A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development.

Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. Our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.

Participación de los radicales libres del oxígeno en el proceso de cicatrización de las anastomosis cólicas isquémicas / Role of oxygen free radicals in healing of ischemic colonic anastomosis

Introducción. Se estudia la participación de los radicales libres del oxígeno en la cicatrización de las anastomosis cólicas realizadas en condiciones de isquemia. Métodos. Se han utilizado ratas adultas a las que se realizó una anastomosis en colon normal y en colon previamente desvascularizado (anastomosis isquémica).Se han cuantificado las concentraciones de radicales super óxido (medida de los aniones superóxido y de la mieloperoxidasa), las principales enzimas desintoxicantes (superóxido-dismutasa y glutatión-peroxidasa), la producción de colágeno (OH-prolina) y la tensión de rotura. Resultados. En las anastomosis realizadas en condiciones de isquemia se observa una menor síntesis de colágeno y, por consiguiente, su tensión de rotura es significativamente menor. Las concentraciones detectadas de radicales libres de oxígeno (mayores valores de anión superóxido y mayor grado de infiltración leucocitaria) son significativamente más elevadas que en las anastomosis realizadas en condiciones normales. Conclusión. Nuestros resultados demuestran que los radicales libres de oxígeno están aumentados en las anastomosis con deficiente perfusión sanguínea de los extremos anastomosad (AU)

[Perfusion of donor tissue improves the preservation of graft in heterotopic tracheal transplantation]. / La perfusión tisular del donante mejora la conservación del injerto en el transplante traqueal heterotópico.

To assess the effect on tracheal graft preservation of perfusion of donor tissue with a Collins solution before extraction and immunosuppression of the recipient. An experimental study was performed in 36 albino rabbits with revascularized heterotopic cervical reconstruction of the trachea with omentum. The animals were distributed in four groups. Groups I (n = 9) and III (n = 9) were transplanted with non perfused donor tissue. Animals in groups II (n = 9) and IV (n = 9) received grafts perfused with Collins solution. Immunosuppression with steroids and cyclosporin was continued for 21 days in groups III and IV. In a mid portion of the trachea viewed under optical microscope, the degree of inflammation or circumferential necrosis was assessed on a scale of 0 to 9 by adding the scores for mucosa, submucosa and cartilage. The mean score for tracheal lesion was lower in group IV, with a likelihood of random difference of less than 5%. Perfusion of peritracheal tissues with Collins solution in the donor, in addition to immunosuppression decreases the extent of tissue damage in the tracheal graft.