An Exploration of the Pillars of Leadership in Cancer Education.

Leadership plays a key role in cancer education (CE) and the success of its practices. Leaders in CE must effectively use their leadership skills to be able to communicate, collaborate, and educate their team members. There is a lack of formalized and standardized curriculums for institutions in developing leadership programs, including what themes to focus on in CE. In this article, the authors describe key pillars of leadership in CE that have presented themselves throughout their experience and within the literature. A search was conducted using the Ovid MEDLINE® database and articles were reviewed for eligibility. In this review, thirty articles were selected for their relevance to CE. With this literature search and the authors' reflections, four pillars of leadership in CE were identified: (1) leadership development, (2) collaboration, (3) diversity and equity, and (4) implementation. Within these themes, key areas of importance were discussed further, and barriers to CE leadership were identified. By reflecting upon pillars of leadership in CE, this article may be helpful for developing future leadership programs within CE. It is vital that initiatives continue to be held and barriers are addressed to increase leadership effectiveness within CE.

Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells.

BACKGROUND: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib. This drug is currently used in combination with other anticancer agents. OBJECTIVES: In this study, the enhancement of bortezomib activity was evaluated using gold nanoparticles coated with poly(ethylene glycol). The uptake mechanism of the gold nanoparticles in pancreatic cell lines, S2-013 and hTERT-HPNE, was assessed by laser scanning confocal microscopy (LSCM). RESULTS: Pancreatic cancer cells internalized the nanoparticles together with the drug in few minutes through the formation of endocytic vesicles. This rapid uptake leads to an increase in the concentration and diffusion of bortezomib in the cytoplasm yielding an increased toxicity on the cells when compared to the drug alone. CONCLUSION: Gold nanoparticles can be used as effective delivery systems to increasing the permeation and retention of drugs in cancer cells.

Human MUC2 mucin gene is transcriptionally regulated by Cdx homeodomain proteins in gastrointestinal carcinoma cell lines.

In intestinal metaplasia and 30% of gastric carcinomas, MUC2 intestinal mucin and the intestine-specific transcription factors Cdx-1 and Cdx-2 are aberrantly expressed. The involvement of Cdx-1 and Cdx-2 in the intestinal development and their role in transcription of several intestinal genes support the hypothesis that Cdx-1 and/or Cdx-2 play important roles in the aberrant intestinal differentiation program of intestinal metaplasia and gastric carcinoma. To clarify the mechanisms of transcriptional regulation of the MUC2 mucin gene in gastric cells, pGL3 deletion constructs covering 2.6 kb of the human MUC2 promoter were used in transient transfection assays, enabling us to identify a relevant region for MUC2 transcription in all gastric cell lines. To evaluate the role of Cdx-1 and Cdx-2 in MUC2 transcription we performed co-transfection experiments with expression vectors encoding Cdx-1 and Cdx-2. In two of the four gastric carcinoma cell lines and in all colon carcinoma cell lines we observed transactivation of the MUC2 promoter by Cdx-2. Using gel shift assays we identified two Cdx-2 binding sites at -177/-171 and -191/-187. Only simultaneous mutation of the two sites resulted in inhibition of Cdx-2-mediated transactivation of MUC2 promoter, implying that both Cdx-2 sites are active. Finally, stable expression of Cdx-2 in a gastric cell line initially not expressing Cdx-2, led to induction of MUC2 expression. In conclusion, this work demonstrates that Cdx-2 activates the expression of MUC2 mucin gene in gastric cells, inducing an intestinal transdifferentiation phenotype that parallels what is observed both in intestinal metaplasia and some gastric carcinomas.

Lewis enzyme (alpha1-3/4 fucosyltransferase) polymorphisms do not explain the Lewis phenotype in the gastric mucosa of a Portuguese population.

The human alpha-1,3/4 fucosyltransferase III (FucT III) catalyses the synthesis of Lewis antigens including Le(b) antigen which is a ligand for Helicobacter pylori adhesion. Several polymorphisms have been described in the FUT3 gene affecting both the transmembrane and catalytic domains, some of which affect the enzyme activity. The aim of the present work was to study the Lewis gene polymorphisms in a Caucasian Portuguese population, with a high rate of H. pylori infection, and to evaluate the implications of mutant enzymes in Le(b) expression in the gastric mucosa. We studied 460 asymptomatic or dyspeptic individuals from northern Portugal. Screening for Lewis gene polymorphisms was performed by SSCP and direct sequencing. Lewis phenotype in gastric mucosa was determined by immunohistochemistry. In 47 individuals with a Lewis negative blood group, we found FUT3 gene polymorphisms that were previously described in other populations: 59T>G, 202T>C, 314C>T, 508G>A and 1067T>A. Among the 47 Lewis negative individuals in blood, only nine were also negative in gastric mucosa, suggesting the existence of another alpha 1-4 fucosyltransferase that is responsible for Le(a) and Le(b) synthesis in gastric mucosa.