Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis.

AIM: To assess the effects and safety of iron-based phosphate binders in adult patients receiving dialysis. METHODS: We electronically searched MEDLINE, EMBASE, CENTRAL, and CBM for randomized controlled trials about iron-based phosphate binders in adult dialysis patients. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by RevMan 5.3. RESULTS: Eight studies with 2018 participants were eligible for our meta-analysis. Iron-based phosphate binders were superior to placebo (MD = -2.43 mg/dL, 95% CI: -3.18 to -1.68, p < 0.00001) and as efficient as sevelamer (MD = 0.04 mg/dL, 95% CI: -0.29 to 0.36, p = 0.83) in reducing serum phosphorus in dialysis patients. No significant differences were found in all adverse events (OR = 1.30, 95% CI: 0.77 to 2.20, p = 0.32) between iron-based phosphate binders and placebo. Iron-based phosphate binders were associated with significant higher serum iron (MD = 9.39 ng/mL, 95% CI 1.48 to 17.30, p = 0.02), higher serum transferring saturation (MD = 6.29%, 95% CI 2.72 to 9.87, p = 0.0006) and lower serum total iron binding capacity (MD = -23.13 µg/dL, 95% CI -35.69 to -10.58, p = 0.0003) in comparison to placebo. CONCLUSION: Iron-based phosphate binders are as effective as sevelamer and well tolerated for hyperphosphatemia in dialysis patients. Iron-based phosphate binders appear to have a beneficial effect on renal anemia in patients receiving dialysis. Therefore, iron-based phosphate binders may represent a new treatment option for dialysis patients.

Effect of lanthanum carbonate versus calcium-based phosphate binders in dialysis patients: a meta-analysis.

BACKGROUND: The effects of lanthanum carbonate (LC) vs. calciumbased phosphate binders in dialysis patients have been a matter of debate. METHODS: We electronically searched PubMed, Embase, CENTRAL, and CBM for all randomized controlled trials comparing LC with calcium-based phosphate binders in adult dialysis patients. Quality assessment was performed using the Cochrane risk of bias tool. Metaanalysis was conducted by RevMan 5.2. RESULTS: Nine studies were eligible for our meta-analysis. There was no significant difference in all-cause mortality (RR 0.84, 95% CI 0.25 - 2.83) and cardiovascular events (RR 0.84, 95% CI 0.55 - 1.29) between LC and calcium-based phosphate binders. LC was associated with similar proportions of phosphate-controlled patients (RR 0.63, 95% CI 0.27 - 1.44) and lower incidence of hypercalcemia (RR 0.13, 95% CI 0.05 - 0.35) in comparison to calcium-based phosphate binders. Compared with calcium salts, LC was associated with significantly lower serum calcium, similar serum Ca x P product and higher serum iPTH. CONCLUSION: Despite the trends observed, we found no statistically significant differences in all-cause mortality and cardiovascular events between LC and calcium-based phosphate binders in dialysis patients. The conclusion was limited by lack of large sample and long-term trials. LC could reduce the incidence of hypercalcemia while comparable with calcium-based phosphate binders in reducing serum phosphorus level.

Retraction: Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

[This retracts the article DOI: 10.18632/oncotarget.12718.].

The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma.

OBJECTIVE: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC.

Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. RESULTS: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h. Compared with the blank group, the tunicamycin, BEZ235 and tunicamycin + BEZ235 groups exhibited decreased expressions of p-PI3K, p-AKT and p-mTOR, and increased expressions of autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis proteins (Bax and procaspase-3), and the most obvious changes were observed in the tunicamycin + BEZ235 group. MATERIALS AND METHODS: CCK-8 assay was applied to select the best cell line from five SCLC cell lines (NCI-H446, H69, H526, H146 and H209). Finally, NCI-H446 and H69 cells were selected for further experiments. NCI-H446/CDDP and H69/CDDP were selected and divided into the blank group, tunicamycin (an ESR inducer) group, BEZ235 (inhibitors of PI3K/AKT/mTOR pathway) group and tunicamycin + BEZ235 group. Cell apoptosis was detected by flow cytometry. Autophagy was observed by fluorescence microscopy and flow cytometry. Western blotting was used to detect the expressions of ERS-related proteins, autophagy-related proteins, apoptosis-related proteins and PI3K/AKT/mTOR pathway-related proteins. CONCLUSIONS: Our findings provide evidence that the activation of ERS could promote autophagy and apoptosis and reverse chemoresistance of human SCLC cells by inhibiting the PI3K/AKT/mTOR pathway.