Protective effects of Yerba mate (IIex paraguariensis) on prostate cancer development.

OBJECTIVES: Prostate cancer (PCa) is the most common adenocarcinoma in men >50 y of age. It has a long latency period, which provides time for preventive strategies like incorporating healthy eating habits. Yerba mate (YM) intake has been associated with numerous health benefits. Since YM is one of the most popular infusions in Argentina, the of this study was to examine the influence of YM on PCa development. METHODS: We carried out an in vivo model of PCa through subcutaneous inoculation of transgenic adenocarcinoma of the mouse prostate-C1 cells in C57BL/6 mice. Subsequently, the animals were divided into two groups: mate (25 mg/mL of YM in drinking water, n = 15), and control (only drinking water, n = 15). We also developed an in vitro model to study the direct effects of YM on three human PCa cell lines: lymph node carcinoma of the prostate (LNCaP), PC-3, and DU-145. RESULTS: Our in vivo model showed that YM intake slightly reduced body weight, increased the latency of tumor appearance (P <0.01), and diminished the tumor volume (P <0.05) compared with the control group. In agreement, the expression of proliferating cell nuclear antigen, and nuclear estrogen receptor α were lower in the tumors of the mate animals (P <0.05). In vitro, YM decreased the viability, proliferation, and adhesion of the three tumor cell lines (P < 0.001) and retarded the migration of LNCaP (P <0.05) and DU-145 (P <0.005), without modifying the migration of PC-3 cells. CONCLUSIONS: YM showed anticancer effects in vitro and in vivo and were more effective on the androgen-sensitive cell line (LNCaP).

Effects of thyroxine on apoptosis and proliferation of mammary tumors.

Hypothyroidism is a protective factor against breast cancer but long-term exposure or overdoses of thyroid replacement therapy with thyroxine (T4) may increase breast cancer risk. OBJECTIVE: to study, in vivo and in vitro, the effects of T4 on the proliferation and apoptosis of mammary tumors of hypo- and euthyroid rats, and the possible mechanisms involved in these effects. MATERIAL AND METHODS: Female Sprague-Dawley rats were treated with a single dose of dimethylbenzathracene (15 mg/rat) at 55 days of age and were divided into three groups: hypothyroidism (HypoT; 0.01% 6-N-propyl-2-thiouracil -PTU- in drinking water, n = 20), hypothyroidism treated with T4 (HypoT + T4; 0.01% PTU in drinking water and 0.25 mg/kg/day T4 via sc; n = 20) and EUT (untreated control, n = 20). At sacrifice, tumor explants from HypoT and EUT rats were obtained and treated either with 10-10 M T4 in DMEM/F12 without phenol red with 1% Charcoalized Fetal Bovine Serum or DMEM/F12 only for 15 min to evaluate intracellular signaling pathways associated with T4, and 24 h to evaluate changes in the expression of hormone receptors and proteins related to apoptosis and proliferation by immunohistochemistry and Western Blot. RESULTS: In vivo, hypothyroidism retards mammary carcinogenesis but its treatment with T4 reverted the protective effects. In vitro, the proliferative and anti-apoptosis mechanisms of T4 were different regarding the thyroid status. In EUT tumors, the main signaling pathway involved was the cross-talk with other receptors, such as ERα, PgR, and HER2. In HypoT tumors, the non-genomic signaling pathway of T4 was the chief mechanism involved since αvß3 integrin, HER2, ß-catenin and, downstream, PI3K/AKT and ERK signaling pathways were activated. CONCLUSION: T4 can regulate mammary carcinogenesis by mainly activating its non-genomic signaling pathway and by interacting with other hormone or growth factor pathways endorsing that overdoses of thyroid replacement therapy with T4 can increase the risk of breast cancer.

Changes in prolactin receptor location in prostate tumors. / Cambios en la localización del receptor prolactina en tumores prostáticos.

INTRODUCTION: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. OBJECTIVE: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. METHODS: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. RESULTS: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p< 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process.In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles.The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. CONCLUSION: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.

INTRODUCCIÓN: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT.OBJETIVO: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopio confocal.RESULTADOS: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentaje de células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino.CONCLUSIÓN: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con la proliferación celular y la supervivencia.

Changes in prolactin receptor location in prostate tumors / Cambios en la ubicación del receptor de prolactina en tumores de próstata

Introduction: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT. Objetive: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns. Methos: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy. Results: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process. In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles. The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner. Conclusion: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.(AU)

Introducción: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT. Objetivo: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopioconfocal. Resultados: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentajede células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino. Conclusión: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con laproliferación celular y la supervivencia.(AU)

Evolución de los pacientes con enfermedad hepática crítica / Prognosis of patients with critical hepatic disease

INTRODUCTION: The acute liver failure on chronic (ACLF), is an entity, whose recognition is increasing. The ACLF and CLIF OF indexes have been recently presented with the objective of predicting mortality in this kind of patients. MATERIAL AND METHODS: All patients admitted to the Ramón y Cajal University Hospital diagnosed of acute liver failure on chronic during 2016 and 2017 were collected. We collect the scores: SOFA, CLIF, APACHE II, SAPS II and ACLF score in patients admitted to the ICU by comparing them with each other and define which stages have worse prognosis. RESULTS: A total of 46 patients were collected. The study presents an intra ICU mortality of 31% (15/46) and a six-month mortality of 59.6% (28/46). Patients classified as death, present ACLF values ​​at admission (49.5 vs 60 p = 0.001), and at three days (46.66 vs 59.4 p = 0.001) higher than survivors. In the analysis of the ROC curve, the area under the curve in relation to six-month mortality is higher in the ACLF index (0.8) compared to the MELD (0.69) SOFA (0.66) SAPS II (0.69) or APACHE II (0.65). Patients with ACLF indexes above 65 had an intra UCI mortality of 54%, however, mortality at 6 months is 90%. Patients with ACLF values ​​greater than 65 present mean values ​​of lactic acid, leukocytes, INR or bilirubin higher than those under 65 in a statistically significant manner. CONCLUSIONS: The data presented in this study suggest that the ACLF index works as an adequate predictor of intra-ICU mortality and at 6 months.

INTRODUCCIÓN: El fallo hepático agudo sobre crónico es una entidad cuyo reconocimiento va en aumento. Los índices ACLF y CLIF OF, han sido presentados recientemente con el objetivo de predecir la mortalidad en este tipo de enfermos. MATERIAL Y MÉTODOS: Se recogen todos los pacientes ingresados en una unidad de cuidados intensivos (UCI) de un hospital terciario universitario, diagnosticados de fallo hepático agudo sobre crónico durante 2016 y 2017. Recogemos los índices SOFA, CLIF, APACHE II, SAPS II Y ACLF en pacientes ingresados en UCI comparándolos entre sí. Definimos que estadios presentan peor pronóstico. RESULTADOS: Se analizan un total de 46 pacientes. El estudio presenta una mortalidad intra-UCI del 31% (15/46) y una mortalidad a los seis meses de 59,6% (28/46). Los pacientes clasificados como éxitus presentan valores ACLF al ingreso (49,5 vs 60 p = 0,001), a los tres días (46,66 vs 59,4 p = 0,001) superiores a los supervivientes. En el análisis de la curva COR, el área bajo la curva en relación a la mortalidad a los seis meses, es superior en el índice ACLF (0,8) en comparación con el MELD (0,69) SOFA (0,66) SAPS II (0,69) o APACHE II (0,65). Los pacientes con índices ACLF superiores a 65 presentaban una mortalidad intra-UCI del 54% sin embargo, la mortalidad a los 6 meses es del 90%. Los pacientes con valores ACLF superiores a 65 presentan a su vez valores medios de láctico, leucocitos, INR o bilirrubina mayores de forma estadísticamente significativa. CONCLUSIONES: Los datos presentados en este estudio sugieren que el índice ACLF funciona como un adecuado predictor de mortalidad intra-UCI y a los 6 meses.