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Portland, OR, United States

Rubin B.P.,Cleveland Clinic | Heinrich M.C.,OHSU Knight Cancer Institute
Seminars in Diagnostic Pathology | Year: 2015

Gastrointestinal stromal tumors (GISTs) were originally thought to harbor either KIT or platelet-derived growth factor receptor A (PDGFRA) mutations only. However, more recent discoveries have highlighted additional, less common oncogenic driver mutations including NF1, BRAF, and succinate dehydrogenase (SDH) mutations. Genotyping GISTs has become more important since not all genotypes respond equally to FDA-approved tyrosine kinase inhibitors. GIST is a paradigm for personalized cancer therapy. Recent studies demonstrate how immunohistochemistry can be used both to diagnose GIST and to screen for specific mutations. DOG1 is particularly useful in the diagnosis of KIT-negative GIST, including tumors with PDGFRA mutations, which can also potentially be identified by immunohistochemistry for PDGFRA. SDHB immunohistochemistry is useful in characterizing GISTs with SDHA-D mutations, whereas SDHA immunohistochemistry is able to identify SDHA mutant GISTs. © 2015 Elsevier Inc. Source

Rhee J.-K.,Seoul National University | Kim K.,Seoul National University | Chae H.,Indiana University Bloomington | Evans J.,Mayo Medical School | And 7 more authors.
Nucleic Acids Research | Year: 2013

Aberrant DNA methylation of CpG islands, CpG island shores and first exons is known to play a key role in the altered gene expression patterns in all human cancers. To date, a systematic study on the effect of DNA methylation on gene expression using high resolution data has not been reported. In this study, we conducted an integrated analysis of MethylCap-sequencing data and Affymetrix gene expression microarray data for 30 breast cancer cell lines representing different breast tumor phenotypes. As well-developed methods for the integrated analysis do not currently exist, we created a series of four different analysis methods. On the computational side, our goal is to develop methylome data analysis protocols for the integrated analysis of DNA methylation and gene expression data on the genome scale. On the cancer biology side, we present comprehensive genome-wide methylome analysis results for differentially methylated regions and their potential effect on gene expression in 30 breast cancer cell lines representing three molecular phenotypes, luminal, basal A and basal B. Our integrated analysis demonstrates that methylation status of different genomic regions may play a key role in establishing transcriptional patterns in molecular subtypes of human breast cancer. © 2013 The Author(s). Published by Oxford University Press. Source

Adkisson H.D.,ISTO Technologies Inc. | Martin J.A.,University of Iowa | Amendola R.L.,University of Iowa | Milliman C.,ISTO Technologies Inc. | And 7 more authors.
American Journal of Sports Medicine | Year: 2010

Background: Donor-site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells. Hypothesis/Purpose: The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts. Study Design: Controlled laboratory study. Methods: Cartilage samples were from juvenile (<13 years old) and adult (>13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity. Results: Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNA in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (P =.002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (P <.001). Juvenile chondrocytes did not stimulate lymphocyte proliferation. Conclusion: These results document a dramatic age-related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo. Clinical Relevance: Juvenile human chondrocytes have greater potential to restore articular cartilage than adult cells, and may be transplanted without the fear of rejection, suggesting a new allogeneic approach to restoring articular cartilage in older individuals. © 2010 The Author(s). Source

Mooney M.,Oregon Health And Science University | Mooney M.,Oregon Clinical and Translational Research Institute | Mooney M.,OHSU Knight Cancer Institute | McWeeney S.,Oregon Health And Science University | And 4 more authors.
Seminars in Immunology | Year: 2013

Vaccines are the most cost effective public health measure for preventing viral infection and limiting epidemic spread within susceptible populations. However, the efficacy of current protective vaccines is highly variable, particularly in aging populations. In addition, there have been a number of challenges in the development of new vaccines due to a lack of detailed understanding of the immune correlates of protection. To identify the mechanisms underlying the variability of the immune response to vaccines, system-level tools need to be developed that will further our understanding of virus-host interactions and correlates of vaccine efficacy. This will provide critical information for rational vaccine design and allow the development of an analog to the "precision medicine" framework (already acknowledged as a powerful approach in medicine and therapeutics) to be applied to vaccinology. © 2013 Elsevier Ltd. Source

Mooney M.A.,Oregon Health And Science University | Mooney M.A.,OHSU Knight Cancer Institute | Wilmot B.,Oregon Health And Science University | Wilmot B.,OHSU Knight Cancer Institute | Wilmot B.,Oregon Clinical and Translational Research Institute
American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics | Year: 2015

To maximize the potential of genome-wide association studies, many researchers are performing secondary analyses to identify sets of genes jointly associated with the trait of interest. Although methods for gene-set analyses (GSA), also called pathway analyses, have been around for more than a decade, the field is still evolving. There are numerous algorithms available for testing the cumulative effect of multiple SNPs, yet no real consensus in the field about the best way to perform a GSA. This paper provides an overview of the factors that can affect the results of a GSA, the lessons learned from past studies, and suggestions for how to make analysis choices that are most appropriate for different types of data. © 2015 Wiley Periodicals, Inc. Source

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