Is docetaxel-free interval a predictive factor for castration-resistant prostate cancer?

OBJECTIVE: Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies. MATERIAL AND METHODS: This clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients' progression time after Dx therapy and the effects on sequential treatment. RESULTS: After Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (p<0.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months. CONCLUSIONS: Our findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.

A New Promising Pathway in Aggressive Prostate Cancer: Treg/mir-let8c/lin28b

Purpose: The progress of prostate cancer entails complex contemporaneous tumor developmental events in diverse stages that they are still yet to be clarified. miRNAs might accompany to balance between regulatory and cytotoxic T cells in tumors. Here, we investigated miRNAs and Regulatory T cell (Treg) marker FOXP3 expressions within prostate cancer spectrum. Methods: Thirty-eight prostate cancer patients enrolled within two groups to the study as having Gleason Score ≤ 7 (Group-1) and ≥ 8 (Group-2) that compared to 19 benign prostate hyperplasia controls. Twelve miRNAs expressions were analyzed by real time PCR from paraffin-embedded prostate tissue samples. Correlations between serum PSA levels, immunohistochemical staining of CD3, CD4, FOXP3 and miRNA expressions were analyzed. Results: In our study, hsa-let7c-3p significantly 1,52 (p=0.018) and 1,84 (p=0.0095) fold down- regulated whereas, miR-141-3p was significantly 2,36 (p=0.0006) and 2,24 (p=0.001) fold upregulated in the prostate cancer patients compared to benign prostate hyperplasia in group 1 and 2, respectively. Only CD4 (p=0.004) and PSA (p<0.001) have statistically significant differences among groups when compared to benign prostate hyperplasia. miR-143-p, miR-221-3p, hsa-let7c-3p and miR-17-3p expressions were significantly correlated with regulatory T cell marker FOXP3 expression. Conclusions: For the first time, we reported significantly altered expression levels of miRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143, miR17) and correlations between Treg marker FOXP3 in the aggressive prostate cancer patients suggesting that prostate cancer progression might be under the regulation of crosstalk between Tregs and miRNAs (AU)

Propósito: El progreso del cáncer de próstata implicaeventos complejos de desarrollo tumoral contemporáneo endiversas etapas que aún no se han aclarado. Aquí, investigamos los MIRNAs y el marcador de células T reguladoras(Treg) FOXP3 expresiones dentro del espectro de cáncer depróstata.Métodos: Treinta y ocho pacientes con cáncer depróstata inscritos dentro de dos grupos para el estudio unapuntuación de Gleason ≤ 7 (Grupo-1) y ≥ 8(Grupo-2)que en comparación con 19 controles benignos de hiperplasia de próstata. Doce expresiones miRNAs fueron analizadas por PCR en tiempo real a partir demuestras detejidoprostático incrustado en parafina. Se analizaronlos nivelesde PSA séricos de correlaciónsetween, la tinción inmunohistoquímica de expresiones CD3, CD4, FOXP3 y miRNA.Resultados: En nuestro estudio, has-let7c-3p significativamente 1,52 (p-0.018) y 1,84 (p-0. 0095) plegarsehacia abajo, mientras que, miR-141-3p fue significativamente 2,36 (p-0.0006) y 2,24 (p-0. 001) plegarse reguladoen los pacientes con cáncer de próstata en comparación conla hiperplasia benigna de próstata en los grupos 1 y 2, respectivamente. Sólo CD4 (p-0.004) y PSA (p<0. 001)tienen diferencias estadísticamente significativas entre losgrupos en comparación con la hiperplasia benigna de próstata. las expresiones miR-143-p, miR-221-3p, has-let7c-3py miR-17-3p se correlacionaron significativamente conlaexpresión FOXP3 del marcador de celda T egulatorio r.Conclusiones: Fo laprimera vez,informamos denivelde expresión significativamente alterado demiRNAs (miR-let7c, miR221, miR-146a, miR-141, miR-143,miR17) y correlaciones entre el marcador Treg DE Treg33en los pacientes agresivos de cáncer de próstata sugiriendoque la progresión del cáncer de próstata podría estar bajo laregulación de la cruz entre Tregtalks y miR. (AU)

Comparison of combined antioxidants and thymoquinone in the prevention of testis ischemia - reperfusion injury.

We aimed to compare the preventive effects of combined antioxidants (CA1, 2) with a single antioxidant drug (thymoquinone; TQ) on experimental testis Ischemia/Reperfusion (I/R) injury. Thirty-five adult male Wistar rats were divided into five groups of seven rats each: control, testis I/R, testis I/R + CA1, testis I/R + CA2, and testis I/R + TQ. After 1 h of testicular ischemia, reperfusion was achieved by detorsion for 4 h. Antioxidants were intraperitoneally administered for 30 min prior to reperfusion. All rats were sacrificed 4 h after reperfusion to evaluate the tissue levels of malondialdehyde (MDA) and total antioxidant status (TAS) and the immunohistochemical evaluation of tissue inducible and endothelial nitric acid synthase (iNOS, eNOS) and apoptosis protease-activating factor 1 (APAF-1). MDA levels were lower and TAS values were higher in the I/R + antioxidant groups than in the I/R group (p < 0.05). iNOS and eNOS levels in the I/R + antioxidant groups were also lower than those in the I/R group (p < 0.05). There were no significant differences between the CA groups and the TQ group according to aforementioned parameters. In addition, tissue APAF-1 values were significantly higher in the I/R group than in the other groups. However, there was a significant difference between the TQ and CA groups in APAF-1 levels, which were highest in the TQ group (p < 0.05). Although TQ alone increased TAS values and reduced tissue iNOS and eNOS levels, combined antioxidant treatment may more effectively reduce apoptosis and increase preventive effects in testis I/R injury.