Purpose: The prodrug cyclophosphamide (CPA) is activated by cytochrome P450 (CYP) enzymes. CPA is one of the corner stones in all cancer treatment. We have studied the effect of repeated doses of CPA given at different time intervals on the mRNA, protein levels, and enzyme activity of CYPs in rats.
Experimental Design: Two groups of animals (A-75 and A-150) were treated with four doses of CPA (75 and 150 mg/kg, respectively) at short time intervals (6 h). The third group of animals (B-150) was treated with 150 mg/kg at 24-h intervals. Three animals were killed 30 min after administration, and three animals immediately before the next dose.
Results: CYP2B1 and CYP2B2 mRNAs were significantly induced at 6 h after each dose in group A-75 (maximum of 2100-fold and 60-fold after the third dose, respectively), whereas the mRNA levels measured at 6 h postadministration in group A-150 were 1,490-fold and 36-fold after the second dose. In group B-150, no significant induction of mRNA levels was observed. CYP2B1 and CYP2B2 protein levels also increased with increased mRNAs. Plasma levels of 4-hydroxy-CPA measured at 30 min after dose correlated well with the increase in protein levels.
Conclusion: Up-regulation of CYP2B mRNA, with a concomitant increase in protein expression and activity, were observed after repeated administration of low doses of CPA compared with that found using higher doses, possibly due to toxicity counteracting induction. These results may help in designing more effective dosing schedules for CPA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1078-0432.CCR-07-0320 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Comparison of urinary excretion patterns among exposures to cosmetic preservative, herbicide, and nootropic stimulant in anti-doping analysis.
J Chromatogr B Analyt Technol Biomed Life Sci
December 2024
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Doctoral Degree Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address:
Doping with meclofenoxate, a nootropic stimulant prohibited in-competition by the World Anti-Doping Agency (WADA), is identified through the primary marker of urinary 4-chlorophenoxyacetic acid (4-CPA). However, the presence of 4-CPA can also arise from permissible sources. This study ventured into comparing urinary excretion patterns among exposures to permitted chemicals (chlorphenesin and 4-CPA) and the banned stimulant (meclofenoxate) and interpreting the analytical findings according to the reporting requirements.
View Article and Find Full Text PDFInteractive plant growth regulator and fertilizer application dataset on growth and yield attributes of tomato ( L.).
Data Brief
December 2024
Department of Horticulture, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur 1706, Bangladesh.
Tomato is known for its remarkable contents of vitamins, minerals and antioxidants. A pot experiment was performed during the winter-summer transition from December 2022 to April 2023 combining low to high fertilizer rates and plant growth regulators (PGRs). The objective was to decrease the utilization of artificial fertilizers through the application of PGRs.
View Article and Find Full Text PDFSuccessful treatment of chronic pulmonary aspergillosis in a patient with early pulmonary tuberculosis and COVID-19: a case report.
Multidiscip Respir Med
December 2024
Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil.
Introduction: Chronic pulmonary aspergillosis (CPA) often develops in residual lesions of pulmonary tuberculosis (PTB). Every year, 112,000 to 160,000 people worldwide will develop post-PTB CPA. The simultaneous occurrence of CPA with the first episode of PTB is rare.
View Article and Find Full Text PDFA framework to model charge sharing and pulse pileup for virtual imaging trials of photon-counting CT.
Phys Med Biol
November 2024
Carl E. Ravin Advanced Imaging Laboratories and Center for Virtual Imaging Trials, Duke University, Durham, NC 27705, United States of America.
This study describes the development, validation, and integration of a detector response model that accounts for the combined effects of x-ray crosstalk, charge sharing, and pulse pileup in photon-counting detectors.The x-ray photon transport was simulated using Geant4, followed by analytical charge sharing simulation in MATLAB. The analytical simulation models charge clouds with Gaussian-distributed charge densities, which are projected on a 3×3 pixel neighborhood of interaction location to compute detected counts.
View Article and Find Full Text PDFGiant Intracranial Meningiomas Requiring Surgery in 2 Transgender Women Treated With Cyproterone Acetate.
JCEM Case Rep
October 2024
Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia.
Article Synopsis
- Progestin-associated meningioma is a rare but serious complication linked to cyproterone acetate (CPA), which is often used in feminizing hormone therapy for transgender individuals.
- Two cases of transgender women developing symptomatic giant meningiomas after using CPA are reported, illustrating that both high and low doses of CPA can lead to this condition.
- The findings emphasize the importance of monitoring for neurological side effects and recommend prescribing the lowest effective dose of CPA, while considering alternatives when possible.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!