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1.  Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen 
Annals of Oncology  2012;23(11):2866-2873.
ER-positive (ER+ ) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.
Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan–Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.
All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%–100%).
Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
PMCID: PMC3477878  PMID: 22532584
breast cancer; genomics; luminal; mammaprint; oncotype; PAM50
2.  Studies on the pathogenesis of heart lesions in dogs infected with pseudorabies virus. 
Pseudorabies virus was inoculated by various routes into dogs to determine the relationship of pseudorabies virus to the development of heart lesions. Electrocardiograms and serum samples for lactate dehydrogenase isoenzymes were taken twice daily. Transitory and persistent arrhythmias were a consistent finding. Heart lesions were noted within each of the inoculated groups. These changes varied from severe multifocal areas of hemorrhage and myocardial degeneration to small zones of myolysis. A ganglioneuritis of the stellate ganglia and autonomic ganglia within the heart were also consistent findings. Herpes-like viral particles were found by electron microscopy in various autonomic ganglia and in myocardial endothelial cells. No viral particles were found in myocardial cells. Significant increases in lactate dehydrogenase-1 were noted. It was concluded that fatal arrhythmias resulted from pseudorabies virus infections in the dog after the occurrence of myocardial and ganglionic lesions.
PMCID: PMC1255198  PMID: 3756678
3.  Characterization of early pathogenic effects after experimental infection of calves with bovine immunodeficiency-like virus. 
Journal of Virology  1992;66(2):1074-1083.
The early pathogenic effects of bovine immunodeficiency-like virus (BIV) were studied in calves experimentally inoculated with BIV. All animals inoculated with BIV R29-infected cells seroconverted by 6 weeks postinoculation, and BIV was recoverable from each animal at 2 weeks postinoculation. However, levels of BIV replication in vivo appeared to be low. In situ hybridization studies indicated that during peak periods of viral replication in vivo, less than 0.03% of peripheral blood mononuclear cells were expressing detectable levels of viral RNA. Moreover, the levels of viral RNA in these cells in vivo were less than 1/10 the levels observed in persistently infected cells in vitro. BIV-inoculated calves had significantly higher numbers of circulating lymphocytes, and follicular hyperplasia was observed in lymph nodes, hemal nodes, and spleen. The histopathological changes observed in BIV-infected calves were similar to changes found early after infection with the immunosuppressive lentiviruses, including human immunodeficiency virus type 1.
PMCID: PMC240811  PMID: 1309889
4.  Construction of Bordetella pertussis strains that overproduce genetically inactivated pertussis toxin. 
Nontoxic analogs of pertussis toxin (PT), produced by in vitro mutagenesis of the tox operon, are immunogenic and protective against infection by Bordetella pertussis. The moderate levels of PT production by B. pertussis, however, make it the limiting antigen in the formulation of multicomponent, acellular, recombinant whooping cough vaccines. To increase production of the highly detoxified Lys9Gly129 PT analog by B. pertussis, additional copies of the mutated tox operon were integrated into the bacterial chromosome at the tox or fha locus by unmarked allelic exchange. Recombinant strains produced in this way secreted elevated levels of the PT analog proportional to gene dosage. The strains were stable during 10-liter fermentations, and yields of up to 80 mg of PT analog per liter were obtained under production-scale conditions. The nontoxic analog was purified and shown to be indistinguishable from material obtained from a B. pertussis strain that contained only a single copy of the toxLys9Gly129 operon. Such strains are therefore suitable for large-scale, industrial production of an acellular whooping cough vaccine containing a genetically detoxified PT analog.
PMCID: PMC195193  PMID: 1539974

Results 1-4 (4)