hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract

hERG1 Channels Regulate VEGF-A Secretion in Human Gastric Cancer: Clinicopathological Correlations and Therapeutical Implications

Purpose: hERG1 channels are aberrantly expressed in several types of human cancers, where they affect different aspects of cancer cell behavior. A thorough analysis of the functional role and clinical significance of hERG1 channels in gastric cancer is still lacking. Experimental Design: hERG1 expression was tested in a wide (508 samples) Italian cohort of surgically resected patients with gastric cancer, by immunohistochemistry and real-time quantitative PCR. The functional link between hERG1 and the VEGF-A was studied in different gastric cancer cell lines. The effects of hERG1 and VEGF-A inhibition were evaluated in vivo in xenograft mouse models. Results: hERG1 was positive in69% of the patients and positivity correlated with Lauren's intestinal type, fundus localization of the tumor, G1-G2 grading, I and II tumor-node-metastasis stage, and VEGF-A expression. hERG1 activity modulated VEGF-A secretion, through an AKT-dependent regulation of the transcriptional activity of the hypoxia inducible factor. Treatment of immunodeficient mice xenografted with human gastric cancer cells, with a combination of hERG1 blockers and anti-VEGF-A antibodies, impaired tumor growth more than single-drug treatments. Conclusion: Our results show that hERG1 (i) is aberrantly expressed in human gastric cancer since its early stages; (ii) drives an intracellular pathway leading to VEGF-A secretion; (iii) can be exploited to identify a gastric cancer patients' group where a combined treatment with antiangiogenic drugs and noncardiotoxic hERG1 inhibitors could be proposed. © 2014 American Association for Cancer Research

\u201cMembership Dynamics in an Insurance Group: Ingroup (local Agency) and Outgroup (Company)\u201d

Research context regards branch agencies of the of an insurance company: the characteristics of such organizations are the dynamics of interdependence between agencies and head office. The study comprised all 19 insurance agencies of one company operating in the province of Verona, with 61 employees and 19 General Insurance Agents (80 interviewees). Individual determinants have been codified: job role characteristics, personal details and sense of power within the organization; and the following psychosocial determinants: cohesion, entitativity and confidence. Results show that Ingroup/Outgroup perceptions are affected by a combination of individual and psychosocial elements, but there are differences if the questions are related that to local agency group or to head office. With head office, the influence of the individuals aspects prevail, whereas correlations regarding psychosocial variables are much stronger in the agencies. We have verified hypotheses in which some psychosocial variables sensitively weigh upon dynamics of organizational membership, and therefore continuous monitoring of such psychosocial elements are strategically important in the "co-construction" of an organizational culture are verified, and appear as: - work satisfaction is bound to the affective elements of membership; - evaluation of the General Sales Agents reveals a pressure to conform: the more the employee aligns him/herself to the local agency culture, the more the manager (GSA) will evaluate positively his /her agency. - there is a relationship between the parameters of productivity of the agencies and the Intragroup cohesion indicators