Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(3), P. 297 - 360

Published: Feb. 4, 2024

Abstract Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well immunotherapy have benefited cancer patients considerably. Tumor protein p53 ( TP53 ), crucial tumor suppressor gene encoding p53, regulates numerous downstream genes cellular phenotypes response to various stressors. The affected are involved diverse processes, including cell cycle arrest, DNA repair, senescence, metabolic homeostasis, apoptosis, autophagy. However, accumulating recent studies continued reveal novel unexpected functions governing the fate tumors, for example, ferroptosis, immunity, microenvironment microbiome metabolism. Among possibilities, evolutionary plasticity most controversial, partially due dizzying array biological that been attributed different regulatory mechanisms signaling. Nearly 40 years after its discovery, this remains somewhat enigmatic. intricate regulating during treatment only tip iceberg respect equally complicated structural biology, which has painstakingly revealed. Additionally, mutation one significant genetic alterations cancer, contributing rapid growth progression. Here, we summarized advances implicate altered modulating therapies, chemotherapy, radiotherapy, immunotherapy. Furthermore, also discussed potential strategies targeting therapeutic option cancer.

Language: Английский

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The role of p53 in male infertility

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 14, 2024

The tumor suppressor p53 is a transcription factor involved in variety of crucial cellular functions, including cell cycle arrest, DNA repair and apoptosis. Still, growing number studies indicate that plays multiple roles spermatogenesis, as well the occurrence development male infertility. representative functions spermatogenesis include proliferation spermatogonial stem cells (SSCs), differentiation, spontaneous apoptosis, damage repair. various infertility-related diseases. Innovative therapeutic strategies targeting have emerged recent years. This review focuses on role infertility analyses possible underlying mechanism involved. All these conclusions may provide new perspective drug intervention for treatment.

Language: Английский

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Radiation-Induced Tissue Regeneration

Hematology/Oncology Clinics of North America, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Establishment and Validation of an Early Detection Model for Gastric Cardia Adenocarcinoma Based on Autoantibody Serological Characteristics

Published: Jan. 1, 2025

Language: Английский

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CENPF as a prognostic marker of glioma: unraveling the molecular mechanisms

Journal of Cancer Research and Clinical Oncology, Journal Year: 2025, Volume and Issue: 151(2)

Published: Feb. 28, 2025

Glioma is the dominant primary intracranial malignancy. The roles of CENPF and - p53 axis in glioma remain elusive. This study uses bioinformatics animal experiments to clarify relationship between glioma. affects spindle assembly chromosomal segregation, while a tumor—suppressor gene. Their dysregulation may interact impact development. Our research aims uncover underlying molecular mechanisms, offering new perspectives for diagnosis treatment. Gene expression data from Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo/ ) were retrieved, specifically datasets GSE50161, GSE104291, GSE12249. Volcano plots generated visualize differentially expressed genes (DEGs), intersecting DEGs identified using Venn diagrams. Weighted gene co-expression network analysis (WGCNA) was employed construct analyze protein–protein interaction (PPI) network. Additionally, ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway analyses conducted. set enrichment (GSEA) utilized comprehensive GO KEGG entire genome. Comparative Toxicogenomics Database (CTD) performed, TargetScan used identify miRNAs regulating central DEGs. An model established analyzed via Western blot. A total 501 (DEGs) identified, which eight significant modules ten core extracted. These exhibited differential patterns tumor non-tumor samples. revealed that associated with (CENPF, PBK, ASPM, KIF2C, KIF20A, CDC20, TOP2A, NUSAP1, TTK, KIF23) significantly upregulated tissues (P < 0.05). They are primarily enriched protein signal transduction, coated membrane structures, AP-type coat adaptor complexes, chloride channel activity. indicated these target mainly involved nicotine addiction, arginine proline metabolism, beta-alanine histidine metabolism. mouse confirmed CDK-1 highly tissues, p53, p21, Caspase9 downregulated, leading inhibition apoptosis exacerbation progression. Overexpression further suppressed key molecules p53-mediated pathway. Conversely, low activated molecules, inducing cells. exhibits elevated levels glioma, potentially inhibiting cell signaling pathway, consequently contributing onset progression

Language: Английский

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Engineering Iridium Nanoclusters for Boosting Ferroptotic Cell Death by Regulating GPX4 and p53 Functions

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Emerging evidence indicates that modulating glutathione peroxidase 4 (GPX4) to induce ferroptosis is a promising strategy for tumor treatment. However, most of the GPX4 small molecule inhibitors face limitations due their poor delivery efficacy and low specificity activation. Herein, ferroptosis‐inducing nanomedicine developed integrates nutlin‐3 with iridium oxide nanoclusters (NUT‐IrO x NCs) enhanced ferroptosis‐driven multimodal therapeutic in colorectal cancer (CRC). This NUT‐IrO NCs can (GSH) depletion via Ir (VI)‐Ir (III) transition, while nutlin‐3, well‐established inhibitor p53‐MDM2 interaction, suppresses GSH production by modulation p53/SLC7A11/xCT signaling pathway. The reduction intracellular results pronounced reductions enzymatic activity, consequently leading lipid peroxidation accumulation further enhancing ferroptosis‐induced CRC therapy. dual‐pronged approach demonstrates robust anticancer effects favorable biocompatibility both vitro vivo models. study provides an effective highlights benefits inhibiting GSH/GPX4 activating multiple regulatory pathways, providing alternative avenue

Language: Английский

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The relationship between p53 and the malignant transformation of nasal inverted papilloma: a meta-analysis

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 19, 2025

Abstract Background The nasal inverted papilloma (NIP) is a neoplasm that originates from the mucosal lining of cavity and paranasal sinuses. A meta-analysis was conducted to investigate link between p53 dysregulation prognosis in patients with NIP. Methods Relevant original articles were identified through comprehensive search PubMed, EMBASE, Web Science databases up until January 14, 2025. Results studies showed low heterogeneity ( I 2 = 31%), allowing use fixed effect model (FEM). forest plot revealed significant association malignant transformation progression NIP, an odds ratio (OR) 7.93 (95% CI 4.74–13.28, P < 0.001). Sensitivity analysis indicated pooled OR ranging 7.13 4.19–12.11, 0.001) 11.39 6.00–21.60, Significant correlations also found subgroups based on region, publication year, Newcastle–Ottawa Scale (NOS) scores. Moreover, Begg's test 0.26) Egger's 0.57) results suggested risk bias. Conclusions underscores strong relationship practical applications identifying NIP have potential significantly impact clinical decision-making patient outcomes.

Language: Английский

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Comprehensive Pan-cancer Analysis Revealed CASP10 As a Promising Biomarker For Diverse Tumor Types

International Journal of Immunopathology and Pharmacology, Journal Year: 2025, Volume and Issue: 39

Published: March 1, 2025

We aimed to explore the comprehensive cancer landscape of Caspase-10 (CASP10). CASP10, a member caspase family, is located at human chromosome locus 2q33-34. Studies have suggested its potential role in development certain cancers. To evaluate CASP10 expression normal and pan-cancer tissues, we integrated data from The Cancer Genome Atlas (TCGA), GEO, Human Protein (HPA), UALCAN databases. diagnostic prognostic significance was analyzed using Receiver Operating Characteristic (ROC), Cox regression, Kaplan-Meier analysis. Correlations with clinical parameters were assessed via Wilcoxon test, Kruskal-Wallis logistic regression Genomic variations explored cBioPortal, GSCALite database, LinkedOmics database used detect function pan-cancer. Interactions between Tumor Immune Microenvironment (TIME) investigated TISIDB, TIMER2, TISCH utilized assess sensitivity small-molecule drugs. In addition, Western Blotting (WB) employed our Liver Hepatocellular Carcinoma (LIHC) Stomach Adenocarcinoma (STAD) cohorts. transcription protein significantly differ across types, marking it as biomarker for diagnosis prognosis. Its correlated characteristics such histological types Alpha-Fetoprotein (AFP) levels. gene exhibited 2% alteration frequency patients, significant SNV CNV profiles, decreased methylation closely related Nuclear Factor-κappa B (NF-κB), TNF, cell cycle, JAK-STAT signal pathways. showed correlation immune components tumor microenvironment, including lymphocytes, stimulators, inhibitors, MHC molecules, chemokines, receptors, Cancer-Associated Fibroblasts (CAFs). Importantly, could predict diverse anti-cancer Finally, WB analysis validated overexpression LIHC STAD tissues. Our bioinformatic reveal on diagnosis, prognosis, progression types.

Language: Английский

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Small molecules that targeting p53 Y220C protein: mechanisms, structures, and clinical advances in anti-tumor therapy

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Language: Английский

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Prunin: An Emerging Anticancer Flavonoid

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2678 - 2678

Published: March 16, 2025

Despite the substantial advances in cancer therapies, developing safe and effective treatment methodologies is critical. Natural (plant-derived compounds), such as flavonoids, might be crucial a methodology without toxicity toward healthy tissues. Prunin flavonoid with potential to used biomedical applications. has yet undergo thorough scientific research, its precise molecular mechanisms of action remain largely unexplored. This review summarizes therapeutic prunin for first time, focusing on underlying an anticancer compound. gained significant attention due antioxidant, anti-inflammatory, effects. aims unlock how functions at level exert effects, primarily modulating key cellular pathways. Furthermore, we have discussed prunin’s adjunctive therapy conventional treatments, highlighting ability strengthen responses while decreasing drug resistance. Moreover, discussion probes into innovative delivery methods, particularly nanoformulations, that address bioavailability, solubility, stability limitations optimize application. By providing comprehensive analysis properties, this stimulate further exploration using agent, thereby progressing development targeted, selective, safe, methods.

Language: Английский

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