RESUMEN
NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T-cell acute lymphoblastic leukaemia (T-ALL), early studies suggested a pro-tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss-of-function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.
Asunto(s)
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Transducción de Señal , Animales , Genes Supresores de Tumor , Humanos , Mutación , Transducción de Señal/genéticaRESUMEN
Oral squamous cell carcinoma (OSCC) is a lethal disease and early death usually occurs as a result of local invasion and regional lymph node metastases. Current treatment regimens are, to a certain degree, inadequate, with a 5-year mortality rate of around 50% and novel therapeutic targets are urgently required. Using expression microarrays, we identified the eps8 gene as being overexpressed in OSCC cell lines relative to normal oral keratinocytes, and confirmed these findings using RT-PCR and western blotting. In human tissues, we found that Eps8 was upregulated in OSCC (32% of primary tumors) compared with normal oral mucosa, and that expression correlated significantly with lymph node metastasis (P=0.032), suggesting a disease-promoting effect. Using OSCC cell lines, we assessed the functional role of Eps8 in tumor cells. Although suppression of Eps8 produced no effect on cell proliferation, both cell spreading and migration were markedly inhibited. The latter cell functions may be modulated through the small GTP-ase, Rac1 and we used pull-down assays to investigate the role of Eps8 in Rac1 signaling. We found that alphavbeta6- and alpha5beta1-integrin-dependent activation of Rac1 was mediated through Eps8. Knockdown of either Eps8 or Rac1, inhibited integrin-dependent cell migration similarly and transient expression of constitutively active Rac1 restored migration of cells in which Eps8 expression had been suppressed. We also showed that knockdown of Eps8 inhibited tumor cell invasion in an organotypic model of OSCC. These data suggest that Eps8 and Rac1 are part of an integrated signaling pathway modulating integrin-dependent tumour cell motility and identify Eps8 as a possible therapeutic target.
Asunto(s)
Carcinoma de Células Escamosas/patología , Movimiento Celular , Integrinas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias de la Boca/patología , Proteína de Unión al GTP rac1/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Antígenos de Neoplasias/metabolismo , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Membrana Celular/metabolismo , Células Cultivadas , Citometría de Flujo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Péptidos y Proteínas de Señalización Intracelular/genética , Queratinocitos/citología , Queratinocitos/metabolismo , Mucosa Bucal/citología , Mucosa Bucal/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , Interferencia de ARN , Receptores de Vitronectina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Proteína de Unión al GTP rac1/genéticaRESUMEN
Screening and identification of Salmonella enteritidis in commercial poultry flocks have assumed principal roles in preventing transmission of this pathogen to humans from hen eggs. Serologic diagnosis of S. enteritidis infection in commercial flocks currently relies on laboratory-based tests for detection of antibodies to the lipopolysaccharide, whole flagella, and bacteria. We amplified a sequence from the g,m flagellin of S. enteritidis, followed by cloning, expression, and purification of the protein. The recombinant protein was first characterized by western blot and subsequently evaluated as enzyme-linked immunosorbent assay (ELISA) antigen for detection of S. enteritidis infection. A total number of 49 positive sera and 40 negative sera were tested for ELISA validation. A cutoff value of 0.14 was shown to be sufficient to discriminate the negative and positive sera. Results obtained by testing sera raised against different bacterial strains/serotypes further confirmed that this recombinant flagellin-based ELISA was indeed specific for the detection of S. enteritidis. Both sensitivity and specificity of the developed ELISA test were comparable with a commercially available test, indicating that it is a highly promising and reliable diagnostic tool for S. enteritidis infection.
Asunto(s)
Pollos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Flagelina/inmunología , Enfermedades de las Aves de Corral/diagnóstico , Salmonelosis Animal/diagnóstico , Salmonella enteritidis/inmunología , Animales , Antígenos Bacterianos/sangre , Células Clonales , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Flagelina/genética , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/microbiología , Proteínas Recombinantes/inmunología , Reproducibilidad de los Resultados , Salmonelosis Animal/inmunología , Sensibilidad y Especificidad , Pruebas SerológicasRESUMEN
One hundred and fifty one house rats, Rattus rattus diardii from five different localities, Jinjang, Dato Keramat, Kuala Lumpur, Sungai Besi and Selayang Baru, were examined for parasites. Nineteen species of parasites were recovered. Hymenolepis diminuta and Nippostrongylus brasiliensis are the predominant species. The dominancy of the parasite species in the rats differed in each locality: Hymenolepis diminuta in Dato Keramat and Kuala Lumpur; Nippostrongylus brasiliensis in Sungai Besi; Gongylomena neoplasticum in Jinjang and Selayang Baru. The influences of human habitats on the parasite fauna of house rats are discussed.
Asunto(s)
Ratas/parasitología , Animales , Cestodos/aislamiento & purificación , Etnicidad , Eucariontes/aislamiento & purificación , Humanos , Malasia , Moniliformis/aislamiento & purificación , Nematodos/aislamiento & purificación , Población Rural , Trematodos/aislamiento & purificación , Población UrbanaRESUMEN
Dog sera, collected from different communities throughout Selangor, Peninsular Malaysia, were investigated for the presence of antibodies to R. tsutsugamushi and R. typhi. Scrub typhus antibodies were present in animals from the rural areas only, whereas murine typhus antibodies were observed in equal numbers of dogs from both rural and metropolitan areas. Greater percentage of dogs from suburban areas had demonstrable antibody titers to murine typhus than from the urban area.
Asunto(s)
Anticuerpos Antibacterianos/análisis , Enfermedades de los Perros/epidemiología , Tifus por Ácaros/veterinaria , Tifus Endémico Transmitido por Pulgas/veterinaria , Animales , Perros , Técnica del Anticuerpo Fluorescente/métodos , Malasia , Orientia tsutsugamushi/inmunología , Rickettsia typhi/inmunología , Tifus por Ácaros/diagnóstico , Tifus Endémico Transmitido por Pulgas/diagnósticoRESUMEN
Malaysian Sciuridae are often parasitised by 2 species of Hepatocystis which were described as a single species Hepatocystis vassali malayensis by Field and Edeson, (1950). One of them corresponds to the majority of forms seen by Field and Edeson; it is redescribed herein and raised to specific status: H. v. malayensis becomes H. malayensis Field and Edeson, 1950. By the morphological characteristics of its gametocytes and schizonts, H. malayensis is related to H. kochi. The evolution of tissue schizonts studied at liver biopsies and autopsies of squirrels captured shortly before examination is of a peculiar type: an immunological tissue reaction appears with the hyperinfestation of the Rodents and controls the growth of the schizonts.
Asunto(s)
Apicomplexa/clasificación , Sciuridae/parasitología , Animales , Apicomplexa/citología , Hígado/parasitología , MalasiaRESUMEN
A new Haemoproteid of Malaysian Microchiroptera (Hepatochstis rodhaini n. sp.) is described; it is classified in the genus Hepatocystis because of the morphology of its gametocytes and tissue schizonts.