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- Hemminki, K, et al.
(author)
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A population-based study of familial cutaneous melanoma
- 2001
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In: MELANOMA RESEARCH. - : LIPPINCOTT WILLIAMS & WILKINS. - 0960-8931. ; 11:2, s. 133-140
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Journal article (peer-reviewed)abstract
- We studied familial risks in cutaneous melanoma by comparing the occurrence of melanoma, or discordant cancer, in two generations, based on the Swedish Family-Cancer Database of 9.6 million individuals. Offspring were from 0 to 61 years of age. Cancers we
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- Lonnstedt, I., et al.
(author)
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Empirical Bayes microarray ANOVA and grouping cell lines by equal expression levels
- 2005
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In: Statistical Applications in Genetics and Molecular Biology. - : Walter de Gruyter GmbH. - 1544-6115 .- 1544-6115 .- 2194-6302. ; 4
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Journal article (peer-reviewed)abstract
- In the exploding field of gene expression techniques such as DNA microarrays, there are still few general probabilistic methods for analysis of variance. Linear models and ANOVA are heavily used tools in many other disciplines of scientific research. The usual F-statistic is unsatisfactory for microarray data, which explore many thousand genes in parallel, with few replicates. We present three potential one-way ANOVA statistics in a parametric statistical framework. The aim is to separate genes that are differently regulated across several treatment conditions from those with equal regulation. The statistics have different features and are evaluated using both real and simulated data. Our statistic B-1 generally shows the best performance, and is extended for use in an algorithm that groups cell lines by equal expression levels for each gene. An extension is also outlined for more general ANOVA tests including several factors. The methods presented are implemented in the freely available statistical language R. They are available at http://www.math.uu.se/staff/pages/?uname=ingrid.
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| 7. |
- Schmidt, Linnéa, et al.
(author)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 8. |
- Tollet-Egnell, P, et al.
(author)
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Growth hormone-mediated alteration of fuel metabolism in the aged rat as determined from transcript profiles
- 2004
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In: Physiological genomics. - : American Physiological Society. - 1531-2267 .- 1094-8341. ; 16:2, s. 261-267
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Journal article (peer-reviewed)abstract
- Age-related changes in body composition and serum lipids resemble symptoms of adult-onset growth hormone (GH) deficiency. GH treatment has been shown to normalize these changes in both GH-deficient adult patients and elderly subjects. The aim of this study was to identify GH-responsive genes that might mediate positive effects of GH treatment on fuel metabolism and body composition. cDNA microarrays were used to analyze age- and GH-induced changes in gene expression patterns in male rats. Tissues analyzed were liver, adipose tissue, and skeletal muscle from animals on or off GH treatment. A value of 1.5 was chosen to denote differences (increased or decreased expression) in the level of mRNA expression. In the liver, 7.3% of the expressed genes were affected by age and 6.5% by GH. Similar values for the other tissues were 8.3% and 5.3% (fat), and 7.9% and 9.6% (muscle), respectively. Among the differentially expressed genes, we identified several that encode proteins involved in fuel metabolism. Old rats were shown to have induced expression of genes involved in hepatic glucose oxidation and lipid synthesis, whereas these pathways were reduced in adipose tissue. GH treatment induced the expression of genes for lipid oxidation in liver and for glucose oxidation in skeletal muscle. In adipose tissue, GH reduced the expression of genes involved in lipogenesis even further. Changes in transcript levels were reflected in serum in terms of altered lipid profiles. Serum levels of triglycerides, high-density lipoprotein (HDL) cholesterol, and total cholesterol were higher in the old animals than in the young and normalized by GH treatment.
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