Invariable region (IR)(6), an immunodominant conserved region of VlsE, the antigenic variation protein of Borrelia burgdorferi, is currently used for the serologic diagnosis of Lyme disease in humans and canines. A longitudinal assessment of anti-IR(6) antibody levels in B. burgdorferi-infected rhesus monkeys revealed that this level diminished sharply after antibiotic treatment (within 25 weeks). In contrast, antibody levels to P39 and to whole-cell antigen extracts of B. burgdorferi either remained unchanged or diminished less. A longitudinal analysis in dogs yielded similar results. In humans, the anti-IR(6) antibody titer diminished by a factor of > or =4 in successfully treated patients and by a factor of <4 in treatment-resistant patients. This result suggests that the quantification of anti-IR(6) antibody titer as a function of time should be investigated further as a test to assess response to Lyme disease therapy or to determine whether a B. burgdorferi infection has been eliminated.
BackgroundMedulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models.MethodsUsing cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo.ResultsCurcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model.ConclusionsThe in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.
Objective
This study was designed to investigate the pathogenic contributions of fibroblast-like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA.
Methods
FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease. Biologically relevant differentially expressed genes were confirmed by RNA and protein analysis.
Results
Exploration of global gene expression profiles of the JIA FLS revealed important dysregulated pathways, including the transforming growth factor β (TGFβ) signaling, as well as endochondral bone formation, cartilage formation, and β-catenin networks. Importantly, bone morphogenetic protein 4 (BMP-4) was significantly overexpressed in the JIA FLS. FLS from patients with oligoarticular JIA exhibit a chondrocyte phenotype, as evidenced by expression of type II collagen and aggrecan.
Conclusion
Dysregulation of the pathways involved in the pathogenesis of oligoarticular JIA were revealed through gene expression profiling. JIA FLS displayed dysregulated TGFβ signaling and exhibited a hypertrophic chondrocyte phenotype. These characteristics, along with contributions from the β-catenin network may have implications for endochondral bone formation and local growth disturbances in oligoarticular JIA. Overexpression of BMP-4 in FLS from patients with oligoarticular JIA in particular may play an important role in disease pathogenesis, with a direct effect on functional outcome and with implications for future treatment.
Management of Lyme disease would benefit from a test to assess therapy outcome. Such a test could be employed to ascertain if treatment of early Lyme disease was successful and would be helpful to clinicians assessing patients with lingering posttreatment symptoms. We reported recently that levels of the antibody to C 6 , a Borrelia burgdorferi-derived peptide that is used as an antigen in the C 6 -Lyme diagnostic test, declined after successful antibiotic treatment of Lyme borreliosis patients. We assessed retrospectively the change in anti-C 6 antibody titers in 131 patients with either early localized disease (erythema migrans) or disseminated disease. All of these patients were treated with antibiotics and were free of the clinical signs shown at presentation within 12 weeks after the initiation of treatment. Decreases in reciprocal geometric mean titers (rGMT) of the anti-C 6 antibody were quantified for the subpopulation of 45 patients whose baseline rGMT were >80 and whose second serum specimens were obtained at least 6 months after the baseline specimen. Eighty percent of this patient group (36 of 45) experienced a >4-fold decrease in their rGMT (P < 0.0003). These results suggest that a change in the anti-C 6 antibody titer may serve as an indicator of therapy outcome for patients with localized or disseminated Lyme borreliosis.
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