WT1 expression as a potential biomarker of malignancy in canine breast tumor / La expresión de WT1 como un biomarcador potencial maligno en un tumor de mama canino

SUMMARY: Veterinary oncology is very important nowadays to get a better understanding of human carcinogenesis. Estrogen receptor, progesterone receptor and Human Epidermal Growth Factor receptor 2 are frequently evaluated by immunohistochemistry (HIC) in human breast tumor. WT1 is an oncogene, its overexpression has been detected in leukemia and diverse solid tumors like breast cancer, lung cancer and mesothelioma in humans. WT1 expression was evaluated in 15 canine breast tumors (CBT) diagnosed by histopathological analysis to find its relationship with neoplasia and malignancy. IHC and RT-PCR were performed in CBT tissues. Fisher´s test was used to analyze WT1 relationship with malignancy. Of the 15 tumors, 9 (60 %) were diagnosed as benign and 6 (40 %) were malignant. With IHC, WT1 expression was positive only in biopsies diagnosed as malignant. Expression of WT1 by RT-PCR was detected in 14 of the 15 tumors (93.33 %) as well as in control healthy mammary gland. Clinical significance: This study describes for the first time a close correlation between CBT and a positive result for WT1 expression with IHC; hence, it can be used as a biomarker for this neoplasia and as an indicator of malignancy. RT-PCR analysis also showed to be good option to detect WT1 expression. These results will be useful to further investigations to elucidate WT1-related signaling pathways in CBT. Also to know molecules that regulate the translation of this protein as a marker for tumor progression.

RESUMEN: La oncología veterinaria es muy importante hoy en día para comprender mejor la carcinogénesis humana. El receptor de estrógeno, el receptor de progesterona y el receptor 2 del factor de crecimiento epidérmico humano se evalúan con frecuencia mediante inmunohistoquímica (HIC) en tumores de mama humanos. WT1 es un oncogén, su sobreexpresión se ha detectado en leucemia y en diversos tumores sólidos como el cáncer de mama, cáncer de pulmón y mesotelioma en humanos. La expresión de WT1 se evaluó en 15 tumores de mama caninos (TCC) diagnosticados mediante análisis histopatológico para encontrar su relación con la neoplasia y la malignidad. IHC y RT-PCR se realizaron en tejidos CBT. La prueba de Fisher se utilizó para analizar la relación de WT1 con la malignidad. De los 15 tumores, 9 (60 %) fueron diagnosticados como benignos y 6 (40 %) fueron malignos. Con IHC, la expresión de WT1 fue positiva solo en biopsias diagnosticadas como malignas. La expresión de WT1 por RT-PCR se detectó en 14 de los 15 tumores (93,33 %), así como en el control de la glándula mamaria sana. Importancia clínica: este estudio describe por primera vez una estrecha correlación entre la TCC y un resultado positivo para la expresión de WT1 con IHC; por lo tanto, se puede utilizar como un biomarcador para esta neoplasia y como un indicador de malignidad. El análisis por RT-PCR también demostró ser una buena opción para detectar la expresión de WT1. Estos resultados serán útiles para futuras investigaciones para dilucidar las vías de señalización relacionadas con WT1 en la TCC. También para conocer moléculas que regulan la traducción de esta proteína como marcador de progresión tumoral.

Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current enotyping procedures: a population-based study in northeast Mexico

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman’s rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

Early administration of peroxisomicine A1 (T-514 extracted from K. parvifolia seeds) causes necrosis of implanted TC-1 cells without affecting target organs in a murine model / La administración temprana de peroxisomicina A1 (T-514 extraída de las semillas de K. parvifolia)causa necrosis de células TC-1 implantadas sin afectar órganos blanco en un modelo murino

Peroxisomicine A1 (PA1), one of the toxins isolated from seeds of plants of the Karwinskia genus, whose targets organs are the liver, kidney, and lungs. There is a selective toxicity in vitro to cancer-cell lines derived from the lungs, liver, and colon, compared to normal cell lines. PA1 caused apoptosis in several cancer-cell lines in culture. In toxic doses to rodents, it causes extensive apoptosis in the liver, kidney, and lungs. In our study we were interested in evaluating, for the first time, the morphological effects of administration of PA1 to implanted TC-1 cells and in the target organs in vivo. The TC-1 cells were cultured and injected into the hind limb of C57BL-6 mice. The animals were divided into 3 groups; those treated with four doses of 1 mg/kg each of PA1, the untreated control, and the vehicle-control groups. All mice were killed 10 days after cell implantation. Samples were obtained from TC-1 cells at the implantation site and from the liver, kidney, and lungs. The samples were processed for examination under light and electron microscopy. In the PA1-treated group, the TC-1 cells had necrosis, whereas in the control groups the tumor cells were undamaged. The target organs did not show any lesions. We demonstrated for the first time that there is a selective toxic effect of PA1 on the TC-1 cells in vivo.

Peroxisomicina A1 (PA1), una de las toxinas aisladas de las semillas de plantas del género Karwinskia, cuyos órganos blanco son hígado, riñón y pulmón. Hay una toxicidad selectiva in vitro contra líneas celulares cancerosas derivadas de pulmón, hígado y colon, comparadas con líneas celulares normales. PA1 causa apoptosis en varias líneas celulares malignas en cultivo. En dosis tóxicas a roedores, causa extensa apoptosis en hígado, riñón y pulmón. En nuestro estudio, estuvimos interesados en evaluar por primera vez los efectos morfológicos de la administración temprana de PA1 sobre células TC-1 implantadas y los órganos blanco in vivo. Las células TC-1 fueron cultivadas e implantadas en la extremidad posterior de ratones C57BL-6. Los animales fueron divididos en tres grupos: tratado con cuatro dosis de 1 mg/kg de peso de PA1, control sin tratamiento y control vehículo. Todos los animales fueron sacrificados 10 días posterior al implante de las células. Se colectaron muestras del sitio del implante de las células TC-1 y de hígado, riñón y pulmón. Las muestras fueron procesadas para su análisis a microscopía de luz y microscopia electrónica de transmisión. En el grupo tratado con PA1, las células TC-1 presentaron necrosis, mientras que en los grupos control las células tumorales se observaron sin daño. Los órganos blanco no mostraron lesión alguna. Demostramos por primera vez que existe un efecto tóxico selectivo de PA1 sobre las células TC-1 in vivo.