Analysis of free cisplatin in microdialysates and plasma ultrafiltrate by liquid chromatography-tandem mass spectrometry.

Cisplatin is a potent cytotoxic agent used in the treatment of various malignancies and exerts its antitumor effect through malignant cell DNA damage and apoptosis induction. Evaluation of systemic delivery of cisplatin is important in optimization of cisplatin treatment. However, accurate quantification of systemic cisplatin is challenging due to its various forms in circulation. This study aimed to develop a sensitive (LOQ < 0.1 µg/mL) and precise Ultra Performance Liquid Chromatography (UPLC) - Tandem Mass Spectrometry (MS/MS) method for quantifying free cisplatin in microdialysates and plasma. Furthermore the aim was to compare free cisplatin concentrations measured in standard plasma samples with those obtained from intravenous microdialysis catheters in a porcine model. The method developed utilizes dichloro(ethylenediamine)platinum(II) as an internal standard that co-elutes with cisplatin, ensuring precise correction for ion suppression/enhancement effects. The method was validated, demonstrating linearity up to 100 µg/mL and good intermediate precision (CV% < 6 %) in the range of 1.0-100 µg/mL, with an LOQ of 0.03 µg/mL. The pharmacokinetic parameters (AUC0-last, Cmax, T1/2, and Tmax) showed no significant differences between the two sampling methods. This validated LC-MS/MS method provides a reliable tool for quantifying systemic free cisplatin concentrations, facilitating future systemic and local pharmacokinetic evaluations for optimization of cisplatin-based cancer treatments.

Knockdown of OCT4 may sensitize NSCLC cells to cisplatin

Purpose. Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin. Methods. Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes. Results. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC. Conclusion. Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity (AU)

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Molecular biology of testicular germ cell tumors

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies (AU)

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