Wang J.,Beijing Chaoyang Hospital |
Li A.,Harbin Medical University |
Jin M.,First Hospital of Qiqihar |
Zhang F.,Heilongjiang University of Chinese Medicine |
Li X.,Heilongjiang University of Chinese Medicine
Experimental and Therapeutic Medicine | Year: 2016
Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) therapy is one of the most promising therapeutic strategies for the treatment of cholangiocarcinoma, which is the second most common hepatobiliary cancer. The aim of the present study was to evaluate the enhanced therapeutic effects of HSV-TK/GCV with gemcitabine on cholangiocarcinoma. QBC939 cholangiocarcinoma cells and mouse models of cholangiocarcinoma (established via tumor xenografts) received one of the following treatments: i) Gemcitabine therapy (3 μg/ml); ii) HSV-TK/GCV monotherapy; iii) HSV-TK/GCV + gemcitabine; and iv) control group, treated with phosphate-buffered saline. Cell proliferation was quantified using MTT assay and post-treatment tumor alterations were monitored using ultrasound imaging and optical imaging. For the in vitro experiments, the MTT assays demonstrated that the relative cell viabilities in the gene therapy, gemcitabine and gemcitabine + gene groups were 70.37±9.07, 52.64±8.28 and 34.21±6.63%, respectively. For the in vivo experiments, optical imaging indicated significantly decreased optical signals in the combination therapy group, as compared with the gemcitabine and gemcitabine + gene groups (1.68±0.74 vs. 2.27±0.58 and 2.87±0.82, respectively; Р<0.05). As demonstrated by ultrasound imaging, reduced tumor volumes were detected in the combination therapy group, as compared with the three control groups (114.32±17.17 vs. 159±23.74, 201.63±19.26 and 298.23±36.1 mm3, respectively; P<0.05). The results of the present study demonstrated that gemcitabine enhances the antitumoral effects of HSV-TK/GCV on cholangiocarcinoma, which may provide a novel therapeutic strategy for the management and treatment of cholangiocarcinoma using gemcitabine and gene therapy. © 2016, Spandidos Publications. All rights reserved.
Wu T.,Harbin Medical University |
Wang X.,Harbin Medical University |
Li J.,First Hospital of Qiqihar |
Song X.,Frontier Corps Hospital in Heilongjiang Province |
And 5 more authors.
PLoS ONE | Year: 2015
Breast cancer is a highly heterogeneous disease that is clinically classified into several subtypes. Among these subtypes, basal-like breast cancer largely overlaps with triple-negative breast cancer (TNBC), and these two groups are generally studied together as a single entity. Differences in the molecular makeup of breast cancers can result in different treatment strategies and prognoses for patients with different breast cancer subtypes. Compared with other subtypes, basal-like and other ER+ breast cancer subtypes exhibit marked differences in etiologic factors, clinical characteristics and therapeutic potential. Anthracycline drugs are typically used as the first-line clinical treatment for basal-like breast cancer subtypes. However, certain patients develop drug resistance following chemotherapy, which can lead to disease relapse and death. Even among patients with basal-like breast cancer, there can be significant molecular differences, and it is difficult to identify specific drug resistance proteins in any given patient using conventional variance testing methods. Therefore, we designed a new method for identifying drug resistance genes. Subgroups, personalized biomarkers, and therapy targets were identified using cluster analysis of differentially expressed genes. We found that basal-like breast cancer could be further divided into at least four distinct subgroups, including two groups at risk for drug resistance and two groups characterized by sensitivity to pharmacotherapy. Based on functional differences among these subgroups, we identified nine biomarkers related to drug resistance: SYK, LCK, GAB2, PAWR, PPARG, MDFI, ZAP70, CIITA and ACTA1. Finally, based on the deviation scores of the examined pathways, 16 pathways were shown to exhibit varying degrees of abnormality in the various subgroups, indicating that patients with different subtypes of basal-like breast cancer can be characterized by differences in the functional status of these pathways. Therefore, these nine differentially expressed genes and their associated functional pathways should provide the basis for novel personalized clinical treatments of basal-like breast cancer. © 2015 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Lu S.-k.,First Hospital of Qiqihar
Chinese Journal of Tissue Engineering Research | Year: 2012
BACKGROUND: With rapid development of cell biology, molecular biology technique, and tissue engineering, increasing studies focus on seed cells for constructing skin wound surface by tissue engineering. OBJECTIVE: To summarize the biological characteristics of epidermal stem cells and investigate their regenerative and clinical application value in repair of skin wound surface. METHODS: A computer-based online retrieval of SNKI and PubMed database for searching papers describing epidermal stem cells for repair of skin injury using the key words of "epidermal stem cells, tissue engineering skin, wound surface" in English and Chinese. Papers related to research progress in epidermal stem cells for repair of skin injury were selected. Papers that were published recently in the same research field or in high-impact journals were selected. A total of 129 papers were initially retrieved. According to inclusion criteria, 25 papers were included for final analysis. RESULTS AND CONCLUSION: Epidermal stem cells support for epidermal generation, differentiation and wound healing. Epidermal stem cells provide the condition for maintaining skin normal structure and intracellular environment due to their normal proliferation and differentiation and are the ideal seed cells of skin tissue engineering. They show satisfactory prospects in treatment of large-area skin defects, cell therapy of skin disease, and gene therapy. In vitro culture of epidermal stem cells is a prerequisite for studying tissue engineering of artificial skin. As the isolation, purification and culture technology of epidermal stem cells continues to improve, we can quickly build epidermis. Nevertheless, application of epidermal stem cells requires further investigation.
Zhao J.,Harbin Medical University |
Zhao J.,First Hospital of Qiqihar |
Liu S.,Harbin Medical University |
Wang H.,Harbin Medical University |
And 6 more authors.
Journal of Clinical Neuroscience | Year: 2011
Mitotic arrest deficient protein MAD2B, an enzyme involved in translesion DNA synthesis, has been implicated in several cancers. However, its role in human glioma has not been defined. In the present study, we investigated the expression levels of MAD2B in human gliomas and normal brain tissues, and determined whether depletion of MAD2B enhanced the sensitivity of glioma cells to ionizing radiation. Using reverse transcription-polymerase chain reaction and immunohistochemical analysis, MAD2B was found to be overexpressed in glioma specimens compared with normal brain tissue. Silencing of MAD2B markedly reduced clonogenic survival of glioma cells and significantly enhanced apoptosis in response to ionizing radiation. This effect was associated with caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, disruption of MAD2B potentiated radiation-induced genomic damage, as evidenced by increased phosphorylation of gamma histone H2AX (γ-H2AX). Our findings reveal that expression of MAD2B is deregulated in glioma, and targeting MAD2B may be a potential strategy for improving the efficacy of radiotherapy. © 2010 Elsevier Ltd. All rights reserved.
Gao B.,Harbin Medical University |
Wang D.,First Hospital of Qiqihar |
Sun W.,Harbin Medical University |
Meng X.,Harbin Medical University |
And 2 more authors.
Molecular Medicine Reports | Year: 2016
Acute pancreatitis (AP) is a common acute digestive tract disease, with increased morbidity and mortality, and an unclear pathogenesis. Trypsinogen activation in pancreatic acinar cells may be the primary mechanism underlying the development of AP. Previous studies reported that autophagy participates in the formation of acinar cell vacuoles in AP and in the process of trypsinogen activation as an important cause of AP. Furthermore, microRNAs (miRNAs) maintain the autophagy process by regulating the expression of autophagy-associated genes. In the present study, an in vitro pancreatic acinar cell autophagy model was established using the AR42J starvation-induced pancreatic acinar cell line. Twenty differentially expressed microRNAs were identified using miRNA microarray. Bioinformatics analysis was used to predict the target genes of miRNAs and analyze the functions of differentially expressed miRNAs. The results demonstrated that only the downregulated miRNA rno-miR-148b-3p predicted 593 target genes with a statistical significance (P<.05), from which 10 genes were autophagy-associated. The results of gene ontology and pathway analyses demonstrated that the target genes of miRNAs were enriched in the Response to insulin stimulus, Regulation of cell death and the Insulin signaling pathways (P<.05, FDR<.05). In addition, protein-protein interaction network analysis demonstrated a widespread interaction among the 593 target genes. The results of the present study may provide novel targets for research on the mechanisms of autophagy-promoted AP and AP treatment.
Weng J.,Zhejiang University |
Dong S.,Zhejiang University |
He H.,Zhejiang University |
Chen F.,Zhejiang University |
Peng X.,First Hospital of Qiqihar
PLoS ONE | Year: 2015
Spatial normalization is an essential process for group comparisons in functional MRI studies. In practice, there is a risk of normalization errors particularly in studies involving children, seniors or diseased populations and in regions with high individual variation. One way to minimize normalization errors is to create a study-specific template based on a large sample size. However, studies with a large sample size are not always feasible, particularly for children studies. The performance of templates with a small sample size has not been evaluated in fMRI studies in children. In the current study, this issue was encountered in a working memory task with 29 children in two groups. We compared the performance of different templates: A study-specific template created by the experimental population, a Chinese children template and the widely used adult MNI template. We observed distinct differences in the right orbitofrontal region among the three templates in between-group comparisons. The study-specific template and the Chinese children template were more sensitive for the detection of between-group differences in the orbitofrontal cortex than the MNI template. Proper templates could effectively reduce individual variation. Further analysis revealed a correlation between the BOLD contrast size and the norm index of the affine transformation matrix, i.e., the SFN, which characterizes the difference between a template and a native image and differs significantly across subjects. Thereby, we proposed and tested another method to reduce individual variation that included the SFN as a covariate in group-wise statistics. This correction exhibits outstanding performance in enhancing detection power in group-level tests. A training effect of abacus-based mental calculation was also demonstrated, with significantly elevated activation in the right orbitofrontal region that correlated with behavioral response time across subjects in the trained group. © 2015 Weng et al.
Qi H.-P.,Harbin Medical University |
Wang Y.,Harbin Medical University |
Zhang Q.-H.,Harbin Medical University |
Guo J.,Harbin Medical University |
And 8 more authors.
Cellular Physiology and Biochemistry | Year: 2015
Background/Aims: Cardiac remodeling is a common pathophysiological change along with chronic hypertension and myocardial infarction. Recent evidence indicated that cardiac tissue expressed peroxisome proliferator-activated receptor γ (PPARγ). However, the functional role of PPARγ in cardiac remodeling remained unclear. The present study was designed to investigate the relationship between PPARγ activation and pressure overload-induced cardiac remodeling. Methods: Cardiac remodeling model was successfully established by abdominal aorta ligation. Cardiac fibrosis and cardiomyocyte hypertrophy were simulated by 100 nM angiotensin II (Ang II) in vitro. Haemodynamic parameters, the expressions of Brg1, α-MHC, β-MHC, transforming growth factor beta 1 (TGF-β1), collagen-I, collagen-III and NF-κB were examined. Results: Morphological and haemodynamic measurements showed that the activation of PPARγ improved the impaired cardiac function and decreased interstitial fibrosis in cardiac remodeling rats. Further results also showed that the activation of PPARγ inhibited the expressions of Brg1 and TGF-β1 in the cardiac remodeling hearts. The activation of PPARγ also inhibited the proliferation and collagen production of cardiac fibroblasts, and down-regulated the activity of Brg1 and the expression of TGF-β1 induced by Ang II in cultured neonatal rat cardiomyocytes and cardiac fibroblasts, respectively, through NF-κB pathway. Conclusions: These results suggested that PPARγ activation effectively inhibited cardiac remodeling processes by suppression of Brg1 and TGF-β1 expressions through NF-κB pathway in the pressure-overloaded hearts induced by abdominal aorta ligation in rats. © 2015 S. Karger AG, Basel.
Pang C.,Liaoning Medical University |
Guan Y.,Liaoning Medical University |
Zhao K.,First Hospital of Qiqihar |
Chen L.,Liaoning Medical University |
And 4 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2015
Recent studies have demonstrated that microRNA-15b (miR-15b) regulates cell cycle progression, proliferationnd apoptosis in glioma cells by targeting Cyclins. However, the clinical significance of miR-15b in human glioma remains unclear. Therefore, the aim of this study was to investigate the significance of miR-15b expression in diagnosis, prognosis and malignant progression of glioma. Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to examine miR-15b expression levels in 76 glioma tissues (13 grade II, 13 grade III and 50 grade IV gliomas) and seven glioma cell lines, as well as 10 non-neoplastic brain tissues and human astrocyte as control. MiR-15b showed significant increased expression in high-grade gliomas (P ≤ 0.001) and glioma cells (fold change 2.8-7.6) relative to non-neoplastic brains and astrocyte, respectively. Additionally, high miR-15b expression was significantly associated with advanced WHO grade (P ≤ 0.001), advanced patient age (P ≤ 0.001) and low Karnofsky performance score (KPS, P ≤ 0.001). Furthermore, Kaplan-Meier survival analysis and Cox regression analysis showed that patients with high miR-15b expression had significantly poor overall survival rate (P ≤ 0.001) and miR-15b expression was an independent prognosis-predicting factor for glioma patients (P ≤ 0.001; risk ratio = 5.6), respectively. Moreover, miR-15b expression was examined in seven independent patients with primary grade II or III gliomas that spontaneously progressed to grade III or IV gliomas. Statistically significant higher expression (P = 0.01) in the recurrent tumor compared with the corresponding primary tumor was observed in all of the seven patients. Our results suggest that miR-15b may be a prognostic predictor and be involved in malignant progression of glioma.
Yang W.,Harbin Medical University |
Han W.,Harbin Medical University |
Ye S.,Harbin Medical University |
Liu D.,Harbin Medical University |
And 4 more authors.
Experimental and Molecular Pathology | Year: 2013
Fibroblast activation protein-α (FAPα) is secreted by activated stromal fibroblasts and can promote ovarian cancer cell proliferation, migration and invasion. However, the molecular mechanism by which FAPα promotes tumor cell proliferation and invasion is unknown. The role of the non-enzymatic activities of FAPα in tumor migration and invasion and the intracellular and extracellular signaling mechanisms of FAPα were investigated. In this study, we confirm that FAPα promote ovarian cancer cell proliferation, migration and invasion by extracellular and intracellular signaling mechanisms. These results provide evidence that FAPα, together with integrin α3β1 and the uPAR signaling complex, mediate cancer cell migration in the HO-8910PM cell line via the small GTPase Rac1. FAPα-mediated upregulation of p-ERK occurred in a time-dependent manner. © 2013 Elsevier Inc.
Exendin-4 protects bone marrow-derived mesenchymal stem cells against oxygen/glucose and serum deprivation-induced apoptosis through the activation of the cAMP/PKA signaling pathway and the attenuation of ER stress
He J.,Harbin Medical University |
Wang C.,Harbin Medical University |
Sun Y.,First Hospital of Qiqihar |
Lu B.,Harbin Medical University |
And 5 more authors.
International Journal of Molecular Medicine | Year: 2016
Exendin-4 (ex-4) is a long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist which exerts beneficial effects on glycemic control and promotes cell viability. In the present study, we investigated the anti-apoptotic effects of ex-4, as well as the potential mechanisms responsible for these effects in rat bone marrow-derived mesenchymal stem cells (BM-MSCs) under conditions of oxygen, glucose and serum deprivation (OGD). The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. The MSCs were pre-conditioned with ex-4 for 12 h prior to being subjected to OGD conditions, and the expression levels of an apoptotic marker (cleaved caspase-3), endoplasmic reticulum (ER) stress markers [phosphorylated (p-)protein kinase RNA-like endoplasmic reticulum kinase (PERK), PERK, binding immunoglobulin protein (BIP), activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP)], as well as those of a survival marker (Bcl-2) were measured by western blot analysis. Furthermore, the mRNA levels of ATF-4 and CHOP were determined by RT-qPCR. ELISA was used to examine the activity of intracellular cAMP. Moreover, the GLP-1R antagonist, exendin9-39 (ex9-39), the protein kinase A (PKA) inhibitor, H89, and small interfering RNA (siRNA) targeting rat ATF-4 and CHOP were co-incubated with the MSCs. The apoptotic rate was markedly diminished following pre-conditioning with ex-4 in a dose-dependent manner (P<0.05). The ER stress markers, p-PERK, BIP, ATF-4 and CHOP, were upregulated in the cells subjected to OGD conditions. Ex-4 pre-conditioning significantly decreased the mRNA and protein levels of ATF-4 and CHOP (P<0.05), and increased the activity of intracellular cAMP (P<0.05). Furthermore, the anti-apoptotic effects of ex-4 were almost reversed by treatment with either H89 or ex9-39 (P<0.05); transfection with siRNA-CHOP significantly reduced the apoptotic rate of the MSCs and did not impair the cytoprotective effects of ex-4. Taken together, these findings suggest that ex-4 protects rat BM-MSCs from OGD-induced apoptosis through the activation of the PKA/cAMP pathway and the attenuation of the ER stress signaling pathway. Ex-4 may thus prove to be a therapeutic agent with the potential to improve the viability of MSCs in the ischemic milieu, and consequently, to optimize the therapeutic effects of MSC therapy in acute myocardial infarction.