Browsing by Author "Pirisola, Ayomikun Joshua"

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ASSOCIATION OF COMT AND CYP1B1 POLYMORPHISMS WITH PROSTATE CANCER RISK IN NIGERIAN MEN
(Covenant University Ota, 2025-09) Pirisola, Ayomikun Joshua; Covenant University Dissertation
Prostate cancer (PCa) disproportionately affects men of African descent, with Nigeria recording high mortality rates, yet genetic studies in this population remain sparse. This study investigated the association between COMT rs4680 Val158Met, rs9332377, and CYP1B1 rs1056836 genetic variants and PCa risk and severity in Nigerian men. This case-control study involved 65 histologically confirmed PCa patients aged (median) 65 years old and 59 healthy controls aged (median) 60 years old. Genomic DNA was extracted from whole blood. Genotyping was conducted via TaqMan real-time PCR. Chi-square tests were conducted to compare genotype/allele frequencies, and associations were estimated using unadjusted logistic regression odds ratios (ORs) with 95% confidence intervals. Kruskal-Wallis tests and Spearman correlations were used to examine correlations with Gleason scores. Findings showed that there is a significant genotype and allele difference in COMT rs4680, where low-activity AA is the genotype that presents high risk (OR=9.50, 95% CI: 3.08-36.42, p<0.001 vs. GG), under genotypic as well as dominant models. In the case of rs9332377, the effect of the TT genotype showed a trend towards a protective effect but did not reach statistical significance (OR=0.21, 95% CI: 0.03-0.94, p=0.062 vs. CC). There were significant differences in CYP1B1 rs1056836, with the C alleles higher in cases (83.7% vs. 13.6%), and the GG risk being borderline (OR=4.074, p=0.056). None of the variants were significantly correlated with Gleason scores (p>0.05), although there was a trend in the case of rs1056836 (Spearman rho=0.263, p=0.089). These results suggest that genetic variation in COMT and CYP1B1 may contribute to PCa susceptibility among Nigerian men, potentially through impaired oestrogen detoxification pathways. Further validation in larger cohorts, with adjustments for environmental factors and comparisons across populations, is needed to clarify these associations.
Unraveling the potential of USP8 as a therapeutic target for overcoming c-Met-mediated resistance in breast cancer: A review
(Cancer Treatment and Research Communications, 2026) Amuji, Doris Nnenna; Zakari, Suleiman; Pirisola, Ayomikun Joshua; Ogunlana, Olubanke Olujoke; Iweala, Emeka E.J.
Therapeutic resistance remains a serious challenge in breast cancer, and abnormal c-mesenchymal epithelial transition factor (c-Met) receptor tyrosine kinase (RTK) activation contributes to therapeutic resistance in many. Ubiquitin-specific peptidase 8 (USP8) has emerged as a modulator of RTK stability through deubiquitination and endosomal trafficking, and preclinical studies show that inhibition of USP8 speeds up ubiquitin-dependent degradation of RTKs, including c-Met and EGFR, suppresses PI3K/Akt and MAPK signaling, and reverses resis tance phenotypes. In this review, we summarize mechanistic evidence for USP8 regulation of c-Met and related RTKs, explore preclinical studies that assess inhibition of USP8 as a strategy to sensitize RTK-driven tumors, and highlight translational limitations such as drug selectivity, toxicity, dosing, pharmacodynamics biomarkers, and patient selection that must be addressed prior to a clinical trial in breast cancer. While the therapeutic targeting of USP8 is promising, direct validation in breast cancer models and the development of robust pharmacodynamic markers and inhibitors that are clinically graded remain crucial next phase
Unraveling the potential of USPS as a therapeutic target for overcoming c-Met-mediated resistnce in breast cancer: A view
(Cancer Treatment and Research Communication, 2026) Amnji, Doris Nnenna; Zakari, Suleiman; Pirisola, Ayomikun Joshua; Ogunlana, Olubanke Olujoke