[Retracted] miR­206 inhibits cancer initiating cells by targeting EHF in gastric cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation assay data shown in Figs. 2, 4 and 8 were strikingly similar to data that had already appeared in another article written by different authors at different research institutes [Chen W, Wang J, Liu S, Wang S, Cheng Y, Zhou W, Duan C and Zhang C: MicroRNA­361­3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. J Exp Clin Cancer Res 35: 76, 732516, 2016]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 38: 1688­1694, 2017; DOI: 10.3892/or.2017.5794].

Up-regulation of long noncoding RNA LINC00858 is associated with poor prognosis in gastric cancer.

BACKGROUND: The present study aimed to investigated the expression pattern of long noncoding RNA LINC00858 (LINC00858) in gastric cancer (GC) patients and its feasibility as a new prognostic biomarker. METHODS: We examined LINC00858 expression in GC tissues and matched normal tissues from 189 patients using a quantitative reverse transcription-polymerase chain reaction. The correlations of LINC00858 levels in GC patients with clinicopathologic features were analyzed using a chi-squared test. The influence of LINC00858 on the overall survival rate of GC patients was precisely calculated using Kaplan-Meier methods (log rank tests). Multivariate Cox regression assays were carried out for the identification of the independent risk factors for GC. RESULTS: We observed that LINC00858 was distinctly up-regulated in GC tissues compared to adjacent non-tumor specimens (p < 0.01). Higher expression of LINC00858 in GC was found to be associated with TNM stage (p = 0.003) and lymphatic metastasis (p = 0.007). Using Kaplan-Meier assays, we found that patients with high expression levels of LINC00858 had a distinctly poor overall survival and disease-free survival compared to those with low expression levels of LINC00858 (p = 0.0102). Multivariate analyses confirmed that LINC00858 (p < 0.05) was an independent prognosis factor for GC patients. CONCLUSIONS: The data obtained in our study indicate that LINC00858 may be used as a novel prognostic indicator in GC patients.

Esculetin enhances the inhibitory effect of 5-Fluorouracil on the proliferation, migration and epithelial-mesenchymal transition of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the most common malignant disease worldwide and thus new therapeutic approaches are needed. 5-Fluorouracil (5-FU) remains the most widely used agent to treat colorectal cancer (CRC). However, its clinical efficacy is currently limited by the development of drug resistance. Esculetin (EST), a coumarin, was found to have anti-proliferative and anti-migration activity in cancer. OBJECTIVE: This research aims to evaluated the influence and possible mechanism of EST on the proliferation, migration and epithelial-mesenchymal transition of CRC cell lines. MATERIALS AND METHODS: Human CRC cell lines HT-29, SW480, HCT-116, and Caco-2 were treated with various concentrations of EST (0.2, 2, 20, 200, 2000 µg/ml) or 5-FU (0.1, 1, 10, 100, 1000 µg/ml) for 48 h, and cell viability was determined by the MTT and CCK-8 assay. The motility of HCT-116 cells was detected by scratch assay. Western blot was applied to detect the protein expression. Besides, levels of Wnt3a and VEGF in HCT-116 cell culture medium supernatant were analyzed by ELISA. The anti-tumor effect was detected with HCT-116 subcutaneous tumor bearing tumor model by monitoring the tumor vomume in vivo. Finally, the tumoral expression of VEGF was measured by immunohistochemistry, and the expression of Ki67, PCNA, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 was measured by Western blot analysis. RESULTS: EST inhibited HCT-116 cell proliferation in a dose-dependent manner. Western blot analysis revealed that EST decreased the expression of Ki67, PCNA, N-cadherin, E-cadherin, vimentin, fibronectin, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7. Furthermore, EST reduced the release of Wnt3a and VEGF into HCT-116 cells culture medium. After EST treatment, the tumor volume was significant smaller than that of the control group, and the tumoral levels of VEGF were decreased. Moreover, western blot analysis indicated that the expression of Ki67, PCNA, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 were also significantly decreased after treated with EST. In addition, in vitro and in vivo anti-tumor results demonstrated that EST combined with 5-FU could increase the inhibitory effect of 5-FU on HCT-116 cells proliferation, migration and epithelial-mesenchymal transition. CONCLUSIONS: EST enhances the inhibitory effect of 5-FU on the proliferation, migration and epithelial-mesenchymal transition of CRC.

Circulating SH2B1 is associated with an increased risk of gastric cancer.

Gastric cancer (GC) is one of the most common types of cancer in humans and the second leading cause of cancer-associated mortality worldwide. Identifying novel risk factors will facilitate the development of therapeutic strategies to prevent and treat GC. Increased expression of the Src homology 2 B adaptor protein 1 (SH2B1) may stimulate the malignant progression of lung cancer, esophageal cancer and neuroblastoma. However, its function in GC has not yet been investigated. To identify whether increased serum SH2B1 is a risk factor for GC, the present study performed a nested case-control study of patients within the Chinese cohort study. Levels of serum SH2B1 were measured in 563 patients diagnosed with GC during the follow-up period and in 1,126 matched healthy controls. The results demonstrated that high levels of serum SH2B1 were associated with an increased GC risk (odds ratio, 3.23; 95% confidence interval, 2.45-5.65). When analyses were stratified further by sex, age and smoking, an association between increased levels of SH2B1 and GC was identified in males but not in females. Furthermore, the association between SH2B1 levels and GC was more evident in younger than in older participants, and statistically significant in current smokers but not in nonsmokers. These results were not altered following the exclusion of outliers. Furthermore, it was demonstrated that overexpression of SH2B1 contributes to the malignant transformation of normal gastric epithelial cells. Thus, the present study demonstrated that elevated serum SH2B1 levels may increase the risk of GC.

miR­206 inhibits cancer initiating cells by targeting EHF in gastric cancer.

Cancer initiating cells (CIC) are defined as the unique subpopulation in the tumors that possess the ability to initiate tumor growth and sustain self-renewal as well as metastatic potential. In this study, we found that EHF overexpression promoted formation of CIC traits and silencing it inhibited the traits in gastric cancer NCI­N87 cells. Overexpressing EHF downregulated the antitumor effect of 5-fluorouracil (5-FU) in NCI­N87 cells. We found that miR­206 downregulated EHF protein expression by targeting its 3'UTR in NCI­N87 cells and GES-1 cells. Overexpressing miR­206 inhibited formation of CIC in NCI­N87 cells. In gastric cancer tissues, EHF protein expression was upregulated and miR­206 was downregulated. We identified a negative correlation between EHF protein and miR­206 expression in gastric cancer tissues. Thus, we concluded that miR­206 inhibits formation of CICs by targeting EHF in gastric cancer.

miR-874 inhibits metastasis-relevant traits via targeting SH2B adaptor protein 1 (SH2B1) in gastric cancer.

Gastric cancer (GC) is one of the most common human cancers and the second leading cause of cancer-related mortality worldwide. The major cause of death is metastasis. Elucidating molecular mechanism of metastasis in gastric cancer will help us to further understand the pathogenesis and progression of the disease, and offer new targets for effective therapies. In this study, we found that SH2B1 overexpression promoted invasion, migration and anoilds resistance and silencing it inhibited invasion, migration and anoilds resistance in gastric cancer SGC-7901 cells. However, over-expressing or silencing it did not affect proliferation in the cells. miR-874 could degrade SH2B1 by targeting its 3'UTR and was negatively associated with metastasis traits in SGC-7901 cells. Its overexpression inhibited proliferation in the cells. Thus, we concluded that miR-874 inhibits metastasis-relevant traits via targeting SH2B1 in gastric cancer SGC-7901 cells.

In vitro and in vivo effect of paclitaxel and cepharanthine co-loaded polymeric nanoparticles in gastric cancer.

PURPOSE: Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize the formulation of paclitaxel (PTX)-cepharanthine (CEP) nanoparticles for gastric cancer. METHODS: Nanoparticles were prepared using nanoprecipitation technique and optimized using central composite rotatable design response surface methodology (CCRD-RSM). Further the optimized nanoparticles were characterised for particle size (PS), zeta potential, entrapment efficiency (EE), drug loading efficiency (DL), anticancer potential against MKN45 (human gastric cancer) cells, in vivo tumor inhibition and survival analysis. RESULTS: Significant findings were the optimal formulation of polymer concentration of 48 mg, surfactant concentration of 45% and EE of 98.12%, DL of 15.61% and mean diameter of 198±4.7 nm. The encapsulation of PTX/CEP into nanoparticles retained the synergistic anticancer efficiency against MKN45 cells. In the in vivo evaluation, PTXsCEP nanoparticles delivered into mice by intravenous injection significantly improved the antitumor efficacy of PTX/CEP. Moreover, PTX/CEP co-loaded nanoparticles substantially increased the overall survival in an established MKN45-transplanted mouse model. CONCLUSION: These data are the first to demonstrate that PTX/CEP co-loaded nanoparticles increased the anticancer efficacy in cell lines and xenograft mouse model. Our results suggest that PTX/CEP coloaded nanoparticles could be a potential useful chemotherapeutic formulation for gastric cancer.

[Outcomes after transanal endoscopic microsurgery for early rectal cancer and risk factors associated with recurrence].

OBJECTIVE: To investigate outcomes after transanal endoscopic microsurgery (TEM) for early rectal cancer, identify risk factors associated with recurrence, and explore the indication of TEM for rectal cancer. METHODS: Sixty patients with rectal cancer undergoing TEM between June 2006 and June 2009 in the Provincial Qianfoshan Hospital of Shandong University were included in this study and data were retrospectively analyzed. RESULTS: There were 12 patients with pTis rectal cancer, 38 with pT1 and 10 with pT2. All the lesions were excised en bloc by full-thickness TEM. No positive resection margins were reported. The operative time was(65.0 ± 36.5) min. Estimated blood loss was (10.5 ± 5.8) ml and hospital stay was(4.5 ± 2.7) d. No perioperative mortality and complications occurred. The median follow-up was 28.5(range, 12-48) months. No recurrence developed in pTis lesions. There was significant difference in local recurrence rate between pT1 and pT2(2.6% vs. 40.0%, P<0.05). The recurrence rate in lesions larger than 3 cm in diameter(19.0%, 4/21) was significantly higher than that in lesions smaller than 3 cm in diameter (2.6%, 1/39) (P<0.05). Multivariate analysis showed that depth of tumour invasion(T stage) and tumour size were independently associated with recurrence after TEM. CONCLUSION: Local excision by TEM is oncologically safe and effective for pTis and pT1 rectal cancers and early lesions smaller than 3 cm in diameter.

Hepatic angiomyolipoma: a retrospective study of 25 cases.

PURPOSE: We report our experience of diagnosing and treating hepatic angiomyolipoma (HAML), a rare benign mesenchymal tumor. METHODS: We analyzed retrospectively the clinicopathologic, radiological, and operative data of 25 patients who underwent surgery for HAML at our institute between November 2001 and May 2006. RESULTS: Most patients (20/25) were asymptomatic and had normal liver function. Ultrasonography (US) showed a heterogeneous hyperechoic mass in 13 of 23 patients, precontrast computed tomography (CT) showed that all of 12 lesions scanned were hypodense, and magnetic resonance imaging (MRI) showed hypointensity on T1-weighted images and hyperintensity on T2-weighted images in most (5/6) lesions. Marked enhancement in the arterial phase was seen in 10 of 12 lesions on CT scans and in 6 of 6 lesions on MRI scans. All tumors were composed of varying proportions of smooth muscle, adipose tissue, and blood vessels, and showed positive immunohistochemical staining for HMB-45. All patients underwent partial hepatectomy and there was no evidence of recurrence after a median follow-up of 43 months. CONCLUSION: The radiological features of HAML vary according to its histological components. The definitive diagnosis of HAML is challenging and depends on the presence of HMB-45-positive myoid cells. Hepatic angiomyolipoma is treated effectively with surgery and the prognosis is good.