Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

A colorectal cancer classification system that associates cellular phenotype and responses to therapy.

Colorectal cancer (CRC) is a major cause of cancer mortality. Whereas some patients respond well to therapy, others do not, and thus more precise, individualized treatment strategies are needed. To that end, we analyzed gene expression profiles from 1,290 CRC tumors using consensus-based unsupervised clustering. The resultant clusters were then associated with therapeutic response data to the epidermal growth factor receptor-targeted drug cetuximab in 80 patients. The results of these studies define six clinically relevant CRC subtypes. Each subtype shares similarities to distinct cell types within the normal colon crypt and shows differing degrees of 'stemness' and Wnt signaling. Subtype-specific gene signatures are proposed to identify these subtypes. Three subtypes have markedly better disease-free survival (DFS) after surgical resection, suggesting these patients might be spared from the adverse effects of chemotherapy when they have localized disease. One of these three subtypes, identified by filamin A expression, does not respond to cetuximab but may respond to cMET receptor tyrosine kinase inhibitors in the metastatic setting. Two other subtypes, with poor and intermediate DFS, associate with improved response to the chemotherapy regimen FOLFIRI in adjuvant or metastatic settings. Development of clinically deployable assays for these subtypes and of subtype-specific therapies may contribute to more effective management of this challenging disease

Variation in feeding behavior and milk production among dairy cows when supplemented with 2 amounts of mixed ration in combination with 2 amounts of pasture

peer-reviewedVariation in feeding behavior and milk production of grazing dairy cows fed a mixed ration was measured. Experiments were conducted in spring (early lactation) and autumn (late lactation) with 48 Holstein-Friesian dairy cows. Pasture allowance (low vs. high) and amounts of supplement (low vs. high) were applied to determine the effect on variation among cows in feeding behavior and milk production. The experiments investigated 4 dietary treatments in a 2×2 factorial arrangement of treatments. Daily pasture allowances were 15kg of DM/cow per day (low) and 37kg of DM/cow per day (high; to ground level); and 12kg of DM/cow per day (low) and 31kg of DM/cow per day (high; to ground level), for the spring and autumn experiments, respectively. Supplements were offered at 6kg of DM/cow per day (low) and 14kg of DM/cow per day (high); and 6kg of DM/cow per day (low) and 12kg of DM/cow per day (high), for the spring and autumn experiments, respectively. There were 2groups of 6 cows per treatment. All treatments received a partial mixed ration, defined as a total mixed ration fed between periods of grazing that contained wheat grain, corn grain, alfalfa hay, and canola meal. The grain-to-forage ratio of the supplements was 78:22 (DM basis) in both spring and autumn. In both experiments, the pre-experimental period was 14d followed by a 10-d experimental period. The variation among cows within a group in feeding behavior was influenced by the amount of supplement but not the amount of pasture offered. The variation among cows in pasture eating time approximately doubled when the amount of supplement offered increased, indicating that to reduce the variability among cows, supplement feeding management strategies need to be considered. Increasing pasture allowance had no effect on pasture eating time although pasture intake increased as a result of increased grazing intensity compared with the low pasture allowance. However, increasing the amount of supplement in the partial mixed ration feeding system reduced pasture eating time by 51min/cow per day