Juan Cabezas

Chemotherapy sensitivity recovery of prostate cancer cells by functional inhibition and knock down of multidrug resistance proteins.

In several cancer types, expression of multidrug resistance (MDR) proteins has been associated with lack of chemotherapy response. In advanced prostate cancer (PCa) the use of chemotherapy is mainly palliative due to its high resistance. Previously, we described that MDR phenotype in PCa could be related with high basal and drug‐induced expression of MDR proteins P‐Glycoprotein (P‐Gp), MRP1, and LRP.

Gonadotropin Releasing Hormone Analogs Induce Apoptosis by Extrinsic Pathway Involving p53 Phosphorylation in Primary Cell Cultures of Human Prostatic Adenocarcinomas

Gonadotropin‐releasing‐hormone (GnRH) analogs are widely used to block hypothalamic–pituitary–gonadal axis and inhibit blood androgen levels in patients with prostate cancer (PCa). In addition, GnRH analogs induce proliferation arrest and apoptosis through GnRH receptors expressed on the membrane of PCa cells. Possible molecular mechanisms involved in GnRH‐mediated apoptosis on prostate cancer cells were studied.

Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma.

7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.

Initial human feasibility study of DC Ablation as a treatment for benign prostatic hyperplasia: 6 month follow-up data

Direct current (DC) ablation is a novel non-thermal technology that causes focused coagulative necrosis in the lateral lobes of the prostate to treat benign prostatic hyperplasia (BPH). The necrosis is caused by a zone of non-physiologic pH which is created in a predictable pattern around each electrode in which a direct current is applied during treatment. The objective of this study was to optimize treatment parameters and assess treatment tolerability using transurethral DC ablation as an office-based treatment for BPH.