CXCR4 and CXCR7 transduce through mTOR in human renal cancer cells.

Treatment of metastatic renal cell carcinoma (mRCC) has improved significantly with the advent of agents targeting the mTOR pathway, such as temsirolimus and everolimus. However, their efficacy is thought to be limited by feedback loops and crosstalk with other pathways leading to the development of drug resistance. As CXCR4-CXCL12-CXCR7 axis has been described to have a crucial role in renal cancer; the crosstalk between the mTOR pathway and the CXCR4-CXCL12-CXCR7 chemokine receptor axis has been investigated in human renal cancer cells. In SN12C and A498, the common CXCR4-CXCR7 ligand, CXCL12, and the exclusive CXCR7 ligand, CXCL11, activated mTOR through P70S6K and 4EBP1 targets. The mTOR activation was specifically inhibited by CXCR4 antagonists (AMD3100, anti-CXCR4-12G5 and Peptide R, a newly developed CXCR4 antagonist) and CXCR7 antagonists (anti-CXCR7-12G8 and CCX771, CXCR7 inhibitor). To investigate the functional role of CXCR4, CXCR7 and mTOR in human renal cancer cells, both migration and wound healing were evaluated. SN12C and A498 cells migrated toward CXCL12 and CXCL11; CXCR4 and CXCR7 inhibitors impaired migration and treatment with mTOR inhibitor, RAD001, further inhibited it. Moreover, CXCL12 and CXCL11 induced wound healing while was impaired by AMD3100, the anti CXCR7 and RAD001. In SN12C and A498 cells, CXCL12 and CXCL11 promoted actin reorganization characterized by thin spikes at the cell periphery, whereas AMD3100 and anti-CXCR7 impaired CXCL12/CXCL11-induced actin polymerization, and RAD001 treatment further reduced it. In addition, when cell growth was evaluated in the presence of CXCL12, CXCL11 and mTOR inhibitors, an additive effect was demonstrated with the CXCR4, CXCR7 antagonists and RAD001. RAD001-resistant SN12C and A498 cells recovered RAD001 sensitivity in the presence of CXCR4 and CXCR7 antagonists. In conclusion, the entire axis CXCR4-CXCL12-CXCR7 regulates mTOR signaling in renal cancer cells offering new therapeutic opportunities and targets to overcome resistance to mTOR inhibitors.

Generación in vitro de un sustituto de pared vesical humana obtenido mediante ingeniería tisular / In vitro generation of a human bladder wall substitute by tissue engineering

Objetivos. Numerosas patologías que afectan a la vejiga, de origen congénito (extrofia) o adquirido (traumatismos, tumores), requieren la reconstrucción de la pared vesical utilizando intestino delgado, sigma o estómago, los cuales no están exentos de complicaciones. Por ese motivo, en el presente trabajo pretendemos desarrollar un nuevo modelo de pared vesical humana mediante ingeniería tisular que pudiese tener una utilidad clínica. Material y métodos. En primer lugar, se procedió a generar cultivos primarios de células epiteliales y estromales de la mucosa vesical a partir de pequeñas biopsias de la pared vesical humana, utilizando para ello técnicas de digestión enzimática mediante tripsina-EDTA y colagenasa. Posteriormente, se generó un sustituto tridimensional de la mucosa vesical utilizando como soporte biomateriales de fibrina-agarosa. El análisis de las muestras se realizó a los 14 días mediante examen histológico de muestras teñidas con hematoxilina-eosina. Resultados. La aplicación de los métodos de digestión enzimática permitió generar eficientemente cultivos primarios de células epiteliales y estromales de la mucosa vesical humana, comprobándose que la tasa de proliferación de las células estromales era superior a la de las células epiteliales. Una vez generados los sustitutos de la pared vesical, se comprobó el adecuado nivel de biocompatibilidad del biomaterial y las células estromales y epiteliales. La estructura histológica de los sustitutos de pared vesical presentaba una gran analogía con la mucosa vesical humana nativa. Conclusiones. El tejido vesical generado por ingeniería tisular muestra importantes similitudes estructurales e histológicas con el tejido vesical nativo. Estos resultados sugieren que los tejidos generados mediante ingeniería tisular podrían tener utilidad terapéutica en el futuro (AU)

Introduction. Certain urological congenital conditions, such as bladder exstrophy and acquired conditions such as trauma and tumors may require the use of different tissues like small bowel, sigmoid colon or stomach for bladder reconstruction. However, these tissues are often associated to important complications. The aim of this study is to develop a novel substitute of the human bladder wall by tissue engineering. Material and methods. We first generated primary cell cultures of epithelial and stromal bladder mucosa cells from small tissue biopsies of human bladder by using enzymatic methods based on trypsin-EDTA and collagenase I. Then, a three-dimensional substitute of the bladder mucosa was generated using fibrin-agarose biomaterials. The analysis of the tissue substitutes was carried out at day 14th of development by histological examination of samples stained with hematoxylin-eosin. Results. The use of enzymatic digestion methods allowed us to efficiently generate primary cell cultures of the human bladder epithelial and stromal cells. The proliferation rate was higher in stromal cells as compared to epithelial cells. Once the bladder mucosa substitutes were generated, a good biocompatibility of the stromal and epithelial cells into the biomaterial was found. The histological structure of the bladder wall substitutes was analogue to that of the native human bladder mucosa. Conclusions. The bladder mucosa substitute generated by tissue engineering showed structural and histological similarities with the native human bladder tissues and open the door to the future therapeutic use of these bioengineered tissues (AU)

[In vitro generation of a human bladder wall substitute by tissue engineering]. / Generación in vitro de un sustituto de pared vesical humana obtenido mediante ingeniería tisular.

INTRODUCTION: Certain urological congenital conditions, such as bladder exstrophy and acquired conditions such as trauma and tumors may require the use of different tissues like small bowel, sigmoid colon or stomach for bladder reconstruction. However, these tissues are often associated to important complications. The aim of this study is to develop a novel substitute of the human bladder wall by tissue engineering. MATERIAL AND METHODS: We first generated primary cell cultures of epithelial and stromal bladder mucosa cells from small tissue biopsies of human bladder by using enzymatic methods based on trypsin-EDTA and collagenase I. Then, a three-dimensional substitute of the bladder mucosa was generated using fibrin-agarose biomaterials. The analysis of the tissue substitutes was carried out at day 14th of development by histological examination of samples stained with hematoxylin-eosin. RESULTS: The use of enzymatic digestion methods allowed us to efficiently generate primary cell cultures of the human bladder epithelial and stromal cells. The proliferation rate was higher in stromal cells as compared to epithelial cells. Once the bladder mucosa substitutes were generated, a good biocompatibility of the stromal and epithelial cells into the biomaterial was found. The histological structure of the bladder wall substitutes was analogue to that of the native human bladder mucosa. CONCLUSIONS: The bladder mucosa substitute generated by tissue engineering showed structural and histological similarities with the native human bladder tissues and open the door to the future therapeutic use of these bioengineered tissues.

Intraparenchymatous adenomatoid tumor dependent on the rete testis: A case report and review of literature.

The adenomatoid tumor is the most frequent paratesticular tumor. It is a benign tumor, which in women is mainly found in the uterus and the fallopian tubes, while in men it is most frequently found in the epididymis. These lesions may also affect the testicular albuginea, the spermatic cord and, in exceptional cases, the testicular parenchyma, of which there are only 4 published cases, the ejaculatory ducts, prostate, etc. The clinical signs and imaging studies are, on many occasions, difficult to differentiate from malign intratesticular solid tumor, which can result in unnecessary orchidectomies. We present a new case of intraparenchymatous adenomatoid tumor dependent on the rete testis.

Efectos adversos inducidos por gadopentotato dimeglumina en resonancia magnética / Adverse reactions induced by gadopentatate dimeglumine in magnetic resonance imaging

Fundamento y objetivos: Se considera que las sales de gadolinio utilizadas como medio de contraste en los estudios de resonancia magnética (RM) presentan un índice de reacciones adversas inferior a los medios de contraste yodado. El objetivo principal de este estudio es determinar la frecuencia e intensidad de las reacciones adversas relacionadas con la administración de gadopentotato dimeglumina (Gd-DTPA) y compararla con la tasa de reacciones adversas inducidas por los medios de contaste yodado. Material y métodos: Durante el periodo comprendido entre el 1 de enero de 2005 hasta el 30 de junio del 2006 se recogieron los efectos adversos de todos los estudios mediante RM en los que se aplicó contraste de Gd-DTPA, programados o urgentes, realizados en 11 Centros de Diagnostico por la Imagen Eresa situados en las provincias de Castellón y de Valencia. En dicho período se recogieron también los efectos adversos inducidos por las sales de yodo. Resultados: Se realizaron un total de 54.909 estudios con resonancia magnética en los diferentes centros de estudio, y 12.791 estudios con MCI. El total de reacciones adversas observado fue de 62 (0,11%) y 47 (0,36%) respectivamente. El perfil de reacciones adversas con ambos medios de contraste fue similar, excepto en las reacciones moderadas donde objetivamos un mayor porcentaje de edema palpebral y disnea con la utilización de MCI que con Gd-DTPA. No se objetivó ningún caso de anafilaxia ni exitus. Conclusiones: Los datos aportados por esta serie avalan un perfil de seguridad del Gadolinio superior al de los MCI

Background and objectives: It is considered that the Gadoliniumsalts used as a contrast medium in the Magnetic Resonance Imaging (MRI) studies present an index of adverse reactions below the iodine contrast mediums. The main objective of this study is to determine, in our medium, the frequency and intensity of the adverse reactions related to the administration of Gadopentotate Dimeglumine (Gd-DTPA) and compareit with the rate of adverse reactions induced by the iodine contrast mediums. Material and methods: During the period comprised between 1st of January 2005 and 30th of June 2006, the adverse affects were collected for all the studies by means of MRI in which the Gd-DTPA contrast was applied, programmed or urgent, performed in Eresa Diagnosis Centres by Image located ( 11 centre in total) in the provinces of Castellón and Valencia. The adverse effects induced by the iodine salts were also collected in this period. Results: A total of 54,909 studies with magnetic resonance were performedin the refered study centres, and 12,791 studies with MCI. The total of adverse reactions observed was 62 (0.11%) and 47 (0.36%) respectively.The profile of adverse reactions with both contrast mediums was similar, except in the moderate reactions where we objectively observed a greater percentage of palpebral edema and dyspnea with theusage of MCI than with Gd-DTPA. No cases of anaphylaxia or exitus were observed. Conclusions: The data contributed by this series support a safety profile of Gadolinium superior to that of the MCI in line with the results shown by extensive published series

[Statistical analysis of the influence of the virus of papilloma human in the development of the vesical carcinoma]. / Análisis estadístico de la influencia del virus del papiloma humano en el desarrollo del carcinoma vesical.

INTRODUCTION: The bladder cancer is an important disease by its morbi-mortality and its multifactorialidad. At the moment, between the possible aetiology agents that they have been indicated is the infection by the virus of papilloma human (VPH). The objective study is to analyse, by meta-analysis, the relationship between bladder cancer and infection by human papillomavirus. MATERIAL AND METHODS: We made a search in the electronic data base MEDLINE of the articles published until September of the 2004 that relate the infection of the VPH to the bladder tumors. Of 414 listed articles, we selected 38 articles. RESULTS: The articles were classified in two groups, according to they use or non methods based on the detection of the DNA. In articles based on the detection of the DNA, it was that the global proportion from the cases that had contact with the virus, through the detection of the genome was of the 19.4% (95% CI 0.160 to 0.228). Of the total of studies based on the detection of the DNA 8 were selected, to show to a group defined control, in which, the OR was investigated. If we combined the ORs, we obtain an OR estimation of 3.2 (95% CI 1.19 to 8.60) and p = 0.02. CONCLUSIONS: Most of these studies showed the relation rose at the beginning of the study. Although the majority lacked a group defined control, is possible to analyze the value of the Odds global ratio due to the homogenous behaviour of the studies with defined cases and controls affluent. This demonstrated to association between VPH and the bladder cancer.

Análisis estadístico de la influencia del virus del papiloma humano en el desarrollo del carcinoma vesical / Statistical analysis of the influence of the virus of pailoma human in the development of the vesical carcinoma

Introducción: El carcinoma de vejiga es una enfermedad importante por su morbi-mortalidad y su multifactorialidad. Actualmente, entre los posibles agentes etiológicos que se han señalado, se encuentra la infección por el virus del papiloma humano (VPH). El objetivo del estudio es analizar, mediante la realización de un meta-análisis, la relación existente entre el cáncer vesical y la infección por el virus del papiloma humano. Material y métodos: Realizamos una búsqueda en la base de datos electrónica MEDLINE de los artículos publicados hasta septiembre del 2004 que relacionan la infección del VPH con los tumores vesicales. De los 414 artículos listados, seleccionamos 38 artículos. Resultados: Los artículos se clasificaron en dos grupos, según empleen o no métodos basados en la detección del ADN. En los artículos basados en la detección del ADN, resultó que la proporción global de los casos que tuvieron contacto con el virus, a través de la detección del genoma fue del 19,4% (IC 95%: 0,160-0,228). Del total de estudios basados en la detección del ADN se seleccionaron 8, por mostrar un grupo control definido, en los cuales, se investigó la OR. Si combinamos las ORs, obtenemos una OR estimada de 3,2 (IC al 95% de 1,19 a 8,60) y una p=0,02. Conclusiones: La mayor parte de estos estudios pusieron de manifiesto la relación planteada al inicio del estudio. Aunque la mayoría carecían de un grupo control definido, es posible analizar el valor de la Odds ratio global debido al comportamiento homogéneo de los estudios con casos y controles bien definidos. Esto demostró una asociación entre VPH y el cáncer de la vejiga

Introduction: The bladder cancer is an important disease by its morbi-mortality and its multifactorialidad. At the moment, between the possible aetiology agents that they have been indicated is the infection by the virus of papilloma human (VPH). The objective study is to analyse, by meta-analysis, the relationship between bladder cancer and infection by human papillomavirus Material and methods: We made a search in the electronic data base MEDLINE of the articles published until September of the 2004 that relate the infection of the VPH to the bladder tumors. Of 414 listed articles, we selected 38 articles. Results: The articles were classified in two groups, according to they use or non methods based on the detection of the DNA. In articles based on the detection of the DNA, it was that the global proportion from the cases that had contact with the virus, through the detection of the genome was of the 19.4% (95% CI 0.160 to 0.228). Of the total of studies based on the detection of the DNA 8 were selected, to show to a group defined control, in which, the OR was investigated. If we combined the ORs, we obtain an OR estimation of 3.2 (95% CI 1.19 to 8.60) and p=0.02. Conclusions: Most of these studies showed the relation rose at the beginning of the study. Although the majority lacked a group defined control, is possible to analyze the value of the Odds global ratio due to the homogenous behaviour of the studies with defined cases and controls affluent. This demonstrated to association between VPH and the bladder cancer

[Adverse reactions induced by gadopentetate dimeglumine in magnetic resonance imaging]. / Efectos adversos inducidos por gadopentotato dimeglumina en resonancia magnética.

BACKGROUND AND OBJECTIVES: It is considered that the Gadolinium salts used as a contrast medium in the Magnetic Resonance Imaging (MRI) studies present an index of adverse reactions below the iodine contrast mediums. The main objective of this study is to determine, in our medium, the frequency and intensity of the adverse reactions related to the administration of Gadopentotate Dimeglumine (Gd-DTPA) and compare it with the rate of adverse reactions induced by the iodine contrast mediums. MATERIAL AND METHODS: During the period comprised between 1st of January 2005 and 30th of June 2006, the adverse affects were collected for all the studies by means of MRI in which the Gd-DTPA contrast was applied, programmed or urgent, performed in Eresa Diagnosis Centres by Image located ( 11 centre in total) in the provinces of Castellón and Valencia. The adverse effects induced by the iodine salts were also collected in this period. RESULTS: A total of 54,909 studies with magnetic resonance were performed in the referred study centres, and 12,791 studies with MCI. The total of adverse reactions observed was 62 (0.11%) and 47 (0.36%) respectively. The profile of adverse reactions with both contrast mediums was similar, except in the moderate reactions where we objectively observed a greater percentage of palpebral edema and dyspnea with the usage of MCI than with Gd-DTPA. No cases of anaphylaxia or exitus were observed. CONCLUSIONS: The data contributed by this series support a safety profile of Gadolinium superior to that of the MCI in line with the results shown by extensive published series.

[Ureteral iatrogenic ligature. Endoscopic resolution]. / Ligadura yatrógena ureteral resuelta via endoscópica.

The iatrogenic trauma of ureter is a complication that appears according to the different series between the 0.05-30% from the abdominal or pelvic surgeries. It the same affects to both ureters, being the rare bilateral ureteral trauma. The most frequent location is in the lower ureter. Maybe this fact must to that that is the patron of ureter more related by viacinity to the structures or organs in wich surgery is made. The most frequent causes are the gynecological ones, followed of the surgery of colon and vascular surgery. The reconstruction techniques depend on the level of the injury. The maneuvers of support and the endourology treatment can be useful for the resolution of these injuries.

Ligadura yatrógena ureteral resuelta vía endoscópica / Ureteral iatrogenic ligature. Endoscopic resolution

Introducción: La medida de las tasas de infección nosocomial constituye un indicador de calidad asistencial, permitiendo adoptar medidas de prevención y control. Se ha desarrollado un plan de vigilancia de infección nosocomial en los hospitales, demostrando ser un método eficaz para disminuir su incidencia. Objetivo: Conocer los indicadores y características de la infección nosocomial en general y de la infección del sitio quirúrgico en particular en un servicio de Urología de forma global y por procedimientos. Material y métodos: Estudio prospectivo mediante el sistema de vigilancia epidemiológica entre 2002-2005 en 4.618 pacientes ingresados al menos 24 horas, practicándose un total de 3.096 intervenciones. Resultados: Se observó una tasa global de infección nosocomial del 6,10%, de infección urinaria del 3,42% y de infección del sitio quirúrgico del 2,81%. De esta última por procedimientos, la cistectomía se sitúa en el 22,8%, seguido de la cirugía del riñón y uréter (6,6%) y de la cirugía abierta de próstata (4,36%). Los gérmenes más frecuentemente aislados en la infección del sitio quirúrgico son Escherichia Coli (43,6%) y Pseudomonas aeruginosa (15%). En la infección urinaria los gérmenes más frecuentes son Escherichia Coli (43,6%) y Pseudomonas aeruginosa (15%) Conclusión: Las tasas de infección nosocomial son inferiores a los valores estandares publicados. La mayor tasa de infección del sitio quirúrgico se presenta en las cirugías más complejas técnicamente, siendo Escherichia Coli, el agente etiológico más frecuente. La vigilancia de la infección del sitio quirúrgico y factores relacionados permiten incorporar elementos de mejora en la práctica clínico-quirúrgica, aportando un indicador de referencia en análisis posteriores

Introduction: Nosocomial infection rates constitute an indicator of welfare quality, permitting to adopt measures of prevention and control. It has been developed a surveillance plan of the nosocomial infection in hospitals, showing to be an efficient method to diminish its incident. Objective: To know the indicators and characteristics of the nosocomial infection and of the infection of the site surgical particularly, in a urology service in a global form and by procedures. Matherial and methods: Prospective study by means of the epidemiological surveillance system from 2002 to 2005 in 4.618 patients hospitalised at least 24 hours, with a total of 3.096 surgical. Results: The overall incidence of nosocomial infection was 6,10%, 3.42% for urinary infection and 2,81% for the infection of the chirurgical site. For procedures, the incidence of the infection of the surgical site for cistectomy was 22,8%, 6,6% for surgery of kidney and ureter and 4,36% for open surgery of prostate. Eschericia Coli (43,6%) was the most frequently isolated organism, accounting for 43,6% of the causative organisms in the infection of the surgical site and 43,6% in the urinary infection. Pseudomonas aeruginosa is the next organism in frecuency with a 15% in both infections. Conclusion: Our nosocomial infection rates are lower than the published standard values. The main infection rate of the surgical sites present in the most complex surgical techniques, whereas Escherichia Coli is the most frecuently isolated ethiological agent. The surveillance of the infection of the surgical site and related factors permit to incorporate improvements in the clinical-surgical practice which will be an indicator of reference in subsequent analysis