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Biomedical subjects

C K Ong

Publications and source records attributed to C K Ong.

At least 19 recordsLinked to original sources
PubMed2006

The role of 5' untranslated region in translational suppression of OKL38 mRNA in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. OKL38 is a pregnancy-induced growth inhibitory gene and its expression is lost in various breast cancer cell lines and kidney tumor. To determine the role of OKL38 expression in HCC, we investigated its expression in various HCC samples and liver cancer cell lines. Western blot analysis revealed that OKL38 protein was absent or reduced in 64.2% (18 of 28) of the HCCs examined and four liver cancer cell lines. Immunohistochemistry study demonstrated that OKL38 protein was undetectable in 41.3% (38 of 92) of HCC, whereas 39.1% (36 of 92) of HCC showed low expression of the protein. Lost or reduced expression level of OKL38 protein was significantly correlated to high tumor stages in HCC (P=0.0042). Overexpression of the OKL38 caused cell death in Chang liver cells. 5' Untranslated region (5'UTR) deletion studies demonstrated that OKL38 was downregulated via translation suppression associated with the 5'UTR of its mRNA. Taken together, the 5'UTRs of OKL38 might play an important role in downregulation of its protein and the absence of OKL38 could lead to the development or progression of HCC.

5' Untranslated Regions↗
PubMed2006

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro.

Ovarian cancer is currently the second leading cause of gynecological malignancy and cisplatin or cisplatin-based regimens have been the standard of care for the treatment of advance epithelial ovarian cancers. However, the efficacy of cisplatin treatment is often limited by the development of drug resistance either through the inhibition of apoptotic genes or activation of antiapoptotic genes. We have previously reported the overexpression of human UO-44 (HuUO-44) in ovarian cancers and the HuUO-44 antisera markedly inhibited NIH-OVCAR3 ovarian cancer cell attachment and proliferation (Oncogene 23: 5707-5718, 2004). In the present study, we observed through the cancer cell line profiling array that the expression of HuUO-44 was suppressed in the ovarian cancer cell line (SKOV-3) after treatment with several chemotherapeutic drugs. Similarly, this suppression in HuUO-44 expression was also correlated to the cisplatin sensitivity in two other ovarian cancer cell lines NIH-OVCAR3 and OV-90 in a dose-dependent manner. To elucidate the function of HuUO-44 in cisplatin chemoresistance in ovarian cancer cell, small interfering RNAs (siRNAs) were employed to mediate HuUO-44 silencing in ovarian cancer cell line, NIH-OVCAR3. HuUO-44 RNA interference (RNAi) resulted in the inhibition of cell growth and proliferation. Importantly, HuUO-44 RNAi significantly increased sensitivity of NIH-OVCAR3 to cytotoxic stress induced by cisplatin (P<0.01). Strikingly, we have also demonstrated that overexpression of HuUO-44 significantly conferred cisplatin resistance in NIH-OVCAR3 cells (P<0.05). Taken together, UO-44 is involved in conferring cisplatin resistance; the described HuUO-44-specific siRNA oligonucleotides that can potently silence HuUO-44 gene expression may prove to be valuable pretreatment targets for antitumor therapy or other pathological conditions that involves aberrant HuUO-44 expression.

Base Sequence↗
PubMed2006

A biphasic parameter estimation method for quantitative analysis of dynamic renal scintigraphic data.

Dynamic renal scintigraphy is an established method in nuclear medicine, commonly used for the assessment of renal function. In this paper, a biphasic model fitting method is proposed for simultaneous estimation of both vascular and parenchymal parameters from renal scintigraphic data. These parameters include the renal plasma flow, vascular and parenchymal mean transit times, and the glomerular extraction rate. Monte Carlo simulation was used to evaluate the stability and confidence of the parameter estimates obtained by the proposed biphasic method, before applying the method on actual patient study cases to compare with the conventional fitting approach and other established renal indices. The various parameter estimates obtained using the proposed method were found to be consistent with the respective pathologies of the study cases. The renal plasma flow and extraction rate estimated by the proposed method were in good agreement with those previously obtained using dynamic computed tomography and magnetic resonance imaging.

Computer Simulation↗
PubMed2006

Subdural empyema post-chemoradiotherapy for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is a common malignancy in the Asian Chinese population. The first-line treatment for Stage III/IV disease has in recent times shifted from radiotherapy to that of concurrent chemoradiotherapy. The treatment is not infrequently associated with in-field complications. We describe a rare case of one such complication -- subdural empyema developing post-chemoradiotherapy in a 56-year-old man with Stage IVB nasopharyngeal carcinoma.

Antineoplastic Agents↗
PubMed2005

Fabrication of size-tunable gold nanoparticles array with nanosphere lithography, reactive ion etching, and thermal annealing.

Two-dimensional ordered arrays of gold (Au) nanoparticles were fabricated using two different variants of the nanosphere lithography technique. First, ordered arrays of polystyrene nanospheres on Si substrate were used as deposition masks through which gold films were deposited by electron beam evaporation. After the removal of the nanospheres, an array of triangular Au nanodisks was left on the Si substrate. After thermal annealing at increasing temperature, systematic shape transition of the nanostructures from original triangular Au nanodisks to rounded nanoparticles was observed. This approach allows us to systematically vary the size and morphology of the particles. In the second and novel technique, we made use of reactive ion etching to simultaneously reduce the dimension of the masking nanospheres and create arrays of nanopores on the substrate prior to the deposition of the Au films. These samples were subsequently annealed, which resulted in size-tunable and ordered Au nanoparticle arrays with the nanoparticles nested in the nanopores of the templated substrate. With the nanoparticles anchored in the nanopores, the substrate could be useful as a template for growth of other nanomaterials.

Journal Article↗
PubMed2005

2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) exhibits p53-dependent and -independent antiproliferative activity in human nasopharyngeal carcinoma cells in vitro and in vivo.

2-Chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU) has been used to treat patients with advanced solid tumours. However, the molecular mechanisms are not well understood. In the present study, we report that SarCNU inhibited proliferation of human HK-1 and CNE-2 nasopharyngeal carcinoma (NPC) in vivo and in vitro. In vitro study showed that wild-type p53 HK-1 cells were 3-fold more sensitive to SarCNU than p53 mutant CNE-2 cells. G2/M arrest, reduction in p21(Cip1/Waf1) and inactivation of cellular cdc-2 activity were seen in both SarCNU-treated HK-1 and CNE-2 cells. Upregulation of p53, phosphorylated p53 at Ser15 and biochemical markers for apoptosis, such as cleaved caspase-3, cleaved caspase-7 and cleaved PARP, were observed in SarCNU-treated HK-1 but not CNE-2 cells. The levels of cyclin B1, Wee1 and phosphorylated cdc-2 but not total cdc-2 in HK-1 cells were significantly reduced by SarCNU treatment. In contrast to HK-1 cells, decrease in total cdc-2 but increase in phosphorylated cdc-2 at Tyr15, cyclin B1 and Wee1 was observed in CNE-2 cells treated with SarCNU. Introduction of mutant p53 into HK-1 cells resulted in growth enhancement in vivo and increased resistance to SarCNU-induced apoptosis in vitro. Furthermore, CNE-2 cells transfected with wild-type p53 became susceptible to SarCNU-induced apoptosis in vitro but not their growth rate in vivo. The data indicate that in NPC cells SarCNU-induced apoptosis was p53-dependent while SarCNU-induced G2/M arrest was mediated by altering the levels of cyclin B1-cdc-2 complex and phosphorylation of cdc-2 at Tyr15 resulting in inactivation of cellular cdc-2 activity. Our data suggest a potential use of SarCNU in the treatment of NPC.

Animals↗
PubMed2003

Subwavelength imaging by a left-handed material superlens.

In this work, a finite-difference time-domain (FDTD) method is employed to justify the superlensing effect of left-handed material (LHM) slabs. Our results demonstrate that subwavelength resolution can be achieved by LHM slabs with certain parameters. We present the dynamic feature of the imaging process and the dependence of physical parameters on the performance of the superlens. These results help to clarify the diverse FDTD results reported previously. We also show that the achievable resolution is limited by the absorption and thickness of the LHM slabs, which introduces difficulties in practical applications of the superlens.

Journal Article↗
PubMed2003

Kaempferol-induced growth inhibition and apoptosis in A549 lung cancer cells is mediated by activation of MEK-MAPK.

A vast variety of naturally occurring substances have been shown to protect against experimental carcinogenesis and an increasing amount of evidence suggests that kaempferol may have cancer chemopreventative properties. However, the precise underlying protective mechanisms are poorly understood. To elucidate these mechanisms, we challenged human lung cancer cell line A549 with kaempferol and investigated its effects upon cellular growth and signal transduction pathways. Treatment of A549 cells with kaempferol resulted in a dose- and time-dependent reduction in cell viability and DNA synthesis with the rate of apoptosis equivalent to 0.9+/-0.5, 5.2+/-1.5, 16.8+/-2.0, 25.4+/-2.6, and 37.8+/-4.5% on treatment with 0, 17.5, 35.0, 52.5, and 70.0 microM kaempferol, respectively. Concomitantly, kaempferol treatments led to a 1.2-, 2.7-, 3.3-, and 3.4-fold increase in Bax. Similar elevations were also observed in Bad which increased 1.2-, 3.3-, 3.7-, and 4.7-fold, respectively, as compared to control. Bcl-2 and Bcl-xL expression were inhibited in a dose-dependent fashion. While the Akt-1 and phosphorylated Akt-1 were inhibited, the mitogen-activated protein kinase (MAPK) was activated upon kaempferol treatment. Kaempferol induced apoptosis was associated with the cleavage of caspase-7 and poly ADP-ribose polymerase (PARP). Inhibition of MEK1/2 but not PI-3 kinase blocked kaempferol-induced cleavage of caspase-7, PARP cleavage, and apoptosis. The results suggest that inactivation of Akt-1 and alteration of Bcl-2 family of proteins are not sufficient for kaempferol to induce apoptosis and activation of MEK-MAPK is a requirement for kaempferol-induced cell death machinery in A549 cells.

Antineoplastic Agents↗
PubMed2002

Reversible structural transition in epitaxial manganite film.

A reversible structural transition of an epitaxial La(2/3)Sr(1/3)MnO3 film deposited on a LaAlO3 substrate has been investigated by means of in situ high-resolution transmission electron microscopy and electron diffraction, combined with image and diffraction calculations. We observe that the crystallographic symmetry of the film can be lowered via electron beam irradiation, leading to a rhombohedral-monoclinic transition. This transition can be attributed to the cooperating effect of the mismatch stress and the irradiation-induced thermal stress.

Journal Article↗
PubMed2001

Induction of apoptosis in mammary gland by a pure anti-estrogen ICI 182780.

The antiestrogen, ICI 182780 (ICI) proves to be clinically useful for the treatment of estrogen receptor positive breast tumours. We report the assessment of the in vivo and in vitro effects of ICI on apoptosis of breast epithelial cells. In vivo, administration of rats with ICI for 3 weeks resulted in a reduction in the size of the lobular structures with the rate of mammary epithelial apoptosis equivalent to 10, 35 and 45% on treatment with 1, 1.5 and 2 mg ICI per kg body weight, respectively. Concomitantly, these treatment led to a 2.0-, 2.2- and 2.5-fold increase in Bax. Similar elevations were also observed in Bad levels which increased 1.7-, 2.6- and 2.7-fold respectively in the ICI treatment as compared to controls. This also resulted in a dose dependent decrease in Bcl-2 and Bcl-xL protein expressions. Growth inhibition and induction of apoptosis were also observed in the MCF-7 cells following in vitro treatment with ICI. This is closely associated with [1] the down-regulation of Bcl-2 and Bcl-xL proteins and [2] upregulation of Bax and Bad, whose gene products are known to be involved the regulation of apoptosis in mammalian cells. Stable over-expression of Bcl-2 resulted in protection of MCF-7 cells from apoptosis and growth inhibitory effects of ICI. Conversely, reduction of Bcl-2 by antisense transfection make MCF-7 cells more sensitive to ICI-induced growth inhibition and apoptosis. These findings suggest that modulation of Bax, Bcl-xL, Bcl-2 and Bad proteins by ICI may be, in part, responsible for the anti-proliferative and apoptotic effect of ICI seen clinically and in animal models.

Animals↗
PubMed2001

Growth hormone receptor and IGF-I receptor immunoreactivity during orthodontic tooth movement in the prednisolone-treated rat.

Bone remodeling during tooth movement is regulated by local and systemic factors. Two regulators of bone metabolism are growth hormone (GH) and insulin-like growth factor-I (IGF-I). Their effects are mediated via binding to GH receptor (GHR) and IGF-I receptor (IGF-IR) in target tissues. Corticosteroids may affect the activity of these growth factors. This study examined the effect of prednisolone on GHR and IGF-IR expression in dental tissues following orthodontic tooth movement. The corticosteroid-treated group (N = 6) was administered prednisolone (1 mg/kg) daily and the control group (N = 6) received equivalent volumes of saline. An orthodontic force (30 g) was applied to the maxillary first molar. Animals were sacrificed 12 days postappliance insertion. Sagittal sections of the first molar were stained for GHR and IGF-IR immunoreactivity. GHR and IGF-IR cell counts were elevated following appliance-treatment. Orthodontic tooth movement appeared to up-regulate GHR and IGF-IR immunoreactivity, but this up-regulation was reduced following prednisolone treatment. The suppression of GHR and IGF-I immunoreactivity in steroid-treated animals infers the mechanism whereby bone resorption and deposition, necessary for orthodontic tooth movement, may be inhibited by prednisolone. However, at 12 days postappliance insertion, no difference in orthodontic tooth movement was observed following low-dose prednisolone treatment.

Alveolar Process↗
PubMed2001

An improved heat pulse method to measure low and reverse rates of sap flow in woody plants.

The compensation heat pulse method (CHPM) is of limited value for measuring low rates of sap flow in woody plants. Recent application of the CHPM to woody roots has further illustrated some of the constraints of this technique. Here we present an improved heat pulse method, termed the heat ratio method (HRM), to measure low and reverse rates of sap flow in woody plants. The HRM has several important advantages over the CHPM, including improved measurement range and resolution, protocols to correct for physical and thermal errors in sensor deployment, and a simple linear function to describe wound effects. We describe the theory and methodological protocols of the HRM, provide wound correction coefficients, and validate the reliability and accuracy of the technique against gravimetric measurements of transpiration.

Eucalyptus↗
PubMed2001

Induction of UO-44 gene expression by tamoxifen in the rat uterus and ovary.

A complementary DNA, uterine-ovarian-specific gene 44 (UO-44), has been isolated from tamoxifen-induced rat uterine complementary DNA library using differential display techniques. UO-44 transcripts are found to be abundant in the uterus and ovary. UO-44 gene expression in the uterus is strictly regulated by estrogens, tamoxifen, and GH, whereas the pure antiestrogen ICI 182780 is inhibitory. Treatment of ovariectomized rats and hypophysectomized rats with tamoxifen and GH, respectively, resulted in up-regulation of UO-44 expression in a dose-dependent manner. In situ hybridization revealed that UO-44 gene expression was restricted to the luminal and glandular epithelial cells of the uterus and to granulosa cells of medium-size ovarian follicles. Transfection studies showed that UO-44 was a membrane-associated protein. Because estrogens, tamoxifen, and GH are stimulators of uterine luminal epithelial cell growth in vivo, UO-44 protein may serve as a mediator of the effect of these compounds in inducing epithelial proliferation and differentiation in these tissues.

Animals↗
PubMed2001

Cloning and characterization of a novel pregnancy-induced growth inhibitor in mammary gland.

Growth factors and growth inhibitors play crucial roles in the growth regulation and differentiation of mammary epithelial cells. Studies have shown that during pregnancy, with the onset of terminal differentiation, there is a dramatic decrease in the proliferation of the mammary epithelial cells. Here we report the cloning and characterization of a novel pregnancy-induced cDNA, OKL38, from a human ovarian cDNA library. This cDNA encodes for a protein of approximately 34.5 kDa. Tissue distribution studies through Northern analyses revealed the ubiquitous nature of OKL38 transcripts in most tissues, with the highest levels observed in the ovary, kidney, and liver. The onset and advancement of pregnancy also gave rise to a concomitant increase in OKL38 gene expression. In situ hybridization revealed that OKL38 mRNA was further detected in mammary secretory epithelial cells. However, low levels of OKL38 transcripts were observed in the various human breast cancer cell lines studied and were barely detectable in all dimethylbenz(A)anthracene-induced mammary tumors examined. Transfection studies with OKL38 cDNA with MCF-7 cells resulted in growth inhibition in vitro and reduction in tumor formation in vivo. These observations led to speculation that OKL38 may play a vital role in the growth regulation and differentiation of breast epithelial cells during pregnancy and its implications in tumorigenesis.

Amino Acid Sequence↗
PubMed2000

Orthodontic tooth movement in the prednisolone-treated rat.

Adverse effects of corticosteroids on bone metabolism raise concerns as to whether steroid treatment may influence orthodontic movement. This study examined the effect of prednisolone on orthodontic movement using an established rat model. The corticosteroid treated group (N = 6) was administered prednisolone (1 mg/kg) daily, for a 12-day induction period; the control group (N = 6) received equivalent volumes of saline. On day 12, an orthodontic appliance was placed which exerted 30 g of mesial force to the maxillary first molar. Animals were sacrificed on day 24 and tooth movement was measured. Sagittal sections of the molars were stained with haematoxylin and eosin, and for tartrate-resistant acid phosphatase (TRAP) activity. While there were no significant differences in the magnitude of tooth movement between the 2 groups, steroid-treated rats displayed significantly less root resorption on the compression side and fewer TRAP-positive cells within the PDL space on the same side. This suggests steroid treatment suppressed clastic activity.

Acid Phosphatase↗
PubMed1997

Elucidating the population histories and transmission dynamics of papillomaviruses using phylogenetic trees.

Using gene genealogies constructed from gene sequence data, we show that both the mucosal and cutaneous papillomaviruses (PV)-supergroups A and B-appear to have been transmitted through susceptible populations faster than exponentially. The data and methods involved (1) examining the PV database for phylogenetic signal in an L1 open reading frame (ORF) fragment and an E1 ORF segment, (2) demonstrating that the same two fragments have evolved in a way consistent with a molecular clock, and (3) applying methods of phylogenetic tree analysis that test different scenarios for the dynamics of viral transmission within populations. The results indicate increases in PV populations of both supergroups A and B in the recent past. This form of the increases, which fit a null model of population growth with an exponent increasing in time, is compatible with the fact that human populations have grown at a faster than exponential rate, thus increasing the numbers of susceptible hosts for HPVs. There are, however, indications that the population of supergroup A has now stopped increasing in size.

Codon↗