TASK DEFINITION: In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
PROBLEM: The EUROCARE project analysed cancer survival data from 45 population-based cancer registries in 17 European countries, revealing wide international differences in cancer survival. We calculated 5-year relative survival for 1836287 patients diagnosed with one of 13 cancers during the period 1978-1989. The data, from 20 cancer registries in 13 countries, were grouped into four regions: Finland, Sweden, Iceland (Northern Europe); Denmark, England and Scotland (UK and Denmark); France, The Netherlands, Germany, Italy and Switzerland (Western Europe); Estonia and Poland (Eastern Europe), and broken down into four periods (1978-1980, 1981-1983, 1984-1986, 1987-1989). For each cancer, mean European and regional survival was estimated as the weighted mean of 5-year relative survival in each country. Survival increased with time for all tumours, particularly for cancers of testis (12% increase, i.e. from 79.9 to 91.9%), breast, large bowel, skin melanoma (approximately 9-10%), and lymphomas (approximately 7%). For most solid tumours, survival was highest in Northern Europe and lowest in Eastern Europe, and also low in the UK and Denmark. Regional variation was less marked for the lymphomas. Survival improved more in Western than Northern Europe, and the differences between these regions fell for bowel cancer (from 8.0% for those diagnosed in 1978-1980 to 2% for those diagnosed in 1987-1989), breast cancer (from 7.4% to 3.9%), skin melanoma (from 13.4% to 11.0%) and Hodgkin's disease (from 7.2 to 0.6%). For potentially curable malignancies such as Hodgkin's disease, large bowel, breast and testicular cancers, there were substantial increases in survival, suggesting an earlier diagnosis and more effective treatment. The persisting regional differences suggest there are corresponding differences in the availability of diagnostic and therapeutic facilities, and in the effectiveness of healthcare systems.

SOLUTION: Cancer survival increases in Europe, but international differences remain wide.

PROBLEM: MAP kinase signaling modules serve to transduce extracellular signals to the nucleus of eukaryotic cells, but little is known about how signals cross the nuclear envelope. Exposure of yeast cells to increases in extracellular osmolarity activates the HOG1 MAP kinase cascade, which is composed of three tiers of protein kinases, namely the SSK2, SSK22 and STE11 MAPKKKs, the PBS2 MAPKK, and the HOG1 MAPK. Using green fluorescent protein (GFP) fusions of these kinases, we found that HOG1, PBS2 and STE11 localize to the cytoplasm of unstressed cells. Following osmotic stress, HOG1, but neither PBS2 nor STE11, translocates into the nucleus. HOG1 translocation occurs very rapidly, is transient, and correlates with the phosphorylation and activation of the MAP kinase by its MAPKK. HOG1 phosphorylation is necessary and sufficient for nuclear translocation, because a catalytically inactive kinase when phosphorylated is translocated to the nucleus as efficiently as the wild-type. Nuclear import of the MAPK under stress conditions requires the activity of the small GTP binding protein Ran-GSP1, but not the NLS-binding importin alpha/beta heterodimer. Rather, HOG1 import requires the activity of a gene, NMD5, that encodes a novel importin beta homolog. Similarly, export of dephosphorylated HOG1 from the nucleus requires the activity of the NES receptor XPO1/CRM1. Our findings define the requirements for the regulated nuclear transport of a stress-activated MAP kinase.

SOLUTION: Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin beta homologs NMD5 and XPO1.

PROBLEM: Inhibition of v3 or v5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Here we report that mice lacking 3 integrins or both 3 and 5 integrins not only support tumorigenesis, but have enhanced tumor growth as well. Moreover, the tumors in these integrin-deficient mice display enhanced angiogenesis, strongly suggesting that neither 3 nor 5 integrins are essential for neovascularization. We also observed that angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF) are augmented significantly in the absence of 3 integrins. We found no evidence that the expression or functions of other integrins were altered as a consequence of the 3 deficiency, but we did observe elevated levels of VEGF receptor-2 (also called Flk-1) in 3-null endothelial cells. These data indicate that v3 and v5 integrins are not essential for vascular development or pathological angiogenesis and highlight the need for further evaluation of the mechanisms of action of v-integrin antagonists in anti-angiogenic therapeutics.

SOLUTION:
Enhanced pathological angiogenesis in mice lacking 3 integrin or 3 and 5 integrins