a methyl-accepting chemotaxis protein (MCP) with elicitor-induced activation attributed to covalent modification via demethylation and not transcriptional …

Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass datab

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… Mechanistically, heparanase recruits the demethylase LSD1, to induce gene activation through histone demethylation, while the methylase MLL, an antagonist of LSD1 function, is recruited to the repressive complex of transcription when heparanase is knocked down [ 8 ]. …

MiR-203a-3p regulates the biological behaviors of ovarian cancer cells through mediating the Akt/GSK-3β/Snail signaling pathway by targeting ATM.

ObjectiveTo investigate whether miR-203a-3p can regulate the biological behaviors of ovarian cancer cells by targeting ATM to affect the Akt/GSK-3β/Snail signaling pathway.MethodsThe expression levels of miR-203a-3p and ATM were detected by qRT-PCR, immunohistochemical staining and Western blotting in ovarian cancer tissues and adjacent normal tissues obtained from 152 subjects. A dual-luciferase reporter gene assay was performed to verify the relationship between miR-203a-3p and ATM. Human ovarian cancer cell lines (A2780 and SKOV3) were used to generate the Blank, miR-NC, miR-203a-3p mimic,

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… Shibuta T Honda E Shiotsu H Tanaka Y Vellasamy S Shiratsuchi M Umemura T Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti-tumor effect of imatinib Leuk Res 2013 37 1278 1286 10.1016/j.leukres.2013.07.019 23953880 34. …

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer.

Endometriosis is associated with ovarian cancers, mainly endometrioid and clear-cell carcinomas. Iron metabolism has been shown to play a role in endometriosis. Therefore, it is vital to explore the relationship between iron metabolism and ovarian cancer and to identify novel markers for diagnostics and therapeutics. The endometriosis dataset GSE51981 and the ovarian cancer dataset GSE26712 were obtained from the gene expression omnibus database, and differentially expressed genes were identified. Iron metabolism genes were obtained from molecular signatures database, and hub genes from the 3

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… MSMO1 is an oxidase-encoding gene that catalyzes the demethylation of c4 methylsterols and stimulates cell hyperproliferation. [ 33 ] Furthermore, MSMO1 is involved in the biosynthesis and metabolism of sterols and cholesterol. [ 34 ] Previous studies reported that MSMO1 expression is up-regulated in …

The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.

Cancer is caused by abnormal proliferation of cells and aberrant recognition of the immune system. According to recent studies, natural products are most likely to be effective at preventing cancer without causing any noticeable complications. Among the bioactive flavonoids found in fruits and vegetables, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties. This review aims to highlight the potential therapeutic effects of quercetin on some different types of cancers including blood, lung and prostate cancers.

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… According to them, quercetin-induced cell death is associated with increased transcription in the promoters of genes involved in the apoptotic pathway through DNA demethylation activity, histone deacetylase (HDAC) repression, and H3ac and H4ac enrichment ( 53 ). … 10, 50 μM | ( 67 ) In vitro | Que | KG‐1 | increased the apoptotic effects of TRAIL against the acute myeloid KG‐1 cells | 10, 50, 100,150, 200, 250, 300 μM | ( 68 ) In vitro | Que | HL60, U-937 | increased transcription in the promoter regions of genes involved in the apoptotic pathway through DNA demethylation …

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

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… In the absence of DNMT1, the replication machinery generates unmethylated DNA strands, leading to a gradual “dilution” of methylation and, consequently, a “passive” demethylation process, which doesn’t involve the active removal of methyl groups from existing methylated cytosines [ 189 , 190 , 191 ]. …

Understanding DMG: current treatment options and prospective solutions using nanoparticles.

Diffuse Midline Gliomas (DMGs), which include the subset formerly known as Diffuse Intrinsic Pontine Glioma (DIPG), are associated with an extremely poor prognosis and a five-year survival rate below 2-3%. The devastating prognosis stems from an inherently invasive nature, a deep, anatomically restricted location, rapid cellular drug efflux mediated by transporters such as P-glycoprotein (ABCB1) and breast cancer resistance protein (BCRP/ABCG2), and an immunologically "cold" microenvironment. Coupled with limited Blood-Brain Barrier (BBB) permeability, these biological factors render conventio

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… Synergistic antitumor effects that prolonged survival in mice were observed when Panobinostat was combined with GSKJ4 (a drug that prevents the demethylation of the mutated H3 histone) [ 91 ] and CBL0137 (a compound promoting chromatin transcription and DNA repair) [ 92 ]. …

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

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… At the epigenetic level, NNMT induces H3K27me3 demethylation in CAFs to trigger complement factor secretion, thereby recruiting MDSCs to form an immunosuppressive microenvironment. … Of note, using demethylating agents (e.g., 5‐azacytidine) or IFNG stimulation reverses resistance caused by HLA transcriptional suppression, reactivating antigen presentation [ 73 ]. …

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… Methylome erosion is a hallmark of both progeroid syndromes and physiological aging [ 29 , 30 ]; promoter demethylation at CDKN2A directly induces senescence through INK4a/ARF upregulation [ 31 ], while pharmacological reversal of the age‐related methylation clock experimentally restores visual function … Amatori S., Bagaloni I., Viti D., and Fanelli M., “Premature Senescence Induced by DNA Demethylating Agent (Decitabine) as Therapeutic Option for Malignant Pleural Mesothelioma,” Lung Cancer 71, no. 1 (2011): 113–115. 32. …

The crosstalk network of non-coding RNAs: Emerging opportunities for the clinical application of osteoporosis.

Current methods for testing bone density lack the capability to detect patients with early bone loss, and existing osteoporosis therapies have limitations in their efficacy and safety. Therefore, the development of more precise and convenient diagnostic technologies and novel treatments is of paramount importance. Extracellular vesicle (EV)-mediated non-coding RNA (ncRNA) interaction networks enable both the detection of early bone loss and targeted therapy for enhanced treatment outcomes. In this review, we highlight the utility of EVs for carrying various ncRNAs (e.g., miRNAs, lncRNAs, and c

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… On the one hand, the diagram summarises the role of m6A modification in regulating bone metabolism; for instance, m6A modification mediated by WTAP/YTHDC1 and piR7472 positively regulates osteogenic differentiation, whereas demethylation mediated by ALKBH5 promotes osteoclast differentiation by regulating … Mechanistically, the molecular sponge effect of circ_0008542 relies on m6A methylation, whereas ALKBH5-mediated demethylation reduces the binding capacity of the circRNA to the miR-185-5p–RANK axis, thereby inhibiting osteoclast differentiation and bone resorption ( Fig. 4 ). …