PurposeWe did a meta-analysis to compare the efficacy and safety of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) versus CCRT with or without adjuvant chemotherapy (AC) for patients with locoregionally advanced nasopharyngeal carcinoma based on randomized controlled trials.MethodsWe searched PubMed, Embase, Web of Science, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, and meeting proceedings of major relevant conferences to identify published and unpublished randomized controlled trials. Progression-free survival (PFS) was the primary endpoint.ResultsThis meta-analysis included 9 randomized clinical trials with 2215 patients. NACT followed by CCRT significantly improved PFS (HR=0.68, 95% CI 0.56 – 0.81, P < 0.001) compared versus CCRT with or without AC, and no heterogeneity was observed (I2 = 0.0%, P = 0.975). NACT was associated with a significant improvement in overall survival (HR = 0.64, 95% CI 0.49 – 0.84, P = 0.001; I2 = 0.0%, P = 0.467) and distant failure-free survival (HR = 0.72, 95% CI 0.53 – 0.97, P = 0.031; I2 = 0.0%, P = 0.744). No significant benefit was shown by NACT for locoregional control. NACT with CCRT increased risks of grade 3 – 4 anemia, thrombocytopenia, leukopenia, and fatigue, compared versus CCRT with or without AC.ConclusionsOur meta-analysis confirmed that the addition of NACT to CCRT significantly improved PFS and OS versus CCRT with or without AC for locoregionally advanced nasopharyngeal carcinoma. These results may alter the standard of care - CCRT with or without AC, for locoregionally advanced nasopharyngeal carcinoma.
Diabetes is a metabolic disorder characterized by hyperglycemia, resulting in low-grade systemic inflammation. Diabetic cardiomyopathy (DCM) is a common complication among diabetic patients, and the mechanism underlying its induction of cardiac remodeling and dysfunction remains unclear. Numerous experimental and clinical studies have suggested that adaptive immunity, especially T lymphocyte-mediated immunity, plays a potentially important role in the pathogenesis of diabetes and DCM. Metallothioneins (MTs), cysteine-rich, metal-binding proteins, have antioxidant properties. Some potential mechanisms underlying the cardioprotective effects of MTs include the role of MTs in calcium regulation, zinc homeostasis, insulin sensitization, and antioxidant activity. Moreover, metal homeostasis, especially MT-regulated zinc homeostasis, is essential for immune function. This review discusses aberrant immune regulation in diabetic heart disease with respect to endothelial insulin resistance and the effects of hyperglycemia and hyperlipidemia on tissues and the different effects of intracellular and extracellular MTs on adaptive immunity. This review shows that intracellular MTs are involved in naïve T-cell activation and reduce regulatory T-cell (Treg) polarization, whereas extracellular MTs promote proliferation and survival in naïve T cells and Treg polarization but inhibit their activation, thus revealing potential therapeutic strategies targeting the regulation of immune cell function by MTs.
Background Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN. Methods Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups. Results The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression. Conclusion Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.
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