Combined Inactivation of MYC and K-Ras Oncogenes Reverses Tumorigenesis in Lung Adenocarcinomas and Lymphomas

Conditional transgenic models have established that tumors require sustained oncogene activation for tumor maintenance, exhibiting the phenomenon known as "oncogene-addiction." However, most cancers are caused by multiple genetic events making it difficult to determine which oncogenes or combination of oncogenes will be the most effective targets for their treatment.To examine how the MYC and K-ras(G12D) oncogenes cooperate for the initiation and maintenance of tumorigenesis, we generated double conditional transgenic tumor models of lung adenocarcinoma and lymphoma. The ability of MYC and K-ras(G12D) to cooperate for tumorigenesis and the ability of the inactivation of these oncogenes to result in tumor regression depended upon the specific tissue context. MYC-, K-ras(G12D)- or MYC/K-ras(G12D)-induced lymphomas exhibited sustained regression upon the inactivation of either or both oncogenes. However, in marked contrast, MYC-induced lung tumors failed to regress completely upon oncogene inactivation; whereas K-ras(G12D)-induced lung tumors regressed completely. Importantly, the combined inactivation of both MYC and K-ras(G12D) resulted more frequently in complete lung tumor regression. To account for the different roles of MYC and K-ras(G12D) in maintenance of lung tumors, we found that the down-stream mediators of K-ras(G12D) signaling, Stat3 and Stat5, are dephosphorylated following conditional K-ras(G12D) but not MYC inactivation. In contrast, Stat3 becomes dephosphorylated in lymphoma cells upon inactivation of MYC and/or K-ras(G12D). Interestingly, MYC-induced lung tumors that failed to regress upon MYC inactivation were found to have persistent Stat3 and Stat5 phosphorylation.Taken together, our findings point to the importance of the K-Ras and associated down-stream Stat effector pathways in the initiation and maintenance of lymphomas and lung tumors. We suggest that combined targeting of oncogenic pathways is more likely to be effective in the treatment of lung cancers and lymphomas

The desirable qualities of future doctors: a study of medical student perceptions

Background: There is a lack of consensus regarding the qualities possessed by the ideal doctor, and very limited research regarding the views of medical students on these qualities. Aims: To investigate the views of commencing medical students regarding the desirable qualities of doctors Methods: A survey containing a set of proposed desirable qualities of doctors identified from the existing literature was completed by 158 first year medical students. Results: The survey had a 75% response rate. Students rated the individual qualities of empathy, motivation to be a doctor, good verbal communication, ethically sound, integrity and honesty as the most important. A factor analysis identified six categories of qualities: Methodical Processing, Cognitive Capacity, People Skills, Generic Work Ethic, Role Certainty and Warmth. Significant differences in factor scores were found across subgroups of students (international and domestic students, with and without prior tertiary studies) on the following factors: Methodical Processing, which was scored highest by domestic students with prior tertiary studies, Cognitive Capacity, which was scored highest by domestic students without prior tertiary studies and Generic Work Ethic, which was scored highest by international students. Conclusions: Medical students identified a range of desirable personal qualities of a doctor which varied according to student characteristics, including their prior educational experience. Future research aiming to define such desirable qualities should include a broader range of stakeholders, including students at different training levels and institutions