Biomedical subjects

W H Kim

Publications and source records attributed to W H Kim.

At least 127 records · Page 7Linked to original sources

PubMed1997

Preoperative evaluation of the curative resectability of gastric cancer by abdominal computed tomography and ultrasonography: a prospective comparison study.

OBJECTIVES: We compared the ability of preoperative abdominal computed tomography (CT) with that of preoperative abdominal ultrasonography (US) in predicting the extent of tumor growth and the curative resectability of gastric cancer. METHODS: Abdominal CT and US were done in 95 patients with gastric adeno-carcinoma. The radiologic findings were prospectively compared with surgical and pathologic findings. RESULTS: The sensitivities of abdominal CT and US in detecting the perigastric lymph node involvement were 26.6% and 20%, respectively. The sensitivity of abdominal CT in predicting the pancreatic invasion (60%) was better than that of abdominal US (20%). However, there were 6 false positive diagnosis of pancreatic invasion by abdominal CT; in contrast, there was no false positive diagnosis of pancreatic invasion by abdominal US. Of 95 patients who underwent surgical exploration, 14 were found to have unresectable tumors because of extragastric organ involvement and distant metastases. Abdominal CT falsely predicted 8 of 14 cases in which curative gastric resection was impossible as resectable. Moreover, abdominal CT falsely predicted 5 of 81 cases in which curative gastric resection was possible as unresectable. Abdominal US falsely predicted 12 of 14 cases in which curative surgery was impossible as resectable. CONCLUSION: Preoperative abdominal Ct and US did not accurately predict the tumor extent and the curative resectability of the gastric cancer. Especially, abdominal CT finding of pancreatic invasion by gastric cancer should not be a contraindication for surgical exploration.

Abdomen↗

PubMed1997

Genetic evidence for the multicentric origin of synchronous multiple gastric carcinoma.

Multiple gastric cancers, which constitute 4% to 10% of all gastric cancers, occur in older people and are associated with more extensive intestinal metaplasia. With regard to the genesis of multiple gastric cancers, multicentricity (independent origin) rather than multifocality (local or lateral spread of one cancer) has been the favored theory. Conventional morphologic study, however, has not been able to provide convincing evidence in support of multicentricity. The purpose of this study was to verify the multicentric origin of multiple gastric cancers at a genetic level. For this purpose, immunohistochemical and molecular techniques were used to define the mutation pattern of APC, MCC and p53 in multiple lesions of synchronous multiple gastric cancers. The study was based on a total of 30 gastric tumors from 13 patients, including 10 double tumors, 2 triple tumors, and 1 quadruple tumor. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53, and loss of heterozygosity was detected on the basis of polymerase chain reaction amplification of polymorphism in exon 10 of MCC and in exon 11 of APC. Twelve of 13 cases showed alteration in one or more genetic markers. Of these, three demonstrated a discordant mutation pattern of p53 in individual lesions, and another two revealed allelic loss of MCC in one lesion and p53 mutation in the other. In six other cases, only one lesion showed alteration of APC, MCC, or p53, and in the remaining case, one lesion carried p53 and MCC mutations and the other carried MCC loss of heterozygosity only. The results of this study showed discordance of the mutation pattern of APC, MCC, and p53 in individual lesions of multiple gastric cancers, providing genetic evidence for a multicentric origin of synchronous multiple gastric carcinomas. Collectively, these findings supported the theory of field cancerization in gastric carcinogenesis.

Adenocarcinoma↗

PubMed1996

Active peptides from the carboxyl-terminal globular domain of laminin alpha2 and Drosophila alpha chains.

The laminin alpha1 chain carboxyl-terminal globular domain (G domain) contains multiple biological activities. Recently, we identified five cell binding sequences from the G domain by screening with overlapping 12-mer peptides encompassing the entire domain. The structures of these five sequences in the alpha1 chain are conserved in the corresponding regions of the different laminin alpha chains. Here we characterize the adhesion activities of the corresponding peptide segments from both the mouse laminin alpha2 chain and Drosophila laminin alpha chain using peptide-coated plastic plates and peptide-conjugated Sepharose beads. Using several cell lines, the laminin alpha2 chain peptides showed cell attachment and/or spreading activities with cell type specificities. Cell spreading on MG-10 was inhibited by integrin antibodies. Four of the Drosophila laminin peptides showed cell attachment activities. These results suggest that biologically active regions in the G domain are conserved in the laminin alpha1 and alpha2 chains, and that these regions in laminin play an important role in cell surface receptor interactions.

Amino Acid Sequence↗

PubMed1996

Overexpression of the 67 kD laminin receptor correlates with the progression of gastric carcinoma.

This retrospective study was designed to investigate the relationship between overexpression of the 67 kD laminin receptor (67LR) using immunohistochemistry, and several clinicopathological parameters including overall survival in human gastric adenocarcinoma. We stained paraffin-embedded sections of 93 resected primary gastric adenocarcinomas using a polyclonal antibody specific for the 67LR as well as monoclonal antibodies for p53 protein, epidermal growth factor receptor, proliferating cell nuclear antigen, carcinoembryonic antigen and chromagranin. The results showed statistically significant correlations between overexpression of the 67LR and types of early or advanced gastric carcinoma (p < 0.001), depth of invasion (p < 0.001), WHO histopathologic classification (p < 0.001), stage (p = 0.001), expression of p53 protein (p = 0.019), expression of epidermal growth factor receptor (p < 0.001) and proliferating cell nuclear antigen labeling index (p = 0.002). A lower proportion of signet ring cells revealed a higher percentage of overexpression of 67LR in both early (p < 0.002) and advanced (p < 0.001) gastric carcinomas. Intestinal type adenocarcinoma (according to Lauren's classification) revealed a higher percentage of overexpression of the 67LR than the diffuse type in both early (p = 0.057) and advanced (p < 0.001) gastric carcinomas. The correlations between overexpression of the 67LR and lymph node metastasis were statistically significant (p < 0.07). Although the overexpression of the 67LR tended to correlate with lower survival rates, the correlation was not statistically significant due to the limited sample size. Our data revealed that overexpression of the 67LR is correlated with the progression of gastric carcinoma. The expression of the 67LR may be important as one of the steps which determines invasiveness during the progression of cancer.

Adenocarcinoma↗

PubMed1996

Primary malignant lymphomas of the stomach. Pathological and clinical analyses of 38 resected cases.

The stomach is the most frequent site of extranodal lymphoma and primary gastric lymphoma might be distinguished from the nodal lymphoma by its different pathogenesis and prognosis. Based on the Isaacson's classification, clinico-pathologic reviews of 38 resected primary gastric lymphomas were done. Immunohistochemical stainings for PCNA, B and T cell markers, bcl-2 and p53 were performed. Eighteen were of low grade and 20 were of high grade. There were significant differences between low and high graders in the aspect of the size, depth of lesion, gross type, immunophenotype, staining intensity for PCNA, expressions of bcl-2 and p53. The overall 2-year survival rate was 85.3%. Factors with prognostic significance on survival by univariate analyses included immunophenotype, histologic grading and PCNA staining pattern. After multivariate analyses, immunophenotype proved to be a significant factor. We think that the histologic grading by Isaacson's classification and the immunohistochemical stainings performed were useful in pathologic and/or clinical aspects. The excellent survival rate in this study was partly due to the selection of resectable cases. However, earlier diagnosis and appropriate treatment might have contributed to the improved prognosis of gastric lymphoma in recent years.

Adult↗

PubMed1995

Identification of cell binding sites in the laminin alpha 1 chain carboxyl-terminal globular domain by systematic screening of synthetic peptides.

The laminin alpha 1 chain carboxyl-terminal globular domain has been identified as a site of multiple biological activities. Using a systematic screening for cell binding sites with 113 overlapping synthetic peptide beads that covered this domain, we found 19 potential active sequences. Corresponding synthetic peptides were evaluated for direct cell attachment, spreading, and inhibition of cell spreading to a laminin-1 substrate using several cell lines. Five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed cell attachment activities with cell-type specificities. Cell spreading on AG-10 was inhibited by beta 1 and alpha 6 integrin antibodies and on AG-32 was inhibited by beta 1, alpha 2, and alpha 6 integrin antibodies. In contrast, cell adhesion and spreading on peptide AG-73 were not inhibited by these antibodies. The minimum active sequences of AG-10, AG-32, and AG-73 were determined to be SIYITRF, IAFQRN, and LQVQLSIR, respectively. These sequences are highly conserved among the different species and different laminin alpha chains, suggesting that they play a critical role for biological function and for interaction with cell surface receptors.

Amino Acid Sequence↗

PubMed1995

Structure-activity study of a laminin alpha 1 chain active peptide segment Ile-Lys-Val-Ala-Val (IKVAV).

The IKVAV sequence, one of the most potent active sites of laminin-1, has been shown to promote cell adhesion, neurite outgrowth, and tumor growth. Here we have determined the structural requirements of the IKVAV sequence for cell attachment and neurite outgrowth using various 12-mer synthetic peptide analogs. All-L- and all-D-IKVAV peptides showed cell attachment and neurite outgrowth activities. In contrast, all-L- and all-D-reverse-sequence peptides were not active. Some of the analogs, in which the lysine and isoleucine residues of the IKVAV peptide were substituted with different amino acids, promoted cell attachment, but none of the analog peptides showed neurite outgrowth activity comparable to that of the IKVAV peptide. These results suggest that the lysine and isoleucine residues are critical for the biological functions of the IKVAV peptide.

Amino Acid Sequence↗

PubMed1995

Adjuvant effect of polyadenylic.polyuridylic acid on antibody production of recombinant hepatitis B surface antigen in mice.

The adjuvant effect of polyadenylic.polyuridylic acid [poly(A).poly(U)] on antibody production against recombinant hepatitis B surface antigen (rHBsAg) was investigated. Immunization of adult Balb/c mice with rHBsAg plus poly(A).poly(U) elicited significantly higher antibody responses than immunization of mice immunized with rHBsAg alone. Such an adjuvant effect was evident even in mice sensitized with subimmunogenic doses of the antigen.

Adjuvants, Immunologic↗

PubMed1995

Systemic gene therapy with p53 reduces growth and metastases of a malignant human breast cancer in nude mice.

We report on an in vivo delivery system that attenuates the growth, in nude mice, of a malignant human breast cancer cell line containing a p53 mutation. Nude mice, inoculated with breast carcinoma cells, were injected every 10-12 days with a liposome-p53 complex via the tail vein. A significant reduction of greater than 60% in primary tumor volume was observed as compared to the control groups. Furthermore, when individual growth patterns of the tumors were assessed, we found that primary tumor size regressed in the majority of p53-treated animals (8/15), whereas only one tumor in the control groups (1/22) regressed. The eight tumors that regressed with the liposome-p53 complex showed no evidence of relapse for 1 month after the cessation of treatment. We also determined that the administration of the liposome-p53 complex reduced the incidence of metastases. The MDA-MB-435 tumor cells, transduced with the lacZ gene, facilitated quantitation of beta-galactosidase activity and tumor burden in the lungs. The number of metastatic cells in the lung was significantly lower in the p53-treated group (0.53 +/- 0.43 x 10(6), p < 0.01) than in either the vector-treated (8.1 +/- 3.7 x 10(6)) or untreated control groups (15.8 +/- 5.9 x 10(6)). Thus, systemic administration of the liposome-p53 complex reduced not only the size of the primary tumors but, more importantly, prevented the relapse and metastases of these tumors.

Animals↗

PubMed1995

Comparison of immunomodulative effects of the histamine-2 receptor antagonists cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells in gastric cancer patients.

BACKGROUND: Histamine-2 receptor antagonist (H2-RA) have been shown to improve the function of various parts of the immune system. The proposed mechanism of the immunomodulative effects of H2-RA has been considered to be the inhibition of suppressor T-lymphocyte activity, an increase in interleukin-2 production, and an enhancement of natural killer cell activity. Most of these studies were done with cimetidine. Comparative data with other H2-RA are limited and conflict on immunomodulative effects. Comparison of the actions of H2-RA on the immune system is required. METHODS: We compared the immunodulative effect of the H2-RAs cimetidine, ranitidine, and famotidine on peripheral blood mononuclear cells (PBMC) in normal controls and patients with gastric cancer. DNA synthesis, cytotoxicity against K562 cells, and the levels of soluble interleukin-2 receptor (sIL-2R) in supernatant were measured after addition of the various H2-RA to PBMC cultures. RESULTS: Subjects with gastric cancer showed significantly higher levels of suppressor lymphocyte activity than normal controls. These levels were restored to levels of normal controls by the addition of cimetidine. Statistically significant lymphoblastogenesis and cytotoxicity against K562 cells were observed only in cimetidine-treated PBMC (p < 0.05); such effects were not observed in ranitidine- or famotidine-treated PBMC. Significantly increased levels of sIL-2R were found in supernatants obtained from culture flasks treated with cimetidine and phytohemagglutinin or ranitidine and phytohemagglutinin (p < 0.01). CONCLUSIONS: Of the three H2-RAs tested, cimetidine had the strongest and famotidine the weakest immunomodulating effect. Only cimetidine augmented the cytotoxicity and proliferative response of lymphocyte to mitogen; neither ranitidine nor famotidine had such an effect. These results might be due to their structural differences. In addition, the immunologic effects of H2-RA are unlikely to be mediated via specific interaction at the H2 receptor.

Adjuvants, Immunologic↗

PubMed1995

Role of antineutrophil cytoplasmic antibodies in an ethnically distinct population: Korean patients with ulcerative colitis.

OBJECTIVES: Studies have suggested that antineutrophil cytoplasmic antibodies (ANCA), known as a useful diagnostic marker in patients with ulcerative colitis (UC), may have a genetic basis, particularly in association with HLA class II genes. Because most studies examining the role of ANCA in UC have been performed in ethnically undefined populations, we have analyzed ANCA status in an ethnically distinct group of patients with UC. METHODS: Serum samples from 24 Korean patients with a known diagnosis of UC and 58 healthy Koreans were examined for the presence of ANCA, using a fixed neutrophil enzyme-linked immunosorbent assay. ANCA-binding patterns were examined by indirect immunofluorescence. RESULTS: The incidence of ANCA in 83.3% of Korean patients with UC was significantly higher than in controls (p < 0.0001). The mean binding level at a 1:100 dilution and the titer of ANCA were significantly higher in patients with UC than in controls. Among UC patients with ANCA, there was also a high incidence of perinuclear binding pattern. In contrast, there was no relationship between ANCA and age of patients, duration, activity, or extent of disease. CONCLUSIONS: High sensitivity and specificity of ANCA in an ethnically distinct group of patients with UC show that ANCA expression may not be ethnically determined, and they confirm the utility of ANCA as a useful diagnostic indicator of UC in an ethnically diverse groups of patients.

Adult↗

PubMed1995

Detection of 17p loss in gastric carcinoma using polymerase chain reaction.

BACKGROUND: The loss of heterozygosity (LOH) of 17p has been previously studied with conventional Southern blot-restriction fragment length polymorphism analysis, but the relatively low informativity was an obstacle to extensive analysis. To overcome this problem and to investigate the significance of 17p LOH in gastric carcinoma, we employed polymerase chain reaction and subsequent silver staining of DNA. EXPERIMENTAL DESIGN: LOH of p53 gene and D17S5 locus on 17p was analyzed using polymerase reaction; the relationships between 17p LOH and conventional clinicopathologic parameters were evaluated. RESULTS: The LOH of p53 gene and D17S5 was found in 36.5% (23 out of 63) and 63.3% (38 out of 60) informative cases, respectively. There was no significant correlation between LOH of these two loci, whereas the frequency of the D17S5 locus was significantly higher (p < 0.01), which suggested that there may be another putative tumor suppressor gene between the two loci or distal to D17S5. The LOH of p53 gene and D17S5 locus was not significantly associated with abnormal p53 expression, depth of invasion, histologic type of the tumor (Lauren's classification), or the status of lymph node metastasis. CONCLUSIONS: The polymerase chain reaction and silver staining of DNA seemed to be a simple and excellent method for the evaluation of chromosomal allelic loss. The 17p LOH was frequently found in gastric carcinoma, but specific association with conventional clinicopathologic parameters was not found.

Adult↗

PubMed1995

Colon cancer surveillance.

Colorectal cancer is one of the most important risk factors affecting the long-term outcome of patients with ulcerative colitis. Therefore, an extensive effort has been devoted to prevent and reduce the mortality related to colorectal cancer through cancer surveillance programs. Studies have demonstrated that cancer surveillance can lead to an improved outcome in patients who go on to develop cancer. Given increasing reports of cancer risk in Crohn's disease, further studies examining the potential impact of a similar program in Crohn's disease should be considered.

Biomarkers↗

PubMed1994

Apoptosis in human fibrosarcoma cells is induced by a multimeric synthetic Tyr-Ile-Gly-Ser-Arg (YIGSR)-containing polypeptide from laminin.

The YIGSR (Tyr-Ile-Gly-Ser-Arg) peptide, derived from the laminin beta 1 chain, decreases tumor metastasis and growth in experimental animals. The mechanism responsible for this inhibition is not known. We now report that a 16-mer branched form of YIGSR, synthesized by the multimeric antigen peptide system, induced the apoptosis of HT-1080 cells in vitro at 30 micrograms/ml (approximately 3 microM). Tumor cells treated with this peptide showed the expected morphological changes associated with apoptosis, acridine orange staining of nuclei, increased numbers of 3'-OH ends of DNA in nuclei, a DNA ladder pattern on agarose gels, and increased transforming growth factor beta 1 mRNA by Northern blot. The specificity of this peptide was confirmed by inhibition of apoptosis with a neutralizing antibody to the peptide. In addition, the branched 16-mer peptides of scrambled sequence did not induce apoptosis. Our in vitro results suggest that apoptosis may play a role in the antimetastatic and antitumor effects associated with the YIGSR peptide.

Amino Acid Sequence↗

PubMed1994

MDR1 gene expression: its effect on drug resistance to doxorubicin in human hepatocellular carcinoma cell lines.

BACKGROUND: Hepatic tumors are resistant to many chemotherapeutic agents. Although elevated MDR1 (also known as PGY1) gene expression has been shown in such tumors, no direct association has been established between the gene expression and multidrug resistance. PURPOSE: To evaluate the role of the MDR1 gene in the drug resistance of hepatoma, we tested nine human hepatoma cell lines for their expression of the MDR1 gene. METHODS: We measured the MDR1 messenger RNA (mRNA) expression by RNA slot-blot analysis and by immunocytochemical staining with a P-glycoprotein-specific monoclonal antibody, MRK16. The in vitro chemosensitivity of these cell lines to fluorouracil, doxorubicin, mitomycin C, cisplatin, and etoposide (VP-16) was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. For doxorubicin cytotoxicity, we also tested the potentiating effect of several multidrug resistance-reversing agents. RESULTS: Slot-blot analysis and immunocytochemistry showed that two cell lines expressed high levels of MDR1 mRNA, one expressed an intermediate level, and all others were low expressors. The MTT assay results showed that all cell lines tested were generally resistant to chemotherapeutic agents. The assay area under the curve (AUC) was within a clinically achievable range only for VP-16 in one of nine cell lines. When the IC50 values were compared among the cell lines, the results revealed a close association with the MDR1 gene expression only for doxorubicin resistance. Verapamil and quinidine lowered the IC50 values of doxorubicin for MDR1-positive cell lines. The lowered assay AUC levels for both reversing agents, however, were still higher than the clinically achievable range. CONCLUSION: These results indicate that the MDR1 gene probably has a role in doxorubicin resistance in hepatocellular carcinoma and that the resistance can be overcome by some multidrug resistance-reversing agents. IMPLICATIONS: Some widely used anticancer agents might be ineffective for treating hepatocellular carcinoma in clinical situations even when combined with reversing agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

The role of radiation treatment in management of extrahepatic biliary tract metastasis from gastric carcinoma.

PURPOSE: To determine the proper role of radiation treatment in the management of patients with extrahepatic biliary tract metastasis due to recurrent gastric cancer. METHODS AND MATERIALS: Twenty patients with malignant biliary obstruction due to recurrent gastric carcinoma after gastrectomy were treated with palliative intent at the Yonsei University College of Medicine from 1986 to 1990. Treatment consisted of external drainage alone in 11 patients (Group I) and external drainage followed by radiation treatment in nine patients (Group II). Five of nine patients in Group II underwent external irradiation in combination with intraluminal brachytherapy using high dose rate Iridium-192 (Ir-192) sources within the expandable intrabiliary prosthesis, a Gianturco stent, inserted transhepatically at the site of obstruction. RESULTS: An excellent local response was observed in five of nine patients in Group II, in whom biliary patency was restored following treatment so that the external drainage catheter could be removed. Prolongation of median survival was observed in Group II (9 months) as compared to Group I (2 months). There were no serious treatment-related complications with this approach. CONCLUSION: This treatment approach with external radiotherapy +/- intraluminal brachytherapy could achieve effective palliation and improve the quality of life in selected patients with extrahepatic biliary metastasis from gastric carcinoma.

Adult↗

PubMed1994

Adenoid cystic carcinoma of the head and neck.

Adenoid cystic carcinoma of the head and neck is relatively rare and is characterized by slow evolution, multiple recurrences, protracted clinical course, and late distant metastasis. This article presents its peculiar clinical course, response to therapy, and long-term treatment results by analyzing 67 cases treated from 1979 to 1991 at the Seoul (Korea) National University Hospital. The most common primary site was the parotid gland in the major salivary glands and the nose and paranasal sinuses in the minor salivary glands. The local control rate was 71.1% at 5 years and 44.3% at 8 years. Late-occurring distant metastases did not allow a plateau in survival curves, even after 8 years. Our study also revealed that surgery combined with postoperative radiotherapy could yield better local control.

Adult↗

PubMed1994

The manifestation of proliferating cell nuclear antigen in adenoid cystic carcinoma.

OBJECTIVE: This study was conducted to evaluate the prognostic value of immunostaining with a genetically engineered monoclonal antibody (PC10) to proliferating cell nuclear antigen in patients with adenoid cystic carcinoma (ACC). DESIGN: Formalin-fixed, paraffin-embedded tissue blocks from patients with ACC were stained with PC10, and an index (percentage of positively staining cells per tumor cells) was calculated. The patients' clinical course was compared with the PC10 index. Follow-up ranged from 12 to 177 months (mean, 64 months). SETTING: Patient selection and immunohistochemical studies were done at Seoul (Korea) National University Hospital. PATIENTS: Twenty-eight cases of ACC were retrieved from our files between January 1979 and December 1992. MAIN OUTCOME MEASURE: All of the cases expressed the PC10 antibody. The PC10 index ranged from 1.0% to 44% (mean, 14.5%). We divided the 28 cases into two groups: group 1 (PC10 index, less than 15%) and group 2 (PC10 index, greater than 15%). RESULTS: The PC10 index (groups 1 and 2) did not correlate with established pathologic grades, tumor staging, local recurrences, or survival rates. However, those with higher PC10 indexes (group 2) exhibited significantly increased distant metastases compared with those with lower indexes (group 1). CONCLUSION: We conclude that the proliferating cell nuclear antigen in ACC may be used as an indicator in the prediction of distant metastasis.

Adult↗