Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.

This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile diabetic rats significantly induced CYP2E1 in the cerebrum and cerebellum without modifying it in the liver, while CYP3A2 protein activity increased both in the brain and in the liver. The induction of CYP2E1 in the brain could have important in situ toxicological effects, given that this CYP isoform is capable of bioactivating various toxic substances. Additionally, CYP3A2 induction in the liver and brain could be considered a decisive factor in the variation of drug response and toxicity.

BACKGROUND: Intratumoral up-regulation of genes coding for drug transporters and metabolizing enzymes, such as MDR1 and CYP3A4, after chemotherapy are linked to cancer drug resistance. However their expression in primary soft tissue sarcomas (STS) pr

Pediatric soft-tissue sarcomas (STSs) are aggressive malignancies with poor prognoses, particularly in recurrent and metastatic cases. Standard therapies, such as cytotoxic chemotherapy, offer limited survival benefits and carry significant toxicities, underscoring the urgent need for innovative therapeutic approaches. CYP2W1, a tumor-specific monooxygenase enzyme, has emerged as a promising therapeutic target due to its aberrant expression in various cancers. However, its role in pediatric STSs remains poorly understood. This study evaluated CYP2W1 expression in 42 pediatric STS samples across seven histological subtypes using qPCR and Western blot analyses. High CYP2W1 expression was detected in 69% of tumor samples at the mRNA level and in 40.5% at the protein level, compared to absent or negligible expression in matched normal tissues (p < 0.001). Synovial sarcoma and rhabdomyosarcoma subtypes exhibited the highest CYP2W1 protein expression, at 70% and 62.5%, respectively. Furthermore, CYP2W1 expression was significantly associated with higher histological grade, advanced tumor stage, and a trend toward reduced overall survival (p = 0.082). These findings indicate that CYP2W1 is aberrantly expressed in a subset of pediatric STSs, contributing to tumor aggressiveness and highlighting its potential as a novel therapeutic target for these challenging malignancies.

Pediatric soft tissue sarcomas (STS) are aggressive malignancies with poor prognoses, particularly in recurrent and metastatic cases. Standard therapies, such as cytotoxic chemotherapy, offer limited survival benefits and carry significant toxicities, highlighting the urgent need for innovative ther-apeutic approaches. CYP2W1, a tumor-associated monooxygenase enzyme, has emerged as a promising therapeutic target due to its aberrant expression in various cancers; however, its role in pediatric STS remains poorly understood. This study evaluated CYP2W1 expression in 42 primary pediatric STS samples across seven histological subtypes using qPCR and Western blot analyses, investigating its association with clinicopathological variables and survival outcomes. High CYP2W1 expression at both mRNA and protein levels was observed in 69% and 40.5% of STS tumor samples, respectively, compared to absent or negligible expression in matched normal tissues (p < 0.001). Aberrant CYP2W1 protein expression was predominantly found in synovial sarcoma and rhabdomyosarcoma subtypes, at 70% and 62.5%, respectively. Additionally, CYP2W1 ex-pression correlated with higher histological grade, advanced tumor stage, and showed a trend toward reduced overall survival (p = 0.082). These findings demonstrate that CYP2W1 is aberrantly expressed in a subset of pediatric STS, contributing to tumor aggressiveness and highlighting its potential as a promising therapeutic target for this malignancy.