Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116323 - 116323

Published: Feb. 23, 2024

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are elements of the deubiquitinase family, overexpressed in gastric (GC). Through regulation several signaling pathways, such as Wnt/β-Catenin nuclear factor-κB signaling, promotion expression deubiquitination- stabilization-associated proteins, USPs promote proliferation, metastasis, invasion, epithelial-mesenchymal transition GC. In addition, closely related to clinicopathological features, patient prognosis, chemotherapy resistance. therefore could be used prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they not yet been tested clinic. This article provides an overview latest fundamental research on GC, aiming enhance understanding how contribute GC progression, identifying possible targets treatment improve survival.

Language: Английский

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Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(25)

Published: June 26, 2024

Abstract Dr. S. Shruthi, Prof. K. Bhasker Shenoy. Cisplatin (CDDP) is the first metal‐based drug and has been a popular in treatment of various types cancer for decades. Cancer cell death promoted by this platinum‐based generating DNA adducts activating apoptotic signaling pathways. The development resistance foremost clinical concern that compromises its efficacy. mechanism CDDP encompasses changes influx efflux, accumulation reduction, enhanced detoxification, repair which may affect therapeutic value. Researchers have paid significant attention to overcoming resistance, provides an opportunity enhance outcomes. Combinational therapy, use analogs, phytochemicals, nanoparticle‐mediated delivery, gene targeting regulation induced epigenetic are specific regimens overcome burden. In review, we summarize mechanisms involved strategies considered these hurdles concerning preclinical studies. This provide insights into further novel approaches uproot ascertain safer more effective therapy.

Language: Английский

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Anticancer effects of zinc ion-mediated DNA demethylation in oesophageal squamous cell carcinoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: May 27, 2025

Background Abnormalities in trace elements and the incidence of oesophageal squamous cell carcinoma (ESCC) have been reported China. Zinc ions (Zn 2+ ) are known to regulate DNA methylation by stabilizing methylase activity. However, relationship between Zn dysregulation ESCC cells remains unclear. In this study, we examined changes biological behavior treated with or without . Methods Biological behaviour were analysed. Differences methylome transcriptome -treated determined reduced representation bisulfite sequencing RNA sequencing. An MTT viability assay was used evaluate cytotoxicity cisplatin combined Results can inhibit malignant cells. CpG levels promoter regions decreased after treatment both control The degree genes encoding metal ion-binding factors MT1E, MT1H MT1X significantly decreased, but their expression increased treatment. may enhance metallothioneins (MTs) via positive feedback through regulation mechanisms. vitro assays showed that IC50 lower than alone. addition, ECa patients high MT1E had a better prognosis. Conclusion reduce level combination increases inhibition. Further study MTs as biomarkers targets is warranted.

Language: Английский

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Strategies to enhance the response of liver cancer to pharmacological treatments

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(1), P. C11 - C33

Published: May 6, 2024

In contrast to other types of cancers, there is no available efficient pharmacological treatment improve the outcomes patients suffering from major primary liver i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation partly due existence in these tumors many different synergistic mechanisms resistance, accounting for lack response patients, not only classical chemotherapy but also more modern agents based on inhibition tyrosine kinase receptors (TKIs) stimulation immune against tumor using checkpoint inhibitors (ICIs). review summarizes efforts develop strategies overcome this severe limitation, including searching novel drugs derived synthetic, semisynthetic, or natural products with vectorial properties therapeutic targets increase drug uptake reduce export cancer cells. Besides, immunotherapy a promising line research that already starting be implemented clinical practice. Although less successful than foreseen future strategy treating cancers considerable. Similarly, epigenetic highly promising. Many “epidrugs,” able act “writer,” “reader,” “eraser” players, are currently being evaluated preclinical studies. Finally, gene therapy broad field fight chemoresistance, impressive advances recently achieved manipulation. sum, although present still dismal, reason hope non-too-distant future.

Language: Английский

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Structure and Functions of HMGB3 Protein

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7656 - 7656

Published: July 12, 2024

HMGB3 protein belongs to the group of HMGB proteins from superfamily nuclear with high electrophoretic mobility. play an active part in almost all cellular processes associated DNA-repair, replication, recombination, and transcription-and, additionally, can act as cytokines during infectious processes, inflammatory responses, injuries. Although structure functions HMGB1 HMGB2 have been intensively studied for decades, very little attention has paid until recently. In this review, we summarize currently available data on molecular structure, post-translational modifications, biological HMGB3, well possible role ubiquitin-proteasome system-dependent degradation tumor development.

Language: Английский

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hTERT Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7331 - 7331

Published: July 4, 2024

Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and further improve the present chemotherapeutic standard. We have concentrated on investigation of alteration hTERT gene, which is frequently epigenetically dysregulated in a number cancers specific developmental stages. Distinct DNA methylation profiles were identified our data early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters distinguish between differentially methylated states. infer from this set, context, related literature that CpG-rich, 2800 bp region, prominent CpG island, surrounding transcription start gene crucial zone for development potent biomarker. In order accurately describe we named it "Acheron" (Ἀχέρων). Greek mythology, river woe misery path underworld. Exploitation focused e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up wide range new possibilities diagnosis, determination prognosis, follow-up, detection residual disease. It may also broad implications choice chemotherapy.

Language: Английский

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LncRNA-Mediated Regulation of Cisplatin Response in Breast Cancer

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 264, P. 155716 - 155716

Published: Nov. 7, 2024

Language: Английский

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