RESUMO
The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)
No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)
Assuntos
Animais , Camundongos , Talidomida/análise , Neoplasias Mamárias Animais/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Imunomodulação , Metástase NeoplásicaRESUMO
The understanding of interactions between electrons and phonons in atomically thin heterostructures is crucial for the engineering of novel two-dimensional devices. Electron-phonon (el-ph) interactions in layered materials can occur involving electrons in the same layer or in different layers. Here we report on the possibility of distinguishing intralayer and interlayer el-ph interactions in samples of twisted bilayer graphene and of probing the intralayer process in graphene/h-BN by using Raman spectroscopy. In the intralayer process, the el-ph scattering occurs in a single graphene layer and the other layer (graphene or h-BN) imposes a periodic potential that backscatters the excited electron, whereas for the interlayer process the el-ph scattering occurs between states in the Dirac cones of adjacent graphene layers. Our methodology of using Raman spectroscopy to probe different types of el-ph interactions can be extended to study any kind of graphene-based heterostructure.
RESUMO
Studies about canine mammary tumors based on single molecular markers probably cannot accurately account for the heterogeneity of this disease, and the investigation of multiple molecular alterations in primary tumors and their metastases, in conjunction, has assumed great importance for the understanding of mammary tumor progression. In the present study, we selected 54 primary mammary carcinomas with lymph node metastasis (T1,2,3N1M0), 29 primary mammary carcinomas without metastasis (T1,2,3N0M0), and 25 canine lymph nodes metastasis to evaluate the immunohistochemical expression of HER-2, EGFR, Cox-2 and Ki67 and its association with clinical-pathological parameters and overall survival. Our results found a concordance between the expression of HER-2 (K coefficient: 0.250), Cox-2 (K coefficient: 0.571), and Ki67 (K coefficient: 0.397) and a discordance between EGFR expression (K coefficient: -0.195) in primary mammary carcinomas and paired lymph node metastasis. Furthermore, a high Ki67 index (>24%), large tumor size and the presence of angiolymphatic invasion in canine primary mammary carcinoma with lymph node metastasis plus the presence of extracapsular extension in lymph nodes metastasis were also related to worse prognoses and shorter overall survival (P<0.05). In conclusion, our study demonstrates that primary mammary carcinomas with high expression of HER-2, Cox-2 and Ki67 also show high expression of these markers in paired lymph node metastasis. Moreover, the expression of these molecular markers in lymph nodes metastasis did not demonstrate a prognostic relevance.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma/veterinária , Doenças do Cão/genética , Neoplasias Mamárias Animais/genética , Animais , Biomarcadores Tumorais/metabolismo , Carcinoma/diagnóstico , Carcinoma/genética , Carcinoma/patologia , Progressão da Doença , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Feminino , Linfonodos/patologia , Metástase Linfática , Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/patologia , PrognósticoRESUMO
BACKGROUND: As in women, regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated regional lymph node metastases in dogs with malignant mammary gland tumors. OBJECTIVES: To estimate overall survival based on the assessments of the lymph node status and the morphologic and morphometric features in female dogs with malignant mammary gland tumors. MATERIALS AND METHODS: In total, 178 lymph nodes from 97 female dogs were assessed and reviewed, and after confirmation by immunohistochemistry (IHC), 161 lymph nodes were selected for analysis of metastases. Animals were considered metastasis-free (negative lymph nodes) only after IHC analysis for cytokeratin AE1/AE3. The number of positive lymph nodes, the number of metastatic foci, the maximum diameter and the area of metastasis were analyzed, and estimates of overall survival were made. RESULTS: Dogs with metastasis had lower mean survival than those with metastasis-free regional lymph nodes, showing a direct relationship between the number of affected lymph nodes and shorter survival. However, histologic analysis of the lymph nodes identified lower survival rates in animals with macrometastases and isolated tumor cells, areas of metastasis >20.11 mm², and metastatic diameters >7.32 mm. CONCLUSION: The identification of ≥1 lymph nodes positive for metastasis and morphometric characterization of lymphatic metastases indicate the prognostic relevance of lymph nodes status in dogs with mammary tumors.
Assuntos
Doenças do Cão/diagnóstico , Neoplasias Mamárias Animais/patologia , Animais , Doenças do Cão/mortalidade , Doenças do Cão/patologia , Cães , Feminino , Humanos , Metástase Linfática , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/mortalidade , PrognósticoRESUMO
ZEB1 and ZEB2 have been recently related to cancer prognosis. We investigated their expression and its association with clinicopathological parameters and overall survival in invasive micropapillary carcinoma (IMPC), which is a metastasising neoplasm of the canine mammary gland. Immunohistochemical evaluation showed nuclear and cytoplasmic staining for ZEB2 and nuclear staining for ZEB1. 'In situ' areas presented higher positivity for cytoplasmic ZEB2 than invasive areas of IMPC did (p = 0.03). ZEB1 positivity was associated with a low histological grade (p = 0.01). A shorter overall survival rate was observed in IMPCs that were positive for cytoplasmic ZEB2 (p = 0.04). Antibodies specificity in canine species was confirmed by western blot. Our results indicated that cytoplasmic ZEB2 appears to be an important factor in the early stages of malignancy and predicts a poor overall survival rate for IMPC in this canine mammary cancer model. ZEB1 downregulation appears to be associated with the dedifferentiation process of IMPC.
Assuntos
Carcinoma Papilar/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Mamárias Animais/metabolismo , Proteínas Repressoras/metabolismo , Animais , Western Blotting , Núcleo Celular/metabolismo , Sobrevivência Celular/fisiologia , Citoplasma/metabolismo , Cães , Feminino , Imuno-HistoquímicaRESUMO
Invasive micropapillary carcinoma (IMPC) of the mammary gland, despite its rare occurrence in humans and dogs, is an important neoplasm due to its aggressive behaviour. The aim of this study was to evaluate the clinicopathological and immunophenotypical characteristics of IMPC and to determine the overall survival of dogs with this tumour. Of the selected cases, the majority had >3 cm neoplasms (15/19, 78.95%) and lymph node metastases (16/16, 100%), but only two cases (2/9, 22.2%) had distant metastases. The IMPCs were classified as either pure (15/22, 68.18%) or mixed (7/22, 31.82%) types. There was a predominance of moderate histological grade tumours (16 grade II) and the average overall survival was 120 days. Positive immunohistochemical staining for epithelial membrane antigen and negative staining for CD-31, p63 and cytokeratin (CK) AE1AE3 in cystic formations confirmed the micropapillary nature of these neoplasms. A proportion of cases exhibited positive epithelial staining for p63 (4/20, 20%) and CK34ßE12 (20/22, 90.9%). Most cases were positive for oestrogen (19/20, 95%) and progesterone (19/20, 95%) receptors, but lacked HER-2 (16/22, 72.72%) and epidermal growth factor receptor (15/22, 68.18%) over-expression. The mean proliferation index was 14.8%. The findings demonstrate that, similar to humans, canine IMPCs behave aggressively with high rates of metastasis to regional lymph nodes and short overall survival times.
Assuntos
Doenças do Cão/patologia , Neoplasias Mamárias Animais/patologia , Animais , Cães , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: Presence of tumor markers in serum might be connected to the number of secreting cells and with the stage of the neoplasm. However, there are few studies regarding these markers in veterinary clinical oncology. OBJECTIVES: To determine the serum concentrations of cancer antigen 15.3 (CA 15.3), carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH) in female dogs with different stages of mammary cancer. ANIMALS: Ninety female dogs, including 30 that were healthy, 40 that had nonmetastatic cancer, 12 with regional metastasis, and 8 with distant lymph node metastasis. METHODS: Prospective case-controlled observational study. Serum samples were collected to measure CA15.3, CEA, and LDH from 60 female dogs with mammary cancer during mastectomy and 30 healthy female dogs during routine check-up. CA15.3 and CEA were determined by chemiluminescent immunoassay and LDH by ultraviolet kinetic method. Western blotting analysis was performed to confirm the specificity and possible cross-reactivity of human CA15.3 and CEA antibodies with canine serum. Group data were compared by ANOVA followed by Student-Newman-Keuls and Tukey's tests. Correlations were investigated by Pearson and Spearman tests. RESULTS: CEA, CA15.3, and LDH were measurable in all groups. Higher serum concentration of CA15.3 and LDH was associated with regional and distant metastases. There was a significantly higher serum CA15.3 concentration in animals with lymph node metastasis when compared with animals without metastasis. There were no significant differences in CEA among groups. Expression of CA15.3 and CEA in canine serum was confirmed by Western blotting. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum CA15.3 can be used to distinguish nonmetastatic from metastatic carcinomas.
Assuntos
Antígeno Carcinoembrionário/sangue , Doenças do Cão/sangue , Regulação Neoplásica da Expressão Gênica/fisiologia , L-Lactato Desidrogenase/sangue , Neoplasias Mamárias Animais/sangue , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adenocarcinoma/veterinária , Animais , Biomarcadores Tumorais , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Carcinoma/sangue , Carcinoma/metabolismo , Carcinoma/veterinária , Estudos de Casos e Controles , Doenças do Cão/metabolismo , Cães , Feminino , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Neoplasias Mamárias Animais/classificação , Neoplasias Mamárias Animais/metabolismoRESUMO
Hydrogen/sodium titanate nanotubes (TNTs) were investigated as hydrogen (H(2)) sensors. TNT films exhibit good sensing properties and a large response, in particular at room temperature. Electrical conductivity measurements performed under different atmospheres from 25 to 300 °C indicate that, for T > 100 °C, conduction is thermally activated and can be attributed to electronic transport, whereas for T < 100 °C conduction is dominated by protonic transport. The T dependence of the H(2) sensitivity was determined and related to this variation in the dominant transport mechanism. For low T, H(2) sensing originates from the modulation in protonic conduction. Such modulation was attributed to the creation/destruction of surface hydroxyl groups.
Assuntos
Surtos de Doenças , Enterobacter/patogenicidade , Infecções por Enterobacteriaceae/epidemiologia , Contaminação de Alimentos , Nutrição Parenteral/efeitos adversos , Sepse/microbiologia , Brasil/epidemiologia , Infecção Hospitalar/etiologia , Eletroforese em Gel de Campo Pulsado , Enterobacter/classificação , Enterobacter/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Testes de Sensibilidade Microbiana , Sepse/etiologiaRESUMO
Vibrio cholerae is an important human pathogen and the cause of cholera. Since genetic variation and antibiotic resistance of strains have implications for effective treatment of the disease, we examined the genetic diversity and antibiotic resistance profile in 92 clinical strains (serogroup O1) and 56 environmental strains (O1 antigen, 42 strains; non-O1 antigen, 14 strains) isolated in Brazil between 1991 and 1999. Clinical and environmental O1 strains showed greater drug resistance compared to environmental non-O1 strains. Nearly all clinical O1 strains were resistant to one or more antibiotics while half of the environmental O1 and non-O1 strains were resistant to one or more antibiotics. No plasmids or class 1 integrons were detected in the strains by PCR analysis. Multilocus enzyme electrophoresis analysis (MLEE) suggests most of the O1 strains belong to a single (South American) clone that is related but different to seventh-pandemic strains isolated from other parts of the world. Our results show that there is a close genetic relationship between clinical and environmental O1 strains and that many serogroups and the environment can be a reservoir for antibiotic resistance.