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Shi Z.,Shanghai University | Liu J.,Hubei University of Medicine | Yu X.,Shanghai University | Huang J.,Shanghai University | And 5 more authors.
Annals of Surgical Oncology | Year: 2016

Background: FOXF2 is a member of the forkhead box (FOX) family of transcription factors. FOXF2 plays an important role in several tumors but its expression and role in hepatocellular carcinoma (HCC) remains unknown. Methods: Using immunohistochemistry, western blot, and real-time polymerase chain reaction, we analyzed FOXF2 expression in 295 clinicopathologically characterized HCC cases. Using RNA interference (RNAi), we investigated the effects of FOXF2 depletion on tumor cell behavior in vitro. Statistical analyses were used to determine associations between FOXF2 levels, tumor features, and patient outcomes. Results: FOXF2 downregulation was observed in HCC tissues (p < 0.001) compared with peritumorous tissues, and its expression levels were closely correlated with overall survival and recurrence-free survival (p = 0.023 and 0.006, respectively) in patients with HCC. RNAi-mediated silencing of the FOXF2 gene in the MHCC-97H cell line significantly promoted proliferation and anti-apoptosis. Conclusions: The results of the present study indicate that FOXF2 may serve as a prognostic biomarker for HCC and may be a promising target in the treatment of patients with HCC. © 2015, Society of Surgical Oncology.


He Z.,Shanghai JiaoTong University | Sun Y.,Shanghai JiaoTong University | Wang Q.,Shanghai JiaoTong University | Shen M.,Shanghai JiaoTong University | And 3 more authors.
Journal of Physical Chemistry C | Year: 2015

Studies have shown that monomethoxy(polyethylene glycol)-poly(d,l-lactic-co-glycolic acid)-poly(l-lysine) (mPEG-PLGA-PLL)-prepared nanoparticles (NPs) are promising drugs carriers, with good drug loading and delivery performance. To further promote the use of this material in clinical applications, its degradation and biosafety were evaluated. This paper describes degradation studies and biosafety evaluations of different block composition ratios (LA/GA = 60/40, 70/30, and 80/20) of the main material, PLGA, for mPEG-PLGA-PLL (PEAL) NPs. The degradation of PEAL NPs was studied by characterizing the change in molecular weight, the chemical composition, and the degradation rate in addition to the pH value, the particle size, the zeta potential, and the lactic acid and lysine contents in degradation solutions by transmission electron microscopy (TEM), gel permeation chromatography (GPC), and 1H NMR. The results show that with prolonged degradation time, the pH, particle size, zeta potential, and molecular weight were reduced and that the lactic acid and lysine contents and the molecular weight distribution were increased. 1H NMR demonstrated that the hydrolysis rate for glycolic units was faster than those for lactic acid and lysine units. The degradation rate of NPs in pH 7.4 PBS was faster than that in pH 5.0 PBS. The degradation rate of PEAL NPs increased as the LA/GA increased from LA/GA = 60/40 to 80/20. Investigations of intracellular protein synthesis, lactate dehydrogenase (LDH) release, 4′,6-diamidino-2-phenylindole (DAPI) nuclear staining and reactive oxygen species (ROS) content in Huh7, L02, and RAW 264.7 cells showed that the PEAL NPs had no effect on protein synthesis or cell membrane integrity and did not induce chromatin agglutination. Although the ROS content was slightly concentration-dependent and time-dependent, the change in content was minimal and diffusely distributed within the cell. After THP-1 cells were induced to differentiate into macrophages, a subsequent incubation with 5 mM PEAL NPs for 24 h did not significantly induce the macrophage release of IL-1β, TNF-α, and TGF-β1 compared with the negative control. Embryos that had their chorion removed were coincubated with PEAL NPs to determine if there were any effects on embryonic development. It is known that zebrafish embryos at 10-24 h post-fertilization (hpf) are most sensitive to PEAL NPs. Zebrafish embryos treated with different concentrations of PEAL NPs within this sensitive time frame demonstrated that PEAL NPs have a high level of biosafety. Our work demonstrates that PEAL NPs are safe candidates for use as biodegradable carriers for drug and gene delivery. © 2015 American Chemical Society.


PubMed | Dahua Hospital, Shanghai JiaoTong University and Shanghai Pudong New District Punan Hospital
Type: Journal Article | Journal: Oncotarget | Year: 2016

Interventional embolization therapy is an effective, most widely used method for inoperable liver tumors. Blood-vessel-embolic agents were essential in transarterial embolization (TAE). In this work, thermo-sensitive composite hydrogels based on poloxamer 407, sodium alginate, hydroxymethyl cellulose and iodixanol (PSHI), together with Ca2+ (PSHI-Ca2+) were prepared as liquid embolic agents for TAE therapy to liver cancer. With increasing temperature, PSHI exhibited two phase states: a flowing sol and a shrunken gel. Rheology tests showed good fluidity and excellent viscoelastic behavior with a gelation temperature (GT) of 26.5C. The studies of erosion indicated that PSHI had calcium ion-related erosion characteristics and showed a slow erosion rate in an aqueous environment. When incubated with L929 cells, the thermo-sensitive composite hydrogels had low cytotoxicity in vitro. The results of analyzing the digital subtraction angiography and computed tomography images obtained from in vitro and in vivo assays indicated a good embolic effect in the renal arteries of normal rabbits. Angiography and histological studies on VX2 tumor-bearing rabbits indicated that PSHI-Ca2+ successfully occluded the tumors, including the peripheral vessels. In conclusion, PSHI-Ca2+ was a promising embolic agent for transarterial embolization therapy.


Zhou Y.,Dahua Hospital | Guo Y.,Dalian Medical University | Ye W.,Dahua Hospital | Wang Y.,Dahua Hospital | And 5 more authors.
International Journal of Clinical Practice | Year: 2014

Objective This study was designed to examine the relevance of single-nucleotide polymorphism (SNP) rs11212617 with treatment success in type 2 diabetes patients from Shanghai local Chinese Han population.Methods We genotyped rs11212617 in incident metformin users of type 2 diabetes patients from Shanghai local Chinese Han population. Association between rs11212617 and changes in HbA1c, fasting plasma glucose and postprandial glucose level were analysed.Results Two hundred and seventy-four incident metformin users were included in the study sample. The SNP rs11212617 was significantly associated with metformin response in Shanghai local Chinese Han population.Conclusion The rs11212617 is associated with a reduction in HbA1c, fasting plasma glucose and postprandial glucose level. These results suggest that metformin treatment may be more efficacious in Shanghai and valuable for Chinese daily clinical practice. © 2014 John Wiley & Sons Ltd.


Qi Z.,Hebei Medical University | Yang D.-Y.,Hebei Medical University | Cao J.,Dahua Hospital
Medical Oncology | Year: 2014

Lung cancer is the most commonly diagnosed type of cancer worldwide. About 90 % lung cancer patients died within 5 years after diagnosis. It is reasonable to assume that early detection of lung cancer could reduce mortality. MicroRNAs (miRNAs) are a class of small noncoding, single-stranded RNAs that regulate gene expression by affecting the stability or the translation efficiency of target messenger RNAs. Altered expressions of miRNAs were associated with the development, invasion, metastasis and prognosis of cancer. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Here, we describe a blood test based on detection of serum miRNAs that distinguish early NSCLC patients from healthy volunteers. Three miRNAs, miR-17, 21 and 192 expression levels were significantly higher in the stage I NSCLC patients than the healthy volunteer groups. This suggests that miR-17, 21 and 192 could be considered as biomarkers for diagnosis of early-stage NSCLC. © 2014 Springer Science+Business Media New York.


PubMed | Tongji University, Dahua Hospital and Southern Medical University
Type: Journal Article | Journal: Cell death & disease | Year: 2017

Poor cell survival and limited functional benefits have restricted mesenchymal stem cell (MSC) efficacy for treating myocardial infarction (MI), suggesting that a better understanding of stem cell biology is needed. The transcription factor HIF-2 is an essential regulator of the transcriptional response to hypoxia, which can interact with embryonic stem cells (ESCs) transcription factor Oct4 and modulate its signaling. Here, we obtained very small embryonic-like mesenchymal stem cells (vselMSCs) from MI patients, which possessed the very small embryonic-like stem cells (VSELs) morphology as well as ESCs pluripotency. Using microarray analysis, we compared HIF-2-regulated gene profiles in vselMSCs with ESC profiles and determined that HIF-2 coexpressed Oct4 in vselMSCs similarly to ESCs. However, this coexpression was absent in unpurified MSCs (uMSCs). Under hypoxic condition, vselMSCs exhibited stronger survival, proliferation and differentiation than uMSCs. Transplantation of vselMSCs caused greater improvement in cardiac function and heart remodeling in the infarcted rats. We further demonstrated that HIF-2 and Oct4 jointly regulate their relative downstream gene expressions, including Bcl2 and Survivin; the important pluripotent markers Nanog, Klf4, and Sox2; and Ang-1, bFGF, and VEGF, promoting angiogenesis and engraftment. Importantly, these effects were generally magnified by upregulation of HIF-2 and Oct4 induced by HIF-2 or Oct4 overexpression, and the greatest improvements were elicited after co-overexpressing HIF-2 and Oct4; overexpressing one transcription factor while silencing the other canceled this increase, and HIF-2 or Oct4 silencing abolished these effects. Together, these findings demonstrated that HIF-2 in vselMSCs cooperated with Oct4 in survival and function. The identification of the cooperation between HIF-2 and Oct4 will lead to deeper characterization of the downstream targets of this interaction in vselMSCs and will have novel pathophysiological implications for the repair of infarcted myocardium.


Zhou Y.,Dahua Hospital | Qiu L.,Xuhui District Central Hospital | Xiao Q.,Dahua Hospital | Wang Y.,Dahua Hospital | And 4 more authors.
Clinical Biochemistry | Year: 2013

Objectives: The objective of the study is to evaluate whether plasma amino acid (AA) differences are related with obesity or diabetes. Design and methods: In 126 diabetes and 100 non-diabetes participants, the plasma concentrations of 42 (AAs) were analyzed with a liquid chromatography tandem mass spectrometry technology (LC-MS/MS). Both groups were divided into obese and lean individuals and we compared intra- and inter-group differences between the groups. Results: In obese non-diabetic participants, 19 AA plasma concentrations were different compared to lean non-diabetic individuals, from which 15 were essential AAs, whereas in the diabetic group only three AAs differed in the obese compared to the lean patients. When comparing the overall AA differences between diabetics and non-diabetics, 16 AA concentrations were enhanced and 11 AA concentrations were reduced in the diabetic patients. A multivariate linear regression analysis revealed correlations between: FBG and Cystathionine, Proline and Citrulline; HbA1c and Glycine, Proline and Sarcosine; Cholesterol and Serine, β-alanine, Proline and Cystathionine; HDL-C and β-alanine, 1-methylhistidine and Proline; and LDL-C and α-Amino n-butyric acid and Hydroxyproline. Triglycerides were related with γ-aminobutyric acid, Serine and Alanine. Fasting insulin was related with 3-methylhistidine, Asparagine, Alanine, γ-aminobutyric acid and Cystathionine. Conclusions: The concentrations of 19 plasma AAs differed between non-diabetic obese and lean individuals, which were mostly superimposed by diabetes. Between diabetic and non-diabetic participants plasma AA concentration differences were obvious and some of these alterations were correlated to other factors like blood glucose, lipids, insulin and hemoglobin status. © 2013.


Zhang S.,Fudan University | Zhang S.,Tongji University | Zhao L.,Dahua Hospital | Shen L.,Fudan University | And 6 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Objective-Comparative studies are lacking that show the effects of different microenvironments on the activity of engrafted stem cells after myocardial infarction (MI). Here, we analyzed the temporal and spatial variations of angiogenesis, collateralization, and the expression of Akt-related signals after MI to test whether the effects of endothelial progenitor cells (EPCs) were different. Methods and Results-After the induction of MI, pigs were selected that did not develop a collateral coronary circulation (R0) or developed a significant collateral coronary circulation (R2). Both sets were allocated randomly to 4 groups: phosphate-buffered saline (intramyocardial injection of phosphate-buffered saline), EPC transplantation, LY294002 (intramyocardial injection of an Akt inhibitor), and EPCs plus LY294002. Infarcted porcine hearts at different time points and under different collateralized conditions exhibited a variety of vascular microenvironments. At 14 days post-MI, angiogenesis and the expression of Akt-mediated angiogenic cytokines predominated in R2 porcine hearts. When grafted into this microenvironment, EPCs induced the greatest effects in impeding the development of heart failure, preserving left ventricular function and dimensions, and inhibiting infarct expansion. LY294002 significantly reduced these effects. Conclusion-These findings suggest that the microenvironment that coexists with collateralization and Akt-mediated angiogenesis appears to be more beneficial to cardiac repair induced by EPC therapy than other niches after MI. © 2012 American Heart Association, Inc.


Qiu Y.-Y.,Shanghai University of Traditional Chinese Medicine | Hu Q.,Dahua Hospital | Tang Q.-F.,Shanghai University of Traditional Chinese Medicine | Feng W.,Shanghai University of Traditional Chinese Medicine | And 4 more authors.
Tumor Biology | Year: 2014

The study aims to investigate the effect of microRNA-497 (miR-497) expression and bufalin treatment in regulating colorectal cancer invasion and metastasis. The expression of miR-497 in colorectal cancer cells with prior treatment with bufalin was determined using real-time quantitative PCR. The nude mouse abdominal aortic ring assay and the human umbilical vein endothelial cell (HUVEC) migration assays were used to measure the angiogenic effect of bufalin. The effect of both bufalin treatment and miR-497 overexpression on colorectal cancer metastasis was measured using an animal tumor model together with in vivo imaging. These results suggested: (1) In the HCT116 cells and HUVECs, proliferation was inhibited in a time-dependent and/or concentration-dependent manner following the administration of bufalin; (2) Bufalin inhibited cell migration in a concentration-dependent manner by cell motility assays; (3) In the aortic ring assay, administration bufalin to the aortic ring significantly promoted micro-angiogenesis of nude mouse abdominal aorta in a concentration-dependent and time-dependent manner; (4) miR-497 was upregulated in human colorectal cancer HCT116 cells treated with different concentrations of bufalin in a concentration-dependent manner; and (5) Combined application of bufalin and miR-497 significantly reduced metastatic lesions and reduced weight loss compared with bufalin alone and control groups in vivo. This study revealed that bufalin inhibited angiogenesis and regulated miR-497 expression and that bufalin and miR-497 acted in synergy to inhibit colorectal cancer metastasis, resulting in improved quality of life in a nude mouse model. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Ye W.-W.,Dahua Hospital | Zhou Y.,Dahua Hospital
International Journal of Clinical and Experimental Medicine | Year: 2016

Objectives: The association between oral bisphosphonate (BP) intake and esophageal cancer risk has been investigated in several recent studies with conflicting results. Methods: We conducted a detailed meta-analysis of observational studies with sub-analysis of duration, type of BPs and cumulative dose. We identified relevant studies by search of PubMed, the Cochrane Library and Embase in October 2014. The studies that provide the risk estimates and CIs between exposure to oral BPs and risk of esophageal cancer were included in our analysis. When data sets were from the same population, the most recent study was included unless the other studies contains largest number of esophageal cancer case or more detailed data. Results: Overall, 7 studies were included in our meta-analysis. The primary analysis suggested that the bisphosphonate treatment was not associated with risk of esophageal cancer in both cohort studies (RR 1.18, 95% CI 0.70 to 1.97) and nested case-control studies (OR 1.06, 95% CI 0.92 to 1.22). No statistically significant risk was found in sub-analysis of both type of BPs and duration of exposure. Conclusions: This meta-analysis suggests that the use of oral bisphosphonate treatment was not significantly associated with excess risk of esophageal cancer. © 2016, E-Century Publishing Corporation. All rights reserved.

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