Biomedical subjects

Hee Sung Kim

Publications and source records attributed to Hee Sung Kim.

10 recordsLinked to original sources

PubMed2004

DNA microarray analysis of the correlation between gene expression patterns and acquired resistance to 5-FU/cisplatin in gastric cancer.

The mechanisms of intrinsic and/or acquired anti-cancer drug resistance have been described in in vitro resistance models, but the clinical relevance has remained undefined. We undertook a prospective study to identify correlations between gene expression and clinical resistance to 5-FU/cisplatin. We compared expression profiles from gastric cancer endoscopic biopsy specimens obtained at a chemosensitive state (partial remission after 5-FU/cisplatin) with those obtained at a refractory state (disease progression), using Affymetrix oligonucleotide microarray technology (U133A). Using 119 discriminating probes and a cross-validation approach, we were able to correctly identify the chemo-responsiveness of 7 pairs of training samples and 1 independent test pair. These exploratory data demonstrate that the gene expression profiles differ between chemosensitive and refractory state gastric cancer biopsy samples.

Adult↗

PubMed2004

CpG methylation of the ERalpha and ERbeta genes in breast cancer.

Aberrant methylation of promoter CpG islands is known to be responsible for the alteration and silencing of genes in cancer. The data presented here describes that the CpG methylations of ERalpha and ERbeta are found in breast cancer tissues, and methylation exerts a considerable effect on gene silencing, investigated by bisulfite genomic sequencing and reverse transcriptase polymerase chain reaction. Consequently, hypermethylation of the ERalpha and ERbeta genes was found in 66.0% and 50.0% of 50 breast cancers, respectively. Eleven of 50 samples (22.0%) did not show any methylation of either ERalpha or ERbeta, whereas 19 samples (38.0%) showed methylation of both ERalpha and ERbeta. The tumors that showed aberrant methylation of ERalpha and ERbeta did not express mRNA, compared with unmethylated cases (p < 0.01). The methylated case was negatively correlated with the expression of the ERalpha protein (p < 0.01). In addition, ERbeta methylation demonstrated significant associations with the lower level of Ki67 (9.36 +/- 2.43 versus 19.68 +/- 3.42, p = 0.02). Although the number of samples was relatively small, our results suggest that DNA methylation in ERalpha and ERbeta are present in breast cancer tissue, and that the methylation causes a significant effect on transcriptional silencing. Furthermore, the CpG methylation of the ERbeta gene seems to play a role in cell proliferation of breast cancer tissue.

Aged↗

PubMed2003

A size-exclusion HPLC method for the determination of sodium chondroitin sulfate in pharmaceutical preparations.

A size-exclusion HPLC method for the determination of sodium chondroitin sulfate (SCS) in pharmaceutical preparations has been developed and validated. The most important feature of this method compared with the previously reported assay methods was improved economical and determinative applications through direct analysis of SCS from pharmaceuticals. The linearity, precision, specificity, and accuracy of the method were established and validated. The intra- and inter-day precision was satisfactory with relative standard deviation lower than 1.0%. The recovery of SCS from multi-components pharmaceutical preparations were from 93.38 to 100.46%. Comparing our HPLC assay results with classical spectrophotometric methods, the developed method was considerably easy, simple and reproducible. As a result, the present method was supposed to be successfully applied to the assay of SCS for the routine quality control in pharmaceutical preparations.

Chondroitin Sulfates↗

PubMed2003

Tumour suppressor gene expression correlates with gastric cancer prognosis.

The loss of tumour suppressor genes (TSGs) is a key event in many human cancers, including gastric carcinoma. Many TSG candidates have been studied, but their roles in gastric carcinogenesis remain unclear. To clarify the clinical significance of TSG expression in gastric carcinoma, the expression of various TSG candidates (p53, E-cadherin, FHIT, smad4, rb, VHL, PTEN, MGMT, p16, and KAI1), as well as other proteins (bcl-2, MUC1, MUC2, MUC5AC, MUC6, CEA, CD44, beta-catenin, C-erbB2, and cyclin B2), was evaluated immunohistochemically in 329 consecutive gastric carcinomas using the tissue array method. The overexpression of p53 and MUC1 (p < 0.01) and the loss of expression of smad4 (p = 0.04), FHIT (p = 0.03), MGMT (p = 0.01), E-cadherin, KAI1, and PTEN (p < 0.01) were found to be significantly associated with poor gastric carcinoma prognosis. Seven out of eight survival-associated proteins were found to be protein products of TSGs. The gastric carcinomas were divided into five groups according to the grade of alteration in TSG expression. No TSG expression loss was found in 32 cases (TSG1). One TSG loss was found in 47 cases (TSG2), two in 67 cases (TSG3), three or four in 64 cases (TSG4), and five, six, or seven in 38 cases (TSG5). The grade of TSG expression was confirmed to be significantly associated with WHO classification (p = 0.04), pTNM stage, lymphatic invasion, and patient survival (p < 0.01 for the latter three). By multivariate analysis, the grade of TSG expression was found to be significantly and independently associated with patient survival (p < 0.01). In conclusion, the findings of this study suggest that the cumulative loss of TSG expression in gastric carcinoma is important in determining patient survival.

Acid Anhydride Hydrolases↗

PubMed2003

Epstein-Barr virus and microsatellite instability in gastric carcinogenesis.

Little information is available concerning the relationship between transforming viruses and microsatellite instability (MSI). We evaluated Epstein-Barr virus (EBV) using in situ hybridization for EBV-encoded small RNAs and MSI using the polymerase chain reaction in surgically resected gastric cancer. The study subjects included 298 consecutive cases of solitary gastric carcinoma, 63 gastric carcinomas in young patients (</=30 years old), 64 cases of gastric cancer coexisting with gastric adenoma in a single lesion, 26 cases of gastric remnant cancer, and 98 carcinomas from 47 patients with synchronous multiple gastric carcinomas. There was no overlapping case among these subsets of gastric cancer. None of these 549 gastric carcinomas demonstrated both EBV positivity and MSI positivity. Furthermore, the EBV-positive and the MSI-positive cases showed a mutually negative association in all subsets of gastric cancer. 5.7% of consecutive solitary gastric carcinomas were EBV positive, and 9.7% were MSI positive. EBV was positive in 1.6% of gastric cancers coexisting with gastric adenoma, 12.7% of younger patients, 28.6% of gastric remnant cancer with previous gastrectomy for benign disease, and 14.5% of synchronous cancers without adenoma. MSI was found in 1.6% of younger patients, 18.8% of gastric cancers coexisting with gastric adenoma, 25% of gastric remnant cancer with previous gastrectomy for gastric cancer, and in 53.3% of synchronous gastric carcinomas having gastric adenoma remote from the cancer. In conclusion, the carcinogenic roles of EBV and MSI may be different in terms of each subset of gastric cancer. EBV and MSI may contribute to functionally equivalent pathways in gastric carcinogenesis.

Adenoma↗

PubMed2002

Distinct clinical features and outcomes of gastric cancers with microsatellite instability.

Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair deficiency that is one of the pathways of gastric carcinogenesis. Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To determine the correlation between MSI status and clinical features, we analyzed 327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker. Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype, cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype. The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated immunohistochemically using the tissue array method. The MSI+ phenotype was found in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were significantly associated with older age, antral location, Borrmann's gross Type II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM stage (P <.05). By multivariate logistic regression, MSI+ gastric cancers had a lower prevalence of lymph node metastasis independent of tumor invasion (P <.001). MSI+ gastric cancers displayed frequent frameshift mutations of transforming growth factor-beta type II receptor (90.3%), BAX (61.3%), hMSH3 (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31) expressions. The MSI+ phenotype correlated with patient survival in advanced gastric carcinoma (P =.046). In conclusion, MSI+ phenotype in gastric cancers was found to have distinct clinicopathologic characteristics and to be predictive of a favorable outcome in advanced carcinoma.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Epstein-Barr virus, p53 protein, and microsatellite instability in the adenoma-carcinoma sequence of the stomach.

To elucidate the adenoma-carcinoma sequence in the stomach, we investigated Epstein-Barr virus (EBV) incorporation, p53 overexpression, and microsatellite instability (MSI) in gastric adenomas and carcinomas. The study involved 66 cases of gastric carcinomas within or adjacent to adenomas (adenoma-carcinoma cases), 81 cases of simple adenomas (without carcinoma), and 306 de novo carcinomas (without adenoma focus). EBV incorporation was revealed in 1 (1.5%) of the adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding carcinomas (kappa = 0.63, P = 0.00). MSI was positive in 12.3% (8 of 65) of the adenomas in the adenoma-carcinoma cases and in 18.8% (12 of 64) of the corresponding carcinomas (kappa = 0.77, P = 0.00). In conclusion, EBV incorporation is not possibly associated with the gastric adenoma-carcinoma sequence, whereas the gastric adenoma-carcinoma sequence seems to be supported in terms of p53 overexpression or MSI. The transcriptional activation of EBV may occur relatively late (after the adenoma stage) in the gastric adenoma-carcinoma sequence.

Adenoma↗

PubMed2002

Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary.

The expressions of cytokeratin (CK) 7 and 20 have been studied in various primary and metastatic carcinomas, and their determination may help distinguish the site of origin of metastatic carcinomas. However, little is known about the factors that determine variations in their expression patterns in primary gastric and colorectal carcinomas. We investigated the expressions of CK7 and CK20 in 289 cases of gastric carcinoma and 225 cases of colorectal carcinoma using a tissue microarray. To evaluate CK7 and CK20 expression patterns of ovarian metastases from gastric or colorectal carcinomas, 54 cases of metastatic carcinomas to the ovary were examined. It was found that 71% (207 of 289) of the gastric carcinomas stained positively for CK7, whereas only 9% (21 of 225) of the colorectal carcinomas proved to be CK7 positive, and that 41% (117 of 289) of the gastric carcinomas and 73% (165 of 225) of the colorectal carcinomas were CK20 positive. The proportion of CK7+/CK20- was highest in the gastric carcinomas at 46% (132 of 289), and was independent of the histologic classification of Lauren (46% of the intestinal type, 45% of the diffuse type). The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histologic grade and location of the tumor. CK7-/CK20+ had the greatest proportion (68%) in colorectal carcinomas, and this was dependent on the tumor's histologic grade (75% of low-grade versus 52% of high-grade) and location (46% of right-sided versus 76% of left-sided). Moreover, 42% (18 of 43) of gastric carcinomas metastatic to the ovary were CK7+/CK20-, whereas 19% (8 of 43) were CK7-/CK20+. All colorectal cancers metastatic to the ovary were CK7-/CK20+, except 1 case that was CK7-/CK20-. In conclusion, the CK7 and CK20 expression patterns in primary gastric carcinomas vary considerably, and those in colorectal carcinomas are associated with histologic grade and tumor location. The CK7-/CK20+ expression pattern is specific for metastatic colorectal carcinomas to the ovary, but has low predictability for colorectal origin in metastatic ovarian carcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Expression of beta-catenin and E-cadherin in the adenoma-carcinoma sequence of the stomach.

beta-catenin plays an important role in the Wnt signaling pathway and the E-cadherin-catenin complex plays a critical role in the maintenance of normal tissue architecture. An alteration of any of the components of the E-cadherin-catenin complex is believed to result in the loss of cell-cell adhesion and to contribute to carcinogenesis. In order to evaluate such alterations in the gastric adenoma-carcinoma sequence, the abnormal expression of beta-catenin and E-cadherin and the mutations of beta-catenin exon 3 were studied. In the case of beta-catenin, nuclear immunoreactivity was noted in 17 (11.3%) out of 150 adenomas and 19 (17.1%) out of 111 carcinomas (p = 0.18). Among 51 gastric adenomas, no mutations were detected by direct sequencing analysis. The loss of membranous expression of both beta-catenin and E-cadherin linearly increased with tumor progression, however, beta-catenin loss was more frequent than E-cadherin. Our results show that the nuclear expression and membranous loss of beta-catenin without exon 3 mutation is relatively frequent in gastric adenomas. These suggest that alteration of other genes is primarily responsible for the nuclear translocation of beta-catenin in gastric adenomas.

Adenoma↗

PubMedDate not supplied

Clinical analysis of right anterior segmentectomy for hepatic malignancy.

BACKGROUND/AIMS: Combined resection of segments 5 and 8, or right anterior segmentectomy, is one of the most difficult hepatic resections because of the danger of bleeding from the two major hepatic veins, the middle and right hepatic veins, during hepatectomy. We describe here the operative procedure and clinical analysis of right anterior segmentectomy in 35 patients with hepatic malignancy. METHODOLOGY: Between March 1993 and December 2004, 35 patients underwent right anterior segmentectomy for hepatic malignancy. The technique used was based on the extraglissonian approach and parenchymal Kelly crushing, during which the two major hepatic veins were almost fully exposed. RESULTS: Thirty-three patients had hepatocellular carcinoma, one had peripheral cholangiocellular carcinoma, and one had primary hepatic sarcoma. The mean operation time was 331 +/- 73 minutes and the mean transfusion of packed RBC was 1.09 +/- 1.57 pints. There was one in-hospital death as a result of sepsis and hepatic failure. The cumulative 1-, 2- and 5-year survival rates were 94%, 72% and 62%, respectively. CONCLUSIONS: For surgeons who accurately know the anatomy of the liver, this procedure is safe and suitable in selected patients with hepatic malignancies and may increase the survival rate.

Carcinoma, Hepatocellular↗