Beta-blockers versus corticosteroids in the treatment of infantile hemangioma: an evidence-based systematic review.

BACKGROUND: The efficacy and safety of beta-blockers versus corticosteroids in the treatment of infantile hemangiomas (IHs) is controversial. This study aimed to summarize evidence described in the literature and to assess the quality of studies involving beta-blockers and corticosteroids for the treatment of cutaneous IHs. METHODS: Comparative studies were collected from 15 online electronic databases, including OVID Medline, PubMed, ISI Web of Science, CENTRAL, CNKI, ChiCTR, JPCTR, CTRIndia, IranCTR, SLCTR, ISRCTRN, NLCTR, GCTR, ANCTR, ClinicalTrial. gov, and associated references. Studies without a control group were excluded, and the remaining studies were assessed by two reviewers independently using the Downs & Black scale for reported quality. The main areas assessed in the included studies were volume changes, overall improvement in appearance, eye function, and adverse events. RESULTS: Ten comparative studies were included with a total of 419 children. A meta-analysis was not performed due to the considerable heterogeneity across studies. Some evidence showed that beta-blockers are superior to steroids in reducing volume and improving the overall appearance of IHs, such as lightening of the color and flattening of the surface. Conclusions regarding improved eye function and adverse events were divided, and no consensus has been reached on the superiority of one treatment over another. No episodes of severe-onset asthma, hypotension, or bradycardia occurred in the beta-blocker treatment due to the rigorous exclusion of patients with contraindications. CONCLUSIONS: Available studies indicate that beta-blockers are an alternative option to corticosteroids for IH treatment with respect to volume shrinkage and improvement in appearance. No evidence has shown a significant difference in improved eye function and adverse events between beta-blockers and corticosteroids in the treatment of IH; indeed, there is a lack of well-designed, high-quality randomized control trials.

Improvement in visual function and quality of life following a blindness prevention surgery program in a rural area of Eastern China.

The aim of this study was to assess the changes in visual function (VF) and quality of life (QOL) among patients following blindness prevention surgery in a rural area of Eastern China. The prospective study selected cataract patients via mobile eye screening camps. VF and QOL questionnaires originally developed by Fletcher et al were completed prior to and 6 months after surgery. Small-incision cataract surgery (SICS) with posterior chamber intraocular lens (IOL) implantation was performed on patients by a blindness prevention surgery group. The VF and QOL scores of 178 cataract patients preoperatively were 48.58±31.18 and 65.97±26.77, respectively. The scores decreased in proportion to decreasing vision status. The VF and QOL scale scores were significantly correlated with the vision grade of the patient (rVF=-17.2093, t=-10.87, P<0.001, rQOL=-13.1399, t=-8.87, P<0.001) and age (rVF=-0.6505, t=-3.87, P<0.001, rQOL=- 0.3309, t=-2.10, P=0.037). A total of 131 patients responded to the second survey, VF and QOL scores increased significantly over a six-month postoperative period (VF=83.21±16.40, P<0.001; QOL=86.53±16.33, P<0.001). The VF scale scores were correlated with the grade of vision and residence area, the QOL scale scores were correlated with the grade of vision and gender. The VF and QOL of patients were significantly improved by performing SICS with posterior chamber IOL implantation collectively in a short period in rural areas of Eastern China. It is important to follow-up cataract patients postoperatively as untreated complications of the surgery may affect the stability of VF and QOL postoperatively.

Functional study on a novel missense mutation of the transcription factor FOXL2 causes blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease caused by FOXL2 gene mutations. However, only one missense mutation has been found in family with BPES type I. Here, we report a novel missense mutation in the forkhead domain of the FOXL2 gene (c.340A > G, NM_023067) resulted in the replacement of lysine by glutamic acid at amino acid position 114 of the FOXL2 protein (p.K114E, NP_075555) that was identified in a Chinese family with BPES type I, members of which displayed clinical symptoms such as shortened palpebral fissures, drooping eyelids, a vertical skin fold arising from the lower eyelid, and premature ovarian failure (POF) in affected females. Based on the patients' clinical features and computational analysis of this missense mutation in a three-dimensional structural model, we hypothesised that the mutation might disturb the intermolecular contacts between FOXL2 and the StAR gene. The disturbance of this interaction might contribute to the POF observed in BPES type I patients. We performed subcellular localisation and functional studies and as expected, observed significant nuclear aggregation and cytoplasmic mislocalization of the mutant type protein and loss-of-function was confirmed by electrophoretic mobility shift assays, transcriptional activity assays and quantitative real-time polymerase chain reaction. This functional study on a novel missense mutation has important implications for the molecular analysis of this gene.

Circulating levels of periostin may help identify patients with more aggressive colorectal cancer.

Elevated levels of periostin have been implicated as playing important roles in tumor invasion and metastasis in various tissues. Thus, we determined whether serum periostin levels were associated with progression and poor prognosis in colorectal cancer (CRC) patients. We measured serum periostin levels by ELISA in 67 CRC patients and 120 controls. We also evaluated periostin expression in human CRC specimens (n=15) using immunohistochemistry, and measured expression of periostin mRNA in 7 CRC tissue samples, matched normal tissues and in 4 colon cancer cell lines by RT-PCR. We analyzed the relationship between serum levels of periostin and other clinicopathologic characteristics in patients with CRC. The serum levels of periostin in CRC patients (40.9+/-15.4 ng/ml) were significantly elevated compared to that in healthy volunteers (21.0+/-7.3 ng/ml, P<0.0001) and benign colorectal polyps or adenomas (22.4+/-8.5 ng/ml, P<0.0001). Higher preoperative serum levels of periostin in CRC were found to correlate with distant metastasis (P=0.003), advanced-stage disease (stage III/IV, P<0.0001) and poor prognosis. Preoperative serum periostin levels of 15 cases were significantly higher than matched postoperative levels (47.2+/-13.5 ng/ml vs. 31.3+/-11.0 ng/ml, P=0.008). Twelve of 15 patients (80%) had positive immunohistochemical periostin staining in CRC samples. Interestingly, periostin mRNA was highly upregulated in CRCs in comparison with matched normal tissues, and no expression of periostin mRNA was detected in 4 colon cancer cell lines. Serum levels of periostin detected by ELISA may be of clinical value in identifying patients who may be at high risk for aggression and metastasis of CRC. Periostin may be produced by the stromal cells surrounding the tumor, but not by the CRC cells themselves.

[Suppression of insulin-like growth factor-1 receptor by RNA interference inhibits cell growth in vitro and induces chemosensitization of HO8910PM cell to cisplatin].

OBJECTIVE: To assess the effect of suppression of insulin-like growth factor-1 receptor (IGF1R) in HO8910PM cell line by small interference RNA (siRNA). METHODS: Transfection of siRNA using lipofectamine 2000 was conducted to silence IGF1R gene expression, the expression levels of IGF1R mRNA and protein were evaluated, and the effects on the cell cycles at 48 hours of transfection were assessed by real-time PCR, western blot and flow cytometry (FCM) assay respectively. The cell growth was detected by cell counting kit-8 (CCK-8) at 24, 48, 72, 96 hours of transfection. After 24 hours of transfection, the cells were cultured with different concentrations of cisplatin (DDP) for 24 hours, the cell growth inhibition rate was evaluated by CCK-8. Following incubation with 10 microg/ml DDP for 24 hours after 24 hours of transfection, the apoptosis cells and the protein expression level of apoptosis-related gene, B cell leukemia/lymphoma 2 (Bcl-2), were identified by FCM and western blot respectively. RESULTS: (1) Expression levels of IGF1R mRNA and protein were markedly decreased respectively at 48 hours of transfection IGF1R siRNA. (2) Suppression of IGF1R accompanied the reduction of cell growth at 48, 72, 96 hours of transfection with IGF1R siRNA, absorbance were 1.71+/-0.13, 2.32+/-0.23, 2.79+/-0.28 respectively (P<0.01). (3) IGF1R siRNA induces arrest of G2 phase, the G2 phase rate of cells were 24.37% (P<0.05). (4) Following treatment with 2.5, 5, 10, 20 microg/ml DDP for 24 hours after 24 hours of transfection, the cell growth inhibition rates were (25.94+/-0.08)%, (40.25+/-0.05)%, (59.48+/-0.03)% and (74.18+/-0.08)% respectively (P<0.01). (5) Treatment with 10 microg/ml DDP for 24 hours after 24 hours of transfection, induces 17.95% of cells apoptosis (P<0.05), and decreases Bcl-2 protein level. CONCLUSION: RNA interference of IGF1R gene induces the IGF1R silence in HO8910PM cell line significantly, inhibits cell growth in vitro, arrests the G2 phase, and enhances the chemosensitization to DDP.

[Effect of CRE-dependent RNA interference targeting Notch1 on proliferation of cervical cancer cell line HeLa].

BACKGROUND & OBJECTIVE: Notch signal transduction pathway mediates cell differentiation and proliferation. Its dysfunction is supposed to be involved in tumorigenesis and development. This study was to construct a course recombination enzyme(CRE)-dependent short hairpin RNA (shRNA) expression plasmid targeting Notch1, and investigate its effect on proliferation of cervical cancer cell line HeLa. METHODS: RNA interfering vectors pSico and pSicoR were used to construct CRE-dependent shRNA expression plasmids targeting GAPDH and Notch1; pBS185-CRE was used as an expression vector of CRE. HeLa cells were divided into 4 groups and transfected with pSico, pSico/CRE, pSicoR, and pSicoR/CRE, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were carried out to assess the efficiency of RNA interference (RNAi), and intracellular Notch signal level was tested by CBF-1 reporter plasmid. The proliferation of HeLa cells after CRE-dependent Notch1 RNAi was detected by MTS assay. RESULTS: After transfection of pSico (R)-GAPDH and pSico (R)-Notch1, CRE-dependent green fluorescent cells were detected; Notch1 expression was inhibited; intracellular Notch1 signal level was decreased; the proliferation of HeLa cells was suppressed. CONCLUSION: RNAi of Notch1 mediated by CRE-dependent shRNA expression plasmid can down-regulate intracellular Notch1 signal level and suppress the proliferation of HeLa cells.

[Reduction of tumorigenicity of SMMC7721 hepatoma cell line by VEGF siRNA].

In this study the small interfering RNA(siRNA) targeting human VEGF effectively inhibited the expression of VEGF in human hepatoma cell line, SMMC7721, and could dramatically decrease the tumorigenicity of SMMC7721 s.c. xenograft tumor. Chemically synthesized siRNA targeting VEGF was transiently transfected into SMMC7721 cells by lipofectamine, RT-PCR and Elisa analysis suggested that the expression of VEGF mRNA and secreted protein in SMMC7721 cells with VEGF siRNA transfection were suppressed with inhibition rates of 76.16% and 96.28% respectively compared with negative control, but the growth rate of SMMC 7721 cells with VEGF siRNA transfection was the same as the control cells. In vivo test, siRNA was injected directly into implanted tumors and the tumors volume were calculated at different time interval. Result showed that VEGF siRNA greatly inhibited the growth of tumors tissues, which was consistent with decrease of VEGF mRNA and protein compared with control. In addition, the VEGF siRNA-treated group exhibited obvious signs of necrosis compared with control.