METHODS: Thirty-two adults with recurrent, nonspecific LBP were randomized into two groups: Appendicular BFR exercise (BFR exercise) or control exercise (CON exercise). All participants trained (two times per week) for 10 wk, with a 12-wk follow-up. Participants performed three sets of leg extension (LE), plantar flexion (PF), and elbow flexion (EF) exercises followed by low-load TE exercise without BFR. Outcome measures included magnetic resonance imaging-derived muscle size (quadriceps and TE), strength (LE, PF, EF, and TE), and endurance (LE and TE).
RESULTS: There was no evidence for a cross-transfer of effect to the TE. There was also no statistically significant enhancement of limb skeletal muscle size or function of BFR relative to CON exercise at any time point; though, moderate effect sizes for BFR exercise were observed for enhanced muscle size and strength in the leg extensors.
CONCLUSIONS: Low-load BFR exercise of the appendicular muscles did not result in a cross-transfer of effect to the TE musculature. There was also no significant benefit of low-load BFR exercise on the appendicular muscle size and function, suggesting no benefit from low-load BFR exercise in adults with recurrent, nonspecific LBP.
RESULTS: Here we report that the treatment of RCC cell lines with azacitidine suppressed cell proliferation in all 15 lines tested. A marked response to azacitidine therapy (>50% reduction in colony formation assay) was detected in the three cell lines with VHL promoter methylation but some RCC cell lines without VHL TSG methylation also demonstrated a similar response suggesting that multiple methylated TSGs might determine the response to demethylating therapies. To identify novel candidate methylated TSGs implicated in RCC we undertook a combined analysis of copy number and CpG methylation array data. Candidate novel epigenetically inactivated TSGs were further prioritised by expression analysis of RCC cell lines pre and post-azacitidine therapy and comparative expression analysis of tumour/normal pairs. Thus, with subsequent investigation two candidate genes were found to be methylated in more than 25% of our series and in the TCGA methylation dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1 (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7 (P = 0.0067) was associated with prognosis.
CONCLUSIONS: These findings provide preclinical evidence that treatment with demethylating agents such as azacitidine might be useful for the treatment of advanced RCC and further insights into the role of epigenetic changes in the pathogenesis of RCC.