Alejandro Mercado

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.

Molecular signature of cancer stem cells isolated from prostate carcinoma and expression of stem markers in different Gleason grades and metastasis

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Chemotherapy response is very poor and resistance to hormone-based treatments is frequent in advances stages. Recently, tumor-initiating cells or cancer stem cells (CSCs) have been identified in several cancers, including PCa. These cells are thought to be responsible for therapy resistance, relapse and metastasis. In the present work, enriched populations of CSCs were obtained using a mixed procedure that included differential clone-forming ability, sphere growing induction (prostatospheres) and magnetic-associated cell sorting (MACS). Also, stem marker expression was determined in PCa biopsies of different histological grades and metastasis samples. The signature for stem markers of the isolated CSCs was CD133+/CD44+/ABCG2+/ CD24-. Expression of stem markers (CD133, CD44, and ABCG2) was higher in medium Gleason biopsies than in lower and higher grades, and lymph-node and bone metastasis samples. These results suggest that the CSCs in PCa reach an important number in medium Gleason grades, when the tumor is still confined into the gland. At this stage, the surgical treatment is usually with curative intention. However, an important percentage of patients relapse after treatment. Number and signature of CSCs may be a prognosis factor for PCa recurrence.

Comparación entre cirugía retrógrada intrarrenal y litotricia extracorpórea para el tratamiento de la litiasis de polo inferior renal de hasta 15 mm. Estudio prospectivo aleatorizado

INTRODUCTION Extracorporeal Shock Wave Lithotripsy (ESWL) is currently the recommended treatment for intra-renal calculi smaller than 2 cm. However the low Stone Free Rate (SFR) in lower pole calculi gives rise to new techniques, such us retrograde intrarenal surgery (RIRS), for improve the surgery outcomes. OBJECTIVE To compare the efficacy of a treatment with ESWL with RIRS, in terms of SFR after surgery, in patients with kidney stones up to 15 mm in the lower pole. MATERIAL AND METHODS A prospective study was carried out in order to assess the results of ESWL and RIRS in patients with lower pole stones less than 15 mm. Among a total of 55 patients, 31 were underwent to ESWL (Group 1) and the remaining 24 to RIRS (Group 2). Clinical data recorded, including general characteristics of each patient, were: calculi size, side, operative time, complications according to Clavien scale, SFR and the presence of residual fragments at 2 months post-treatment assessed by a CT scan. STATA 11 was used to perform the statistical analysis. RESULTS There were no differences for general descriptors among groups with the exception of a significantly longer operative time for RIRS. The rates of SFR and residual fragments lesser than 3 mm. were lower in the RIRS group than in ESWL ones. RIRS also showed a lower rate of clinically significant fragments (0% vs 42.3%. P < .05). In the subgroup of patients with stones between 10/15 mm RIRS showed higher SFR (75% vs. 41.2%) and a lower rate of stones>3 mm (0% vs. 58.8%), being statistically significant (P < .05). Clavien III or higher complications were not reported in any of the groups. CONCLUSIONS In the treatment of lower pole stone RIRS has the same results than ESWL in terms of SFR. Regarding absence of a clinically significant residual fragment, RIRS was superior to ESWL. A bigger sample size is required in order to confirm this results.

Laparoscopic partial nephrectomy: A series of one hundred cases performed by the same surgeon

Introduction: Laparoscopic partial nephrectomy (LPN) has become the first-line surgical technique for the management of renal tumors smaller than 4 cm. Its main advantages are an excellent oncologic control together with the preservation of nephron units. Moreover, it implies a shorter length of hospital stay, less postoperative pain, and shorter recovering times for patients. Context: We included 100 patients who consecutively underwent LPN between years 2000 and 2010 in our institution. Aims: The aim was to present our experience and to compare it with the results reported in the literature by other centers. Settings and Design: This was a prospective study. Subjects and Methods: One hundred consecutive patients (67 men and 33 women) who underwent LPN within years 2000 and 2010 were included in the study. In all cases, surgery was performed by the same surgeon (JMC). Data were collected retrospectively, including clinical and histopathologic information, as well as surgical and functional results. Statistical Analysis Used: Statistical analysis was performed using the chi-square test and SPSS v17 software. A P–value < 0.05 was considered significant in all the analyses. Results: The indication for LPN was a renal tumor or a complex renal cyst in the 96% of the cases. A retroperitoneal or transperitoneal approach was performed in the 62% and 38% of the cases, respectively. The average size of the tumor was 3.3 cm (range 1–8). The mean surgical time was 103.5 min (range 40–204). The mean estimated blood loss was 193.7 cc. The average hospital length of stay was 50.2 h. Six (6%) patients had complications related to the surgery. The majority (n = 2) was due to intraoperative bleeding. With an average follow-up time of 42.1 months, there is no tumor recurrence reported up to now. Conclusions: Our results are similar to those reported in the international literature. LPN is a challenging surgical technique that in hands of a trained and experienced surgeon has excellent and reproducible results for the management of small renal masses and cysts.

Pharmacoperone IN3 enhances the apoptotic effect of leuprolide in prostate cancer cells by increasing the gonadotropin-releasing hormone receptor in the cell membrane.

Gonadotropin-releasing hormone (GnRH) agonists are widely used for the treatment of advanced prostate cancer (PCa). Agonists activate the GnRH receptor (GnRH-R), triggering apoptosis in PCa cells. In gonadotropes, the amount of GnRH-R in the plasma membrane is regulated by protein folding and endoplasmic reticulum retention, mechanisms that can be overcome by the pharmacoperone IN3. Our aim was to describe the intracellular distribution of GnRH-R in PCa cells and its relation to response to GnRH analog treatments. The expressions of GnRH-R in PCa biopsies were evaluated by immunohistochemistry and the intracellular distribution was determined by immunofluorescence in primary cell cultures from human PCa samples. Cultured cells were pretreated with IN3 and then with leuprolide. Cell survival was evaluated by 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) thiazolyl blue formazan and cell cycle and apoptosis by flow cytometry. We observed that the expression of GnRH-R decreased according to malignant progression. Most GnRH-R are located inside the cell, colocalizing with endoplasmic reticulum markers. The treatment with IN3 decreased cellular GnRH-R retention, increasing plasma membrane expression in approximately 60%. Pretreatment with IN3 decreased PCa cell survival compared with leuprolide-alone treatment, primarily because of an increase in apoptosis. We conclude that the response of PCa cells to leuprolide is related to the amount of GnRH-R in the plasma membrane. Therefore, pretreatment evaluation of the amount of these receptors may be a predictor of the outcome of leuprolide treatment in PCa patients. Assessment of systemic IN3 effect would be necessary to determine its utility as an adjuvant treatment in hormone-resistant tumors.