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Biomedical subjects

Jong Wan Kim

Publications and source records attributed to Jong Wan Kim.

9 recordsLinked to original sources

Up-regulation of Mac-2 binding protein by hTERT in gastric cancer.

Mac-2 binding protein (Mac-2BP) is a secreted tumor antigen that is elevated in many cancers and implicated in tumor metastasis, as well as cell adhesion and immune functions. We focused on the human telomerase reverse transcriptase (hTERT) induced Mac-2BP expression and the relationship between Mac-2BP expression and the progression of gastric cancer. A cDNA expression array analysis was performed on the telomerase-negative cell line, SW13, which was engineered to overexpress hTERT when compared with the parental SW13 cell. hTERT-induced Mac-2BP expression was confirmed via RT-PCR and Northern blotting. ELISA and flow cytometric analyses revealed that Mac-2BP protein was increased by 2- to 4-fold in hTERT-overexpressing cells compared with the mock control. Mac-2BP expression was significantly reduced when the overexpressed hTERT was neutralized by the introduction of hTERT-specific siRNA. These results suggest that Mac-2BP expression is modulated by hTERT. Mac-2BP levels in both gastric cancer cells and tumor tissues were determined via Northern blot analysis and immunohistochemistry. Mac-2BP protein was highly expressed in most gastric cancer cell lines, and gastric tumor tissues were stained more densely than normal tissues. The intracellular and secreted Mac-2BP levels were also evaluated via ELISA, indicating that Mac-2BP was expressed and secreted more abundantly in gastric cancer patients than in healthy donors. The elevated serum Mac-2BP level in gastric tumor patients was also significantly associated with distant metastasis (p = 0.05) and higher tumor stage (p = 0.04). Our findings suggest that Mac-2BP is induced by hTERT, and that it may prove to be a useful prognostic marker for the detection of malignant progression of metastatic stomach cancers.

Adult↗

NF-kappaB inhibition increases chemosensitivity to trichostatin A-induced cell death of Ki-Ras-transformed human prostate epithelial cells.

Chemoresistance has been one of the major problems in anticancer therapy. In our effort to find a potential molecular target for overcoming the chemoresistance in prostate cancer, a promising anticancer drug trichostatin A (TSA) induced cell death was found to be compromised by enhanced NF-kappaB activation in 267B1/K-ras human prostate epithelial cancer cells. However, both the NF-kappaB activation and chemoresistance were reduced by pretreatment with proteasome inhibitor-I (ProI), accompanied by accumulations of both IkappaBalpha and p65/RelA (but not p50/NF-kappaB1) in the cytoplasm. Clonogenic cell survival and soft agar assays further confirmed the increased TSA chemosensitivity of 267B1/K-ras cells by ProI treatment. Moreover, dominant negative mutant of IKKbeta, IkappaBalpha and p65 enhanced the chemosensitization, too. Unexpectedly, using LY294002 and PD98059, phosphatidylinositol-3-kinase and mitogen-activated protein kinase were also implied in TSA chemoresistance through NF-kappaB activation, while these compounds had showed no effect on radiosensitization in the cells. On the other hand, together with TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, activations of caspase-8 and caspase-3 by TSA and ProI were noticed, suggesting the involvement of apoptotic process in chemosensitization of 267B1/K-ras cells. Altogether, these results suggest that blocking the NF-kappaB activation pathway could be an efficient target for improving the TSA chemosensitization and applying to the development of anticancer therapeutics in Ki-Ras-overexpressing tumorigenic cells, including prostate cancer.

Animals↗

Impaired responses of leukemic dendritic cells derived from a human myeloid cell line to LPS stimulation.

Several myeloid leukemia-derived cells have been reported to possess the ability to differentiate into dendritic cells (DC). MUTZ-3, a myeloid leukemia cell line, responds to GM-CSF, IL-4 and TNF-alpha, and acquires a phenotype similar to immature monocyte-derived DC (MoDC). In the present study, MUTZ-3-derived DC (MuDC) showed high level expression of HLA class II molecules, CD80 and CD86, and were able to function as potent antigen presenting cells as previously reported. Interestingly, MuDC maturation was induced by CD40- mediated stimulation, but not by LPS stimulation. We analyzed CCR1, CCR7 and Toll-like receptor (TLR) expressions in MuDC, and measured IL-10 and IL-12 production after maturation stimuli. Although MuDC expressed the mRNA for TLR4, a major component of the LPS receptor system, they did not show an enhanced level of CCR7 or cytokine production after LPS stimulation. In contrast, they responded to CD40 stimulation, which resulted in increased levels of CD83, CD86 and CCR7. Moreover, while LPS- stimulated MoDC could potently stimulate NK cells in a DC-NK cell co-culture, LPS-stimulated MuDC failed to stimulate primary NK cells. Taken together, our findings suggest that, although MuDC express TLR4, unlike TNF-alpha and IL-1beta, LPS does not stimulate MuDC to acquire mature phenotypes, and they may have impaired activity to initiate innate immune response.

B7-1 Antigen↗

Microsatellite alterations in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

A series of 20 hepatocellular carcinomas and 8 intrahepatic cholangiocarcinomas was screened from the Korean population for microsatellite alterations, including a loss of heterozygosity and replication errors using nine microsatellite markers containing several genes. The microsatellite results and our previous comparative genomic hybridization results of two tumors were compared at each locus, and the correlations between these and clinicopathologic variables were examined. The most characteristic findings were found at 13q. Replication errors were prevalent at D13S160 (13q21.2 approximately q31) and D13S292(13q12). The incidence of loss of heterozygosity, however, was higher at D13S153 (13q14.1 approximately q14.3) and D13S265(13q31 approximately q32). In contrast, there were higher deletion frequencies observed in hepatocellular carcinoma (HCC) and higher amplification frequencies observed in intrahepatic cholangiocarcinoma at 13q in our previous comparative genomic hybridization (CGH) study. Higher frequencies of replication errors were observed at D16S408 (13q12 approximately q21) and D16S504(13q23 approximately q24) in the HCC. This study found that significant differences in the patterns of genetic instability of microsatellites were dependent on the chromosomal loci. It is believed that certain genes at altered CGH regions, which are relevant to the development and/or progression of these cancers, are activated by different mutation mechanisms.

Adult↗

The correspondence between the labeling patterns of antibody RT97, neurofilaments, microtubule associated protein 1B and tau varies with cell types and development stages of chicken retina.

The correspondence between the labeling patterns of antibody RT97, neurofilaments (NF-M and NF-H), microtubule associated protein 1B (MAP1B) and tau, were studied in the developing chicken. At embryonic day 3 (E3), intense RT97 immunoreactivity (IR) was found to be localized in cells in the region adjacent to the intraretinal space, which separates the inner and outer layers of the optic cup, and this was sustained at E8. However, this pattern changed dramatically at E12, as the intensities of RT97 IR increased in the inner retinal layer, while the outermost layers showed only weak IR. The adult stage retina showed RT97 IR within the nerve fibers of the ganglion cells, the processes of the amacrine cells and the photoreceptors. Additional immunostainings for NF-M, -H, MAP1B and tau showed that the observed changes in RT97 IRs were due to the different expressions of these proteins at different development stages.

Animals↗

Caveolin-3 expression during early chicken development.

Caveolin-3, a protein that is correlated with caveolae, is found in muscle cells, especially during their differentiation. Although the distribution of caveolin-3 has been studied in cases such as adult and late embryonic mammalians, the expression of caveolin-3 has not been clearly defined during chicken development. In this study, we detected intense caveolin-3 immunoreactivity (IR) as early as embryonic day 4 (E4), most of the signals were localized within the neural tube and myotome. While IRs in the brain occurred in radial glia at E6, these intensities were reduced to an almost undetectable level at E8. In the case of muscle cells, the exclusive localization of caveolin-3 in the cytoplasmic membrane was detected even at E11, much earlier than in mammalian muscle tissues. Although the caveolin-3 IR pattern was similar to that reported by previous studies, we found some interesting mismatches in the case of avian tissues. Although we are unable to explain caveolin-3 expression patterns in the early embryonic stages, this study could provide a basis for further study on the function of caveolin-3 in avian embryogenesis.

Animals↗

Ultramicroscopical immunolocalization of PAX6 in the adult chicken retina.

Cell type-specific PAX6 protein expression was examined in all retinal layers of the normal chicken retina. The most intense PAX6 immunostaining was found in the ganglion cell and inner nuclear layers, and in lower amounts in the optic nerve fiber, the inner plexiform and the photoreceptor layers. PAX6 immunostaining was variable in terms of its subcellular localization, even within one cell. PAX6 immunostaining was mainly localized in nuclear heterochromatin of the ganglion cell and inner nuclear layers whereas in the outer nuclear layer, PAX6 immunostaining was only observed in the intercellular space and the cytoplasm. In photoreceptors, the myoid portion of the inner segment showed PAX6 immunostaining, but the ellipsoid portion and the outer segment did not. The ultrastructural distribution pattern of PAX6 in the adult chicken retina suggests that normal expression of PAX6 is variable even in subcellular structures in the same cell type.

Animals↗

Molecular analysis of the accumulation of the transcripts of the large subunit gene of ribulose-1,5-bisphosphate carboxylase/oxygenase by light.

We previously reported that the rbcL transcript level was significantly increased by light signal [Lee and Sim (1995)]. To investigate whether or not the accumulation of rbcL mRNA by light signal is caused by an increase of transcription activity of the rbcL gene, runon transcription assays were performed The results indicated that the accumulation of rbcL mRNA is due to an increase in the transcriptional activity of the rbcL gene by light. An electrophoretic mobility shift assay (EMSA) was also carried out to elucidate the specific binding proteins that interact with the rbcL promoter region. As a result of EMSA, a plastid protein designated as the rbcL promoter binding (RLPB) protein factor was detected in the plastid extract of light-grown seedlings, but not in that of dark-adapted seedlings before harvesting. It was also ascertained in this study that the promoter core region for the RLPB protein factor to bind is between -3 and -32 nucleotide sequences from the transcription initiation site of the rbcL gene. These results suggest that the stimulation of rbcL transcription by light is, in part, due to the increase in binding of the RLPB protein factor to the rbcL promoter.

DNA-Binding Proteins↗

The clinical features of Behcet's disease in Yongdong districts: analysis of a cohort followed from 1997 to 2001.

This study was undertaken to evaluate the clinical features of a cohort of Behcet's disease (BD) followed up from January 1997 to July 2001 in Yongdong districts in Korea, and to compare the results with the literature. Overall features of clinical manifestations were similar to those described in the literature. However, the frequency of gastrointestinal (GI) ulcerations was much higher than those of other Korean studies. The Korean studies including ours revealed a lower frequency of vascular lesions and epididymitis compared with studies of other countries. The most common site and pattern of inflammatory arthritis were knees and monoarticular involvement, respectively. In addition, in most patients, the ocular lesions involved the posterior uveal tract, and the terminal ileum and cecum were the most common sites of GI involvement. Patients with ocular lesions or GI lesions showed a good prognosis during the follow-up. The HLA-B51 antigen was positive in 50.7% of patients, and it was more commonly found in patients with a familial BD.

Adult↗