Publications (252) View all
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Article: In vivo evidence of gamma-tocotrienol as a chemosensitizer in the treatment of hormone-refractory prostate cancer.
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ABSTRACT: gamma-Tocotrienol (gammaT3) is known to selectively kill prostate cancer (PCa) cells and to sensitize the cells to docetaxel (DTX)-induced apoptosis. In the present study, the pharmacokinetics of gammaT3 and the in vivo cytotoxic response of androgen-independent prostate cancer (AIPCa) tumor following gammaT3 treatment were investigated. Here, we investigated these antitumor effects for PCa tumors in vivo. The pharmacokinetic and tissue distribution of gammaT3 after exogenous gammaT3 supplementation were examined. Meanwhile, the response of the tumor to gammaT3 alone or in combination with DTX were studied by real-time in vivo bioluminescent imaging and by examination of biomarkers associated with cell proliferation and apoptosis. After intraperitoneal injection, gammaT3 rapidly disappeared from the serum and was selectively deposited in the AIPCa tumor cells. Administration of gammaT3 alone for 2 weeks resulted in a significant shrinkage of the AIPCa tumors. Meanwhile, further inhibition of the AIPCa tumor growth was achieved by combined treatment of gammaT3 and DTX (p < 0.002). The in vivo cytotoxic antitumor effects induced by gammaT3 seem to be associated with a decrease in expression of cell proliferation markers (proliferating cell nuclear antigen, Ki-67 and Id1) and an increase in the rate of cancer cell apoptosis [cleaved caspase 3 and poly(ADP-ribose) polymerase]. Additionally, the combined agents may be more effective at suppressing the invasiveness of AIPCa. Overall, our results indicate that gammaT3, either alone or in combination with DTX, may provide a treatment strategy that can improve therapeutic efficacy against AIPCa while reducing the toxicity often seen in patients treated with DTX.Pharmacology 04/2010; 85(4):248-58. · 1.79 Impact Factor -
Article: Education and Imaging. Hepatobiliary and pancreatic: Hemobilia caused by bleeding from hepatic artery aneurysms.
Journal of Gastroenterology and Hepatology 03/2010; 25(3):648. · 2.87 Impact Factor -
Article: Computed tomography in left-sided and right-sided blunt diaphragmatic rupture: experience with 43 patients.
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ABSTRACT: To investigate differences in the radiographic signs for left and right-sided blunt diaphragmatic rupture (BDR) in order to provide guidance to avoid missing these injuries. A retrospective review of the computed tomography (CT) examinations of 43 patients with BDR treated at our hospital between January 1995 and 2007 was undertaken. The presence of diaphragmatic discontinuity, diaphragmatic thickening, herniation of abdominal organs into the thoracic cavity, collar/hump sign, dependent viscera sign, abnormally elevated 4 cm or more above the dome of the other-sided hemi-diaphragm, and of associated injuries was recorded and their relationship to each other and to BDR diagnosis examined. A comparison between the use of axial and sagittal/coronal reconstruction images in diagnosis was also performed in 15 patients. On axial imaging, left-sided diaphragmatic rupture occurred in 31 patients (72%) and right-sided in 12 (28%). Twenty-nine patients had associated injuries. More than 60% of the patients showed the "dependent viscera" sign, "abdominal organ herniation" sign, diaphragm thickening, or had a more than 4 cm elevation of one side of the diaphragm. "Diaphragmatic discontinuity" and "stomach herniation" were seen almost exclusively in left-sided rupture. Those with BDR and haemothorax had a significantly lower incidence of "diaphragm discontinuity" (p=0.034) than those without haemothorax. Sagittal/coronal reconstruction slightly increased the number of band signs, diaphragmatic discontinuities and diaphragmatic thickenings seen. Of the CT signs examined in this study, when herniation of abdominal organs was used as a diagnostic marker, only a very small fraction of trauma patients identifiable by CT would be missed. Further, CT signs differ for left-sided and right-sided BDR, thus the possibility of BDR should be considered when any of the reported CT signs are present.Clinical radiology 03/2010; 65(3):206-12. · 1.65 Impact Factor -
Article: Prostate cancer cells modulate osteoblast mineralisation and osteoclast differentiation through Id-1.
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ABSTRACT: Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed. Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N=110). We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-beta and this correlation was confirmed in human prostate cancer specimens (P=0.03). Furthermore, addition of recombinant TNF-beta to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation. In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-beta, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.British Journal of Cancer 12/2009; 102(2):332-41. · 5.04 Impact Factor -
Article: Fetal choroid plexus cysts and their association with aneuploidy
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ABSTRACT: Summary Thirty-nine fetuses with choroid plexus cysts were studied prospectively. All had detailed sonography to detect other structural abnormalities, and either had fetal karyotyping or were examined at birth to detect chromosomal abnormalities. There were two fetuses with trisomy 21 and seven with trisomy 18. There were 31 fetuses with choroid plexus cysts alone, without other structural defects. The incidence of fetal aneuploidy in the fetuses with isolated choroid plexus cysts and those with other structural defects was 10 and 75 per cent respectively. No association between persistence of the cyst, cyst size or laterally and fetal aneuploidy was found. Fetal karyotyping may still be necessary for fetuses with choroid plexus cyst and no other structural abnormalities.07/2009; 15(6):359-362.
