Biomedical subjects

S I Hong

Publications and source records attributed to S I Hong.

At least 37 records · Page 2Linked to original sources

PubMed1998

Increased susceptibility of the c-Myc overexpressing cell line, SNU-16, to TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is a macrophage-derived multifunctional cytokine that acts as a cytostatic or cytotoxic agent in many tumor cells. However, the molecular mechanisms by which tumor cells become sensitive to the cytotoxic action of TNF-alpha are not clear. In this study we demonstrated that the cytotoxicity of TNF-alpha markedly increased in c-Myc overexpressing tumor cells. The stomach cancer cell line, SNU-16, in which c-Myc expression is high due to gene amplification, showed programmed cell death detected by DNA fragmentation and morphological changes. An antisense c-myc S-oligonucleotide specifically inhibited the TNF-alpha-induced apoptosis of SNU-16 cells, provided that the oligonucleotide was added 4 h prior to TNF-alpha treatment. Western immunoblot analysis of p53 and Bax showed that in this cell line, TNF-alpha increased the level of these proteins in a time-dependent manner and that this effect lasted for 12 h. Taken together these data indicate that the deregulation of c-Myc plays an important role in sensitizing tumor cells to TNF-alpha. Furthermore, TNF-alpha-induced apoptosis in the SNU-16 cell line showed increased expression of p53 and Bax protein levels following TNF-alpha treatment. Therefore, we suggest that TNF-alpha-induced apoptosis, which is cytotoxic to tumor cells, is coupled with a p53 and Bax apoptotic pathway.

Apoptosis↗

PubMed1998

Expression of Bfl-1 in normal and tumor tissues: Bfl-1 overexpression in cancer is attributable to its preferential expression in infiltrating inflammatory cells.

Bfl-1, a member of the Bcl-2 gene family, blocks p53-mediated apoptosis and has oncogenic transforming activity. In normal tissues, the transcript of Bfl-1 is expressed abundantly in bone marrow and at a low level in several other tissues. In previous experiments, elevated expression of Bfl-1 was observed by Northern analysis of stomach cancer samples. To study the role of Bfl-1 in normal cell development and in tumorigenesis, we have analyzed the expression of Bfl-1 in normal and tumor tissues by the in situ hybridization technique. The Bfl-1 transcript was detected in the white pulp of the spleen and in the germinal center of lymphatic tissues. In tumor tissues, its expression was preferentially detected in infiltrating inflammatory cells rather than in cancer cells, suggesting that Bfl-1 is not involved in tumorigenesis.

Colonic Neoplasms↗

PubMed1998

Nuclear overexpression of bcl-2 oncoprotein during the progression of human stomach cancer.

We unexpectedly observed strong nuclear overexpression of bcl-2 protein in advanced stomach cancer. As far as we know, such expression has not yet been reported. To investigate the significance of nuclear expression of bcl-2 protein in gastric carcinoma, we immunohistochemically analyzed bcl-2 overexpression in a gastric carcinogenic sequence, including 19 tubular adenomas (TA), 20 early carcinomas (EGC), and 20 advanced carcinomas (AGC). While TA displayed a specific granular and supranuclear cytoplasmic staining pattern, adenocarcinomas showed a strong nuclear staining pattern. Nuclear staining of bcl-2 was observed in 50% of AGC, 30% of EGC, and 10% of TA; cytoplasmic staining, on the other hand, was observed in all TA, 5% of EGC, and 10% of AGC. Nuclear bcl-2 overexpression differed according to the histologic type of AGC, occurring in 67% of the diffuse type and 25% of the moderately-to-well differentiated type. In the diffuse type, nuclear bcl-2 positive AGC predominated. In metastatic lesions, the pattern of bcl-2 immunostaining was almost identical to that seen in primary tumor. These results suggest that nuclear expression of bcl-2 may be related to malignant transformation in the stomach and is frequently associated with diffuse type advanced gastric adenocarcinomas.

Adenoma↗

PubMed1998

Antigenic diversity and serotypes of Helicobacter pylori associated with peptic ulcer diseases.

OBJECTIVES: Clinical presentation of Helicobacter pylori (H. pylori) infection has marked variation mainly due to the strain diversity and host susceptibility. Although H. pylori is identified as a major risk factor for gastric and duodenal ulcers, the ulcerogenic or pathogenic strain has not been documented yet. The objective of this study was to investigate antigenic types of the ulcerogenic strain of H. pylori. METHODS: The sera of 64 patients were tested by Western blot using Helicoblot 2.0 for six major anti-H. pylori antibodies, together with CLO test and histological examination of gastric biopsy tissues. Thirty-five, nine and 20 patients had duodenal ulcer, gastric ulcer and chronic active gastritis, respectively. The antigenic types of H. pylori were analyzed in 54 patients with positive H. pylori infection. In this study, H. pylori was divided into four serotypes according to the presence and absence of CagA and VagA: type I; CagA (+) and VacA(+), type Ia: CagA (+) and VacA(-), type Ib: CagA(-) and VacA(+), and type II: CagA(-) and VacA(-). RESULTS: There was no difference in the number of bands for six antigens: 3.2 +/- 1.4, 3.0 +/- 1.2 and 3.1 +/- 1.4 in 35 duodenal ulcer, 7 gastric ulcer and 12 chronic gastritis, respectively. The band with 119 kDa was 90.7%, which was the most common band with the order of 35, 30, 26.5, 89 and 19.5 kDa. Type I, la and Ib were positive in 22.2, 42.6 and 27.8%, respectively, which were significantly higher than type II (p < 0.05). There was no difference in the positive rates of four urease subtypes between the four serotypes.

Adult↗

PubMed1997

Adult T-cell leukemia/lymphoma with features of CD30-positive anaplastic large cell lymphoma--a case report.

We experienced a 58-year-old Korean man with adult T-cell leukemia/lymphoma with features of histologically anaplastic large cell lymphoma involving the skin and testis. The patient had cutaneous nodules in both extremities and a palpable right testicular mass. Right orchiectomy was performed and specimens of removed testicle and skin nodules showed immunohistologically anaplastic large cell lymphoma with T-cell phenotype, and CD30 antigen was positive. A human T-cell lymphotropic virus type 1 (HTLV-1) antibody titer was over 1 : 256 and integration of HTLV-1 proviral DNA pX gene was identified in the peripheral blood mononuclear cells and lymphoma tissue by polymerase chain reaction. Peripheral blood and bone marrow did not show any evidence of characteristic neoplastic T-cells.

Diagnosis, Differential↗

PubMed1997

Role of the nm23-H1 gene in the metastasis of gastric cancer.

The nm23 gene is now generally accepted as one of the suppressor genes for metastasis in many types of human cancer. To investigate the role of the nm23 gene in gastric cancer, we examined the expression of nm23-H1 mRNA, mutations, and loss of heterozygosity (LOH) of the nm23-H1 gene in gastric cancers. The expression of nm23-H1 mRNA was examined by Northern blot analysis in eight paired sets of specimens. The expression was higher in primary cancer specimens and metastatic lymph nodes than their corresponding normal gastric mucosa in all eight sets of specimens examined, while it was similar between primary cancer specimens and metastatic lymph nodes. The mutations of the nm23-H1 gene were examined in an additional 11 sets of specimens, including eight sets of analysed by Northern blotting, by polymerase chain reaction single-strand conformation polymorphism analysis, no mutation being found in any of the 11 sets of specimens tested. LOH of the nm23-H1 gene was also examined in additional 12 sets of specimens, among which seven (58%) specimens were informative for LOH. LOH was identified in one (14%) out of these seven informative sets. These results suggest that nm23 may not be the metastasis suppressor gene and the alteration of this gene not play an important role in the process of metastasis of gastric cancer.

Gene Expression↗

PubMed1996

Expression of urokinase-type plasminogen activator, its receptor, and its inhibitor in gastric adenocarcinoma tissues.

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.

Adenocarcinoma↗

PubMed1996

Deletion of Rb1 gene in late osteosarcoma from survivor of unilateral retinoblastoma--a case report.

It has been well known that the survivors of retinoblastoma are prone to have osteosarcoma. But the secondary tumor usually occurs in bilateral, hereditary type of retinoblastoma. We report one case of osteosarcoma in a survivor of unilateral, sporadic retinoblastoma. A fourteen year old male presented with a painfully swollen distal forearm of 2 month duration. He had enucleated his left eye 10 years ago due to retinoblastoma with no other adjuvant therapy. We managed him with our conventional protocol and identified deletion of Rb gene from his pathological specimen by using the PCR-RFLP method. This result is unusual for unilateral nonhereditable retinoblastoma and may suggest gene level change even in sporadic cases. And Rb gene study may be helpful for unilateral, sporadic retinoblastoma patient in detecting the possibility of late osteosarcoma.

Adolescent↗

PubMed1996

Enhanced expression of cathepsin L in metastatic bone tumors.

Cathepsin L is a kind of cystein proteases which are known to facilitate the invasion and metastasis of tumor cells by degrading the components of basement membrane and extracellular matrix. This study was undertaken to investigate the expression of cathepsin L by Northern blot analysis with radiolabeled cDNA specific for cathepsin L in six normal tissues, two osteosarcoma cell lines, MG-63 and Saos-2, six primary bone tumors and six metastatic bone tumors. In six normal tissues, the highest level of cathepsin L was expressed in liver with the descending order of liver > lung > thymus > ovary > kidney > esophagus. One of the two osteosarcoma cell lines established from the primary sites expressed a high level of cathepsin L mRNA. Out of six primary bone tumors, three (50%) expressed cathepsin L mRNA, while all (100%) of six metastatic bone tumors expressed the mRNA. These results demonstrating the higher frequency of expression of cathepsin L in metastatic bone tumors suggest that cathepsin L may participate in tumor invasion and metastasis.

Adolescent↗

PubMed1996

Overexpression of tissue inhibitors of metalloproteinase-1 and -2 in the stroma of gastric cancer.

The fundamental event of cancer invasion and metastasis is the complicated interaction of cancer cells with host cells, in which event, a number of proteases and their inhibitors are involved. Matrix metalloproteinases are the potent proteases in degrading the basement membrane and extra cellular matrix and are inhibited by specific endogeneous inhibitors, tissue inhibitors of metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2 was investigated by Northern blot analysis in specimens taken from 27 patients with primary gastric adenocarcinoma; 25 samples from the primary site, six from the metastatic lymph nodes and two from the peritoneal fluids. The expression for TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP-2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared with the those of primary cancer tissues, while one (50%) specimen overexpressed TIMP-2. Immunohistochemical staining was done to investigate the localization of TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was clearly detected in the cytoplasm of the stromal cells. These results suggest that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by stromal cells, may play an important role in inhibiting the proteolytic activity of matrix metalloproteinases originated from cancer cells, in gastric cancer.

Adenocarcinoma↗

PubMed1995

A novel Bcl-2 related gene, Bfl-1, is overexpressed in stomach cancer and preferentially expressed in bone marrow.

Programmed cell death (apoptosis) is an active process which is genetically encoded and plays an important role in several cellular activities such as embryonic development, deletion of autoreactive T-cells and homeostasis. Several genes regulating apoptosis have been reported, including p53, one of the tumor suppressor genes, c-myc, one of the proto-oncogenes, and various kinds of Bcl-2 related genes. A new cDNA clone which is homologous to Bcl-2, named as Bfl-1 were isolated from a human fetal liver at 22 week of gestation. This clone was identified by computer analysis of random cDNA sequences that were obtained in an effort to expand the expressed sequence tag (EST) databases to be used for human genome analysis. The homology was recognized by 72% amino acid identity to the murine A1 gene, a member of the Bcl-2-related genes. The homology to the BH1 and BH2 domains of Bcl-2 was especially significant, suggesting that Bfl-1 is a new member of the Bcl-2-related genes. Bfl-1 is abundantly expressed in the bone marrow and at a low level in some other tissues. Interestingly, a correlation was noted between the expression level of Bfl-1 gene and the development of stomach cancer in eight sets of clinical samples. It is conceivable that Bfl-1 is involved in the promotion of the cell survival in the stomach cancer development or progression.

Amino Acid Sequence↗

PubMed1995

Over-expression of p53 protein in squamous cell carcinoma of the skin.

p53 gene mutations have been known to be highly related to the particular stage of transformation in various types of human cancers. This study was conducted to investigate the p53 mutations at the protein level by an immunohistochemical method using anti-p53 antibody, NCL-p53-DO-7. Twenty-five cancer specimens were obtained surgically from patients with squamous cell cancer of the skin at the Korea Cancer Center Hospital. The cancers were classified according to the possible etiology into two groups, burn scar originated and UV-related cancers. Overexpression of p53 protein was detected in ten (40%) out of 25 cases tested: six (40%) of 15 cases associated with burn scar and four (40%) of ten cases related to UV exposure. In all normal skin cells in specimens, p53 protein was not stained at all. The stages and histological grades were evaluated for their relationship with the overexpression of p53 protein. No significant difference was found between the overexpression of p53 protein and the stages or histological grades. These results demonstrating that 40% of skin cancers were positive for p53 overexpression suggest that the alterations of the p53 gene may play a role and the exact role of p53 gene in the development of squamous cell carcinoma of the skin will be studied.

Adult↗

PubMed1995

Peripheral blood lymphocyte subsets in patients with stomach cancer.

The present study was conducted in order to investigate the immunologic alterations alongside the numerical changes in peripheral blood lymphocytes(PBL) and their subsets in stomach cancer patients. Lymphocyte surface markers were determined in 85 stomach cancer patients and 49 controls by indirect immunofluorescence technique using monoclonal antibodies. Monoclonal antibodies used were Leu 2a(CD8, suppressor/cytotoxic T cells), Leu 3a(CD4, inducer/helper T cells), Leu 4(CD3, pan T reagent), Leu 11(CD16, natural killer cells) and Leu 12(CD19, B cells). The numbers of PBL, CD3+, CD4+, CD8+, CD16+ and CD19+ cells significantly decreased and the CD4: CD8 value increased in 85 patients with stomach cancer compared to those in controls(p < 0.01). In stage I(n = 17), neither PBL, their subsets nor the CD4: CD8 value were significantly different from those of the controls. In stage II(n = 17), the numbers of PBL, CD3+, CD4+ and CD8+ cells decreased(p < 0.01). In stage III(n = 24) and IV(n = 27), PBL and all subsets measured decreased(p < 0.01). The CD4: CD8 value showed significant increases in stages III and IV(p < 0.01), because the CD8+ cells decreased to a greater extent than did the CD4+ cells. The results demonstrating that the lymphocyte subsets are depressed differentially with the stage suggest that host immunity is impaired with the progression of stomach cancer.

Adult↗

PubMed1995

Loss of heterozygosity on chromosome 10, 13q(Rb), 17p, and p53 gene mutations in human brain gliomas.

Using the methods of restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) analyses, we have examined 33 cases of human gliomas with various malignant grades to detect the deletions of putative tumor suppressor gene loci, chromosome 10, 13q(retinoblastoma gene, Rb), 17p, and p53 mutation. We observed loss of heterozygosity (LOH) at loci on chromosome 10 (36%), 13q(Rb) (54%), and 17p(50%) in malignant gliomas. There, however was no allelic loss on chromosome 10 and 17p in low-grade gliomas. Rb gene deletions were seen in low-grade gliomas, including oligodendroglioma and ependymoma. This finding suggests that Rb inactivation may be an early genetic event in the development and progression of gliomas. We correlated the results of LOH on chromosome 17p and p53 mutation. Among the 8 cases which showed LOH on chromosome 17p, only three cases (38%) revealed p53 mutations. Low incidence of p53 mutations in cases with chromosome 17p deletions suggests that some other tumor suppressor genes may be located on chromosome 17p.

Astrocytoma↗

PubMed1994

Aberrant expression of p53 gene product in malignant melanoma.

According to the current concept of carcinogenesis, the alterations of p53 tumor suppressor gene have been the most frequently detected in both human cancer cell lines and cancer tissues freshly isolated. This study was conducted to investigate the p53 gene alteration in malignant melanoma. Nineteen tumor tissues were obtained from 19 patients with malignant melanoma and examined for the expression of p53 protein by immunohistochemical staining with mouse monoclonal anti-p53 antibody, NCL-p53-DO-7. Twelve out of 19 cases (63%) showed positive reactions for p53 protein: 26, 21 and 16% of which had low, intermediate and high reactivity, respectively. p53 alteration more frequently expressed in female (10/12) than male patients (2/7) with malignant melanoma (p < 0.05). The incidence of expression of p53 protein was compared according to the stages and the sites of tissue obtained. The positive rate for p53 protein was not significantly different between the stages. The positive rates for p53 protein were five out of five (100%), one out of two (50%) and six out of twelve (50%) in tissues obtained from the metastatic, lymph node, and primary sites, respectively. The difference in the positive rates, however, is not statistically significant. These results suggest that p53 gene is a frequent target for mutation in the development of malignant melanoma.

Adult↗

PubMed1994

Adult T-cell leukemia/lymphoma in a Korean--a case report.

The clinicopathologic features of a Korean patient with adult T-cell leukemia/lymphoma(ATLL) are presented. A 51-year-old man, who has lived in Korea since birth, had multiple cutaneous nodules and multiple lymphadenopathy for the previous two months. A histopathologic study of the lymph node and skin lesion revealed T-cell non-Hodgkin's lymphoma of pleomorphic type, medium and large cell type. Peripheral blood examination showed leukemic features with 30% of abnormal lymphoid cells. HTLV-I proviral DNA pX region was detected in the DNA from peripheral blood mononuclear cells(PBMC) and the specific gag, pol, and env HTLV-I sequences were detected in the lymph node using polymerase chain reaction technique. Human T-cell leukemia/lymphoma type I(HTLV-I) antibodies were present in the serum. An immunophenotypic study of the lymph node revealed CD4 positive and CD8 negative helper/inducer T cell type surface markers. This case is the acute type, i.e. prototypic ATLL. He was treated with an intensive chemotherapy including cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone. Despite initial transient improvement, the tumor progressed after three cycles of the regimen and became refractory to further chemotherapy. These clinicopathologic findings, including the immunophenotypic analysis, established with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Effect of non-tumor cell contamination on detection of p53 gene mutations in human gastric cancer cells by polymerase chain reaction single-strand conformation polymorphism analysis.

BACKGROUND: We have previously studied p53 gene mutations in 25 primary gastric cancer tissues by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis for exon 4-8 and immunohistochemical staining with anti-p53 antibody. In four cases, the discrepancy of the results was observed between the two methods. In one case positive by PCR-SSCP but negative by immunohistochemical staining, the mutation was silent. In three cases, the p53 gene mutations were detected only by immunohistochemical staining. This discrepancy may be due to the contamination of the samples by cells without p53 gene mutation, such as non-tumor cells. This study was conducted to investigate the sensitivity of PCR-SSCP analysis to p53 gene mutations when the sample was contaminated with non-tumor cells. METHODS: Genomic DNA was extracted by the digestion with proteinase K and phenol-chloroform-ethanol method from two human gastric adenocarcinoma cell lines, MKN-45 and KATO III. To investigate the sensitivity of PCR-SSCP, DNA extracted from cancer cells was mixed with DNA obtained from normal gastric mucosal cells at various ratios. PCR-SSCP analysis for exon 4-8 of the p53 gene was performed with the mixed DNA samples. RESULTS: In KATO III, no PCR products were generated in exon 4-8 of the p53 gene by PCR, suggesting that both alleles from exon 4-8 of the p53 gene were deleted. In MKN-45, the mobility shift was observed in exon 4. Therefore, the effect of non-tumor cell contamination on the detection of p53 gene mutations was conducted using MKN-45 and normal gastric mucosal cells. In the mixed DNA samples of MKN-45 and normal gastric mucosal cells, an extra band with the migration similar to that of MKN-45 was found in the samples of 1:8 dilution or less, while no extra band was grossly detectable in DNA of normal gastric mucosal cells and in the samples of more than 1:16 dilution. CONCLUSIONS: These results suggest that the detection of p53 mutations by PCR-SSCP analysis may be underestimated in samples contaminated by a large number of non-tumor cells.

Base Sequence↗

PubMed1993

Enhanced expression of the c-myc protooncogene in human intracranial meningiomas.

We examined the alteration and expression of c-myc protooncogene in 11 human intracranial meningiomas using Southern blot, Northern blot and immunohistochemical techniques. Southern blot showed neither amplification nor rearrangement but Northern blot and immunohistochemical study revealed enhanced expression of the c-myc gene. Immunohistochemically, c-myc product was found in all of the 11 cases and seven of these cases showed an above moderate degree of immunoreaction in semiquantitative analysis. Loss of heterozygosity at IGLC2 locus on chromosome 22 was detected in four of the 8 informative cases. But extent and intensity of immunoreactivity did not correlated with loss of heterozygosity on chromosome 22. These genetic changes may play important roles in the pathogenesis of human intracranial meningioma.

Adult↗