Biomedical subjects

Jin Cheon Kim

Publications and source records attributed to Jin Cheon Kim.

25 records · Page 2Linked to original sources

PubMed2002

A novel telomere elongation in an adriamycin-resistant stomach cancer cell line with decreased telomerase activity.

Actively dividing cells show progressive loss of telomeric DNA during successive rounds of replication due to end-replication problem. Telomere shortening has been proposed as a regulatory mechanism that controls the replicative capacity of primary cells before undergoing cellular senescence. In immortal cells including cancer, cellular senescence can be overcome by reactivation of telomerase or by a telomerase-independent mechanism for lengthening telomeres. In this work, we present a novel example of telomere elongation mechanism in a human stomach adenocarcinoma cell line which was selected for resistance to adriamycin. The resistant cell line (MKN/ADR) had long terminal restriction fragments (TRFs) of up to approximately 50 kb, while its parent cell line (MKN-45) had the TRFs, consisting of a smear extending from approximately 4 to approximately 25 kb. The very large TRFs in MKN/ADR cell line were proven to be telomeric by digestion with the exonuclease Bal31. When telomerase activity was examined using the PCR-based telomeric repeat amplification protocol (TRAP) assay, MKN/ADR cell line showed reduced activity to about 10% of that in MKN-45 cell line. The correlation between reduced telomerase activity and mRNA expression of telomerase subunits in MKN/ADR cell line was assessed by the reverse transcriptase-PCR analysis. The level of human telomerase reverse transcriptase (hTERT) mRNA was lower in MKN/ADR cell line than in MKN-45 cell line. This observation correlates with the finding that telomerase activity is reduced about 10-fold in MKN/ADR cell line. Reverse transcriptase-PCR analysis also revealed a close correlation between telomerase-associated protein (TP1) mRNA expression and telomerase activity in MKN/ADR cell line. In contrast, expression levels of human telomerase RNA (hTR) were identical in both MKN/ADR and MKN-45 cell lines. Taken together, these data suggest that telomeres in MKN/ADR cell line may be regulated through a novel mechanism other than telomerase. Although the basis for telomere elongation mechanism in MKN/ADR cell line is not yet understood, the occurrence of alternative mechanism for telomere elongation in drug-resistant cancer cells may have an important implication for use of telomerase inhibitors in human cancer treatment.

Adenocarcinoma↗

PubMed2002

Comparison of clinicopathologic characteristics and genetic alterations between microsatellite instability-positive and microsatellite instability-negative sporadic colorectal carcinomas in patients younger than 40 years old.

PURPOSE: Many studies have demonstrated that sporadic microsatellite instability-positive colorectal cancers share several clinicopathologic features with hereditary nonpolyposis colorectal cancers, including right-sided location, young age of onset, characteristic histomorphologic features, and a good prognosis. The aim of this study was to define distinct clinicopathologic features of sporadic microsatellite instability-positive colorectal cancers and to compare genotypic characteristics between microsatellite instability-positive and microsatellite instability-negative colorectal cancers in a young group. METHODS: We analyzed 61 cases of young patients (<40 years old) with colorectal cancers for microsatellite instability at five mononucleotide and three dinucleotide repeats, loss of heterozygosity at APC and DCC, and K-ras and p53 mutations. Microsatellite instability status was correlated with molecular genetic factors and clinicopathologic parameters. RESULTS: Microsatellite instability positivity was detected in 19 (31.1 percent) of 61 cases. Allelic alterations in TGFbetaRII, BAX, and IGFIIR were observed exclusively in microsatellite instability-positive tumors (63.1, 26.3, and 26.3 percent, respectively). Microsatellite instability-positive tumors exhibited a lower frequency of the p53 mutation (10.5 percent) than microsatellite instability-negative tumors (47.6 percent; P < 0.05). However, microsatellite instability status was not associated with APC or DCC allelic deletion or with the K-ras mutation. Microsatellite instability-positive colorectal cancers exhibited a proclivity toward proximal location, expansive growth pattern, and large tumor size (P < 0.05). Microsatellite instability-positive colorectal cancers had lower preoperative serum carcinoembryonic antigen levels (P < 0.05), a less advanced stage at presentation (P < 0.05), and a tendency toward better prognosis (P = 0.051) than microsatellite instability-negative colorectal cancers. However, there was no difference between microsatellite instability-positive and microsatellite instability-negative colorectal cancers regarding gross features, tumor grade, and extracellular mucin production. CONCLUSION: These results suggest that sporadic microsatellite instability-positive colorectal cancers in young patients have different histomorphologic features from microsatellite instability-negative colorectal cancers and hereditary nonpolyposis colorectal cancers, some overlap of genetic alterations on multistep carcinogenesis with microsatellite instability-negative colorectal cancers, and a tendency for better prognosis.

Adult↗

PubMed2002

Epstein-barr virus-positive gastric carcinoma demonstrates frequent aberrant methylation of multiple genes and constitutes CpG island methylator phenotype-positive gastric carcinoma.

CpG island methylation is an important mechanism for inactivating the genes involved in tumorigenesis. Gastric carcinoma (GC) is one of the tumors that exhibits a high frequency of aberrant CpG island methylation. There have been many reports suggesting a close link between Epstein-Barr virus (EBV) and the development of GC. However, little is known about the oncogenic mechanism of EBV in gastric carcinogenesis. Twenty-one cases of EBV-positive GC and 56 cases of EBV-negative GC were examined for aberrant DNA methylation of the CpG islands of 19 genes or loci and the differences in the methylation frequency between EBV-positive and -negative GCs were investigated to determine a role of aberrant methylation in EBV-related gastric carcinogenesis. The average number of methylated genes or loci was higher in EBV-positive GCs than in EBV-negative GCs (13.4 versus 7.8, respectively, P < 0.001). EBV-positive GCs showed methylation in at least 10 CpG islands (52.6% of the tested genes), whereas 62.5% of EBV-negative GCs showed methylation in <10 CpG islands. THBS1, APC, p16, 14-3-3 sigma, MINT1, and MINT25 were methylated at a frequency >90% in EBV-positive GCs. The methylation frequency difference in the respective CpG islands between EBV-positive and -negative GCs was statistically significant (P < 0.05). Among these genes or loci, the methylation frequency of p16 in the EBV-positive GCs was more than three times higher than in the EBV-negative GCs. The PTEN, RASSF1A, GSTP1, MGMT, and MINT2 were methylated in EBV-positive GCs at a frequency of more than three times that of the EBV-negative GCs. These results demonstrate a relationship between EBV and aberrant methylation in GC and suggest that aberrant methylation may be an important mechanism of EBV-related gastric carcinogenesis.

CpG Islands↗

PubMed2002

The role of colonoscopy in the diagnosis of appendicitis in patients with atypical presentations.

BACKGROUND: Acute appendicitis is one of the most common causes of acute abdomen. Despite recent advances in radiologic imaging, the diagnosis of acute appendicitis may be difficult on occasion. The aims of this study were to describe the colonoscopic features of appendicitis and to determine whether colonoscopy can be used as an adjunct for the diagnosis of appendicitis in patients with atypical presentations. METHODS: The colonoscopic findings in 21 patients (14 men, 7 women; average age 55 years) with a colonoscopic or histopathologic diagnosis of appendicitis were analyzed retrospectively. Colonoscopy was performed because diagnoses suggested by CT were other than acute appendicitis (11 patients), and/or the presenting clinical features were atypical for acute appendicitis with the duration of symptoms being 10 days or longer (17 patients). RESULTS: The colonoscopic diagnosis was acute appendicitis for all 21 patients. Seventeen underwent appendectomy, the diagnosis being verified in all cases. Of the 4 patients whose symptoms improved without appendectomy, 3 were considered to have acute appendicitis because pus was seen to drain from the appendiceal orifice at colonoscopy. A definite diagnosis could not be made in the remaining 1 patient. Therefore, the diagnosis of appendicitis was considered confirmed in 20 of 21 patients. Colonoscopic findings in these 20 patients included hyperemia (15) and bulging (18) at the appendiceal orifice area with surrounding mucosal edema (19), and drainage of pus from the appendiceal orifice (7). CONCLUSION: Colonoscopy may be useful in the diagnosis of appendicitis when the clinical presentation is atypical for appendicitis and/or imaging studies are nondiagnostic.

Abdomen, Acute↗

PubMed2002

Profile of methylated CpG sites of hMLH1 promoter in primary gastric carcinoma with microsatellite instability.

A recent study using colorectal cancer cell lines has identified methylation on a small region of hMLH1 promoter (-248 to -178 relative to the transcription start site) to be critical for gene silencing, but shown that methylation on a more upstream region is frequent in cell lines with hMLH1 expression. Because cultured cell lines have a higher degree of CpG methylation than primary tumors, we attempted to examine methylation profiles of CpG sites of hMLH1 promoter in primary gastric carcinomas with or without microsatellite instability (MSI). Seven cases with MSI and six cases without MSI were assessed for the methylation status of hMLH1 promoter by bisulfite-sequencing. All of the MSI-positive cases previously showed loss of hMLH1 expression and six cases displayed methylated alleles in methylation-specific PCR (MSP) for hMLH1. Sequencing analysis revealed that: (i) CpG sites were overall methylated in MSI-positive tumors with positive MSP results; (ii) a small region (-248-178) was almost invariably methylated in MSI-positive tumors; and (iii) the vast majority of CpG sites were unmethylated in MSI-negative tumors, including a more upstream region (proximal to -248). Our study suggests that methylation of a more upstream region observed in colon cancer cell lines may be an acquired change during cell line establishment and it was not identified in primary gastric carcinomas without MSI.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Reduced E-cadherin expression as a cause of distinctive signet-ring cell variant in colorectal carcinoma.

Colorectal signet-ring cell carcinoma (SRCC) is a rare type of adenocarcinoma and presents with distinctive clinicopathological features. This study was performed to assess the biological characteristics of colorectal SRCC regarding the E-cadherin expression. Seventeen patients with primary colorectal SRCC were identified and their clinicopathological characteristics were analyzed. The mean age of the 17 patients was 45.3 yr (14-68). Immunohistochemical staining of E-cadherin and beta-catenin were performed in ten colorectal SRCCs and in 30 ordinary colorectal adenocarcinomas as control. Primary colorectal SRCC occurred in 0.7% of 2,388 colorectal adenocarcinomas. Most patients had advanced stage tumor at surgery (stage III and IV, AJCC: 82%). Five-year survival rate was 16%. Peritoneal seeding was the most common recurrence pattern (41%) and liver metastasis was not identified. All SRCCs showed a markedly reduced or absent expression of E-cadherin on immunohistochemical staining, whereas seven (23.3%) of ordinary carcinomas showed reduced expression, thereby indicating a significant difference between the two groups (p<0.005). In immunohistochemical staining for beta-catenin, eight of ten SRCCs showed reduced membrane expression that did not attain statistical significance compared to ordinary adenocarcinomas. It is suggested that aberrant E-cadherin expression may explain the distinct clinicopathological features in primary colorectal SRCC.

Adolescent↗

PubMedDate not supplied

Significance of mismatch repair protein expression in the chemotherapeutic response of sporadic invasive ductal carcinoma of the breast.

The mismatch repair (MMR) gene plays a key role in the correction of DNA damage, and the loss of MMR has been implicated in resistance to a variety of chemotherapeutic drugs. The purpose of this study was to assess whether the reduced expression of hMLH1 and/or hMSH2 affects the chemotherapeutic responsiveness of sporadic invasive ductal carcinoma of the breast. Immunohistochemical studies were performed on 71 histologic specimens of breast cancer taken from the patients treated with surgery and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) chemotherapy for stage II or III primary breast cancer. Single-strand conformational polymorphism polymerase chain reaction (PCR-SSCP) and sequencing were carried out in 16 patients. A combined immunoreactivity score (hMLH1-IS and hMSH2-IS) was calculated by multiplying the staining grade by the intensity score. Positive expression (>4) of hMLH1-IS and hMSH2-IS were 57.7% and 60.6%, respectively, and complete losses of hMLH1 and hMSH2 were observed in 4.2% of patients. Of the patients with advanced cancer with lymph node metastasis, those having a low hMLH1-IS had a significantly higher failure rate with the CMF regimen than those having a high hMLH1-IS (p = 0.03). No significant difference was noted in chemotherapeutic response according to hMLH1 and hMSH2 expression in the CAF group. Both hMLH1-IS (p = 0.03) and progesterone receptor (PR) status (p = 0.03) were well correlated with CMF chemotherapy response in breast cancers with lymph node metastasis. Our study shows that a lack of hMLH1 expression may play a role in drug resistance, especially in the CMF group, and immunohistochemical assay for MMR protein can be used as a convenient tool for evaluating chemotherapeutic response in patients with breast cancer.

Adaptor Proteins, Signal Transducing↗