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Woo-Ho Kim

Publications and source records attributed to Woo-Ho Kim.

11 recordsLinked to original sources
PubMed2006

Analysis of long-term survivors after surgical resection for pancreatic cancer.

OBJECTIVES: The purpose of this study was to determine the outcome of surgical resection for pancreatic cancer and to characterize the clinicopathologic features of actual long-term survivors. METHODS: Of the 789 pancreatic cancer patients, we retrospectively analyzed 242 patients who underwent an operation between 1985 and 1999. Surgical resection with curative intent was performed in 123 patients. We analyzed the overall results of surgical treatment, compared the clinicopathologic features between long-term and short-term survivors, and reevaluated the histological slides of the long-term survivors. RESULTS: Median survival and cumulative 5-year survival rate after surgical resection were 14.8 months and 12.1%. Tumor size, American Joint Committee on Cancer stage, resection margin involvement, and lymph node metastases were the significant prognostic factors. Eleven patients survived for more than 5 years. Some patients with poor prognostic factors such as lymph node metastasis and big tumor size survived for more than 5 years. Histological reevaluation in the long-term survivors revealed 4 cases of variant adenocarcinoma (anaplastic carcinoma, mucinous noncystic adenocarcinoma [n = 2], and undifferentiated carcinoma). CONCLUSIONS: Active surgical resection should be attempted even in patients with poor prognostic factors. As there were various types of pathology among the long-term survivors, typical ductal adenocarcinoma of the pancreas might have a poorer survival rate.

Carcinoma, Pancreatic Ductal↗
PubMed2005

Prognostic implication of isolated tumor cells and micrometastases in regional lymph nodes of gastric cancer.

AIM: To determine the prognostic significance of isolated tumor cells (ITCs) and lymph node micrometastases in gastric cancer. METHODS: Hematoxylin and eosin-stained slides of lymph node dissections of 632 consecutive gastric cancers were reviewed. Cytokeratin immunostaining was performed in 280 node-negative cases and 5 cases indefinite for lymph node metastases. Lymph node metastases were divided into ITCs, micrometastases, or macrometastases, according to the sizes of tumor deposits in largest dimension. ITCs were further classified into four groups according to metastasis pattern. RESULTS: Lymph node metastases were identified by immunostaining in 58 of 280 node-negative cases (20.7%) and were not significantly associated with patient survival (P = 0.3460). After cytokeratin immunostaining, 196 cases were classified as pN1, which consisted of 20 cases with micrometastases detected by immunostaining (pN1mi(i+)), 34 cases with only micrometastases (pN1mi), and 142 cases with pN1 with one or more macrometastases (pN1). Cases with pN1mi and pN1mi(i+) had a significantly better prognosis than the cases with pN1 (P = 0.0037). ITCs were found in 38 of these 58 cases, and could be divided into four groups: 12 cases with only a single cell pattern, 7 cases with multiple individual cells, 5 cases with single small cluster, and 14 cases with multiple small clusters. Among these four groups, cases with ITCs of multiple individual cell pattern showed the worst survival (median survival: 28 mo, P<0.0001). CONCLUSION: Both size and pattern of lymph node metastases can give prognostic information on the survival of gastric cancer patients.

Humans↗
PubMed2004

Lymph node metastasis in early gastric cancer with submucosal invasion: feasibility of minimally invasive surgery.

AIM: To explore the feasibility of performing minimally invasive surgery (MIS) on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS: A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995. Besides investigating many clinicopathological features such as tumor size, gross appearance, and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS: The rate of lymph node metastasis in cases where the depth of invasion was <500 microm, 500-2000 microm, or >2000 microm was 9% (2/23), 19% (7/36), and 33% (15/46), respectively (P<0.05). In univariate analysis, no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age, sex, tumor location, gross appearance, tumor differentiation, Lauren's classification, and lymphatic invasion. In multivariate analysis, tumor size (>4 cm vs <=2 cm, odds ratio = 4.80, P = 0.04) and depth of invasion (>2000 microm vs <=500 microm, odds ratio = 6.81, P = 0.02) were significantly correlated with lymph node metastasis. Combining the depth and size in cases where the depth of invasion was less than 500 microm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm. In cases where the tumor size was less than 2 cm, lymph node metastasis was found only where the depth of tumor invasion was more than 2000 microm. CONCLUSION: MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 microm in depth.

Adult↗
PubMed2004

Aberrant methylation of integrin alpha4 gene in human gastric cancer cells.

Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been explored. In the present study, we found that the integrin alpha4 expression is lost in human gastric cancer cell lines and that this is recovered by treatment with DNA methyltransferase inhibitor, implying transcriptional silencing by DNA methylation. Methylation-specific PCR (MSP) and bisulfite genomic DNA sequencing demonstrated the CpG methylation-dependent silencing of integrin alpha4 expression in eight of nine (88.8%) gastric cancer cell lines and in 84.7% of 46 primary tumors. We also investigated whether the restoration of integrin alpha4 in integrin alpha4-inactivated cells affects their ability to invade extracellular matrix, using matrigel assays. Interestingly, integrin alpha4-stable transfectants had markedly less invasive ability than the parental cells. Taken together, these results suggest that the transcriptional repression of the integrin alpha4 gene is caused by aberrant DNA methylation, and that this may play an important role in human gastric carcinogenesis.

Cell Line, Tumor↗
PubMed2004

Synergistic induction of in vivo angiogenesis by the combination of insulin-like growth factor-II and epidermal growth factor.

Tumor growth is accelerated by induction of angiogenesis regulated by many cytokines and growth factors. In a tumor mass, various angiogenic factors and their receptors are simultaneously expressed and the overlapped expressions of various factors may contribute to the aggressive growth of tumor. However, the possible combined effect and mechanism of growth factors involved in angiogenesis are still under investigated. Insulin-like growth factor-II (IGF-II) has been identified as an angiogenic factor and highly expressed in solid tumors. Here we demonstrated that another angiogenic factor, epidermal growth factor (EGF), synergistically induced the angiogenic activity when co-treated with IGF-II in vivo. We performed mouse Matrigel plug assay. Cotreatment of IGF-II and EGF resulted in a significant induction of functional new vessels in mouse Matrigel plug more than additive amount of vessels induced by each growth factor. However, synergism of these two factors was not found in in vitro angiogenic assays, i.e., in migration and proliferation assays. The metalloproteinase-2 (MMP-2) protein level was enhanced by co-treatment of IGF-II and EGF, similar to that of individual treatment of them or PMA or bFGF. EGF down-regulated hypoxia-induced IGF-II binding protein-3 (IGFBP-3), which may contribute to the enhancement of free IGF-II accessibility to its receptors in vivo. Moreover, the combination of IGF-II with EGF significantly induced bFGF mRNA level, a potent angiogenic molecule, which may also contribute to synergistic effect in vivo. These results suggest that IGF-II and EGF may synergistically cooperate to induce angiogenesis in vivo by indirect mechanisms, i.e., synergistic induction of another angiogenic factor and modulation of IGF-II's bioavailability.

Angiogenesis Inducing Agents↗
PubMed2003

Robust microsatellite instability (MSI) analysis by denaturing high-performance liquid chromatography (DHPLC).

Microsatellite instability (MSI) plays an important biological role in various types of cancers, and especially in colorectal cancers. This study aimed to develop a simple, efficient, new method for robust MSI analysis. DNA was extracted from 175 (105 proximal colon and 70 distal colorectal) cancer samples and matched normal tissues, and five Bethesda microsatellite markers (BAT-25, BAT-26, D5S346, D2S123, and D17S250) were examined for MSI by denaturing high-performance liquid chromatography (DHPLC) analysis at a temperature of 50 degrees C and a flow rate of 0.9 ml/min. It took just 9 min per PCR product to determine MSI or microsatellite stability (MSS) using the new protocol. The DHPLC results were confirmed with conventional gel-based electrophoresis and capillary-based sequencing method. Of 175 samples, 45 (26%) showed high microsatellite instability (MSI-H), 12 (7%) showed low microsatellite instability (MSI-L), and 118 (67%) showed MSS. All MSI samples were deletion mutants and all 12 MSI-L cases had MSI in dinucleotide markers (D5S346, D2S123, and D17S250). MSI was significantly associated with proximal colon cancers ( p<0.0001), as previously reported. The MSI-H tumors were also associated with tumor node metastasis (TNM) I/II stages ( p=0.05) and high-grade tumors ( p<0.01). Here, we propose a DHPLC-based method as an alternative for MSI analysis.

Chemistry Techniques, Analytical↗
PubMed2003

Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers.

PURPOSE: This study was designed to investigate the frequency of mutations in DNA mismatch repair genes in sporadic colorectal cancers. METHODS: Genomic DNAs procured from paraffin blocks of the pathologic specimens from 230 consecutive patients with colorectal cancer were examined for their microsatellite instability status using a mononucleotide microsatellite marker, BAT-26, and also evaluated expressions of hMLH1, hMSH2, and hMSH6 proteins by immunohistochemical staining. Any of these 230 patients did not have family histories of hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, colorectal cancer, or hereditary nonpolyposis colorectal-related cancers, such as endometrial, small bowel, and ureteral and renal pelvic cancers. When microsatellite instability was positive, mutations in the simple repeated sequences of TGF-betaRII, BAX, IGF IIR, hMSH3, and hMSH6 genes were examined. In microsatellite instability-positive or staining-negative cases, polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing detected mutations of hMLH1, hMSH2, and hMSH6 genes. If mutations were found in tumor tissue samples, we tested for a germline mutation with a microdissected corresponding normal tissue. RESULTS: Among 230 cases of sporadic colorectal cancer, 21 (9.1 percent) manifested microsatellite instability. In the immunohistochemical staining, 20 (8.6 percent) showed loss of expressions. All 20 staining-negative cases were microsatellite instability-positive. Only 1 of 21 (4.8 percent) microsatellite instability-positive cases showed intact staining for three proteins. The frame-shift mutations of the simple repetitive sequences were found in 17 cases (81.0 percent) in TGF-betaRII, 11 (52.4 percent) in BAX, 5 (23.8 percent) in IGF IIR, 7 (33.3 percent) in hMSH3, and 8 (38.1 percent) in hMSH6 genes. Germline mutation was observed in only one case, which accounts for 4.8 percent among positive microsatellite instability and 0.4 percent of total patients, and was found in hMSH2. Five somatic mutations (2 in hMLH1, 2 in hMSH2, and 1 in hMSH6) also were found. CONCLUSION: The results indicated that a germline mutation of DNA mismatch repair gene was a rare event in sporadic colorectal cancers.

Base Pair Mismatch↗
PubMed2003

Prognostic significance of p53, nm23, PCNA and c-erbB-2 in gastric cancer.

BACKGROUND: Although the TNM stage is the most important prognostic factor for gastric cancer, there is a need for new prognostic and predictive factors, because the prognosis varies among patients of the same stage. The purpose of this study was to clarify the relationship of p53, nm23, proliferating cell nuclear antigen (PCNA) and c-erbB-2 with the clinicopathological parameters and the survival results. METHODS: For 841 patients who had undergone gastrectomy for gastric cancer at Seoul National University Hospital from July 1996 to December 1997, the expression levels of p53, nm23, PCNA and c-erbB-2 in gastric cancer tissues were examined immunohistochemically. Also, the clinicopathological parameters such as gender, age, operation type, TNM stage and size of the tumor, histology and Lauren classification were analyzed retrospectively. RESULTS: There were 568 males and 273 females (2.07:1) with a mean age of 56 years (range:25-82 years). The percentages of positive expression of p53, nm23 and c-erbB-2 were 43, 74 and 17%, respectively; 59% of tumors expressed PCNA index > or =50. p53 expression was associated with age, gender, tumor size, histology, Lauren classification, stage, nm23 expression, PCNA index >or =50 and c-erbB-2 expression. nm23 expression was associated with age, tumor size, Borrmann type, histology, Lauren classification and stage. PCNA index > or =50 was associated with age, gender, tumor size, Borrmann type, histology, Lauren classification and c-erbB-2 expression. c-erbB-2 expression was associated with gender, Borrmann type, histology and Lauren classification. p53 and nm23 were related with poor prognosis in univariate analysis. nm23 was related with poor prognosis of stage III and diffuse-type gastric cancer in univariate subgroup analysis. However, in a multivariate study, these prognostic impacts were not maintained. CONCLUSION: The expression of p53 and nm23 seems to be related with poor prognosis of gastric cancer patients who have undergone gastrectomy. However, the prognostic significance was not revealed by a multivariate analysis.

Adult↗
PubMed2002

Establishment and characterization of four human pancreatic carcinoma cell lines. Genetic alterations in the TGFBR2 gene but not in the MADH4 gene.

We characterized four pancreatic carcinoma cell lines (designated SNU-213, SNU-324, SNU-410, and SNU-494) established from histopathologically varied primary or liver metastatic tumor samples of Korean patients. Three cell lines grew as adherent monolayers and one as adherent and floating cell clumps. All lines had: (1) relatively high viability; (2) an absence of mycoplasma or bacterial contamination; (3) genetic heterogeneity as assessed by DNA-fingerprinting analysis; (4) an absence of MADH4 mutation. Among the lines, three lines had mutations in codon 12 in K- ras, two lines harbored p53 mutations within the DNA-binding domain; two lines had homozygous deletions in both p16 and p15 genes; and one line had a missense mutation. Two lines (SNU-324 and SNU-410) had genetic alterations in the TGFBR2 gene: the SNU-324 line had a -1-bp or +1-bp mutation in 10-bp polydeoxyadenine repeat tracts; the SNU-410 line had a genomic deletion in this gene. Mutation analysis of mismatch repair genes demonstrated that SNU-324 has two heterozygous missense mutations in different exons of the hMLH1 gene. In addition, this line showed microsatellite instability and harbored frameshift mutations in simple repeated sequences of the coding regions of the TGFBR2, BAX, and hMSH3 genes. These defects of microsatellite instability and mismatch repair genes suggest the possibility of a new mutator phenotype for pancreatic carcinogenesis. These cell lines should be very useful for studying the biology of pancreatic carcinoma, particularly those related to mutator phenotype and genetic alterations in the TGFBR2 gene.

Base Pair Mismatch↗
PubMed1999

Establishment and characterization of four human hepatocellular carcinoma cell lines containing hepatitis B virus DNA.

AIM:To investigate the characteristics of newly established four hepatocellular carcinoma cell lines (SNU-739, SNU-761, SNU-878 and SNU-886) from Korean hepatocellular cancer patients.METHODS:Morphologic and genetic studies were done.RESULTS:All four lines grew as a monolayer with an adherent pattern, and their doubling times ranged from 20 to 29 hours. The viability rate was relatively high (88%-94%).Neither mycoplasmal nor bacterial contamination was present.The lines showed different patterns in fingerprinting analysis. The hepatitis B virus (HBV) DNA was integrated in the genomes of all four lines, and in all of them HBx,HBc and HBs transcripts were detected by reverse transcriptase-PCR methods. Among the three cell lines used as control (Hep 3B, SK Hep1 and Hep G2),only Hep 3B showed HBx expression, and this line was used as a HBV integrated control.The RNA of albumin was detected in three lines (SNU-761, SNU-878 and SNU-886), that of transferrin in two lines (SNU-878, SNU-886), and that of IGF-II was detected in none of the cell lines.CONCLUSION:These well characterized cell lines may be very useful for studying the biology of hepatocellular carcinoma in association with the hepatitis Bvirus.

Journal Article↗