Background: While numerous studies have characterized primary ovarian tumors, little information is available regarding expression patterns of metastatic sites of this cancer. To define sets of genes that distinguish primary and metastatic ovarian tumors, we used cDNA microarrays to characterize global gene expression patterns in 38 effusions (28 peritoneal, 10 pleural) and 8 corresponding primary ovarian tumors, and searched for associations between expression patterns and clinical parameters.
Results: We observed multidimensional variation in expression patterns among the cancers. Coordinate variation in expression of genes from two chromosomal regions, 8q and 19q, was seen in subsets of the cancers indicating possible amplifications in these regions. A set of 112 unique genes of known function was differentially expressed between primary tumors and effusions using supervised analysis. Relatively few differences were seen between effusions isolated from the pleural and peritoneal cavities or between effusions from patients diagnosed with stage III and stage IV cancers. A set of 84 unique genes was identified that distinguished high from lower grade ovarian cancers. The results were corroborated using immunocytochemistry, mRNA in situ hybridization, and immunoblotting.
Conclusion: The extensive variation in expression patterns observed underscores the molecular heterogeneity of ovarian cancer, but suggests a similar molecular profile for ovarian carcinoma cells in serosal cavities.
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http://dx.doi.org/10.1186/1476-4598-4-26 | DOI Listing |
Background: Alzheimer's disease (AD) agitation is a distressing neuropsychiatric symptom characterized by excessive motor activity, verbal aggression, or physical aggression. Agitation is one of the causes of caregiver distress, increased morbidity and mortality, and early institutionalization in patients with AD. Current medications used for the management of agitation have modest efficacy and have substantial side effects.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: The vicious cycle between depression and dementia increases the risk of Alzheimer's Disease (AD) pathogenesis and pathology. This study investigates therapeutic effectiveness versus side effects and the underlying mechanisms of intranasal dantrolene nanoparticles (IDNs) to treat depression behavior and memory loss in 5XFAD mice.
Method: 5XFAD and wild-type B6SJLF1/J mice were treated with IDNs (IDN, 5 mg/kg) in Ryanodex formulation for a duration of 12 weeks.
Background: Progranulin (GRN) plays a critical role in familial frontotemporal dementia (fFTD), where GRN haploinsufficiency leads to reduction in PGRN levels in the brain, resulting in degeneration of neurons in the frontal lobe of brain responsible for personality, language, and behavior. FTD is the most common dementia in people under 60. Sortilin (Sort1), expressed by neurons, endocytoses, and delivers PGRN rapidly to lysosomes for degradation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A., Philadelphia, PA, USA.
Background: This study investigates the therapeutic versus side effects of intranasal lithium chloride (LiCl) in Ryanodex formulation vehicle (RFV) to inhibit inflammation and pyroptosis and to ameliorate on cognitive dysfunction and depressive behavior in 5XFAD mice.
Method: 5XFAD and wild type (WT) B6SJLF1/J mice were treated with intranasal or oral LiCl (3 mM/kg) dissolved in RFV starting at 2 or 9 months old and the continuous treatment lasted for 12 weeks. Behavior was examined for depression, cognition, olfaction, and motor function at the ages of 5 or 12 months.
Background: Memory is influenced by epigenetic mechanisms that regulate gene expression. Histone acetyltransferases (HATs), and histone deacetylases (HDACs), are two competitive enzymes regulating histone acetylation. Histone acetylation is reduced in Alzheimer's disease (AD) brains, and evidence has shown a synergistic regulation of HDACs and HATs activities.
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