BackgroundRecent studies have reported that radial extracorporeal shock wave therapy (rESWT) reduces pain and improves function in patients with mild to moderately severe carpal tunnel syndrome (CTS) compared to a placebo. However, most of those studies used multi-session rESWT combined with wrist support and evaluation of efficacy was limited to a maximum of 14 weeks.MethodsThe prospective randomized controlled trial compared efficacy in relieving pain and improving clinical function between single-dose rESWT and local corticosteroid injection (LCsI) over the mid-term (24 weeks). Twenty-five patients with mild to moderately severe CTS were randomized to receive either single-dose rESWT (n = 13) or LCsI (n = 12). Primary outcomes were evaluated using the Boston self-assessment questionnaire (BQ), while secondary outcomes used the Visual analogue scale (VAS) and electrodiagnostic parameters. Evaluations at baseline and at 1, 4, 12 and 24 weeks after treatment were performed.ResultsThere was significantly greater improvement in symptom severity scores, functional scores and Boston questionnaire scores at weeks 12 to 24 in the rESWT group compared to the LCsI group. When compared to the baseline, there was significant reduction of VAS and functional score in the rESWT group at weeks 12 and 24. The LCsI group had no statistically significant differences in VAS reduction and functional score of the same period.ConclusionsTreatment of CTS using single-dose rESWT has a carry-over effect lasting up to 24 weeks suggesting that single-dose rESWT is appropriate for treatment of mild to moderate CTS and provides longer-lasting benefits than LCsI.Trial registration(TCTR20150709001). Registered 9 July 2015
Background This study identifies the overall survival status of lung cancer patients with bone metastasis and metastasis patterns. Poor prognostic factors were identified to develop a scoring system for estimating survival period after bone metastasis. Methods A retrospective cohort analysis was performed at Chiang Mai University for the period January 1, 2006 and December 31, 2013. Time-to-event analysis was performed to estimate survival rate. The primary end point was death related to lung cancer. Univariate and multivariate analysis of the prognostic variables was done using the Cox's regression model. The score was derived from the corresponding estimated regression coefficients of significantly poor prognostic factors. Results A total of 505 lung cancer with bone metastasis patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis and 103 (20.4%) were subsequent diagnosis. The median survival time of lung cancer after bone metastasis 148 days. Male gender and ECOG 3–4 were significant poor prognostic factors for lung cancer after bone metastasis, with hazard ratios of 1.42 (95% CI 1.17–1.73), and 1.30 (95% CI 1.06–1.60), respectively. Prognosis score was determined using the binary term present/not-present for those factors. The curve from prognostic score summations of 2, 1 and 0 presented a good discrimination of survival expectancy, showing an expected median survival time of approximately 109, 146, and 225 days, respectively. Conclusions Prognostic score is a clinically simple and easy method for estimating life expectancy and for guiding interventions in bone metastasis of lung cancer.
Epigenetic aberrations are recognized as having pivotal roles in cancer etiology and progression. Histone deacetylases are among the most studied epigenetic modulators in various cancer types. The expression levels of class I histone deacetylase isoforms 1, 2, and 3 in patient-derived primary osteosarcoma cells (6 cases) was investigated, comparing them to normal bone graft-derived osteoblasts (6 cases) using the immunoblotting technique. Expression profiles of histone deacetylases in high-grade osteosarcoma tissue of 89 patients were examined and their association with clinicopathologic parameters and the patient survival was evaluated. Histone deacetylases were immunohistochemically stained on formalin-fixed paraffin-embedded biopsied tissue. Primary osteosarcoma cells expressed higher levels of histone deacetylase 1 and histone deacetylase 2, but lower levels of histone deacetylase 3 compared to benign osteoblasts. Overall, 82, 99, and 93% of 89 osteosarcomas showed nuclear expression of the histone deacetylase isoforms 1, 2, and 3, respectively. Low levels of histone deacetylase 1 were significantly associated with a high Enneking stage (P=0.014) and the presence of initial metastasis (P=0.040), while low levels of histone deacetylase 3 were significantly correlated with age >15 years (P=0.026). Univariate survival analysis found significantly shorter survival in the patients with a high Enneking stage (P<0.001), axial location (P=0.009), presence of initial metastasis (P<0.001), low-histone deacetylase 1 expression (P=0.038), and low-all-histone deacetylases expression (P=0.016). Multivariate survival analysis showed that only axial location (P=0.011) and low-all-histone deacetylases expression (P=0.039) were independent prognostic factors. In subgroup analysis of stage IIB patients (n=45), only axial location and low-all-histone deacetylases expression were associated with shorter survival in both univariate and multivariate analysis (axial location, P=0.008 and 0.010; low-all-HDACs, P=0.013 and 0.038, respectively). Low levels of all-histone deacetylases expression were significantly associated with advanced disease status and short survival. These findings may be a guide to future use of histone deacetylase inhibitors in osteosarcoma patients.
Our previous review of proteomics data showed that in osteosarcoma, some overexpressed proteins were targets of FDAapproved immunosuppressive and anti-arrhythmic drugs, including mycophenolate mofetil (MMF), ribavirin, leflunomide, azathioprine and digoxin. Here, these drugs were screened for growth inhibitory effects in human osteosarcoma cell lines, including MNNG/HOS, U2OS, SaOS-2, MG-63 and 143B cells. Only mycophenolic acid (MPA), an active metabolite of MMF, efficiently inhibited osteosarcoma cell growth with IC 50 values of 0.46-7.3 μM; these values are in the therapeutic range for organ transplant patients. At a therapeutic dose (10 μM), MPA significantly inhibited colony formation, caused cell cycle arrest in the S phase, and induced apoptosis. Moreover, the in vitro invasion of osteosarcoma cells was reduced by MPA by inhibiting cell migration capability. The in vivo antitumor effect of MMF was determined in nude mice harboring 143B cell xenografts. Daily oral administration of 200 mg/kg/day MMF for 2 weeks significantly suppressed tumor growth in treated mice, achieving 57.4 AE 11.1% tumor growth inhibition. Compared with the vehicle group, the MMF group treated with 50-200 mg/kg/day for 3 weeks had a significant reduction in the number of lung metastatic nodules in a tail vein-lung metastasis model of 143B cells. MMF doses of 50, 100 and 200 mg/kg/day are approximately equivalent to the non-toxic doses of 0.25, 0.5 and 1 g/day in humans, respectively. These findings indicate that MPA/MMF can effectively control osteosarcoma tumor growth and metastasis. Thus, the potential to repurpose MPA/MMF for use in osteosarcoma chemotherapy is of great interest.Additional Supporting Information may be found in the online version of this article.
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