CEP72 (Centrosomal Protein 72)

Vincristine, a cornerstone vinca alkaloid in pediatric oncology, has historically been regarded as a low-risk agent for drug-induced acute pancreatitis (DIAP). Vindesine may serve as a safe and effective alternative agent. These findings underscore the importance of updating pediatric chemotherapy safety guidelines for vinca alkaloid-containing regimens.

Concurrent methotrexate use was found to exacerbate VCR-induced neurotoxicity. VCR-induced neurotoxicity remains a significant challenge in ALL therapy. Standardized neurotoxicity assessment tools and prospective studies are needed to improve early detection and optimize management strategies, ultimately balancing treatment efficacy with minimizing neurological morbidity.

Drug sensitivity analysis showed increased responsiveness to chemotherapeutic agents like 5-fluorouracil and alpelisib in high-CCDC138 tumors. These findings underscore CCDC138's role in UCEC progression, immune modulation, and therapeutic responsiveness, highlighting its potential as a prognostic biomarker and therapeutic target. Its shared relevance in UCEC and ciliopathies suggests broader implications for targeted therapies.

Future work to validate biomarkers like CEP72 may allow clinicians to identify patients who may benefit from altered chemotherapy dosages relative to CIPN risk.

Based on our findings, CEP72 is a prognostic biomarker for HCC, and the miRNA-mediated expression of CEP72 may affect the prognosis of HCC patients.

A variety of chemotherapeutic agents can contribute to the development of CIPN, including vinca alkaloids, platinum-based antineoplastic agents, epothilones (ixabepilone), proteasome inhibitors (bortezomib), taxanes, and immunomodulatory drugs (thalidomide), along with the genetic factors...Pharmacological interventions, such as anticonvulsants, gabapentin, and pregabalin, are commonly used to manage neuropathic pain. Tricyclic antidepressants like amitriptyline and nortriptyline can be effective, but their use may be limited due to side effects...The lidocaine or capsaicin creams and patches can provide localized pain relief...Transcutaneous electrical nerve stimulation and spinal cord stimulation are invasive procedures that may be considered for severe, intractable pain. Complementary therapies and cognitive-behavioural therapy can help patients cope with pain and improve their quality of life.

Last, we show that MLL and WDR5 recruit Cep72 to the centrosome. Our studies provide insight into an undiscovered role of MLL at the centrosome and elucidate how centriolar satellite proteins like Cep72 can be recruited to the centrosome.

The results showed that allometric scaling, ABCB1-rs1128503 genotype, and posaconazole (POS) significantly improved the PopPK model fit...No significant effects on VIPN were observed for CYP3A5 (rs776746), CYP3A4 (rs2242480), CEP72 (rs924607), or various ABCB1 variants (rs1128503, rs2032582, rs1045642, rs4728709, rs4148737, and rs10276036), nor with the co-administration of fluconazole or dasatinib. In summary, co-administration of POS increased VCR exposure by 0.4-fold and raised the risk of VIPN, with an occurrence probability generally exceeding 0.7. Therapeutic drug monitoring of VCR in clinical practice may be necessary to enable appropriate dose adjustments and individualized treatment.

Thus, the SNP rs924607 in the CEP72 gene is associated with increased VIPN incidence in female patients with aggressive B-NHL treated with CHOP chemotherapy. Trial registration ClinicalTrials.gov identifier: NCT00052936, submission date: 2005-06-23, EudraCT Number: 2010-019587-36.

No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN.

Among the polymorphisms examined, 14 across 13 genes showed significant associations with MTX-PG2-5 levels, even after adjusting for the false discovery rate (ABCC5, ATG16L1, CEP72, FSTL5, GMPS, HTR3A, IMPDH1, NT5C2, SLC28A3, SLCO1B3, SUCLA2, TPMT, and TYMS). This study enhances our understanding of genetic polymorphisms in MTX metabolism and therapeutic monitoring for MTX maintenance, promoting personalized medicine in acute lymphoblastic leukemia patients.

P=N/A, N=137, Completed, St. Jude Children's Research Hospital | Suspended --> Completed | N=200 --> 137