The PI3K/AKT/mTOR pathway is related to proliferation, protein synthesis, survival, angiogenesis, apoptosis, and cell motility. Genetic alterations in either activation of oncogenes or inactivation of tumor suppressor make it the second most altered pathway in neoplastic processes. The PI3K/AKT/mTOR pathway is currently considered an attractive target for the development of anti-tumor molecules. Specific inhibitors of this pathway are under development, and those already recognized are being tested in clinical trials, representing a promising approach for the treatment of cancer patients. It is believed that, as this pathway is involved in the development of many human cancers, its activation may also be related to the development of various canine neoplasms. Therefore, this review aims to describe the state-of-the-art knowledge about the PI3K/AKT/mTOR pathway and highlight some research performed with either canine tumors or cellular lines.

La vía de PI3K/AKT/mTOR se relaciona con la proliferación, la síntesis de proteínas, sobrevida, angiogénesis, apoptosis y la motilidad celular. Alteraciones genéticas, ya sean en la activación de oncogenes o inactivación de genes supresores de tumor hacen de esta la segunda vía más alterada en los procesos neoplásicos. La vía de PI3K/AKT/mTOR actualmente es considerada un objetivo clave para el desarrollo de moléculas antitumorales. Los inhibidores específicos de esta vía se encuentran en desarrollo, y los ya conocidos se encuentran siendo evaluados en ensayos clínicos, lo que representa una alternativa promisoria para el tratamiento de pacientes con cáncer. Se cree que, como esta vía está implicada en el desarrollo de muchos cánceres en humanos, su activación pueda también estar relacionada con el desarrollo de diversos tumores en caninos. Por tanto, esta revisión tiene como objetivo describir el conocimiento actual de la vía PI3K/AKT/mTOR y resaltar algunas investigaciones realizadas, tanto en tumores y linajes celulares caninas.

Cutaneous inflammatory apocrine carcinoma is a non-common reported tumor which affects the skin causing multiple erosive lesions. The aim of this report is to describe two different cases of this atypical disease. Both cases presented with ulcerative and infiltrative lesions on cervical region. A surgical procedure was ruled out due to local infiltration and erosive condition. Case 1 was treated with bleomycin. Case 2 received just palliative treatment. In both cases the response was poor with survival times of 35 days and 15 days respectively. Clinical information about this disease is lacking on literature and more studies are warranted in order to describe better clinical presentation, treatment possibilities and prognostic.

El carcinoma apocrino inflamatorio cutáneo es un tumor poco reportado e infrecuente que afecta la piel causando lesiones múltiples erosivas. El objetivo de este reporte es describir dos diferentes casos que presentaron este infrecuente tumor. Ambos casos presentaron lesiones ulcerativas e infiltrativas en región cervical. Debido a la condición inflamatoria y erosiva de las lesiones, fue descartado un procedimiento quirúrgico. El caso 1 fue tratado con bleomicina, mientras que el caso 2 solo recibió tratamiento paliativo. En ambos casos la respuesta fue pobre con tiempos de sobrevida de 35 y 15 días respectivamente. En la literatura actualmente existe poca información acerca de esta enfermedad y es necesario que existan más estudios que logren describir mejor la presentación clínica, posibilidades de tratamiento y el pronóstico.

Foram utilizadas 24 vacas Nelore P.O., em anestro pós-parto, diagnosticado pelo histórico reprodutivo, por avaliações ultrassonográficas transretais e por dosagem de progesterona plasmática, que foram submetidas à colheita de fragmento uterino via transcervical. Os animais foram divididos em dois grupos conforme o máximo diâmetro folicular: grupo 1: folículos <6mm (n=12); grupo 2: folículos >6mm (n=12). Para avaliar receptor de estrógeno e receptor de progesterona no epitélio glandular e no estroma, foi utilizada a técnica de imunoistoquímica. Altas contagens relativas e alta intensidade de marcação para receptor de estrógeno e progesterona no epitélio glandular e no estroma foram observadas nos dois grupos. No entanto, a intensidade de marcação para o receptor de progesterona no epitélio glandular foi mais alta no grupo 2 comparado ao grupo 1. Quando o epitélio glandular e o estroma foram comparados, o número relativo de receptor de estrógeno no grupo 1 foi mais alto no epitélio glandular comparado ao estroma, e a intensidade de marcação para o receptor de progesterona no grupo 2 foi mais alta no epitélio glandular comparado ao estroma. Os resultados sugerem que os mecanismos que controlam a expressão de receptores no anestro são semelhantes aos observados durante o ciclo estral.

Twenty-four postpartum anestrous Nelore purebred cows were used in the study. Anestrous was determined based on the reproductive history which was confirmed in each cow based on plasma progesterone concentration and by transrectal ultrasonography. Endometrial biopsies were collected. The animals were separated into two groups according to maximum follicular diameter- Group 1: follicles <6mm (n=12) and Group 2: follicles >-6mm follicles (n=12). The immunohistochemistry technique was employed to evaluate the presence of estrogen and progesterone receptors in the uterine glandular epithelium and stroma. High counts of positive nuclei and high intensity of immunostain for estrogen and progesterone receptors in the glandular epithelium and stroma were observed in the two groups. However, the immunostain intensity of progesterone receptors in the glandular epithelium was higher in Group 2 compared to Group 1. When glandular epithelium and stroma were compared within each group, the relative number of estrogen receptors in the Group 1 was higher in the glandular epithelium compared to stroma and the immunostain intensity for the progesterone receptor in Group 2 was higher in the glandular epithelium compared to stroma. The results suggest that the mechanisms that control the expression of endomerial receptors in the anestrus are similar to the ones observed during the estrus cycle.

É descrito o carcinoma de células escamosas (CCE) no fundo vaginal de uma vaca. O diagnóstico de CCE moderadamente diferenciado foi confirmado através do exame histopatológico. Os testes imunoistoquímicos com os marcadores p53 e Ki67 realizados em amostras do tumor confirmaram a mutação na p53 e aumento da proliferação celular.

Interleukin-10 (IL-10) appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α). However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15) and Wistar rats with streptozotocin (STZ)-induced diabetes (N = 15). At term, the dams (100 days of life) were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL). The placental scores of immunostaining intensity did not differ between groups (P > 0.05). Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.