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1.  Fucosylated TGF-β receptors transduces a signal for epithelial–mesenchymal transition in colorectal cancer cells 
British Journal of Cancer  2013;110(1):156-163.
Transforming growth factor-β (TGF-β) is a major inducer of epithelial–mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear.
Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis.
Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.
Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.
PMCID: PMC3887298  PMID: 24253505
colorectal cancer; fucosyltransferase; TGF-β; EMT
2.  Ex vivo imaging of mouse brain using micro-CT with non-ionic iodinated contrast agent: a comparison with myelin staining 
The British Journal of Radiology  2012;85(1019):e973-e978.
We investigated the use of micro-CT with contrast agent for the non-invasive characterisation of fixed mouse brain tissue specimens as a means to differentiate between grey and white matter.
Nine mice were divided into two groups for micro-CT (n=6) and myelin staining (n=3) experiments. Six mice underwent in vivo micro-CT and were then prepared for brain specimens by transcardiac perfusion with paraformaldehyde. The six mouse brains were soaked in two different concentrations of non-ionic iodinated contrast agents (60 and 150 mg ml−1). Immersion times used for each concentration of iodine were for 3, 7 and 14 days. Three-dimensional ex vivo micro-CT images were acquired with a resolution of 39 μm3 to create isotropic images. The other three mice were stained for evaluation of the myelin structure.
Soaking the brains in non-ionic iodinated contrast agent resulted in clear differences in signal between the grey matter, the white matter and the ventricular spaces. The 150 mg ml−1 contrast agent solution yielded images with better contrast-to-noise ratio (CNR) than 60 mg ml−1 iodine contrast agent solution. 14 days of soaking yielded images with better CNR than 3 and 7 days. The CT contrast of grey and white matter derived from the iodine-soaked fixed brains was strongly related to tissue myelin.
The present study demonstrated that micro-CT can be used to detect the mouse brain myelin structure at 3, 7 and 14 days after fixation using a CT contrast agent.
PMCID: PMC3500820  PMID: 22674712
3.  Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms 
Blood Cancer Journal  2012;2(9):e87-.
Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34+ cells, CD34+ blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34+ acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO+ leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO+ leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells.
PMCID: PMC3461706  PMID: 22961059
acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); human hedgehog-interacting protein (HHIP); stromal cells
4.  Experimental verification of protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT 
The British Journal of Radiology  2010;83(990):509-514.
Our aim was to assess the protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT (DCE-CT). DCE-CT studies were performed in 30 rats (8 weeks old) on days 0, 2, 4 and 7 using multidetector row CT. The rats were divided into three groups: a control group (n = 6) with free access to standard water and without cisplatin injection, a non-treatment group (n = 12) with free access to standard water and injected with cisplatin (3.6 mg kg–1 body weight) intraperitoneally on day 0 and a treatment group (n = 12) with free access to hydrogen-rich water starting from 7 days before cisplatin injection. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The contrast clearance of the entire kidney (K) was obtained by multiplying K1 by the renal volume. The serum creatinine level was also measured on day 7. The K1 and K values normalised by those on day 0 in the treatment group were significantly greater than those in the non-treatment group on days 2, 4 and 7. There were no significant differences in the normalised K value between the treatment and control groups on days 2 and 7. The serum creatinine level in the treatment group was significantly lower than that in the non-treatment group and was not significantly different from that in the control group. This study demonstrated that hydrogen-rich water ameliorates renal dysfunction due to cisplatin-induced nephrotoxicity in rats.
PMCID: PMC3473599  PMID: 20505032
5.  Enhancement of antibody production to hepatitis B surface antigen by anti-idiotypic antibody. 
Gut  1986;27(9):1069-1072.
Studies were undertaken to determine whether anti-idiotypic antibody (anti-Id) against antibody to hepatitis B surface antigen (anti-HBs) could modulate in vitro anti-HBs production by human peripheral blood mononuclear cells stimulated with pokeweed mitogen. Peripheral blood mononuclear cells from patients positive for serum anti-HBs produced significantly increased amounts of anti-HBs by the addition of IgG fraction of anti-anti-HBs as well as purified HBsAg in a soluble form when compared to those in cultures with pokeweed mitogen alone. F(ab')2 but not Fc fragments of anti-anti-HBs significantly enhanced anti-HBs levels in cultures. Anti-anti-HBs or HBsAg alone, however, did not induce anti-HBs production. Anti-HBs production was not observed by the additions of these additives when peripheral blood mononuclear cells from chronic HBsAg carriers and control individuals were used. These findings indicate that anti-Id modulates the immune response to HBsAg.
PMCID: PMC1433783  PMID: 3489655

Results 1-5 (5)