New Oncogenic Drivers in Hepatocellular Carcinoma: Role of the RNA Binding Protein Hu antigen R

156 p. : graf.

Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

Background: The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D) growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods: The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of <300 mu m in diameter, produced by the hanging-drop method to mimic the microenvironment of avascular micrometastases prior to hypoxia occurrence. Results: Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF) secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE) cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA)-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM)-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX)-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion: 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

Fiabilidad de diferentes pruebas que se utilizan para evaluar el riesgo de lesión del miembro inferior en mujeres deportistas

233 p. : il. + anexo (247 p.)

Plan de Cuidados Estandarizado en Pacientes con Amputación Traumática de Miembro Inferior

La amputación traumática de miembro inferior constituye un proceso complicado de adaptación y superación en el que se producen repercusiones en la persona tanto a nivel físico como psicológico y social. Este tipo de cirugía supone un cambio drástico en la vida de quienes las padecen y sus familias, siendo a menudo adultos jóvenes. En consecuencia, todo el equipo multidisciplinar, pero la enfermera de atención domiciliaria especialmente, juega un papel decisivo a la hora de realizar un seguimiento, estabilizar emocionalmente al paciente e integrarle con el entorno, alcanzando el mayor nivel posible de independencia y autonomía (Modelo de Virginia Henderson). Ésta, garantiza la continuidad de cuidados mediante la supervisión, realización de intervenciones y apoyo a la persona y a la familia, tarea que quizás queda relegada por la actuación inicial de la enfermera hospitalaria. Con el objetivo de brindar unos cuidados integrales y de calidad en el domicilio, se elabora un Plan de Cuidados Estandarizado (PCE) específico para este grupo de pacientes. Se utiliza el Lenguaje Enfermero Estandarizado (LEE) a través de las taxonomías NANDA-NOC-NIC, tal y como se recoge en el Real Decreto 1093/2010 del Boletín Oficial del Estado y se adapta en el 2012 al Boletín Oficial del País Vasco.

Interacciones entre las células madre pluripotentes del carcinoma embrionario y las células mioides peritubulares del testículo

112 p.+ anexos

¿Actividad cotidiana o práctica ritual? Agrupación de 14 colgantes líticos del Magdaleniense Inferior en la cueva de Praileaitz 1 (Deba, Gipuzkoa)

Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas

Snail heterogeneity in clear cell renal cell carcinoma

Background: Intratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist' perspective is still pending. Methods: Four distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman's grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, beta-catenin, PTEN, p-Akt, p110 alpha, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm. Results: Cell type and Fuhrman's grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110a and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases. Conclusions: Intratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.