Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer

AIM:To investigate the association between human papilloma virus(HPV) infection and colorectal cancer.METHODS:Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage Ⅰ,24 stage Ⅱ,21 stage Ⅲ,and 18 stage Ⅳ patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis.Nested-polymerase chain reaction(nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization(ISH).In addition,immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors.To verify whether E6 could inactivate the p53 transcriptional function,the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription(RT)-PCR.RESULTS:Of the 69 colorectal tumors,HPV16 DNA was detected in 11(16%) by nested-PCR,and HPV16 DNA was present in 8 of the 11(73%) tumors which was confirmed by ISH.The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age,gender,smoking status,tumor site;however,HPV16 infection was more common in stage Ⅰ patients than in late-stages patients(Ⅱ,Ⅲ and Ⅳ).We next asked whether HPV16 infection could be linked with colorectal cancer development.Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression.Moreover,we also observed that the adjacent normal tissues including endothelial cells,lymphocytes,fibroblasts,and gland cells in E6-positive tumors had E6 oncoprotein expression.In addition,3 of the 4(75%) E6-positive tumors carrying p53 wild-type had negative immunostaining,but one tumor had less p53 immunostaining.We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity.Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues;as expected,E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues.These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation.CONCLUSION:These results suggest that HPV16 infection may be involved in a subset of colorectal cancer,and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.

Why Insisting in Being Volunteers? A Practical Case Study Exploring from Both Rational and Emotional Perspectives

This study explored the mechanism on how volunteers as rationalists use rationalism during their cognitive appraisal process when dealing with emotional events in their social helping behavior such as international rescue events.The authors used the triangulation method to include three studies(Study 1 is a qualitative research which explored ways of TCF leader’s inspiring their volunteer workers;Study 2 is a quantitative research on the decision-making process of volunteer individuals involving in international rescue activities;Study 3 is a quantitative research on individuals’motivation for joining social helping behavior)for validation of Tzu Chi Foundation(TCF),which is a famous non-profit organization worldwide,to prove that volunteers as rationalists rely on the reasonable cognitive appraisal method to substantially evaluate the necessity of social helping behavior,including their emotional responses and arousals.Economic evaluation theory was used to depict volunteers as volunteers as rationalists’way of cognitive appraisal perspective towards emotional events such as international rescue cases or when participating in activities by non-profit organizations.Accordingly,this study found that volunteers as rationalists adhere to the principles of altruism,egoism,compensation,and reciprocity as part of their cognitive appraisal when responding to emotional situations.The researchfindings of this study depicted the volunteers’behavioral intention as volunteers as rationalists in responding to emotional events in the form of NPO helping behaviors and international rescue events.Social helping behaviors often rely on people’s emotional compassion and empathy at the beginning,but social helping behaviors cannot rely solely on emotional support.To create long-term support for non-profit organizations’action plans,it is still neces-sary to plan rationally,turning the actions of volunteers into reasonable plans.In this way,even if the volun-teers have experienced many difficulties during devotion,hindrance,and stress afterward,they can still keep in a rationalist’mindset continuously.This paper provided directions for volunteer training for non-profit organizations.