A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia

Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer

Effects of electromagnetic field on proliferation, differentiation, and mineralization of MC3T3 cells

The steep increasing incidence of bone diseases and fractures provides a commanding impetus and growing demands for bone tissue engineering research. Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and to enhance the maturation of osteoblastic cell, which is the key element in bone tissues. However, the optimal parameters for PEMF stimulation are still being explored. In this study, we investigated the effects of PEMF treatment on the proliferation, differentiation, and mineralization of osteoblast precursor cells MC3T3-E1 to explore the cell growth profile under different PEMF exposure durations (15, 30, and 60 min daily) with a magnetic field strength of 0.6 mT, at a frequency of 50 Hz, and cultured in media with or without osteogenic supplements for 28 days. Cell viability and metabolic activity were accessed by confocal microscopy, and alamarBlue time-course measurements and results indicated that there were no adverse effects under designated PEMF condition. After 7 days of PEMF exposure, in comparison with negative controls, cell numbers increased when exposed to PEMF in culture medium and were independent of osteogenic supplements. However, PEMF might not have significant impact on cellular mineralization as observed from calcium deposition analysis, even though osteogenic gene expression was upregulated for cells with PEMF exposure. Von Kossa and Alizarin Red staining indicated that extracellular matrix mineralization occurred at day 28 with osteogenic supplements only, and no significant differences were found among those samples with different PEMF treatment durations. In summary, our results suggested that PEMF stimulation for as short as 15 min could improve cell proliferation but not mineralization in vitro. Thus, this study highlights the importance of choosing appropriate PEMF parameters to achieve the desired effect on target cells. The optimization of PEMFs will enhance the efficiency of its usage as a clinical, adjuvant therapeutic treatment for bone defect regeneration. Impact Statement We present the study about how the parameters of pulsed electromagnetic field (PEMF) stimulus affected calvarial osteoblast precursor cell in terms of growth, viability, and differentiation. This research provides insight and foundation to clinical application of noninvasive therapy using PEMF to improve bone regeneration.ASTAR (Agency for Sci., Tech. and Research, S’pore)Accepted versio

Expression and localization of Hsps in the heart and blood vessel of heat-stressed broilers

The objective of this study was to investigate the kinetics of Hsp60, Hsp70, Hsp90 protein, and messenger RNA (mRNA) expression levels and to correlate these heat shock protein (Hsp) levels with tissue damage resulting from exposure to high temperatures for varying amounts of time. One hundred broilers were heat-stressed for 0, 2, 3, 5, and 10 h, respectively, by rapidly increasing the ambient temperature from 22 ± 1°C to 37 ± 1°C. Obvious elevations of plasma creatine kinase indicate damage to myocardial cells after heat stress. Hsp70 and Hsp90, and their corresponding mRNAs in the heart tissue of heat-stressed broilers, elevated significantly after 2 h of heat exposure and decreased quickly with continued heat stress. However, the levels of hsp60 mRNA in the heart of heat-stressed broilers increased sharply (P < 0.01) at 2 h of heat stress but then decreased quickly after 3 h, while the level of Hsp60 protein in the heart increased (P < 0.01) at 2 h of heat stress and maintained a high level throughout heat exposure. The results indicate that the elevation of the three Hsps, especially Hsp60 in heart, may be important markers at the beginning of heat stress and act as protective proteins in adverse environments. The reduction of Hsp signals in the cytoplasm of myocardial cells implies that myocardial cell lesions may have an adverse impact on the function of Hsps during heat stress. Meanwhile, the localization of Hsp70 in blood vessels of broiler hearts suggests another possible mechanism for protection of the heart after heat exposure