scholarly journals Automated Dose-Response Analysis of the Relative Hepatic Gene Expression Potency of TCDF in C57BL/6 Mice

2009 ◽  
Vol 112 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Lyle D. Burgoon ◽  
Qi Ding ◽  
Alhaji N'jai ◽  
Ed Dere ◽  
Ashley R. Burg ◽  
...  
2017 ◽  
Vol 16 ◽  
pp. 117693511774013 ◽  
Author(s):  
Hien H Nguyen ◽  
Susan C Tilton ◽  
Christopher J Kemp ◽  
Mingzhou Song

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.


2012 ◽  
Vol 264 (1) ◽  
pp. 32-41 ◽  
Author(s):  
Joshua F. Robinson ◽  
Aart Verhoef ◽  
Vincent A. van Beelen ◽  
Jeroen L.A. Pennings ◽  
Aldert H. Piersma

2013 ◽  
Vol 35 ◽  
pp. 81-88 ◽  
Author(s):  
Sjors H.W. Schulpen ◽  
Joshua F. Robinson ◽  
Jeroen L.A. Pennings ◽  
Dorien A.M. van Dartel ◽  
Aldert H. Piersma

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.


2010 ◽  
Author(s):  
Elizabeth A. Hanchak ◽  
Meredith L. Smith ◽  
Jessie J. Smith ◽  
Marla K. Perna ◽  
Russell W. Brown

Pneumologie ◽  
2017 ◽  
Vol 71 (S 01) ◽  
pp. S1-S125
Author(s):  
I Pouliquen ◽  
D Austin ◽  
N Gunsoy ◽  
SW Yancey

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