Squamous cell carcinoma (SCC) of the lung is the second most common subtype of lung cancer. With limited treatment options, the 5-year survival rate of SCC is only 15%. Although genomic alterations in SCC have been characterized, identifying the alterations that drive SCC is critical for improving treatment strategies. Mouse models of SCC are currently limited. Using lentiviral delivery of Sox2 specifically to the mouse lung, we tested the ability of Sox2 to promote tumorigenesis in multiple tumor suppressor backgrounds. Expression of Sox2, frequently amplified in human SCC, specifically cooperates with loss of Lkb1 to promote squamous lung tumors. Mouse tumors exhibit characteristic histopathology and biomarker expression similar to human SCC. They also mimic human SCCs by activation of therapeutically relevant pathways including STAT and mTOR. This model may be utilized to test the contribution of additional driver alterations in SCC, as well as for preclinical drug discovery.

Idiopathic spontaneous intraperitoneal hemorrhage is a rare and often fatal condition that has been historically referred to as abdominal apoplexy. The presentation varies widely, and preoperative diagnosis is seldom obtained. Immediate surgical exploration remains the treatment of choice. At the time of exploration a through examination of the visceral arteries and solid organs should be done, as these are common sites for intra-abdominal bleeding. Often the site of hemorrhage cannot be localized at time of surgery despite thorough exploration. Today a postoperative diagnosis can often be confirmed and treated with interventional radiology. In rare cases the site of bleeding remains unknown despite intraoperative exploration and radiographic studies.

The majority of lung cancers are smoking-related, with environmental and genetical factors contributing. The interplay between environmental and genetical contributions in non-smoking-related lung cancers is less clear. We analysed a population-based computerised genealogy resource linked to a state-wide cancer registry of lung cancer cases (n=5544) for evidence of a genetical contribution to lung cancer predisposition in smoking (n=1747) and non-smoking cases (n=784). Statistical methods were used to test for significant excess relatedness of cases and estimate relative risk (RR) in close and distant relatives of lung cancer cases. Significant excess relatedness was observed for all lung cancer cases (p<0.001) and for the subsets of smoking-related (p<0.001) and non-smoking-related (p<0.001) cases when all pairwise relationships were considered. Only the non-smoking-related subset of cases showed significant excess relatedness when close relationships were ignored (p=0.020). First-degree, second-degree, and fourth-degree relatives of non-smoking-related lung cancer cases had significantly elevated RR. An even higher elevated RR was observed for first-degree, second-degree, third-degree and fourth-degree relatives of smoking-related lung cancer cases. Non-smoking-related lung cancer cases show significant excess relatedness for close and distant relationships, providing strong evidence for a genetical contribution as well as an environmental contribution. Significant excess relatedness for only close family relationships in all lung cancer cases and in only smoking-related lung cancer cases implies environmental contribution. Additionally, the highest RR for lung cancer was observed in the relatives of smoking-related lung cancer, suggesting predisposition gene carriers who smoke are at highest risk for lung cancer. Screening and gene identification should focus on high-risk pedigrees.