Nimbolide Inhibits SOD2 to Control Pancreatic Ductal Adenocarcinoma Growth and Metastasis.

Reactive oxygen species are frequently associated with various cancers including pancreatic ductal adenocarcinomas (PDACs). Superoxide dismutase 2 (SOD2) is an enzyme that plays an important role in reactive oxygen species (ROS) signaling. Investigating the molecular function and biological functions of SOD2 can help us develop new therapeutic options and uncover new biomarkers for PDAC diagnosis and prognosis. Here, we show that nimbolide (NB), a triterpene limonoid, effectively blocks the growth and metastasis of PDACs by suppressing the expression and activity of SOD2. To identify the role of SOD2 in NB-induced anticancer activity, we used RNA interference to silence and plasmid transfection to overexpress it. Silencing SOD2 significantly reduced the growth and metastatic characteristics like epithelial-to-mesenchymal transition, invasion, migration, and colony-forming capabilities of PDACs, and NB treatment further reduced these characteristics. Conversely, the overexpression of SOD2 enhanced these metastatic characteristics. ROS signaling has a strong feedback mechanism with the PI3K/Akt signaling pathway, which could be mediated through SOD2. Finally, NB treatment to SOD2-overexpressing PDAC xenografts resulted in significant inhibition of tumor growth and metastasis. Overall, this work suggests that NB, a natural and safe phytochemical that silences SOD2 to induce high levels of ROS generation, results in increased apoptosis and reduced growth and progression of PDACs. The role of SOD2 in regulating NB-induced ROS generation presents itself as a therapeutic option for PDACs.

Pathology Laboratory Policies and Procedures for Releasing Diagnostic Tissue for Cancer Research.

CONTEXT.­: The Surveillance, Epidemiology, and End Results (SEER) cancer registry program is currently evaluating the use of archival, diagnostic, formalin-fixed, paraffin-embedded (FFPE) tissue obtained through SEER cancer registries, functioning as honest brokers for deidentified tissue and associated data. To determine the feasibility of this potential program, laboratory policies for sharing tissue for research needed to be assessed. OBJECTIVE.­: To understand the willingness of pathology laboratories to share archival diagnostic tissue for cancer research and related policies. DESIGN.­: Seven SEER registries administered a 27-item questionnaire to pathology laboratories within their respective registry catchment areas. Only laboratories that processed diagnostic FFPE specimens and completed the questionnaire were included in the analysis. RESULTS.­: Of the 153 responding laboratories, 127 (83%) responded that they process FFPE specimens. Most (n = 88; 69%) were willing to share tissue specimens for research, which was not associated with the number of blocks processed per year by the laboratories. Most laboratories retained the specimens for at least 10 years. Institutional regulatory policies on sharing deidentified tissue varied considerably, ranging from requiring a full Institutional Review Board review to considering such use exempt from Institutional Review Board review, and 43% (55 of 127) of the laboratories did not know their terms for sharing tissue for research. CONCLUSIONS.­: This project indicated a general willingness of pathology laboratories to participate in research by sharing FFPE tissue. Given the variability of research policies across laboratories, it is critical for each SEER registry to work with laboratories in their catchment area to understand such policies and state legislation regulating tissue retention and guardianship.

Hepatocyte nuclear factor 1 alpha influences pancreatic cancer growth and metastasis.

Hepatocyte nuclear factor 1 homeobox alpha (HNF1α) is a transcription factor involved in endodermal organogenesis and pancreatic precursor cell differentiation and development. Earlier studies have reported a role for HNF1α in pancreatic ductal adenocarcinoma (PDAC) but it is controversial. The mechanism by which it impacts PDAC is yet to be explored in depth. In this study, using the online databases we observed that HNF1α is upregulated in PDAC, which was also confirmed by our immunohistochemical analysis of PDAC tissue microarray. Silencing HNF1α reduced the proliferative, migratory, invasive and colony forming capabilities of pancreatic cancer cells. Key markers involved in these processes (pPI3K, pAKT, pERK, Bcl2, Zeb, Snail, Slug) were significantly changed in response to alterations in HNF1α expression. On the other hand, overexpression of HNF1α did not induce any significant change in the aggressiveness of pancreatic cancer cells. Our results demonstrate that reduced expression of HNF1α leads to inhibition of pancreatic cancer growth and progression, which indicates that it could be a potential oncogene and target for PDAC.

Sequential Stereotype Priming: A Meta-Analysis.

Psychological interest in stereotype measurement has spanned nearly a century, with researchers adopting implicit measures in the 1980s to complement explicit measures. One of the most frequently used implicit measures of stereotypes is the sequential priming paradigm. The current meta-analysis examines stereotype priming, focusing specifically on this paradigm. To contribute to ongoing discussions regarding methodological rigor in social psychology, one primary goal was to identify methodological moderators of the stereotype priming effect-whether priming is due to a relation between the prime and target stimuli, the prime and target response, participant task, stereotype dimension, stimulus onset asynchrony (SOA), and stimuli type. Data from 39 studies yielded 87 individual effect sizes from 5,497 participants. Analyses revealed that stereotype priming is significantly moderated by the presence of prime-response relations, participant task, stereotype dimension, target stimulus type, SOA, and prime repetition. These results carry both practical and theoretical implications for future research on stereotype priming.

Utilización de un índice pronóstico de morbilidad y mortalidad por enfermedad cardiovascular asociada con factores de riesgo aterogénico / Use of a prognostic indicator of morbidity and mortality from cardiovascular disease associated with atherogenic factors

Se realizó un estudio observacional analítico de casos y controles, para evaluar la influencia de algunos factores de riesgos aterogénicos en la morbilidad y mortalidad por enfermedad cardiovascular y establecer a partir de estos un índice sintético para estratificar los grupos de riesgo del daño vasculovisceral. La muestra integrada por 200 pacientes fue seleccionada de forma aleatoria en pacientes ingresados en el Instituto Superior de Medicina Militar ôDr. Luis Díaz Sotoö durante el año 2000. Se definieron como enfermos a pacientes con diagnóstico inequívoco de enfermedad cardiovascular y controles, a pacientes con características similares a los casos anteriores, excepto no presentar daño vasculovisceral. Al efectuar el análisis de significación estadística, los factores de riesgo aterogénico que permanecieron asociados con la morbilidad y mortalidad por enfermedad cardiovascular, con un poder predictor independiente, fueron en orden decreciente de razones cruzadas (OR), la hipertensión arterial, la hipercolesterolemia, la diabetes mellitus, el sedentarismo y el hábito de fumar. No mostraron diferencias significativas el estrés, el índice de masa corporal y los antecedentes patológicos personales y familiares. Estas variables integradas en una puntuación sintética fueron estratificadas y comparadas, y mostraron diferencias significativas los casos en relación con los controles, con estimaciones de la probabilidad de enfermar 6,9 veces superiores en el grupo expuesto (estratos 2 y 3), como demostración preliminar del valor discriminativo del índice para la estratificación de la población por grupos de riesgo, el cual puede constituir una alternativa apropiada por su simplicidad, relación costo-beneficio y utilidad para la implementación de estrategias de intervención contra las enfermedades crónicas no transmisibles en el nivel primario de salud

Utilización de un índice pronóstico de morbilidad y mortalidad por enfermedad cardiovascular asociada con factores de riesgo aterogénico / Use of a prognostic indicator of morbidity and mortality from cardiovascular disease associated with atherogenic factors

Se realizó un estudio observacional analítico de casos y controles, para evaluar la influencia de algunos factores de riesgos aterogénicos en la morbilidad y mortalidad por enfermedad cardiovascular y establecer a partir de estos un índice sintético para estratificar los grupos de riesgo del daño vasculovisceral. La muestra integrada por 200 pacientes fue seleccionada de forma aleatoria en pacientes ingresados en el Instituto Superior de Medicina Militar ôDr. Luis Díaz Sotoö durante el año 2000. Se definieron como enfermos a pacientes con diagnóstico inequívoco de enfermedad cardiovascular y controles, a pacientes con características similares a los casos anteriores, excepto no presentar daño vasculovisceral. Al efectuar el análisis de significación estadística, los factores de riesgo aterogénico que permanecieron asociados con la morbilidad y mortalidad por enfermedad cardiovascular, con un poder predictor independiente, fueron en orden decreciente de razones cruzadas (OR), la hipertensión arterial, la hipercolesterolemia, la diabetes mellitus, el sedentarismo y el hábito de fumar. No mostraron diferencias significativas el estrés, el índice de masa corporal y los antecedentes patológicos personales y familiares. Estas variables integradas en una puntuación sintética fueron estratificadas y comparadas, y mostraron diferencias significativas los casos en relación con los controles, con estimaciones de la probabilidad de enfermar 6,9 veces superiores en el grupo expuesto (estratos 2 y 3), como demostración preliminar del valor discriminativo del índice para la estratificación de la población por grupos de riesgo, el cual puede constituir una alternativa apropiada por su simplicidad, relación costo-beneficio y utilidad para la implementación de estrategias de intervención contra las enfermedades crónicas no transmisibles en el nivel primario de salud(AU)