RESUMO
PURPOSE: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N 4-arylsubstituted thiosemicarbazone (N 4-TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. METHODS: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. RESULTS: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. CONCLUSION: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed anti-invasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.
RESUMO
Las lesiones precursoras de malignidad (gastritis crónica atrófica, metaplasia intestinal y displasia leve), según lo demuestran múltiples estudios, están claramente relacionadas con el riesgo que presentan como predictoras del cáncer gástrico y más aún en nuestra región considerada como de alto riesgo de esta patología. Se realizó un estudio prospectivo descriptivo con 212 pacientes entre 11 y 89 años de edad procedentes de la zona amarilla del departamento de Nariño, atendidos en el Centro de Investigaciones de Enfermedades Digestivas (CIED) del Centro Hospital La Rosa dependiente de la ESE Pasto Salud a quienes se tomaron 7 biopsias de mucosa gástrica sometidas a un procesamiento y coloración especial de Giemsa modificado para detectar lesiones precursoras de malignidad y presencia de Helicobacter Pylori. La prevalencia para gastritis crónica atrófica antrocorporal fue de 38,6%, metaplasia intestinal 24,4% y displasia leve 1,5%; presencia de infección para Helicobacter pylori en gastritis crónica atrófica 73,5%, para metaplasia intestinal 52% y displasia leve 100%; en relación a la severidad de las lesiones precursoras de malignidad de acuerdo a la escala de OLGA, 11,5% se clasificó como estadios III y IV; a excepción de un solo caso clínico todos fueron Helicobacter Pylori positivos. Se pone en consideración de la comunidad médica el protocolo del CIED para seguimiento y vigilancia de las lesiones precursoras de malignidad tratando de demostrar que la mayor estrategia sigue siendo la prevención para el control del cáncer gástrico en las regiones de alto riesgo.
Atrophic chronic gastritis (ACG), intestinal metaplasia (IM) and mild dysplasia (MD)) are all precursor lesions which have been clearly demonstrated by many studies to be related to risks for development of gastric cancer (GC). This is especially true in our region which is considered to be a high risk area for this disease. We conducted a prospective study of 212 patients between the ages of 11 and 89 years who were from the yellow zone of Nariño. Patients were cared for in the Centro de Investigaciones de Enfermedades Digestivas (CIED - Center for the Investigation of Digestive Diseases) at the Centro Hospital la Rosa which is part of the public health care system of Pasto. Seven gastric mucosa biopsies were taken from each subject and stained with specially modified Giemsa stain to detect precursor lesions and the presence of Helicobacter pylori. The prevalence of ACG was 38.6%, the prevalence of IM was 24.4%, and the prevalence of MD was 1.5%. Prevalence of H. pylori infections among patients with ACG was 73.5% while among patients with IM it was 52%, but prevalence rose to 100% among patients with MD. When severity of precursor lesions on the OLGA-staging (Operative Link for Gastritis Assessment) scale was 11.5%, lesions were classified as stage III and IV. With one exception, all of these patients were H. pylori positive. We would like to ask the medical community to consider CIED's Follow-up and Monitoring Protocol for precursor lesions in order to demonstrate that the best strategy continues to be GC prevention in high risk regions.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Gastrite , Gastrite Atrófica , Metaplasia , Lesões Pré-Cancerosas , Neoplasias GástricasRESUMO
Antecedentes: La exploración ecográfica entre las semanas 11 y 14 tiene un papel fundamental en el cribado de anomalías cromosómicas, siendo la medida de la translucencia nucal un método bien establecido y ampliamente aceptado para este fin. Objetivo: Evaluar retrospectivamente la evolución de los fetos con translucencia nucal aumentada y cariotipo normal. Método: Se recogieron los datos de 104 fetos con TN >percentil 95 (p95) entre las semanas 11 y 14, evaluados en nuestro centro. En los 61 que resultaron eu-ploides, se estudió la incidencia de anomalías estructurales diagnosticadas tanto prenatalmente como tras el nacimiento, así como las pérdidas fetales anteparto. De estos fetos, nacieron sanos el 80 por ciento cuando la TN estaba entre p95 y 3,4 mm, el 50 por ciento con TN entre 3,5 y 4,4 mm, el 30 por ciento con TN entre 4,5 y 5,4 mm, y el 18 por ciento con TN > 5,5 mm. Entre los 4 recién nacidos euploides con patología, hubo 3 con cardiopatía. Conclusión: La presencia de TN aumentada entre las 11 -14 semanas en fetos euploides se asocia a un incremento del riesgo de anomalías estructurales mayores, principalmente cardiacas. La prevalencia de malformaciones aumenta significativamente con TN >3,5 mm, y el pronóstico gestacional adverso empeora conforme aumenta la medida de la TN.
Background: Ultrasound scan has a main role at the 11-14 weeks screening for chromosomal abnormalities. The measurement of nuchal translucency (NT) thickness is a widespread stablished method to achieve this target. Objective: To assess retrospectively the outcome of fetuses with increased nuchal translucency and normal karyotype. Method: Data were collected from 104 fetuses with NT > 95th percentile at 11 to 14 weeks of gestation, followed in our institution. The sixty one euploid fetuses were studied in order to determine the incidence of structural abnormalities, diagnosed either before or after delivery, as well as antenatal fetal loss. Among these fetuses, there were no malformations at birth in 80 percent for NT between the 95th percentile and 3.4 mm; 50 percent for NT between 3.5 and 4.4 mm; 30 percent for NT of 4.5-5.4 mm; and 18 percent for NT > 5.5 mm. There were 4 euploid newborns with some kind of structural defect at birth, 3 of them presented a cardiac malformation. Conclusion: The presence of increased NT at 11-14 weeks scan in euploid fetuses it's associated with a higher risk of major structural abnormalities, mainly cardiac ones. The prevalence of malformations is significantly increased for NT > 3.5 mm, and the adverse perinatal outcome is directly associated with the thickness of NT.
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Anormalidades Congênitas , Doenças Fetais , Medição da Translucência Nucal , Peneiramento de Líquidos , Anormalidades Congênitas/epidemiologia , Pescoço , Diagnóstico Pré-Natal/métodos , Doenças Fetais/epidemiologia , Doenças do Recém-Nascido/epidemiologia , Cariotipagem , Natimorto/epidemiologia , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Medição de RiscoRESUMO
An indirect enzyme-linked immunosorbent assay was used to obtain epidemiologic information on bovine neosporosis in dairy herds of the Mexican central plateau. Sera were collected from 1,003 cows from 50 dairy herds. Forty-three herds (group A) had been experiencing a high abortion rate. The abortion rates for the remaining 7 herds (group B) were within normal limits for Mexico. Five-hundred sixty-one (56%) of the 1,003 sera were positive. The seroprevalence of Neospora caninum antibodies was 72% (95% CI = 68-75%) in group A and 36% (95% CI = 31-40%) in group B. These results clearly show that infection with N. caninum is widespread in Mexican dairy herds, as indicated by seropositive cows in group A and group B herds at the time of the sample collection.
Assuntos
Anticorpos Antiprotozoários/análise , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Neospora/imunologia , Neospora/patogenicidade , Criação de Animais Domésticos , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/imunologia , Coccidiose/epidemiologia , Coccidiose/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , México/epidemiologia , Estudos SoroepidemiológicosRESUMO
Of 211 aborted bovine fetuses collected from Mexican dairy herds between January 1996 and March 1999, 73 showed microscopical lesions consistent with neosporosis. Of these 73 fetuses, 58 (79%) showed lymphocytic myocarditis, 39 (53%) showed microgliosis and multifocal necrosis in the brain, 39 (53%) showed lymphocytic hepatitis, and 19 (26%) showed lymphocytic myositis. Immunohistochemical examination of brain, myocardium and liver from 53 of the same 73 fetuses demonstrated Neospora caninum antigens in 41 (77%), of which 19 (46%) gave positive results in one of the three sites, 15 (37%) in two, and seven (17%) in three. The results indicated the presence of neosporosis in a number of the main dairy farming regions of Mexico.
Assuntos
Aborto Animal/parasitologia , Doenças dos Bovinos/parasitologia , Coccidiose/veterinária , Doenças Fetais/veterinária , Neospora/isolamento & purificação , Complicações Parasitárias na Gravidez/veterinária , Aborto Animal/epidemiologia , Animais , Encéfalo/parasitologia , Encéfalo/patologia , Bovinos , Doenças dos Bovinos/epidemiologia , Coccidiose/epidemiologia , Coccidiose/parasitologia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/parasitologia , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Coração/parasitologia , Fígado/parasitologia , Fígado/patologia , México/epidemiologia , Músculo Esquelético/parasitologia , Músculo Esquelético/patologia , Miocárdio/patologia , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Complicações Parasitárias na Gravidez/parasitologiaRESUMO
This study was carried out in order to obtain base-line data concerning the epidemiology of American Visceral Leishmaniasis and Chagas' Disease in an indigenous population with whom the government is starting a dwelling improvement programme. Information was collected from 242 dwellings (1,440 people), by means of house to house interviews about socio-economic and environmental factors associated with Leishmania chagasi and Trypanosoma cruzi transmission risk. A leishmanin skin test was applied to 385 people and 454 blood samples were collected on filter paper in order to detect L. chagasi antibodies by ELISA and IFAT and T. cruzi antibodies by ELISA. T. cruzi seroprevalence was 8.7% by ELISA, L. chagasi was 4.6% and 5.1% by IFAT and ELISA, respectively. ELISA sensitivity and specificity for L. chagasi antibodies were 57% and 97.5% respectively, as compared to the IFAT. Leishmanin skin test positivity was 19%. L. chagasi infection prevalence, being defined as a positive result in the three-immunodiagnostic tests, was 17.1%. Additionally, 2.7% of the population studied was positive to both L. chagasi and T. cruzi, showing a possible cross-reaction. L. chagasi and T. cruzi seropositivity increased with age, while no association with gender was observed. Age (p<0.007), number of inhabitants (p<0. 05), floor material (p<0.03) and recognition of vector (p<0.01) were associated with T. cruzi infection, whilst age ( p<0.007) and dwelling improvement (p<0.02) were associated with L. chagasi infection. It is necessary to evaluate the long-term impact of the dwelling improvement programme on these parasitic infections in this community.