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Results: 1 to 8 of 8

Publication Record


A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project.
Carithers LJ, Ardlie K, Barcus M, Branton PA, Britton A, Buia SA, Compton CC, DeLuca DS, Peter-Demchok J, Gelfand ET, Guan P, Korzeniewski GE, Lockhart NC, Rabiner CA, Rao AK, Robinson KL, Roche NV, Sawyer SJ, Segrè AV, Shive CE, Smith AM, Sobin LH, Undale AH, Valentino KM, Vaught J, Young TR, Moore HM, GTEx Consortium
(2015) Biopreserv Biobank 13: 311-9
MeSH Terms: Biomedical Research, Humans, Tissue Banks, Tissue and Organ Procurement
Show Abstract · Added April 13, 2017
The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.
0 Communities
1 Members
0 Resources
4 MeSH Terms
Barrett's Esophagus Translational Research Network (BETRNet): the pivotal role of multi-institutional collaboration in esophageal adenocarcinoma research.
Abrams JA, Appelman HD, Beer DG, Berry LD, Chak A, Falk GW, Fitzgerald RC, Ginsberg GG, Grady WM, Joshi BP, Lynch JP, Markowitz S, Richmond ES, Rustgi AK, Seibel EJ, Shaheen NJ, Shyr Y, Umar A, Wang KK, Wang TC, Wang TD, Yassin R
(2014) Gastroenterology 146: 1586-90
MeSH Terms: Adenocarcinoma, Animals, Barrett Esophagus, Cooperative Behavior, Databases, Factual, Esophageal Neoplasms, Humans, Interinstitutional Relations, Organizational Objectives, Prognosis, Risk Factors, Tissue Banks, Translational Medical Research
Added February 19, 2015
0 Communities
1 Members
0 Resources
13 MeSH Terms
The Genotype-Tissue Expression (GTEx) project.
GTEx Consortium
(2013) Nat Genet 45: 580-5
MeSH Terms: Consensus Development Conferences, NIH as Topic, Gene Expression, Gene Expression Profiling, Genome-Wide Association Study, Government Programs, Humans, Molecular Sequence Annotation, Organ Specificity, Quantitative Trait Loci, Tissue Banks, United States
Show Abstract · Added April 13, 2017
Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Viable biobanking of primary head and neck squamous cell carcinoma.
Godoy JM, Sewell A, Johnston B, Brown BT, Lu X, Sinard RJ, Rohde S, Mannion K, Netterville JL, Yarbrough WG
(2013) Laryngoscope 123: 641-5
MeSH Terms: Carcinoma, Squamous Cell, Cryopreservation, Feasibility Studies, Head and Neck Neoplasms, Humans, Immunohistochemistry, Keratins, Laryngeal Neoplasms, Mouth Neoplasms, Oropharyngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Tissue Banks, Transplantation, Heterologous, Tumor Cells, Cultured
Show Abstract · Added March 7, 2014
OBJECTIVES/HYPOTHESIS - To determine the feasibility of viable storage of head and neck squamous cell carcinoma (HNSCC) for regrowth of cells in culture.
STUDY DESIGN - Laboratory-based translational study.
METHODS - Methods for intermediate-term frozen storage of viable HNSCC were explored using small pieces of primary tumor and dissociated HNSCC cells after short-term culture. Viable cells after freezing were confirmed by adherence to tissue culture plates, cell morphology, and increased cell or colony density. Two cultures were immunostained for cytokeratin to confirm epithelial origin of viable cultured cells after freezing.
RESULTS - Six primary HNSCCs (two oral cavity, three larynx, one oropharynx) and two HNSCCs that had been passaged through a xenograft (two oral cavity) were dissociated to single cells and grown in short-term cell culture for 0 to 12 passages. After short-term culture, cells were frozen for up to 8 months, thawed, and replated. Frozen cells derived from all tumors (six primary and two xenografts) were successfully replated with cultures lasting >7 days with seven of eight tumors presenting increased colony or cell density over 1 week of growth after freezing. In total, 15 of 15 tested samples derived from six primary and two xenografted HNSCCs were viable after freezing.
CONCLUSIONS - In the current study, we show that biopreservation of primary or xenografted HNSCC using short-term cell culture is feasible. Initial short-term cell culture was required for successful storage and viability of frozen cells. These proof-of-principle studies, if more widely implemented, could improve preclinical testing of new therapies for HNSCC.
Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance.
Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, Sanders ME, Granja-Ingram NM, Smith JJ, Meszoely IM, Salter J, Dowsett M, Stemke-Hale K, González-Angulo AM, Mills GB, Pinto JA, Gómez HL, Arteaga CL
(2012) Nat Med 18: 1052-9
MeSH Terms: Animals, Apoptosis, Breast Neoplasms, Cell Survival, Drug Resistance, Neoplasm, Dual-Specificity Phosphatases, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genes, Neoplasm, Humans, Ki-67 Antigen, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinase Phosphatases, Neoadjuvant Therapy, Neoplasm, Residual, Paraffin Embedding, RNA, Messenger, Tissue Banks, Tissue Fixation, Treatment Outcome, ras Proteins
Show Abstract · Added September 3, 2013
Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.
1 Communities
6 Members
0 Resources
27 MeSH Terms
Disruption of cerebral cortex MET signaling in autism spectrum disorder.
Campbell DB, D'Oronzio R, Garbett K, Ebert PJ, Mirnics K, Levitt P, Persico AM
(2007) Ann Neurol 62: 243-50
MeSH Terms: Autistic Disorder, Blotting, Western, Cerebral Cortex, Child, DNA, Databases, Factual, Female, Genotype, Hepatocyte Growth Factor, Humans, Male, Nerve Net, Oligonucleotide Array Sequence Analysis, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-met, RNA, Messenger, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Temporal Lobe, Tissue Banks, Transcription, Genetic
Show Abstract · Added May 19, 2014
OBJECTIVE - Multiple genes contribute to autism spectrum disorder (ASD) susceptibility. One particularly promising candidate is the MET gene, which encodes a receptor tyrosine kinase that mediates hepatocyte growth factor (HGF) signaling in brain circuit formation, immune function, and gastrointestinal repair. The MET promoter variant rs1858830 allele "C" is strongly associated with ASD and results in reduced gene transcription. Here we examined expression levels of MET and members of the MET signaling pathway in postmortem cerebral cortex from ASD cases and healthy control subjects.
METHODS - Protein, total RNA, and DNA were extracted from postmortem temporal cortex gray matter samples (BA 41/42, 52, or 22) belonging to eight pairs of ASD cases and matched control subjects. MET protein expression was determined by Western blotting; messenger RNA expression of MET and other related transcripts was assayed by microarray and quantitative reverse transcriptase polymerase chain reaction.
RESULTS - MET protein levels were significantly decreased in ASD cases compared with control subjects. This was accompanied in ASD brains by increased messenger RNA expression for proteins involved in regulating MET signaling activity. Analyses of coexpression of MET and HGF demonstrated a positive correlation in control subjects that was disrupted in ASD cases.
INTERPRETATION - Altered expression of MET and related molecules suggests dysregulation of signaling that may contribute to altered circuit formation and function in ASD. The complement of genes that encode proteins involved in MET activation appears to undergo long-term compensatory changes in expression that may be a hallmark contribution to the pathophysiology of ASD.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Predicting the impact of a new information system on workflow using a discrete event simulation.
Bartos CE, Nigam MK, Fridsma DB, Gadd CS
(2004) Stud Health Technol Inform 107: 706-10
MeSH Terms: Clinical Laboratory Information Systems, Computer Simulation, Histocompatibility Testing, Humans, Kidney, Organizational Innovation, Pennsylvania, Specimen Handling, Task Performance and Analysis, Tissue Banks
Show Abstract · Added January 20, 2015
Computer simulation of an information system prior to its implementation can predict time and workflow changes in a hospital department, while offering a common ground of communication across various levels in the organization. Often, the simulation can predict unexpected effects of changes to the work environment and allow experimentation with alternative scenarios at minimal cost to the department or the organization. In this paper we describe a discrete-event simulation experiment that predicted an unexpected increase in routine specimen processing time with the introduction of an information system in the HLA tissue typing lab at a major transplant center. The computer simulation enabled the reallocation of existing staff prior to the system implementation.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Establishing a tumour bank: banking, informatics and ethics.
Qualman SJ, France M, Grizzle WE, LiVolsi VA, Moskaluk CA, Ramirez NC, Washington MK
(2004) Br J Cancer 90: 1115-9
MeSH Terms: Confidentiality, Ethics, Medical, Genetic Testing, Humans, Medical Informatics, Neoplasms, Quality Control, Tissue Banks
Show Abstract · Added March 5, 2014
The six divisions of the Cooperative Human Tissue Network in the USA bank and distribute tens of thousands of tissue specimens to researchers annually. Major operational concerns include: maintaining tissue integrity, managing informatics, and protecting patient confidentiality. Increasing molecular genetics testing is also resulting in an increased demand for high-quality nucleic acids.
0 Communities
1 Members
0 Resources
8 MeSH Terms