5,565 research outputs found
Knowledge management system on flow and water quality modeling
Author name used in this publication: K. W. Chau2001-2002 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe
Probing gamma-ray emissions of Fermi-LAT pulsars with a non-stationary outer gap model
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Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor
A possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21 CIP1/WAF1 expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth. Copyright © 2006 by The Endocrine Society.postprin
Provision of reinforcement in concrete solids using the generalized genetic algorithm
A generalized genetic algorithm has been developed to find the global optimal reinforcement contents for a concrete solid structure subjected to a general three-dimensional (3D) stress field. Feasible solutions were examined based on the genetic algorithm, and the heterogeneous strategy used ensures that all of the local optimal regions are searched and the most optimal reinforcement content found. The effectiveness of the proposed approach has been validated by comparing the steel contents evaluated using the present method with those obtained from other available methods. A more economic design is achieved by the proposed algorithm. The method developed provides the designer with a valuable tool for the determination of reinforcements in complicated solid concrete structures. © 2011 American Society of Civil Engineers.postprin
An intelligent knowledge processing system on hydrodynamics and water quality modeling
Series: Lecture notes in computer scienceAuthor name used in this publication: K. W. ChauAuthor name used in this publication: O. WaiAuthor name used in this publication: Y. S. Li2001-2002 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe
DIFFERENCES BETWEEN RADIO-LOUD AND RADIO-QUIET γ-RAY PULSARS AS REVEALED BY <i>FERMI</i>
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Emission mechanism of GeV-quiet soft gamma-ray pulsars: a case for peculiar geometry?
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Fermi-lat Detection Of Pulsed Gamma-rays Above 50 Gev From The Vela Pulsar
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Randomized controlled trial of the effect of phytosterols-enriched low-fat milk on lipid profile in Chinese
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Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells
Background and Aims: Increasing evidence has suggested that hepatocellular carcinoma (HCC) might originate from a distinct subpopulation called cancer stem cells (CSCs), which are responsible for the limited efficacy of conventional therapies. We have previously demonstrated that granulin-epithelin precursor (GEP), a pluripotent growth factor, is upregulated in HCC but not in the adjacent non-tumor, and that GEP is a potential therapeutic target for HCC. Here, we characterized its expression pattern and stem cell properties in fetal and cancerous livers. Methods: Protein expression of GEP in fetal and adult livers was examined in human and mouse models by immunohistochemical staining and flow cytometry. Liver cancer cell lines, isolated based on their GEP and/or ATP-dependent binding cassette (ABC) drug transporter ABCB5 expression, were evaluated for hepatic CSC properties in terms of colony formation, chemoresistance and tumorigenicity. Results: We demonstrated that GEP was a hepatic oncofetal protein that expressed in the fetal livers, but not in the normal adult livers. Importantly, GEP+ fetal liver cells co-expressed the embryonic stem (ES) cell-related signaling molecules including β-catenin, Oct4, Nanog, Sox2 and DLK1, and also hepatic CSC-markers CD133, EpCAM and ABCB5. Phenotypic characterization in HCC clinical specimens and cell lines revealed that GEP+ cancer cells co-expressed these stem cell markers similarly as the GEP+ fetal liver cells. Furthermore, GEP was shown to regulate the expression of ES cell-related signaling molecules β-catenin, Oct4, Nanog, and Sox2. Isolated GEP high cancer cells showed enhanced colony formation ability and chemoresistance when compared with the GEP low counterparts. Co-expression of GEP and ABCB5 better defined the CSC populations with enhanced tumorigenic ability in immunocompromised mice. Conclusions: Our findings demonstrate that GEP is a hepatic oncofetal protein regulating ES cell-related signaling molecules. Co-expression of GEP and ABCB5 further enriches a subpopulation with enhanced CSC properties. The current data provide new insight into the therapeutic strategy. © 2011 Cheung et al.published_or_final_versio
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