Long-term survival of cancer patients compared to heart failure and stroke: A systematic review

<p>Abstract</p> <p>Background</p> <p>Cancer, heart failure and stroke are among the most common causes of death worldwide. Investigation of the prognostic impact of each disease is important, especially for a better understanding of competing risks. Aim of this study is to provide an overview of long term survival of cancer, heart failure and stroke patients based on the results of large population- and hospital-based studies.</p> <p>Methods</p> <p>Records for our study were identified by searches of Medline via Pubmed. We focused on observed and relative age- and sex-adjusted 5-year survival rates for cancer in general and for the four most common malignancies in developed countries, i.e. lung, breast, prostate and colorectal cancer, as well as for heart failure and stroke.</p> <p>Results</p> <p>Twenty studies were identified and included for analysis. Five-year observed survival was about 43% for all cancer entities, 40-68% for stroke and 26-52% for heart failure. Five-year age and sex adjusted relative survival was 50-57% for all cancer entities, about 50% for stroke and about 62% for heart failure. In regard to the four most common malignancies in developed countries 5-year relative survival was 12-18% for lung cancer, 73-89% for breast cancer, 50-99% for prostate cancer and about 43-63% for colorectal cancer. Trend analysis revealed a survival improvement over the last decades.</p> <p>Conclusions</p> <p>The results indicate that long term survival and prognosis of cancer is not necessarily worse than that of heart failure and stroke. However, a comparison of the prognostic impact of the different diseases is limited, corroborating the necessity for further systematic investigation of competing risks.</p

Cyclin E-mediated elimination of p27 requires its interaction with the nuclear pore-associated protein mNPAP60

The Cdk2 inhibitor, p27(Kip1), is degraded in a phosphorylation- and ubiquitylation-dependent manner at the G(1)–S transition of the cell cycle. Degradation of p27(Kip1) requires import into the nucleus for phosphorylation by Cdk2. Phosphorylated p27(Kip1) is thought to be subsequently re-exported and degraded in the cytosol. Using two-hybrid screens, we now show that p27(Kip1) interacts with a nuclear pore-associated protein, mNPAP60, map the interaction to the 3(10) helix of p27 and identify a point mutant in p27(Kip1) that is deficient for interaction (R90G). In vivo and in vitro, the loss-of-interaction mutant is poorly transported into the nucleus, while ubiquitylation of p27R90G occurs normally. In vivo, co-expression of cyclin E and Cdk2 rescues the import defect. However, mutant p27(Kip1) accumulates in a phosphorylated form in the nucleus and is not efficiently degraded, arguing that at least one step in the degradation of phosphorylated p27(Kip1) requires an interaction with the nuclear pore. Our results identify a novel component involved in p27(Kip1) degradation and suggest that degradation of p27(Kip1) is tightly linked to its intracellular transport