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ABSTRACT: A problem of goodness-of-fit test for ergodic diffusion processes is
presented. In the null hypothesis the drift of the diffusion is supposed to be
in a parametric form with unknown shift parameter. Two Cramer-Von Mises type
test statistics are studied. The first one is based on local time estimator of
the invariant density, the second one is based on the empirical distribution
function. The unknown parameter is estimated via the maximum likelihood
estimator. It is shown that both the limit distributions of the two test
statistics do not depend on the unknown parameter, so the distributions of the
tests are asymptotically parameter free. Some considerations on the consistency
of the proposed tests and some simulation studies are also given.
03/2012;
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ABSTRACT: A key feature in the molecular pathogenesis of liver fibrosis requires maintenance of the activated hepatic stellate cells (HSCs) phenotype by inhibition of apoptosis. The induction of apoptosis in activated HSCs has been proposed as an antifibrotic treatment strategy. This study aims at evaluating the effect of hydroxysafflor yellow A (HSYA) on apoptosis of culture-activated HSCs and further elucidating the underlying mechanisms. Primary HSCs were isolated from rats. The analysis of the cell cycle be performed by flow cytometry, detection of apoptosis by Annexin V-FITC/ PI staining, and the results were confirmed by DNA fragmentation, and cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Real-time polymerase chain reaction and Western blotting were used to analyze the expression of genes. Our results revealed that HSYA significantly induced apoptosis in a dose- and time-dependent manner. HSYA suppresses the activation of ERK1/2 and ERK1/2-regulated gene expression, including Bcl-2, Cytochrome c, caspase-9, and caspase-3, leading to the enhancement of apoptosis. Pharmacological blockade of ERK1/2 kinase abrogation this action of HSYA. Our data provide a molecular basis for the anti-hepatic fibrosis activity of HSYA.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2012; 46(5):397-404. · 2.61 Impact Factor
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ABSTRACT: Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis.
PLoS ONE 01/2012; 7(12):e46888. · 4.09 Impact Factor
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Shuangmei Ye,
Xing Hao,
Ting Zhou,
Mingfu Wu,
Juncheng Wei,
Yongjun Wang,
Li Zhou,
Xuefeng Jiang, Li Ji,
Yin Chen,
Lanying You,
Yiqun Zhang,
Gang Xu,
Jianfeng Zhou,
Ding Ma,
Shixuan Wang
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ABSTRACT: Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro.
Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKTSer473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining.
Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not affected.
Plexin-B1 expression correlates with malignant phenotypes of serous ovarian tumors, probably via phosphorylation of AKT at Ser473, suggesting that Plexin-B1 might be a useful biomarker and/or a novel therapeutic target.
BMC Cancer 11/2010; 10:611. · 3.01 Impact Factor
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Changyu Wang, Li Zhou,
Shuang Li,
Juncheng Wei,
Wei Wang,
Ting Zhou,
Shujie Liao,
Danhui Weng,
Dongrui Deng,
Yanjie Weng,
Shixuan Wang,
Ding Ma
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ABSTRACT: Gene C4orf7, renamed FDC-SP (follicular dendritic cell secreted protein, FDC-SP) was first isolated from human tonsils. Up to the present, the function of this gene was still poorly understood. In this study, we report the expression of gene C4orf7 in a panel of tumor types. The percentages of C4orf7 positive expression in the tumor patients with metastases were notably higher than those in the cancer without metastases. On the contrary, the expression was hardly noted in normal tissues and corresponding benign lesions. In vitro, the up-regulation of C4orf7 in ovarian cancer cell lines was associated with enhanced motility and invasiveness. Furthermore, the overexpression of C4orf7 resulted in Akt ser473 phosphorylation and decreased E-cadherin expression. The role of C4orf7 in ovarian cancer cell morphology, motility and invasion was demonstrated.
Oncology Reports 10/2010; 24(4):933-9. · 1.84 Impact Factor
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Shuang Li,
Ping Liu,
Lin Xi,
Xuefeng Jiang,
Mingfu Wu,
Dongrui Deng,
Juncheng Wei,
Tao Zhu, Li Zhou,
Shixuan Wang,
Gang Xu,
Li Meng,
Jianfeng Zhou,
Ding Ma
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ABSTRACT: The high-risk human papillomavirus oncoprotein 18 E6 (HPV18 E6) is associated with cervix cancer. This study was conducted in order to identify the transmembrane protein 87B (TMEM87B) as a novel binding protein interacting with the HPV18 E6 oncoprotein and to perform an initial bioinformatics analysis. The yeast strain AH109 was transformed with pGBKT7-HPV18 E6 and the yeast mating assay was utilized to identify the interaction between TMEM87B and HPV18 E6 in the human Hela cDNA library. TMEM87B mRNA was detected in Hela cells by using RT-PCR. The TMEM87B gene structure, genomic localization, physical and chemical characteristics, subcellular localization and functional domain were predicted, as well as the systematic evolution analysis on similar proteins among several species. In the yeast two-hybrid assay, HPV18 E6 mRNA was expressed and there was no self-activation and toxicity in the AH109 strain. The special TMEM87B mRNA expression was detected in Hela cells and the blue clones were validated by the yeast mating assay. An efficient bioinformatics analysis fundamentally identified that TMEM87B is a secretary protein, containing many phosphorylation sites and functional motifs and possibly involved in signal transduction and transcriptional control in carcinogenesis. It was indicated that the yeast two-hybrid system is efficient for screening interacting proteins. The novel gene TMEM87B may interact with HPV18 E6 and may be a potential oncogenesis target according to the bioinformatics analysis.
Oncology Reports 08/2008; 20(2):421-7. · 1.84 Impact Factor
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ABSTRACT: In this paper we study a hybrid system with both manufacturing and remanufacturing. The inventory control strategy we use in the manufacturing loop is an automatic pipeline, inventory and order based production control system (APIOBPCS). In the remanufacturing loop we employ a Kanban policy to represent a typical pull system. The methodology adopted uses control theory and simulation. The aim of the research is to analyse the dynamic (as distinct from the static) performance of the specified hybrid system. Dynamics have implications on total costs in terms of inventory holding, capacity utilisation and customer service failures. We analyse the parameter settings to find preferred “nominal”, “fast” and “slow” values in terms of system dynamics performance criteria such as rise time, settling time and overshoot. Based on these parameter settings, we investigate the robustness of the system to changes in return yield and the manufacturing/remanufacturing lead time. Our results clearly show that the system is robust with respect to the system dynamics performance and the remanufacturing process can help to improve system dynamics performance. Thus, the perceived benefits of remanufacturing of products, both environmentally and economically, as quoted in the literature are found not to be detrimental to system dynamics performance when a Kanban policy is used to control the remanufacturing process.
Omega.
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ABSTRACT: It is well known that forecasting mechanisms can greatly increase "bullwhip" - demand variance amplification of orders as processed by both human and algorithmic decision makers. This paper is concerned with the application of the well-established APIOBPCS Decision Support System (a variant of the Order-Up-To Rule) in such circumstances. It has two feedback controls (based on the inventory and the orders-in-pipeline respectively) with gains set equal according to the Deziel-Eilon Rule. There is one feed-forward control based on exponential forecasting, although this is not a restriction on the application of this system. We consider the pragmatic role of APIOBPCS in the situation where the echelon decision maker may be handling a wide range of SKU's in a non-altruistic environment where upmarket information may either be withheld or simply unavailable. Under such circumstances it has been established via site-based studies that the decision makers output (the orders) reflect a wide range of strategies (or maybe ignorance). Three strategies may be regarded as "appropriate", i.e. Pass-orders-Along; Demand Smoothing; and Level Scheduling depending, on context. APIOBPCS can be adapted to each of these modus operandi. In the first case with the added capability of smoothing the "sharp edges" with a modicum of inventory variation, and in the last case with the advantage of built-in trend detection. "Players" in non-altruistic supply chains must be able to cope with added uncertainties due to lead-time variations. We show that APIOBPCS may be well matched to such situations and is hence "copable" as well as "capable". The paper includes recommended parameter settings according to desired decision-making policies.
International Journal of Production Economics 128(2):556-568. · 1.76 Impact Factor
