Potentiation of epidermal growth factor receptor-mediated oncogenesis by c-Src: implications for the etiology of multiple human cancers.

c-Src is a nontransforming tyrosine kinase that participates in signaling events mediated by a variety of polypeptide growth factor receptors, including the epidermal growth factor receptor (EGFR). Overexpression and continual ligand stimulation of the EGFR results in morphological transformation of cells in vitro and tumor development in vivo. Elevated levels of c-Src and the EGFR are found in a variety of human malignancies, raising the question of whether c-Src can functionally cooperate with the EGFR during tumorigenesis. To address this issue, we generated c-Src/EGFR double overexpressors and compared their proliferative and biochemical characteristics to those of single overexpressors and control cells. We found that in cells expressing high levels of receptor, c-Src potentiated DNA synthesis, growth in soft agar, and tumor formation in nude mice. Growth potentiation was associated with the formation of a heterocomplex between c-Src and activated EGFR, the appearance of a distinct tyrosyl phosphorylation on the receptor, and an enhancement of receptor substrate phosphorylation. These findings indicate that c-Src is capable of potentiating receptor-mediated tumorigenesis and suggest that synergism between c-Src and the EGFR may contribute to a more aggressive phenotype in multiple human tumors.

Modulation of c-Myb-induced transcription activation by a phosphorylation site near the negative regulatory domain.

The c-myb protooncogene encodes a highly conserved transcription factor that functions as both an activator and a repressor of transcription. The v-myb oncogenes of E26 leukemia virus and avian myeloblastosis virus encode proteins that are truncated at both the amino and the carboxyl terminus, deleting portions of the c-Myb DNA-binding and negative regulatory domains. This has led to speculation that the deleted regions contain important regulatory sequences. We previously reported that the 42-kDa mitogen-activated protein kinase (p42mapk) phosphorylates chicken and murine c-Myb at multiple sites in the negative regulatory domain in vitro, suggesting that phosphorylation might provide a mechanism to regulate c-Myb function. We now report that three tryptic phosphopeptides derived from in vitro phosphorylated c-Myb comigrate with three tryptic phosphopeptides derived from metabolically labeled c-Myb immunoprecipitated from murine erythroleukemia cells. At least two of these peptides are phosphorylated on serine-528. Replacement of serine-528 with alanine results in a 2- to 7-fold increase in the ability of c-Myb to transactivate a Myb-responsive promoter/reporter gene construct. These findings suggest that phosphorylation serves to regulate c-Myb activity and that loss of this phosphorylation site from the v-Myb proteins may contribute to their transforming potential.

C. Plini Caecili Secundi Epistulae selectae,

Mode of access: Internet.

C. Plini Caecili Secundi Epistularum libri novem, Epistularum ad Traianum liber, Panegyricus;

"Indiculus librorum": p. xv-xvi.

Traite�� de paix entre les Puissances alliees et associe��es et la Hongrie : Protocole et declaration, du 4 Juin 1920, Trianon = Mirova�� smlouva mezi mocnostmi spojeny��mi a sdruz��eny��mi a Ma��darskem : Protokol a deklarace, ze dne 4 c��ervna 1920, Trianon.

At head of title: Poslanecka�� sne��movna N.S.R.C��. 1920. 1. volebni. 2. zasedani. Pr��i��loha k tisku 531.

Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma

Background: Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC. Aims: To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC. Patients: A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years. Methods: DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at greater than or equal to40% of markers, MSS as no instability, and MSI-L as instability at >0% but,40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival. Results: Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1-3.6)). Conclusions: Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.

Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1

Background: Interferon alpha (IFN-alpha) activated cellular signalling is negatively regulated by inhibitory factors, including the suppressor of cytokine signalling (SOCS) family. The effects of host factors such as obesity on hepatic expression of these inhibitory factors in subjects with chronic hepatitis C virus (HCV) are unknown. Objectives: To assess the independent effects of obesity, insulin resistance, and steatosis on response to IFN-alpha therapy and to determine hepatic expression of factors inhibiting IFN-alpha signalling in obese and nonobese subjects with chronic HCV. Methods: A total of 145 subjects were analysed to determine host factors associated with non-response to antiviral therapy. Treatment comprised IFN-alpha or peginterferon alpha, either alone or in combination with ribavirin. In a separate cohort of 73 patients, real time-polymerase chain reaction was performed to analyse hepatic mRNA expression. Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38 patients with viral genotype 1 who had received antiviral treatment. Results: Non-response (NR) to treatment occurred in 55% of patients with HCV genotypes 1 or 4 and 22% with genotypes 2 or 3. Factors independently associated with NR were viral genotype 1/4 (p < 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and body mass index >= 30 kg/m(2) (p = 0.010). Obese subjects with viral genotype 1 had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p = 0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following multivariate analysis, SOCS-3 mRNA expression remained independently associated with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (p = 0.013) and in non-responders compared with responders (p = 0.014). Conclusions: In patients with chronic HCV viral genotype 1, increased expression of factors that inhibit interferon signalling may be one mechanism by which obesity reduces the biological response to IFN-alpha.

A tumoral and invasive phenotype independent of c-Met mutation

M��moire num��ris�� par la Direction des biblioth��ques de l'Universit�� de Montr��al.

A tumoral and invasive phenotype independent of c-Met mutation

M��moire num��ris�� par la Direction des biblioth��ques de l'Universit�� de Montr��al.

Emiss��o de C-CO2 em solo tropical suplementado com lodo de esgoto.

Lodos de esgoto possuem alto teor de carbono org��nico, por��m, h�� um expressivo consumo de mat��ria org��nica logo ap��s sua aplica����o no solo, resultando novo equil��brio da rela����o C/N. Se parte da mat��ria org��nica presente no lodo de esgoto for resistente �� degrada����o e n��o inibir a atividade microbiana, o teor de carbono org��nico no solo poder�� aumentar. Em solo agr��cola, esse efeito pode ser considerado positivo se houver melhorias em sua qualidade e potencial produtivo, sem qualquer preju��zo ambiental. A persist��ncia de carbono org��nico no solo pode ser avaliada medindo-se as taxas de degrada����o do lodo de esgoto pela atividade microbiana do solo. Esta an��lise faz parte da caracteriza����o qualitativa e quantitativa de lodo de esgoto, exigida na legisla����o para disposi����o em solos agr��colas. O presente trabalho teve como objetivo avaliar a decomposi����o de lodo de esgoto aplicado a um latossolo, medindo-se a emiss��o de CO2. Os tratamentos estudados foram de 1, 2, 4 e 8 vezes a aplica����o da dose recomendada na legisla����o atual, com base no teor de N, al��m de um tratamento com aduba����o mineral NPK e um tratamento testemunha. Avaliaram-se dois lodos de esgoto, um de origem urbana (Franca/SP) e um de origem urbano-industrial (Barueri/SP). As doses de lodo de esgoto foram equivalentes �� aplica����o, numa camada de 0-20 cm de profundidader, de 3, 6, 12 e 24 Mg ha -1 (Franca) e de 8, 16, 32 e 64 Mg ha -1 (Barueri/SP). O solo estudado foi um Latossolo Vermelho distrof��rrico. Avaliou-se o efeito dos tratamentos sobre a emiss��o de carbono na forma de CO2, em c��maras sem circula����o for��ada de ar, durante 57 dias de incuba����o. O padr��o de emiss��o de C-CO2 foi semelhante nos dois tipos de lodo de esgoto. Concluiu-se que as doses utilizadas ou os tipos de lodo de esgoto n��o afetaram a biodecomposi����o da mat��ria org��nica aplicada ao solo a qual foi estimada em 15 %.

Efectos de una intervenci��n educativa en los conocimientos y comportamientos relacionados con la fotoprotecci��n durante la pr��ctica de la actividad f��sica en los estudiantes de un colegio p��blico de Bogot�� D.C., Colombia

Introducci��n: La incidencia del c��ncer de piel melanoma y no melanoma es un problema de salud p��blica a nivel mundial. El incremento en la incidencia del c��ncer de piel en los ��ltimos a��os se debe a m��ltiples factores como: cambios en los estilos de vida, el envejecimiento de la poblaci��n, cambios ambientales, el desconocimiento a la exposici��n a la radiaci��n ultravioleta (RUV) durante la pr��ctica de actividad f��sica sin elementos de fotoprotecci��n, siendo ��ste ��ltimo reconocido como el principal factor de riesgo. Objetivo: Evaluar los efectos de una intervenci��n educativa en los conocimientos y comportamientos relacionados con la fotoprotecci��n durante la pr��ctica de la actividad f��sica en estudiantes de un colegio p��blico de Bogot�� D.C., Colombia. M��todos: Estudio de intervenci��n, antes y despu��s, no controlado en 281 estudiantes de los grados noveno, d��cimo y once de estratos 1-3 de un colegio p��blico de Bogot��, con seguimiento a 1, 3 y 6 meses post-intervenci��n. Se evaluaron los conocimientos y los h��bitos de fotoprotecci��n mediante un cuestionario Cancer Awareness Measure (CAM) y el modelo Transte��rico de cambio comportamental de Prochaska y Di Clemente. El estudio se realiz�� durante el primer semestre de 2015 con 4 sesiones educativas de 60 minutos apoyadas con material audiovisual y pedag��gico, acorde a la Gu��a para la Comunicaci��n Educativa en el marco el control del c��ncer publicada por el Instituto Nacional de Cancerolog��a. Resultados: Del grupo de estudiantes que participaron del estudio, el 52,3% eran hombres, el promedio de edad fue de 15,46 �� 1,2 a��os. El tipo de piel predominante fue la trigue��a con 65,8%. La intervenci��n educativa produjo cambios significativos en los conocimientos de foto protecci��n, finalizado el seguimiento al sexto mes. En cuanto a la prevenci��n los estudiantes refirieron tener conocimiento de c��mo examinar su piel en el momento basal (12,5% n=35), present��ndose un aumento significativo de 62,6% (n=211) al sexto mes (p<0,05). Conclusi��n: El estudio demostr�� la efectividad de la intervenci��n educativa, evidenciando cambios significativos en los conocimientos en fotoprotecci��n y comportamientos preventivos del c��ncer de piel durante la pr��ctica de la actividad f��sica en estudiantes de un colegio p��blico de Bogot�� D.C., Colombia.

Efectos de una intervenci��n educativa en la promoci��n de la actividad f��sica, otros comportamientos saludables y los conocimientos para la prevenci��n del c��ncer de pulm��n en j��venes del colegio La Merced en Bogot�� D.C., Colombia

Introducci��n: El c��ncer de pulm��n es el tipo de c��ncer m��s mortal a nivel mundial, al cual se atribuyen una de cada cinco muertes anualmente. El objetivo de este estudio fue determinar los efectos de una intervenci��n educativa en la promoci��n de la actividad f��sica, otros comportamientos saludables y los conocimientos para la prevenci��n del c��ncer de pulm��n en j��venes estudiantes de una instituci��n educativa p��blica en Bogot��, Colombia. M��todos: Estudio experimental no controlado en 243 estudiantes de sexo femenino (Edad 14��1,5 a��os). La intervenci��n educativa se desarroll�� en tres momentos: una sesi��n educativa con una duraci��n de 60 minutos acorde a la Gu��a para la Comunicaci��n Educativa en el Marco del Control del C��ncer, en Colombia. Segundo, se enviaron tres correos electr��nicos con informaci��n acerca del c��ncer pulmonar; finalmente se desarrollaron actividades grupales. Para la toma de datos se utilizaron el cuestionario C��ncer Awareness Measure (CAM) y el Sistema de Vigilancia de Factores de Riesgo del Comportamiento (BRFSS). La evaluaci��n se realiz�� en un per��odo de seguimiento a 1, 3 y 6 meses post-intervenci��n. Resultados: La intervenci��n educativa increment�� significativamente los conocimientos de las j��venes sobre los signos de alarma del c��ncer pulmonar y los principales factores de riesgo modificables, tales como el consumo de cigarrillo, la exposici��n al humo del mismo y el sedentarismo, al sexto mes post-intervenci��n. Las mejoras en el cambio comportamental no lograron significancia estad��stica. Conclusiones: Una intervenci��n educativa mejora los conocimientos acerca de la detecci��n temprana y la prevenci��n del c��ncer de pulm��n, as�� como los comportamientos saludables en j��venes estudiantes en Bogot��, Colombia. Se requiere de estudios controlados aleatorizados.