941 research outputs found

    Informing a risk prediction model for binary outcomes with external coefficient information

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146799/1/rssc12306-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146799/2/rssc12306_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146799/3/rssc12306.pd

    Effect of frying treatments on texture and colour parameters of deep fat fried yellow fleshed cassava chips

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    Effects of frying treatments on texture (hardness) and colour parameters (L, a, b, Delta) during deep fat frying of yellowfleshed cassava root slices (TMS 01/1371) were investigated. Slices (dimension of 40mm × 25mm × 3 mm) were divided into three portions and subjected to vacuum frying (fresh slices) and atmospheric frying (fresh and predried slices) and equivalent thermal driving forces (ETDF) of 60∘C, 70∘C, and 80∘C were maintained during frying. The quality attributes investigated were best preserved in vacuum fried chips. The overall colour change in chips fried under vacuum conditions at 118∘C and 8 min was the least (21.20) compared to fresh and atmospherically predried ones (16.69 and 14.81, resp.). A sharp reduction in the breaking force was obtained for all frying treatments after 8 min and this effect was the least in vacuum fried chips. First-order kinetics modeled the changes in quality attributes for all the temperatures investigated. Rate constants k (min−1) obtained for vacuum frying were almost equal to that of atmospheric frying while activation energies for hardness and colour change were 53.30 and 467.11 KJ/mol, respectively. Quality attributes studied were best preserved during vacuum frying

    Overexpression of Full-Length ETV1 Transcripts in Clinical Prostate Cancer Due to Gene Translocation

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    ETV1 is overexpressed in a subset of clinical prostate cancers as a fusion transcript with many different partners. However, ETV1 can also be overexpressed as a full-length transcript. Full-length ETV1 protein functions differently from truncated ETV1 produced by fusion genes. In this study we describe the genetic background of full-length ETV1 overexpression and the biological properties of different full-length ETV1 isoforms in prostate cancer. Break-apart FISH showed in five out of six patient samples with overexpression of full-length ETV1 a genomic rearrangement of the gene, indicating frequent translocation. We were able to study the rearrangements in more detail in two tumors. In the first tumor 5′-RACE on cDNA showed linkage of the complete ETV1 transcript to the first exon of a prostate-specific two exon ncRNA gene that maps on chromosome 14 (EST14). This resulted in the expression of both full-length ETV1 transcripts and EST14-ETV1 fusion transcripts. In chromosome spreads of a xenograft derived from the second prostate cancer we observed a complex ETV1 translocation involving a chromosome 7 fragment that harbors ETV1 and fragments of chromosomes 4 and 10. Further studies revealed the overexpression of several different full-length transcripts, giving rise to four protein isoforms with different N-terminal regions. Even the shortest isoform synthesized by full-length ETV1 stimulated in vitro anchorage-independent growth of PNT2C2 prostate cells. This contrasts the lack of activity of even shorter N-truncated ETV1 produced by fusion transcripts. Our findings that in clinical prostate cancer overexpression of full-length ETV1 is due to genomic rearrangements involving different chromosomes and the identification of a shortened biologically active ETV1 isoform are highly relevant for understanding the mechanism of ETV1 function in prostate cancer

    Impact of the SPOP Mutant Subtype on the Interpretation of Clinical Parameters in Prostate Cancer.

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    Purpose: Molecular characterization of prostate cancer, including The Cancer Genome Atlas, has revealed distinct subtypes with underlying genomic alterations. One of these core subtypes, SPOP (speckle-type POZ protein) mutant prostate cancer, has previously only been identifiable via DNA sequencing, which has made the impact on prognosis and routinely used risk stratification parameters unclear. Methods: We have developed a novel gene expression signature, classifier (Subclass Predictor Based on Transcriptional Data), and decision tree to predict the SPOP mutant subclass from RNA gene expression data and classify common prostate cancer molecular subtypes. We then validated and further interrogated the association of prostate cancer molecular subtypes with pathologic and clinical outcomes in retrospective and prospective cohorts of 8,158 patients. Results: The subclass predictor based on transcriptional data model showed high sensitivity and specificity in multiple cohorts across both RNA sequencing and microarray gene expression platforms. We predicted approximately 8% to 9% of cases to be SPOP mutant from both retrospective and prospective cohorts. We found that the SPOP mutant subclass was associated with lower frequency of positive margins, extraprostatic extension, and seminal vesicle invasion at prostatectomy; however, SPOP mutant cancers were associated with higher pretreatment serum prostate-specific antigen (PSA). The association between SPOP mutant status and higher PSA level was validated in three independent cohorts. Despite high pretreatment PSA, the SPOP mutant subtype was associated with a favorable prognosis with improved metastasis-free survival, particularly in patients with high-risk preoperative PSA levels. Conclusion: Using a novel gene expression model and a decision tree algorithm to define prostate cancer molecular subclasses, we found that the SPOP mutant subclass is associated with higher preoperative PSA, less adverse pathologic features, and favorable prognosis. These findings suggest a paradigm in which the interpretation of common risk stratification parameters, particularly PSA, may be influenced by the underlying molecular subtype of prostate cancer
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