Inpatient and outpatient treatment by specialist infant nutrition centres in Argentina effectively reduced child malnourishment.

AIM: We evaluated the impact of inpatient and outpatient treatment provided by an infant nutrition foundation in Las Heras, Mendoza, Argentina and identified the factors that influenced nutritional recovery. METHODS: This 2010-2018 retrospective study was based on 300 children up to 5 years of age with primary malnutrition, who were treated by an inpatient recovery centre, then an outpatient prevention centre. We analysed the children's height, weight, psychomotor development and living conditions when they were admitted, discharged and had received 1 year of outpatient treatment. There were full data on 241 children and just admission and discharge data for 59. RESULTS: The children's mean age on admission and weight were 14.8 ± 12.4 months and 6.9 ± 2.3 kg and they stayed in hospital for a mean of 59.5 ± 49.7 days. We observed a significant increase in the weight-for-age, height-for-age and weight-for-height z-scores when all three time points were compared (p < 0.001). Psychomotor development improved considerably in all patients after treatment. The factors that negatively influenced nutritional recovery were higher age at admission, suboptimal breastfeeding practices, low birth weight, longer hospital stays, younger maternal age and overcrowded housing. CONCLUSION: Combining inpatient recovery and outpatient preventive treatment was effective for undernourished children in Argentina.

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).

Long-term impact of hypothyroidism during gestation and lactation on the mammary gland.

The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.

Salvage Radical Prostatectomy in Nonmetastatic Castration-Resistant Prostate Cancer.

OBJECTIVE: To analyze the perioperatory and short-oncological outcomes in 5 cases with CRPC M0 developed after pRT that underwent salvage laparoscopic RP (sLRP) and review the current evidence. MATERIAL AND METHODS: Perioperatory and oncological outcomes were prospectively analyzed. Inclusion criteria were patients that had received pRT and posteriorly presented with CRPC M0 in standard imagines and positron emission tomography MRI coline. Evidence was reviewed in PUBMED database. RESULTS: No surgical complications and blood transfusion were reported. Two patients required an endoscopic urethrotomy due to bladder neck contracture (Clavien IIIb). Final pathological findings were T3 or more, multifocal with 3 positive surgical margins. Four patients reach undetectable PSA after surgery except one that continuous under ADT without disease progression. After 12 months follow-up, 4 patients persist with undetectable PSA and one with stable disease under ADT. Current evidence demonstrated that CRPC M0 treated with open, laparoscopic or robotic RP a biochemical recurrence of 68.7% as a hormone-sensitive PC; however, 17.4% were disease-free after 4 years of follow-up. CONCLUSION: Our serie, 4 cases are disease free after 12 months follow-up. Current evidence is a retrospective and multicenter experience with few cases and intermediate oncological follow-up. More cases with longer follow-up and better evidence are required to opt for this treatment as a first line.

Salvage Radical Prostatectomy in Nonmetastatic Castration-Resistant Prostate Cancer

Objective: To analyze the perioperatory and short-oncological outcomes in 5 cases with CRPC M0 developed after pRT that underwent salvage laparoscopic RP (sLRP) and review the current evidence. Material and Methods: Perioperatory and oncological outcomes were prospectively analyzed. Inclusion criteria were patients that had received pRT and posteriorly presented with CRPC M0 in standard imagines and positron emission tomography MRI coline. Evidence was reviewed in PUBMED database. Results: No surgical complications and blood transfusion were reported. Two patients required an endoscopic urethrotomy due to bladder neck contracture (Clavien IIIb). Final pathological findings were T3 or more, multifocal with 3 positive surgical margins. Four patients reach undetectable PSA after surgery except one that continuous under ADT without disease progression. After 12 months follow-up, 4 patients persist with undetectable PSA and one with stable disease under ADT. Current evidence demonstrated that CRPC M0 treated with open, laparoscopic or robotic RP a biochemical recurrence of 68.7% as a hormone-sensitive PC; however, 17.4% were disease-free after 4 years of follow-up. Conclusion: Our serie, 4 cases are disease free after 12 months follow-up. Current evidence is a retrospective and multicenter experience with few cases and intermediate oncological follow-up. More cases with longer follow-up and better evidence are required to opt for this treatment as a first line (AU)

Renal peritumoral adipose tissue undergoes a browning process and stimulates the expression of epithelial-mesenchymal transition markers in human renal cells.

Tumor cells can interact with neighboring adipose cells and adipocyte dedifferentiation appears to be an important aspect of tumorigenesis. We evaluated the size of adipocytes in human adipose explants from normal (hRAN) and kidney cancer (hRAT); changes in the expression of WAT and BAT/beige markers in hRAN and hRAT; the expression of epithelial-mesenchymal transition (EMT) cell markers in human kidney tumor (786-O, ACHN and Caki-1); and non-tumor (HK-2) epithelial cell lines incubated with the conditioned media (CMs) of hRAN and hRAT. We observed that hRAT adipocytes showed a significantly minor size compared to hRAN adipocytes. Also, we observed that both Prdm16 and Tbx1 mRNA and the expression of UCP1, TBX1, PPARγ, PCG1α, c/EBPα LAP and c/EBPα LIP was significantly higher in hRAT than hRAN. Finally, we found an increase in vimentin and N-cadherin expression in HK-2 cells incubated for 24 h with hRAT-CMs compared to hRAN- and control-CMs. Furthermore, desmin and N-cadherin expression also increased significantly in 786-O when these cells were incubated with hRAT-CMs compared to the value observed with hRAN- and control-CMs. We observed a significant decrease in E-cadherin expression in the ACHN cell line incubated with hRAT-CMs versus hRAN- and control-CMs. However, we did not observe changes in E-cadherin expression in HK-2, 786-O or Caki-1. The results obtained, together with the results previously published by our group, allow us to conclude that perirenal white adipose tissue browning contributes to tumor development in kidney cancer. In addition, hRAT-CMs increases the expression of mesenchymal markers in renal epithelial cells, which could indicate a regulation of EMT due to this adipose tissue.

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.

The epigenetic role of breastfeeding in mammary differentiation.

Maternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.

[Expression of Hemeoxygenase-1 and clear cell renal cell carcinoma aggressiveness.] / Expresión de Hemo Oxigenasa-1 y agresividad del carcinoma renal de células claras.

OBJECTIVE: Hemoxigenase 1 (HO-1) is an enzyme that has anti-apoptotic and proliferative effects on tumor cells. However, there is little epidemiological and clinical evidence on the role of HO-1 in urologic tumors. OBJECTIVE: To determine if there is correlation between the expression of HO-1 and the histological characteristics, evolution, Disease Free Survival (DFS) and cancer mortality in Clear Cell Renal Cell Carcinoma (cRCC). MATERIALS AND METHODS: A retrospective study including 34 patients (9 women and 25 men) with cRCC from the "Servicio de Urología del Policlínico Neuquén" (Argentina) throughout 2003-2008. The expression of HO-1 by Immunohistochemistry (IHC) was determined. The statistical analysis was performed using the Student'sT test and Pearson correlation coefficient (p≤0.05). RESULTS: HO-1 was expressed in the epithelial cells of the tubules from normal kidney tissue and in the cytoplasmof cRCC tumor cells. There were no differences in the HO-1 expression related to the gender, age, tumorsize, stage of disease and 5 years DFS. High FuhrmancRCC had a greater expression of HO-1 compared with low Fuhrman cRCC (p≤0.05). The score of immunostaining for HO-1 was greater in those tumors located in the mesorrenal area, which coincidentally presented a more advanced stage of the disease. CONCLUSIONS: Over expression of HO-1 in tumors located in the interpolar zone and with high Furhman grade suggest that HO-1 could be a good adjunctive marker for the aggressiveness of the cRCC.

OBJETIVO: Hemoxigenasa 1 (HO-1) es una enzima que tiene efectos antiapoptóticos y proliferativos en células tumorales. Sin embargo, existe poca evidencia epidemiológica y clínica sobre el rol de la HO-1 en los tumores urológicos. Objetivo: determinar si existe correlación entre la expresión de HO-1 y las características histológicas, evolución, Sobrevida Libre de Enfermedad (SLE) y mortalidad por cáncer en Carcinomas Renales de Células Claras (cRCC). MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo en 34 pacientes (9 mujeres y 25 hombres) con cRCC del Servicio de Urología del Policlínico Neuquén, reclutados entre los años 2003 y 2008. Se determinó la expresión de HO-1 por Inmunohistoquímica (IHQ). El análisis estadístico se realizó mediante la prueba T de Student y Coeficiente de correlación de Pearson (p<0,05). RESULTADOS: HO-1 se expresó en el epitelio de los túbulos del tejido renal normal y en el citoplasma de las células tumorales de cRCC. No se observaron diferencias en la expresión de HO-1 según género, edad, tamaño tumoral, estadio de la enfermedad y SLE a los 5 años. Los tumores con Fuhrman alto presentaron una mayor expresión de HO-1 que los Furhman bajo (p≤0,05). El score de inmunotinción de HO-1 fue mayor en los tumores localizados en la zona interpolar, que coincidentemente presentaban un estadio más avanzado de la enfermedad. CONCLUSIONES: La sobreexpresión de HO-1 en tumores localizados en la zona interpolar y con grado de Furhman alto sugieren que HO-1 podría ser un buen marcador complementario de la agresividad del cRCC.

Expresión de Hemo Oxigenasa-1 y agresividad del carcinoma renal de células claras / Expression of Hemeoxygenase-1 and clear cell renal cell carcinoma aggressiveness

OBJETIVO: Hemoxigenasa 1 (HO-1) es una enzima que tiene efectos antiapoptóticos y proliferativos en células tumorales. Sin embargo, existe poca evidencia epidemiológica y clínica sobre el rol de la HO-1 en los tumores urológicos. OBJETIVO: determinar si existe correlación entre la expresión de HO-1 y las características histológicas, evolución, Sobrevida Libre de Enfermedad (SLE) y mortalidad por cáncer en Carcinomas Renales de Células Claras (cRCC). MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo en 34 pacientes (9 mujeres y 25 hombres) con cRCC del Servicio de Urología del Policlínico Neuquén, reclutados entre los años 2003 y 2008. Se determinó la expresión de HO-1 por Inmunohistoquímica (IHQ). El análisis estadístico se realizó mediante la prueba T de Student y Coeficiente de correlación de Pearson (p < 0,05). RESULTADOS: HO-1 se expresó en el epitelio de los túbulos del tejido renal normal y en el citoplasma de las células tumorales de cRCC. No se observaron diferencias en la expresión de HO-1 según género, edad, tamaño tumoral, estadio de la enfermedad y SLE a los 5 años. Los tumores con Fuhrman alto presentaron una mayor expresión de HO-1 que los Furhman bajo (p≤0,05). El score de inmunotinción de HO-1 fue mayor en los tumores localizados en la zona interpolar, que coincidentemente presentaban un estadio más avanzado de la enfermedad. CONCLUSIONES: La sobreexpresión de HO-1 en tumores localizados en la zona interpolar y con grado de Furhman alto sugieren que HO-1 podría ser un buen marcador complementario de la agresividad del cRCC

OBJECTIVE: Hemoxigenase 1 (HO-1) is an enzyme that has anti-apoptotic and proliferative effects on tumor cells. However, there is little epidemiological and clinical evidence on the role of HO-1 in urologic tumors. OBJECTIVE: To determine if there is correlation between the expression of HO-1 and the histological characteristics, evolution, Disease Free Survival (DFS) and cancer mortality in Clear Cell Renal Cell Carcinoma (cRCC). MATERIALS AND METHODS: A retrospective study including 34 patients (9 women and 25 men) with cRCC from the "Servicio de Urología del Policlínico Neuquén" (Argentina) throughout 2003-2008. The expression of HO-1 by immunohistochemistry (IHC) was determined. The statistical analysis was performed using the Student's T test and Pearson correlation coefficient (p≤0.05). RESULTS: HO-1 was expressed in the epithelial cells of the tubules from normal kidney tissue and in the cytoplasm of cRCC tumor cells. There were no differences in the HO-1 expression related to the gender, age, tumor size, stage of disease and 5 years DFS. High Fuhrman cRCC had a greater expression of HO-1 compared with low Fuhrman cRCC (p≤0.05). The score of immunostaining for HO-1 was greater in those tumors located in the mesorrenal area, which coincidentally presented a more advanced stage of the disease. CONCLUSIONS: Overexpression of HO-1 in tumors located in the interpolar zone and with high Furhman grade suggest that HO-1 could be a good adjunctive marker for the aggressiveness of the cRCC

[Management of lithiasis associated with intrarrenal stenosis using the flexible videoureteroroscope.] / Manejo de la litiasis asociada a estenosis intrarrenales mediante el uso del videoureterorrenoscopio flexible.

OBJECTIVE: Intrarenal stenosis, even caliceal diverticula or neck diverticular stenosis, associated with lithiasis are infrequent therefore their management is a challenge. The aim of this article is to report two cases who underwent retrograde intrarenal surgery and Holmium laser as a modern technological tool, proposing a new gold standard. METHODS: We report 2 cases of intrarenal stenosis associated with lithiasis managed with flexible videoureteroscope (STORZ) and Holmium laser (CALCULASE II). One case presented a caliceal diverticulum and the other a caliceal ostium stenosis secondary to previous percutaneous surgery. The ostium was incised with laser to access the diverticulum in the first case and in the second case a dilatation was required. Lithiasis treatment was performed with laser. Disease free rate was defined when the cavity completely disappeared and lithiasis fragments were less than 2 mm on CT Scan one month after procedure. RESULTS: Surgical time were 60 and 82 minutes for cases 1 and 2, respectively. Both patients evolved satisfactorily with 8 hours hospital stay and without perioperative complications. The disease-free rate was 100%. CONCLUSION: Flexible videoureterorrenoscopy and Holmium laser for the management of intrarenal stenosis are highly effective and safe with the advantages of less perioperative complications, less invasiveness and being an outpatient procedure compared to percutaneous surgery.

OBJETIVO: Reportar dos casos de estenosis intrarrenales asociado a litiasis manejados con el videoureterrenoscopio flexible (STORZ) y el láser de Holmium (CALCULASE II) como herramienta tecnológica y moderna.MATERIAL Y MÉTODOS: El caso 1 presentaba un divertículo calicial el cual fue tratado mediante la incisión del ostium diverticular con láser y posterior tratamiento de la litiasis. El segundo caso presentaba una estenosis del ostium caliceal secundario a una cirugía percutánea previa pudiendo acceder al cáliz mediante la dilatación del mismo. RESULTADOS: El tiempo quirúrgico fue de 60 y 82 minutos para el caso 1 y 2, con una estancia hospitalaria de 8 horas y sin complicaciones perioperatorias. La tasa libre de enfermedad fue del 100%. CONCLUSIONES: El videoureterorrenoscopio flexible y laser de Holmium para el manejo de las estenosis intrarrenales es altamente efectivo y seguro con las ventajas de presentar menos complicaciones perioperatorias, menos invasividad y ser ambulatorio comparado con la cirugía percutánea.

Manejo de la litiasis asociada a estenosis intrarrenales mediante el uso del videoureterorrenoscopio flexible / Management of lithiasis associated with intrarrenal stenosis using the flexible videoureteroroscope

OBJETIVO: Reportar dos casos de estenosis intrarrenales asociado a litiasis manejados con el videoureterrenoscopio flexible (STORZ) y el láser de Holmium (CALCULASE II) como herramienta tecnológica y moderna. MATERIAL Y MÉTODOS: El caso 1 presentaba un divertículo calicial el cual fue tratado mediante la incisión del ostium diverticular con láser y posterior tratamiento de la litiasis. El segundo caso presentaba una estenosis del ostium caliceal secundario a una cirugía percutánea previa pudiendo acceder al cáliz mediante la dilatación del mismo. RESULTADOS: El tiempo quirúrgico fue de 60 y 82 minutos para el caso 1 y 2, con una estancia hospitalaria de 8 horas y sin complicaciones perioperatorias. La tasa libre de enfermedad fue del 100%. CONCLUSIONES: El videoureterorrenoscopio flexible y laser de Holmium para el manejo de las estenosis intrarrenales es altamente efectivo y seguro con las ventajas de presentar menos complicaciones perioperatorias, menos invasividad y ser ambulatorio comparado con la cirugía percutánea

OBJECTIVE: Intrarenal stenosis, even caliceal diverticula or neck diverticular stenosis, associated with lithiasis are infrequent therefore their management is a challenge. The aim of this article is to report two cases who underwent retrograde intrarenal surgery and Holmium laser as a modern technological tool, proposing a new gold standard. METHODS: We report 2 cases of intrarenal stenosis associated with lithiasis managed with flexible videoureteroscope (STORZ) and Holmium laser (CALCULASE II). One case presented a caliceal diverticulum and the other a caliceal ostium stenosis secondary to previous percutaneous surgery. The ostium was incised with laser to Access the diverticulum in the first case and in the second case a dilatation was required. Lithiasis treatment was performed with laser. Disease free rate was defined when the cavity completely disappeared and lithiasis fragments were les than 2 mm on CT Scan one month after procedure. RESULTS: Surgical time were 60 and 82 minutes for cases 1 and 2, respectively. Both patients evolved satisfactorily with 8 hours hospital stay and without perioperative complications. The disease-free rate was 100%. CONCLUSION: Flexible videoureterorrenoscopy and Holmium laser for the management of intrarenal stenosis are highly effective and safe with the advantages of les perioperative complications, less invasiveness and being an outpatient procedure compared to percutaneous surgery

Human renal adipose tissue from normal and tumor kidney: its influence on renal cell carcinoma.

Tumor cells can interact with neighboring adipose tissue. We evaluated components present in human adipose explants from normal (hRAN) and kidney cancer (hRAT) tissue, and we evaluated the effects of conditioned media (CMs) from hRAN and hRAT on proliferation, adhesion and migration of tumor and non-tumor human renal epithelial cell lines. In addition, we evaluated the expression of AdipoR1, ObR, CD44, vimentin, pERK and pPI3K on cell lines incubated with CMs. hRAN were obtained from healthy operated donors, and hRAT from patients who underwent a nephrectomy. hRAT showed increased levels of versican, leptin and ObR; and decreased levels of perilipin, adiponectin and AdipoR1, compared to hRAN. Cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRAT-CMs vs. hRAN- or control-CMs. Surprisingly, HK-2, 786-O and ACHN cells showed a significant decrease in cell migration after incubation with hRAN-CMs vs. control-CMs. No difference in proliferation of cell lines was found after 24 or 48 h of treatment with CMs. AdipoR1 in ACHN and Caki-1 cells decreased significantly after incubation with hRAT-CMs vs. hRAN-CMs and control-CMs. ObR and CD44 increased in tumor line cells, and vimentin increased in non-tumor cells, after incubation with hRAT-CMs vs. hRAN-CMs and control-CMs. We observed an increase in the expression of pERK and pPI3K in HK-2, 786-O and ACHN, incubated with hRAT-CMs. In conclusion, results showed that adipose microenvironment can regulate the behavior of tumor and non tumor human renal epithelial cells.

Estradiol and progesterone regulate proliferation and apoptosis in colon cancer.

Epidemiological studies describe estrogens as protectors in the development of colon cancer in postmenopausal women treated with hormone replacement therapy. However, the role of progesterone in colon cancer has been minimally studied and the results are controversial. For the above, the objective of this work was to determine the hormonal regulation exerted by natural ovarian steroids on proliferation and apoptosis in an experimental model of colon cancer in ovariectomized rats treated with 17-beta estradiol and progesterone. Sprague-Dawley rats were exposed to the carcinogen 1,2-dimethylhydrazine to induce colon tumors. Thirty days later, the rats were ovariectomized and treated with estradiol (60 µg/kg), progesterone (10 mg/kg), estradiol plus progesterone (60 µg/kg and 10 mg/kg) or vehicle. We observed no significant differences in colon cancer incidence and tumor multiplicity between the groups. Nevertheless, we observed a decrease in PCNA expression and a greater number of apoptotic index, higher expression of caspase 3, cleaved PARP and cleaved caspase 8 in tumors, confirming the activation of the extrinsic pathway of apoptosis by the combined treatment. In addition, we observed a higher expression of estrogen receptor beta in these tumors. We conclude that the action of both hormones, estradiol and progesterone, is necessary to reduce proliferation and increase apoptosis in colon tumors, probably through estrogen receptor beta activation.

Human renal adipose tissue induces the invasion and progression of renal cell carcinoma.

We evaluated the effects of conditioned media (CMs) of human adipose tissue from renal cell carcinoma located near the tumor (hRATnT) or farther away from the tumor (hRATfT), on proliferation, adhesion and migration of tumor (786-O and ACHN) and non-tumor (HK-2) human renal epithelial cell lines. Human adipose tissues were obtained from patients with renal cell carcinoma (RCC) and CMs from hRATnT and hRATfT incubation. Proliferation, adhesion and migration were quantified in 786-O, ACHN and HK-2 cell lines incubated with hRATnT-, hRATfT- or control-CMs. We evaluated versican, adiponectin and leptin expression in CMs from hRATnT and hRATfT. We evaluated AdipoR1/2, ObR, pERK, pAkt y pPI3K expression on cell lines incubated with CMs. No differences in proliferation of cell lines was found after 24 h of treatment with CMs. All cell lines showed a significant decrease in cell adhesion and increase in cell migration after incubation with hRATnT-CMs vs. hRATfT- or control-CMs. hRATnT-CMs showed increased levels of versican and leptin, compared to hRATfT-CMs. AdipoR2 in 786-O and ACHN cells decreased significantly after incubation with hRATfT- and hRATnT-CMs vs. control-CMs. We observed a decrease in the expression of pAkt in HK-2, 786-O and ACHN incubated with hRATnT-CMs. This result could partially explain the observed changes in migration and cell adhesion. We conclude that hRATnT released factors, such as leptin and versican, could enhance the invasive potential of renal epithelial cell lines and could modulate the progression of the disease.

Human breast adipose tissue: characterization of factors that change during tumor progression in human breast cancer.

BACKGROUND: Adipose microenvironment is involved in signaling pathways that influence breast cancer. We aim to characterize factors that are modified: 1) in tumor and non tumor human breast epithelial cell lines when incubated with conditioned media (CMs) from human breast cancer adipose tissue explants (hATT) or normal breast adipose tissue explants (hATN); 2) in hATN-CMs vs hATT-CMs; 3) in the tumor associated adipocytes vs. non tumor associated adipocytes. METHODS: We used hATN or hATT- CMs on tumor and non-tumor breast cancer cell lines. We evaluated changes in versican, CD44, ADAMTS1 and Adipo R1 expression on cell lines or in the different CMs. In addition we evaluated changes in the morphology and expression of these factors in slices of the different adipose tissues. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post-hoc tests were performed within each individual treatment. RESULTS: hATT-CMs increase versican, CD44, ADAMTS1 and Adipo R1 expression in breast cancer epithelial cells. Furthermore, hATT-CMs present higher levels of versican expression compared to hATN-CMs. In addition, we observed a loss of effect in cellular migration when we pre-incubated hATT-CMs with chondroitinase ABC, which cleaves GAGs chains bound to the versican core protein, thus losing the ability to bind to CD44. Adipocytes associated with the invasive front are reduced in size compared to adipocytes that are farther away. Also, hATT adipocytes express significantly higher amounts of versican, CD44 and Adipo R1, and significantly lower amounts of adiponectin and perilipin, unlike hATN adipocytes. CONCLUSIONS: We conclude that hATT secrete a different set of proteins compared to hATN. Furthermore, versican, a proteoglycan that is overexpressed in hATT-CMs compared to hATN-CMs, might be involved in the tumorogenic behavior observed in both cell lines employed. In addition, we may conclude that adipocytes from the tumor microenvironment show a less differentiated state than adipocytes from normal microenvironment. This would indicate a loss of normal functions in mature adipocytes (such as energy storage), in support of others that might favor tumor growth.

Effects of parity and serum prolactin levels on the incidence and regression of DMBA-induced tumors in OFA hr/hr rats.

Prolactin (PRL) is a key player in the development of mammary cancer. We studied the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17ß-estradiol). The tumor incidence was similar in the three groups. However, a higher percentage of regressing tumors was evident in the PL group. Serum PRL, mammary development, and mammary ß-casein content were higher in I rats compared to Null. The expression of hormone receptors was similar in the different groups. However, mammary tissue from PL rats bearing tumors had increased expression of PRL and estrogen alpha receptors compared to rats free of tumors. Our results suggest that serum PRL levels do not have relevance on the incidence of tumors, probably because the low levels of PRL in OFA rats are not further decreased by PL like in other strains. However, supraphysiological levels of PRL affect carcinogenesis. PL induces regression of the tumors due to the differentiation produced on the mammary cells. Alterations in the expression of hormonal receptors may be involved in progression and regression of tumors.

Experimental hypothyroidism increases apoptosis in dimethylbenzanthracene-induced mammary tumors.

Epidemiological and in vitro data have not provided conclusive evidence concerning the involvement of thyroid hormones (THs) on mammary carcinogenesis. We used an in vivo model to assess the relationship between THs, adipose tissue and breast cancer development. Female Sprague­Dawley rats were treated with a dose of 7,12-dimethylbenz(a)anthracene (15 mg/rat) at 55 days of age and were then divided into four experimental groups: hypothyroid rats (HypoT, 0.01% 6-N-propyl-2-thiouracil in drinking water), untreated control (EUT); hyperthyroid rats (HyperT, 0.25 mg/kg/day T4 s.c.) and vehicle-treated control rats. The latency of tumor appearance and the incidence and progression of tumors were determined. At sacrifice, blood samples were collected for hormone determinations and samples of tumor and mammary glands were obtained for immunohistological studies. HypoT rats had retarded growth and an increase in mammary fat. The latency was longer (p<0.0001), the incidence rate was lower (p<0.05) and tumor growth was slower in HypoT rats compared to EUT and HyperT rats. Mitotic index and PCNA immunostaining were similar in all groups. HypoT rats showed increased apoptosis (p<0.05) as evaluated by the apoptotic index and TUNEL staining. No differences in serum prolactin and progesterone were observed. However, circulating estradiol (E2) was significantly lower in HypoT and HyperT rats. Serum leptin levels were reduced in HypoT rats even though the abdominal fat mass was similar in all groups. To note, the leptin level was higher in HypoT rats that developed mammary tumors than the level in non-tumoral HypoT rats. In conclusion, hypothyroidism altered animal growth, breast morphology, body composition, leptin secretion and serum E2 enhancing apoptosis and, consequently, retarding mammary carcinogenesis in rats.

Relación entre el índice de masa corporal y antígeno prostático específico en varones libres de enfermedad prostática / Relationship between body mass index and prostate-specific antigen in men without prostatic diseases / Relação entre índice de massa corporal e antígeno prostático específico em homens livres de doença prostática

Introducción: Estudios recientes indican que los varones obesos tienen menor concentración plasmática de antígeno prostático específico (PSA) que los que tienen peso normal, posiblemente debido a un mayor volumen plasmático (hemodilución) y/o a una menor actividad androgénica, dificultando la detección precoz del câncer de próstata. No está establecido claramente si esta relación se acompaña de menores cantidades absolutas dePSA. El objetivo del presente trabajo fue determinar la asociación entre el índice de masa corporal (IMC), la concentración de PSA y sus cantidades absolutas circulantes (“PSA masa”). Material y Métodos: Se determinó PSA total en 570 varones de 45 a 80 años, con PSA considerado no sospecho-so de patologías prostáticas (<4ng/mL). Se evaluaron el peso, la talla y el IMC, se estimó el volumen plasmático (VP) y el PSA masa fue calculado a partir de la concentración plasmática de PSA y el VP. El análisis estadístico se realizó mediante coeficiente de correlación de Pearson o Spearman según la normalidad de las variables (p<0,05). Resultados: El IMC se asoció significativamente con un mayor VP (r = 0,512; p<0,0001). Dado que las concentraciones de PSA se asociaron positivamente con la edad (r = 0,248; p<0,0001), se analizaro...

Recent studies indicate that obese men have lower plasma prostate-specific antigen (PSA) concentrations than normal weight men, which may probably be explained by higher plasma volume (hemodilution) and/or a lower androgenic activity. This may interfere with the ability to detect early-stage prostate cancer. It is not clear whether this relationship is accompanied by lower absolute amounts of PSA. The aim of this study was to determine the association between the body mass index (BMI), the PSA concentrations and the totalamount of PSA in circulation (“PSA mass”). Material and methods: The total amount of PSA was determined in 570 men aged 45-80 years, whose PSA values were not indicators of prostate disease (<4ng/mL). Weight, height and BMI were measured, plasma volume(PV) was estimated, and PSA mass was calculated taking into account plasma PSA concentrations and PV. The statistical analysis was performed using Pearson orSpearman/'s correlation coefficient according to the normality of the variables (P<0.05). Results: The BMI was significantly associated with a higher PV (r = 0.512; P<0.0001). Due to the positive correlation between PSA concentrations and age (r = 0.248;P<0.0001), partial correlations adjusted for...

Estudos recentes indicam que os homens obesos têm menor concentração plasmática de antígeno prostático específico (PSA) que os que têm peso normal, possivelmente devido a um maior volume plasmático (hemodiluição) e/ou a uma menor atividade androgênica,dificultando a detecção precoce do câncer de próstata. Não está estabelecido claramente se esta relação está acompanhada de menores quantidades absolutas de PSA. O objetivo do presente trabalho foi determinar a associação entre o índice de massa corporal (IMC), a concentração de PSA e suas quantidades absolutas circulantes (/"PSA masa/"). Material e Métodos: Determinou-se PSA total em 570 homens de 45 a 80 anos, com PSA considerado não suspeitoso de patalogias prostáticas (<4ng/mL). Foram avaliados o peso, a altura e o IMC, estimou-se o volume plasmático (VP) e o PSA massa foi calculado a partir da concentração plasmática de PSA e o VP. A análise estatística foi realizada mediante coeficiente de correlação de Pearson ou Spearman segundo a normalidade das variáveis(p<0,05). Resultados: O IMC se associou significativamente com um maior VP (r = 0,512; p<0,0001). Dado que as concentrações de PSA se associaram positivamente com a idade (r = 0,248; p<0,0001), analisaram-se as correlações parciais corrigidas para esta variável. Assim, o IMC se associou com uma menor concentração de PSA (r = -0,298;p<0,0001) e menor PSA massa...

The inhibitory effect of progesterone on lactogenesis during pregnancy is already evident by mid- to late gestation in rodents.

Lactogenesis is a very complex process highly dependent on hormonal regulation. In the present study the time-course of the inhibitory actions of progesterone on prolactin secretion, mammary gland morphology and lactogenesis from mid- to late gestation in rodents was investigated. Groups of pregnant rats were luteectomised or administered with mifepristone on Day 10, 13, 15 or 17 of gestation and decapitated 28 or 48h later. Whole-blood samples and the inguinal mammary glands were taken for determinations of hormone levels and for measurement of mammary content of casein and lactose and for tissue morphology analyses, respectively. Luteectomy or mifepristone evoked prolactin increases only after Day 17 of gestation. Mammary content of casein was increased by both treatments regardless of timing or duration. Mifepristone was less effective than luteectomy in inducing lactose production and the effect was only observed after Day 15 of gestation. Analysis of mammary gland morphology confirmed the observed effect of progesterone on lactogenesis. Both treatments triggered remarkable secretory activity in the mammary gland, even without a parallel epithelial proliferation, demonstrating that the mammary epithelium is able to synthesise milk compounds long before its full lobulo-alveolar development is achieved, provided that progesterone action is abolished. Thus, the present study demonstrates that progesterone is a potent hormonal switch for the prolactin and prolactin-like effects on mammary gland development and its milk-synthesising capacity during pregnancy, and that its inhibitory action is already evident by mid-pregnancy in rodents.