Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal >= 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 over-expression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients.published_or_final_versio

Maternal-fetal evaluation of oxidized lipid products of polyunsaturated fatty acid induced by environmental contaminant perfluorooctante sulfonate

Poster Session 3: abstract no. N9.06The Conference abstracts' website is located at http://www.issfal.org/conferences/2014-stockholm/abstractsPerfluorooctane sulfonate (PFOS) is synthetic fluorinated hydrocarbons. However the carbon-fluoride bonds render these compounds to be non-biodegradable, leading to their persistence in the environment and lengthy elimination half-life in vivo. PFOS could also penetrate the placental barrier and the blood brain barrier, and produce neurotoxic effect. High dose of PFOS leads to neonatal mortality and neurologic delays. It is known PFOS generate a dose-dependent ROS production, but the effect in PUFA lipid peroxidation, especially adrenic, arachidonic, docosahexaenoic and eicosapentaenoic acids that are ...postprin

Transcriptomic Responses Of Corpuscle Of Stannius Gland Of Japanese Eels (anguilla Japonica) To Changes In Water Salinity

Physiological studies of a unique endocrine gland in fish, named corpuscles of Stannius (CS), described a Ca2+-regulatory function for this gland mediated by stanniocalcin-1, a hypocalcemic polypeptide hormone. However, to date, the endocrine functions of the glands have not been completely elucidated. We hypothesized that other unidentified active principles in the glands are involved in the regulation of plasma ion (Na+, Ca2+) and/or blood pressure. In this study, transcriptome sequencing of CS glands was performed using Japanese eels (Anguilla japonica) adapted to freshwater (FW) or seawater (SW) to reveal the presence and differential expression of genes encoding proteins related to the ion-osmoregulatory and pressor functions. We acquired a total of 14.1 Mb and 12.1 Mb quality-trimmed reads from the CS glands collected from FW and SW adapted eels, respectively. The de novo assembly resulted in 9254 annotated genes. Among them, 475 genes were differentially expressed with 357 up- and 118 down-regulated in the SW group. Gene ontology analysis further demonstrated the presence of natriuresis and pressor related genes. In summary, ours is the first study using high-throughput sequencing to identify gene targets that could explain the physiological importance of the CS glands.published_or_final_versio

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

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The endocrine disruptor TCDD modulates microRNA expression in preimplantation mouse embryos and spheroids attachment on human endometrial epithelial cells in vitro

Conference Theme: The Intersection Between Genetics, Genomics, and Reproductive BiologyThe endocrine disruptor (ED) is an exogenous substance that acts on the endocrine system and modulates normal physiological functions of the body. Although EDs such as 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) affect normal reproductive function in humans and affects the growth and reproductive functions in rodents, the underlying mechanism that modulates these changes remains unclear. Accumulating evidence suggested preimplantation embryo development is controlled by ...postprintThe 43rd Annual Meeting of the Society for the Study of Reproduction (SSR), Milwaukee, WI., 30 July-3 August 2010. In Biology of Reproduction, 2010, v. 83 Meeting abstracts, p. 62, abstract no. 27

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses spheroids attachment on endometrial epithelial cells through the down-regulation of the Wnt-signaling pathway

The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects embryo development, implantation and fertility in humans. The underlying molecular mechanism by which TCDD suppresses implantation remains largely unknown. We used the trophoblastic spheroids (embryo surrogate)-endometrial cells co-culture assay to study the attachment of trophoblastic spheroids (BeWo and Jeg-3) onto the endometrial epithelial (RL95-2 and Ishikawa) cells. TCDD dose-dependently induced cytochrome P450 1A1 (Cyp1A1) expression in trophoblastic and endometrial epithelial cells. Moreover, TCDD at 1 and 10. nM suppressed β-catenin (a Wnt-signaling molecule) and E-cadherin expression, as well as spheroids attachment onto endometrial cells. Interestingly, activation of the canonical Wnt-signaling pathway via Wnt3a or lithium chloride reverted the suppressive effect of TCDD on β-catenin and E-cadherin expressions in the BeWo and RL95-2 cells, and restored the spheroids attachment rate to be comparable to the untreated controls. Taken together, TCDD induces Cyp1A1 expression, modulates the Wnt-signaling pathway and suppresses spheroids attachment onto endometrial cells. © 2011 Elsevier Inc.postprin

De novo transcriptome analysis of Perna viridis highlights tissue-specific patterns for environmental studies

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A prospective interventional study to examine the effect of a silver alloy and hydrogel--coated catheter on the incidence of catheter-associated urinary tract infection

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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

Tissue-specific transcriptome assemblies of the marine medaka Oryzias melastigma and comparative analysis with the freshwater medaka Oryzias latipes

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