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ABSTRACT: Obesity is a well-established risk factor for endometrial cancer, due in part to the adipokines generated by adipose tissue, such as adiponectin (also known as Acrp30) and leptin, which are associated with many endocrine-related cancers. Recent reports suggested that Acrp30 inhibits leptin-stimulated cell proliferation in HEC-1A and RL95-2 endometrial cancer cell lines, and that the serum leptin/Acrp30 ratio plays an important role in endometrial cancer development. We explored whether Acrp30 could reverse the leptin-induced metastasis phenotype in the SPEC-2 endometrial cancer cell line. Transcripts for Acrp30 receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rb) were detected by quantitative real-time RT-PCR (qRT-PCR) in six endometrial cancer cell lines. Leptin (1 µg/ml) treatment stimulated SPEC-2 cell proliferation by inducing cell cycle arrest and apoptosis, while Acrp30 (10 µg/ml) treatment inhibited the growth of SPEC-2 cells. Importantly, Acrp30 was able to inhibit leptin-induced SPEC-2 cell proliferation. Leptin promoted SPEC-2 cell invasion in a Matrigel transwell assay, while Acrp30 partly suppressed the invasion stimulated by leptin. To investigate the molecular mechanism underlying this phenomenon, we monitored the AMPK and JAK/STAT3 signaling pathways by western blotting and cell immunofluorescence. Acrp30 reduced leptin-induced STAT3 phosphorylation and nuclear translocation via activation of the MAPK pathway. AG490 (JAK/STAT3 inhibitor) reduced MMP-2 and MMP-9 protein levels in cells treated with leptin, while IL-6 (JAK/STAT3 stimulator) and Compound C (AMPK inhibitor) elevated MMP-2 and MMP-9 protein levels in cells treated with Acrp30. In conclusion, we demonstrated that Acrp30 effectively reversed the invasion stimulated by leptin, and AMPK and JAK/STAT3 pathways mediated the invasive phenotype of SPEC-2 cells.
Oncology Reports 05/2012; 27(5):1488-96. · 1.84 Impact Factor
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ABSTRACT: Special AT-rich sequence binding protein 1 (SATB1) is a master chromatin organizer that has recently been reported to directly upregulate metastasis-associated genes and downregulate tumor suppressor genes. However, its clinical significance in the case of ovarian cancer remains unclear. In the current study, we assessed the expression levels of SATB1 in ovarian cancer and aimed to show whether it may be a conventional clinicopathological parameter. Epithelial ovarian cancer (n=91), borderline cystadenoma (n=13) and normal ovarian background tissues (n=8) were collected immediately following excision during surgery. The mRNA expression levels of SATB1, VEGF-A and MMP-9 were determined using real-time quantitative PCR. Western blotting and immunohistochemical staining were carried out to detect the protein expression levels of SATB1. Expression levels within the ovarian cancer specimens were compared to the normal background tissues and analyzed against FIGO stage, lymph node involvement and histological type. SATB1 mRNA in malignant and borderline ovarian cystadenoma tissues was 6.74- and 5.70-fold higher compared with normal ovarian tissue, respectively (P<0.01). Western blot analysis revealed that a strong positive band of SATB1 expression was present in ovarian cancer tissues. Immunohistochemical staining showed that the positive expression rates of SATB1 in ovarian cancer, borderline ovarian cystadenoma and normal ovarian tissues were 69.2, 61.5 and 0% (P<0.01), respectively. SATB1 expression increased concomitantly with increasing FIGO stage and lymph node involvement. Survival curves showed that a higher SATB1 expression was correlated with shorter survival. Our results provide evidence that SATB1 expression is significantly associated with progression, metastasis and prognosis of epithelial ovarian cancer. SATB1 may therefore serve as a conventional clinicopathological parameter of ovarian cancer.
Oncology letters 04/2012; 3(4):865-870. · 0.11 Impact Factor
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ABSTRACT: In ovarian cancer, CD44(+) /CD117(+) stem cells, also known as cancer-initiating cells (CICs), are highly proliferative, have a low degree of differentiation, and are resistant to chemotherapeutics. Therefore, the CD44(+) /CD117(+) subpopulation is thought to be an important target for novel therapeutic strategies. In this study, we investigated the role of microRNA-199a (miR-199a) in ovarian cancer stem cells. Luciferase reporter gene assays confirmed that miR-199a targets CD44 via an miR-199a-binding site in the 3'-UTR. CD44(+) /CD117(+) ovarian CICs were enriched from human primary ovarian tumor tissues and confirmed by flow cytometric sorting. miR-199a was cloned and transfected into ovarian CICs. CD44 mRNA and protein expression was significantly decreased in miR-199a-transfected ovarian CICs as compared with miR-199a mutant-transfected and untransfected cells. Cell cycle analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide proliferation assays, the colony formation assay and the transwell migration assay indicated that miR-199a significantly affected cell cycle regulation and suppressed the proliferation and invasive capacity of ovarian CICs in vitro. miR-199a significantly increased the chemosensitivity of ovarian CICs to cisplatin, pacitaxel, and adriamycin, and reduced mRNA expression of the multidrug resistance gene ABCG2 as compared with miR-199a mutant-transfected and untransfected cells. The expression of stemness markers was also significantly reduced in miR-199a-transfected CICs as compared with miR-199a mutant-transfected and untransfected ovarian cells. Furthermore, xenograft experiments confirmed that miR-199a suppressed the growth of xenograft tumors formed by ovarian CICs in vivo. Thus, expression of endogenous mature miR-199a may prevent tumorigenesis in human ovarian cancer by regulating expression of its target gene CD44.
FEBS Journal 03/2012; 279(11):2047-59. · 3.79 Impact Factor
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ABSTRACT: This study investigated the role of miR-206 in estrogen receptor-α (ERα)-positive endometrial endometrioid adenocarcinoma (EEC). We profiled miR-206 expression in 30 EEC clinical samples using qRT-PCR, and explored its relationship with ERα and clinical parameters. A luciferase reporter assay assessed the ERα targeting potential of miR-206. Functional analyses of miR-206 were performed in EEC cell lines. MiRNA-206 expression decreased in ERα-positive EECs, and its expression was negatively correlated with ERα. MiRNA-206 overexpression inhibited ERα-dependent proliferation, impaired invasiveness and induced cell cycle arrest of ERα-positive EEC cell lines. Therefore, aberrantly expressed miRNA-206 may be associated with the development of ERα-positive EEC.
Cancer letters 01/2012; 314(1):41-53. · 4.86 Impact Factor
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ABSTRACT: Our previous studies have identified that miR-125b was overexpressed in type II endometrial carcinoma (EC) cells compared with type I using microRNAs microarray. Although recent studies have shown the important role of miR-125b in several tumors and overexpression of miR-125b in advanced EC, its function in this disease has not yet been defined. In the present study, we tried to confirm the result of microRNAs microarray and further investigated the functions of miR-125b in EC, and tried to find new downstream targets of miR-125b.
Differential expression of miR-125b was detected between type II EC cells (KLE, AN3CA) with ER negative and type I EC cells (ishikawa, RL95-2) with ER positive by qRT-PCR and northern blotting. The effects of miR-125b of on proliferation, migration, and target protein expression were evaluated by CCK8 assay, wound healing assay, transwell migration assay, western blotting, and Tumorigenicity assays in nude mice. In addition, luciferase reporter plasmid was constructed to demonstrate the direct target of miR-125b.
MiR-125b was overexpressed in type II EC cells compared with type I. Exogenous miR-125b expression increased proliferation and migration of ishikawa cells and abrogating expression of miR-125b suppressed proliferation, and migration of AN3CA cells in vitro. In addition, in vivo tumor formation assay confirmed that forced miR-125b expression promoted proliferation potential of ishikawa cells, and tumor suppressor gene Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1) was identified to be the direct target of miR-125b.
TP53INP1 was newly identified to be the direct downstream target of miR-125b. MiR-125b, which was overexpressed in type II EC cells compared with type I, contributes to malignancy of type II EC possibly through down-regulating TP53INP1.
BMC Cancer 01/2011; 11:425. · 3.01 Impact Factor
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ABSTRACT: To investigate the genes that were differentially expressed between clear cell carcinoma (CCC) and serous carcinoma (SAC) of the ovary with complementary DNA microarray.
Complementary DNA microarray was carried out in 8 CCCs and 8 SACs of the ovary. Differentially expressed genes were identified and verified by real-time polymerase chain reaction. The expression of the protein was also verified with immunohistochemistry and Western blot in cells and tissues of ovarian CCC.
Comparison of the gene expression profiling identified 21 genes with more than 2-fold different expression between CCC and SAC of the ovary. The up-regulated and down-regulated genes were 9 and 12, respectively. The verification of Annexin IV in the cell line and tissues was in accordance with the result of the microarray.
The complementary DNA microarray technique is a feasible way to explore the difference of the gene expression profiling between the 2 types of ovarian carcinoma. The overexpression of Annexin IV may be an ovarian CCC-specific molecular marker.
International Journal of Gynecological Cancer 12/2009; 19(9):1545-9. · 1.65 Impact Factor
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ABSTRACT: To determine the concentration difference in protoporphyrin in cancerous intestine and to discuss its application in laser-induced autofluorescence diagnosis for colorectal cancer at early stage.
We detected the concentration of protoporphyrin IX in 30 patients with colorectal cancer and 30 control patients, as well as that in 60 cases of intestinal tissues (30 control tissues and 30 cancer tissues).
The concentration of blood protoporphyrin IX in patients with colorectal cancer was significantly higher than that in the controls (P<0.05). Protoporphyrin IX concentration in the cancer tissue was significantly higher than that in the control tissues (P<0.05).
That the concentration of protoporphyrin in cancerous intestine becomes abnormally high may be the material basis for spectrum intensity peak of (644.3+/-5.7) nm in laser-induced autofluorescence diagnosis for colorectal cancer at early stage.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 09/2009; 34(9):846-9.
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ABSTRACT: To discuss the feasibility of anus-preserving laparoscopic rectal resection for lower rectal cancer.
We retrospectively analyzed 75 patients with lower rectal cancer treated with anus-preserving laparoscopic rectal resection.
All the 75 patients were successfully operated and rehabilitatedly discharged. In the follow-up period in 68 patients, all lived healthy except 5 patients with hepatic metastasis and 1 with in-situ recurrence 1 year after the operation.
With the development of laparoscopic technique and laparoscopic total mesorectum excision technique as well as the application of stapler, the operation field is expanded, which benefits the separation and anastomosis of the lower intestine, with more chances to preserve anus.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 09/2009; 34(9):902-4.
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ABSTRACT: The purpose of this study was to investigate the expression of tumor-associated glycoprotein 72 (TAG-72) in primary gallbladder carcinoma (PGC) with an attempt to determine the potential usefulness of it in diagnostic and prognostic applications.
Tissue samples from 118 patients with PGC, 30 patients with chronic cholecystitis, and 20 normal gallbladders were stained with anti-TAG-72 antibodies for immunohistochemical analysis. Then, the clinical outcome of the patients after a maximum follow-up of 5 years was determined in 110 out of 118 patients.
Clinicopathological characteristics of the carcinomas and clinical outcome of the patients were associated with the TAG-72 expression. TAG-72 was expressed more frequently in cancerous tissues of larger size, with lymph nodes metastasis, and with poor differentiation. Especially, a statistical association was found with more advanced UICC stages of the disease (55.77%, 65.38%, 92.86%, 93.75% and 100% in stages IA, IB, IIA, IIB, and III, respectively, p=0.02). Using a proportional hazard model, the survival rate of the patients with PGC expressing TAG-72 was significantly lower than the patients without TAG-72 expression (p<0.01), and including information of TAG-72 staining patterns within cancerous tissues along with clinical cancer staging may improve the accuracy of predicting patients' prognosis.
These data suggest that TAG-72 expression is associated with clinicopathological parameters of aggressiveness in PGC. The detection of it combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with PGC.
Surgical Oncology 06/2009; 19(2):82-7. · 2.44 Impact Factor
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ABSTRACT: TrkB is a neurotrophic tyrosine kinase receptor (Trk). To investigate its role in anoikis suppression in human ovarian cancer, we used reverse transcription-polymerase chain reaction and real-time polymerase chain reaction, immunohistochemistry, and western blotting to compare the expression levels of TrkB and its ligand brain-derived neurotrophic factor between (i) 20 epithelial ovarian cancers, their multicellular spheroids in ascites or great omentum metastatic lesions, and eight borderline or benign ovarian tumors, as well as four normal ovarian tissues; and (ii) three ovarian cancer cell lines cultured under different conditions: monolayer adhesive culture (adhesive cells), anchorage-independent culture (cell spheroids), and trypsinized cell spheroids placed in monolayer adhesive dishes (cell spheroids replaced). TrkB and brain-derived neurotrophic factor were overexpressed in epithelial ovarian cancers, and full-length TrkB was more often overexpressed in high-grade carcinomas and multicellular spheroids in ascites. Expression of TrkB mRNA was higher in OVCAR-3 cell spheroids than in adhesive cells. The expression of full-length TrkB protein was highest in OVCAR-3 cell spheroids, but its precursor was expressed highly in OVCAR-3 cells under all three culture conditions. The relationship between TrkB overexpression and phosphatidylinositol 3'-kinase (PI3K)-AKT pathway activation in OVCAR-3 cells was studied by western blotting and RNA interference. The PI3K-AKT pathway was highly activated in anoikis-survived cells and was inhibited when TrkB was silenced by small interfering RNA. Finally, the chemosensitivity and invasiveness of OVCAR-3 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium, fluorescence-activated cell sorting, Matrigel invasion assay, and in vivo studies. Adhesive cells showed higher chemosensitivity and lower invasion ability than anoikis-survived cells. Our study suggests that TrkB might mediate anoikis suppression by activating the PI3K-AKT pathway in ovarian cancer cells.
Cancer Science 04/2008; 99(3):543-52. · 3.33 Impact Factor
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ABSTRACT: ObjectiveTo study the gene expression profiles of human endometrial cancers at various differentia0ted grade levels and to identify
the genes related to differentiation of the endometrial cancers.
MethodscDNA microarray technology was used to analyze the differentially-expressed genes among different differentiated grades of
32 cases of endometrial cancer. Hierarchical cluster analysis (HCA) for the gene expression profiles of the cases was employed.
ResultsThe tissue samples were grouped based on the various differentiated tumor grades with 33 differentiation-related genes identified
out (P<0.001). Based on the results from the HCA, the conformity rate was 91% among the 33 differentially-expressed genes
and the analysis of pathological classification.
ConclusionGenes related to the differentiation of endometrial cancer can be identified by using gene chips to analyze the expression
profiles of endometrial cancers at various differentiated grades; HCA of the gene expression profiles can be helpful for distinguishing
high-risk endometrial cancers before surgery.
Chinese Journal of Clinical Oncology 01/2007; 4(2):77-82.
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Chinese medical journal 10/2003; 116(9):1438-40. · 0.86 Impact Factor
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ABSTRACT: Parenteral nutrition (PN) support containing long-chain triglycerides (LCT) plays a critical supportive role in surgical patients' management. This study aims to investigate the effects of intravenous (IV) LCT emulsion on human immune function in adult patients receiving a gastrointestinal surgical procedure.
Sixty adult patients were randomly assigned either to the LCT treatment group (n = 32) or to the control group (n = 28). After an abdominal operation, the subjects received PN treatment with or without LCT for 5 days. Neutrophil, peripheral blood mononuclear cell (PBMC), lymphocyte and CD4/CD8, serum immunoglobulin A (IgA), IgG, IgM, complement C3 and C4, interleukin (IL)-2, IL-4, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma were measured and statistically analyzed.
The LCT and control groups did not differ significantly at entry in terms of general features. Except for a significant increase of neutrophil number at 24 hours after the surgery in both groups (p < .01), all parameters representing the patients' immune function had no significant difference between the LCT and the control groups with respect to neutrophil and PBMC count, lymphocyte, CD4/CD8, serum IgA, IgG, IgM, complement C3, C4, IL-2, IL-4, IL-10, IL-12, TNF-alpha, and IFN-gamma (p > .05, respectively) 24 hours before the operation, and 24 hours and 120 hours after the operation.
The regimens of LCT administration may have diverse effects on human immune function in different patient populations. However, LCT emulsion at an appropriate dose and infusion speed does not alter human immune function of adult patients undergoing moderate gastrointestinal surgery.
Journal of Parenteral and Enteral Nutrition 31(3):167-72. · 3.29 Impact Factor
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ABSTRACT: A novel finite element method (FEM) based direct method is developed for the material reconstruction inverse problem in soft tissue elastography. The solution is obtained by minimising an objective function, defined as the sum of the square of the residual norms at all nodes, where the nodal residual norm is defined as a linear function of elasticity parameters of the associated elements. The measured deformation is enforced directly and satisfying the equilibrium at every node is utilised as the optimisation objective. As a result, the soft tissue elastography can be obtained directly by solving the resulting set of linear equations.
Computers & Structures.
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ABSTRACT: Ventricular fibrillation leading to sudden cardiac death can occur even in the absence of structural heart disease. One form of this so-called idiopathic ventricular fibrillation (IVF) is characterized by ST segment elevation (STE) in the electrocardiogram. Recently we found that IVF with STE is linked to mutations of SCN5A, the gene encoding the cardiac sodium channel α -subunit. Two types of defects were identified: loss-of-function mutations that severely truncate channel proteins and missense mutations (e.g. a double mutation, R1232W and T1620M) that cause only minor changes in channel gating. Here we show that co-expression of the R1232W+T1620M missense mutant α -subunits in a mammalian cell line stably transfected with human sodium channel β1-subunits results in a phenotype similar to that of the truncation mutants. In the presence of β1subunits the expression of both ionic currents andα -subunit-specific, immunoreactive protein was markedly suppressed after transfection of mutant, but not wild-typeα -subunits when cells were incubated at physiological temperature. Expression was partially restored by incubation at reduced temperatures. Our results reconcile two classes of IVF mutations and support the notion that a reduction in the amplitude of voltage-gated sodium conductance is the primary cause of IVF.
Journal of Molecular and Cellular Cardiology.
