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Biomedical subjects

G H Kang

Publications and source records attributed to G H Kang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ca2+ influx mediates apoptosis induced by 4-aminopyridine, a K+ channel blocker, in HepG2 human hepatoblastoma cells.

Apoptosis appears to be implicated in the pathogenesis and therapeutic applications of cancer. In this study we investigated the induction of apoptosis by 4-aminopyridine (4-AP), a K(+) channel blocker, and its mechanism in HepG2 human hepatoblastoma cells. 4-AP reduced cell viability and induced DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. In addition, 4-AP induced a sustained increase in intracellular Ca(2+) concentration, which was completely inhibited by the extracellular Ca(2+) chelation with EGTA. 4-AP also induced Mn(2+) influx, indicating that the 4-AP-induced increased intracellular Ca(2+) levels were due to activation of Ca(2+) influx pathway. 4-AP also depolarized membrane potential that was measured by using di-O-C(5)(3), a voltage-sensitive fluorescent dye. 4-AP-induced Ca(2+) influx was significantly inhibited not by voltage-operative Ca(2+) channel blockers (nifedipine or verapamil), but by flufenamic acid (FA), a known nonselective cation channel blocker. Quantitative analysis of apoptosis by the flow cytometry revealed that treatment with either FA or BAPTA, an intracellular Ca(2+) chelator, significantly inhibited the 4-AP-induced apoptosis. Taken together, these results suggest that the observed 4-AP-induced apoptosis in the HepG2 cells may result from Ca(2+) influx through the activation of voltage-sensitive Ca(2+)-permeable non-selective cation channels. These results further suggest that membrane potential change by modulation of K(+) channel activity may be involved in the mechanism of apoptosis in human hepatoma cells.

4-Aminopyridine↗
PubMed2000

Isolated splenic metastasis from colorectal carcinoma: a case report.

Isolated splenic metastasis arising from colorectal carcinoma is very rare and there has been only 6 cases reported in the English literature. A new case is presented, and its possible pathogenesis was considered with previously reported cases. A 65-year-old male patient had received a right hemicolectomy for ascending colon cancer 36 months earlier. He was followed up regularly with serial measurement of serum carcinoembryonic antigen (CEA). Rising serum CEA was discovered from 33 months postoperatively and CT revealed an isolated splenic metastasis. He therefore underwent splenectomy, which was proven to be a metastatic adenocarcinoma with similar histological feature to the original tumor. As all reported cases showed elevated serum CEA at the time of metastasis, isolated splenic metastasis might be associated with CEA in regard to its biological functions of immunosuppression and adhesion.

Adenocarcinoma↗
PubMed2000

5' CpG island methylation of p16 is associated with absence of p16 expression in glioblastomas.

Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is an important mechanism in the inactivation of p16INK4 tumor suppressor gene. This study is designed to clarify the significance of p16INK4 hypermethylation in 23 cases of glioblastomas (GBMs) by methylation-specific polymerase chain reaction (PCR) and p16 immunostaining. Fourteen cases (60.9%) out of 23 GBMs revealed hypermethylation on p16. p16 immunostaining revealed that 13 (93%) of these 14 hypermethylation cases showed complete loss of immunoreactivity and only one (7%) case retained immunoreactivity. Among 9 methylation-negative cases, 4 were immunonegative, which might be related to mutations or deletions other than hypermethylation. The most significant finding was that of 17 cases with immunonegativity, 13 cases (76.5%) showed hypermethylation. We reconfirmed that p16 hypermethylation may be one of the major mechanisms of tumorigenesis of GBMs and the results between the methylation specific-PCR study and p16 immunostaining had a good correlation.

5' Untranslated Regions↗
PubMed1999

Somatic mutations of the first 14 exons of APC in hamartomatous polyps of the colon.

Although hamartomatous or hyperplastic polyps are rarely accompanied by adenomatous or carcinomatous foci, the role of APC (MIM# 175100) mutations in these polyps is not clear. The neoplastic potential of these polyps was assessed with regard to somatic mutation of the first 14 exons of APC. DNA from 14 hamartomatous polyps (12 patients with juvenile polyp, JP; two patients with Peutz-Jeghers syndrome, PJS) and 27 hyperplastic polyps was used. Exons 1-14 of APC were amplified using verified oligonucleotide primers, and PCR-SSCP analysis was performed. Translation-terminating mutation in exon 15 was also screened using the protein truncation test. All mutations found were transitions or transversions with heterozygous alleles of both wild-type and mutant APC in exons 2, 9, 10, and 11. Four hamartomatous polyps (three from JP and one from PJS) showed seven, new mutations and one common APC variant (codon 486), whereas no hyperplastic polyps demonstrated mutation. APC mutation was not correlated with previous history of colorectal carcinoma or number of polyps. Since all mutations were missense or silent mutations occurred in exons not previously known to have functionally relevant area, their phenotypic implication appeared to be limited.

Colonic Polyps↗
PubMed1999

Appendiceal orifice inflammation as a skip lesion in ulcerative colitis: an analysis in relation to medical therapy and disease extent.

BACKGROUND: Although several reports have claimed that the appendix can be involved as a skip lesion in ulcerative colitis, they do not exclude the possibility that this skip lesion occurs as a result of medical therapy. Also, little is known about the relation between the presence of appendiceal orifice inflammation and the extent of the disease. METHODS: The presence of appendiceal orifice inflammation was prospectively assessed both endoscopically and histologically in 94 patients with active ulcerative colitis, the extent of whose disease had not been beyond the hepatic flexure. To evaluate the effect of prior medical therapy on the prevalence of appendiceal orifice inflammation, all cases were divided into two groups. Group A consisted of 66 patients who had been treated before inclusion; group B was composed of 28 patients newly diagnosed at inclusion. RESULTS: Appendiceal orifice inflammation was diagnosed in 24 (26%) of 94 patients with active subtotal ulcerative colitis, with no statistical difference observed between group A (23%) and group B (32%). In all 94 patients, the frequency of appendiceal orifice inflammation decreased significantly as the extent of disease increased, i.e., 37% in proctitis (n = 49), 17% in left-sided colitis (n = 36), and 0% in extensive colitis (n = 9) (p < 0.05). CONCLUSIONS: Appendiceal orifice inflammation as a skip lesion of ulcerative colitis is not rare, is more frequently observed in patients with less extensive disease, and is not the result of patchy improvement due to medical therapy.

Adult↗
PubMed1999

Usefulness of cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to intrahepatic stones.

BACKGROUND: Intrahepatic duct strictures are usually caused by intrahepatic duct stones and cholangitis. However, focal strictures of the intrahepatic duct unrelated to intrahepatic stones often pose diagnostic problems. This study was undertaken to prospectively evaluate the usefulness of percutaneous transhepatic cholangioscopy in patients with focal intrahepatic duct stricture and no evidence of a stone. METHODS: Seventeen patients with focal strictures of the intrahepatic duct without any evidence of a stone were included. Percutaneous transhepatic cholangioscopic examination including procurement of biopsy specimens was performed after percutaneous transhepatic biliary drainage. RESULTS: A histopathologic diagnosis was obtained in all patients (9 adenocarcinomas, 1 squamous cell carcinoma, 2 hepatocellular carcinomas, 2 adenomas, and 3 benign strictures). Of the 9 patients with bile duct adenocarcinoma, 8 underwent surgery and a curative resection was possible in 7 patients (88%). Five patients (63%) had early-stage bile duct cancer in which cancer invasion was limited to the mucosa or fibromuscular layer and there was no evidence of lymph node metastasis. CONCLUSIONS: Percutaneous transhepatic cholangioscopy in patients with focal stricture of the intrahepatic duct unrelated to choledocholithiasis is useful for diagnosis including the detection of early bile duct cancer.

Adult↗
PubMed1999

Development of intracytoplasmic lumens in colon cancer cells cultured on non-adhesive surface.

Cell-matrix interactions have important effects on phenotypic features, such as morphology, differentiation and cell growth. Several papers have suggested that when cell-matrix interaction is interrupted, cells grow as multicellular spheroids and eventually undergo apoptosis. We found that when ET(-), a laminin non-adherent colon cancer cell line, was cultured on poly-2-hydroxyethyl methacrylate (HEMA) coated plastic, the cells floated as cellular aggregates of spheroids or as single cells. Some of the single cells contained large intracytoplasmic lumens (ICL) and appeared similar to signet ring cells. These ICL were lined by a layer of short microvilli. The number of the cell did not increase when cultured on poly-HEMA. Another type of single cells, usually without ICL, demonstrated the characteristics of apoptotic cells by histologic examination. Acridine orange staining, flow cytometry and electron microscopy confirmed the apoptotic nature of those cells. On immunohistochemical staining for proliferating cell nuclear antigen, spheroids of cells and single cells with ICL were immunoreactive, while most of the single cells without ICL were negative. These results suggest that multicellular aggregates and formation of ICL were induced by the adaptation of ET(-) colon cancer cells in a harmful environment caused by reduced adhesiveness, and these changes might be related to cell survival.

Apoptosis↗
PubMed1999

Portal vein embolization with use of a new liquid embolic material: an experimental study.

PURPOSE: To evaluate the efficacy and safety of a new liquid embolic material in portal vein embolization (PVE). MATERIALS AND METHODS: A new embolic material (Embol) was percutaneously injected into the left portal vein of 13 swine, using a balloon catheter to prevent reflux. The swine were killed immediately (n = 6), 2 weeks (n = 4), and 4 weeks (n = 3) after the PVE, and the volumes of the right and left lobes were measured. The changes in body temperature, aspartate aminotransferase (AST) (formerly SGOT), alanine aminotrasferase (ALT) (formerly SGPT), and bilirubin levels after the PVE were studied, and the histopathologic changes in the embolized and nonembolized lobes were examined with light microscopy. RESULTS: The average volume ratio of the right:left lobe immediately after the PVE was 55(+/-2):45(+/-1), and changed to 71(+/-3):29(+/-3) at 2 weeks and 82(+/-3):18(+/-3) at 4 weeks after embolization. There were only mild changes in AST, ALT, and bilirubin levels, and only one pig showed a significant elevation in body temperature after PVE. Microscopically, the embolized lobe showed contraction of hepatocyte without any sign of necrosis and the nonembolized lobe expansion of hepatocyte. CONCLUSIONS: The new embolic material seems effective and safe for PVE.

Animals↗
PubMed1999

Gross type-matched study of clinicopathologic features of advanced gastric carcinoma with replication error.

Sporadic gastric carcinomas with replication error (RER) have been described and have distinct clinicopathological features, such as: older age group, predominant antral location, elevated gross type, near-diploidy, expanding pattern (Ming's classification), intestinal type, low desmoplastic response, and less frequent lymph node metastasis. Previous study revealed that replication error-positive (RER+) advanced gastric carcinomas (AGC) had a preponderance of Borrmann type 2. Regardless of RER status, AGC of Borrmann type 2 usually exhibit expanding pattern (Ming's classification), intestinal type, and low desmoplastic reaction. Therefore, to better characterize the clinicopathological features of RER+ gastric carcinomas, gross type-matched analysis would be necessary. We analyzed 53 cases of Borrmann type 2 AGC for RER status using polymerase chain reaction analysis of eight microsatellite loci and compared the clinicopathological features between RER+ and RER-negative (RER-) tumors. Sixteen (30.2%) out of 53 cases were RER+ phenotype which had a significant association with female sex, older age, expanding pattern, small and uniform nuclei, and low DNA index (P < 0.05). However, RER status was not significantly associated with histological differentiation, histological type (Lauren's classification), desmoplastic response, intratumoral lymphoid infiltration, and tumor location. Most of the previously known clinicopathological features of RER+ AGC were related to Borrmann type 2, except for female sex, older age, expanding pattern, and low DNA index.

Adenocarcinoma, Mucinous↗
PubMed1999

Clonal analysis of a solitary follicular nodule of the thyroid with the polymerase chain reaction method.

Solitary follicular nodules of the thyroid occasionally create a diagnostic problem, especially in the differential diagnosis between adenoma and nodular hyperplasia To obtain confident histologic parameters of clonal lesions, we analyzed DNA samples prepared from paraffin-embedded archival tissue from 20 solitary follicular nodules of the thyroid for clonality with the polymerase chain reaction (PCR) method. On the base of X chromosome inactivation mosaicism, we tested restriction fragment-length polymorphism of the phosphoglycerate kinase (PGK) gene and a highly polymorphic short tandem repeat of the human androgen receptor (HUMARA) gene. Of 18 informative cases, 10 were monoclonal, 7 were polyclonal, and 1 showed microsatellite instability. All of the five completely encapsulated nodules were monoclonal. Four of the five unencapsulated nodules showed polyclonality. Of the seven partially encapsulated nodules, four were monoclonal, and the others were polyclonal. The former showed 50% or more of encapsulation degree, whereas the latter showed less than 50%. The capsule tended to be thicker in monoclonal nodules (mean, 0.33 mm) than in polyclonal nodules (mean, 0.13 mm). Other histologic features of the nodules and surrounding parenchymal changes had no significance with respect to predicting clonality. This study suggests that the degree of encapsulation and capsular thickness are morphologically important for predicting the clonality of the thyroid nodule.

Adult↗
PubMed1999

Multifocal meningioangiomatosis: a report of two cases.

We report the CT and MR findings in two patients with multifocal meningioangiomatosis, neither of whom had a family history or stigmata of neurofibromatosis. All lesions were located in the cortical and subcortical areas and had round dense calcifications with eccentric cysts. The masses were associated with surrounding edema and gliosis.

Angiomatosis↗
PubMed1999

Correlation of methylation of the hMLH1 promoter with lack of expression of hMLH1 in sporadic gastric carcinomas with replication error.

Recent studies have demonstrated that the majority of sporadic colorectal carcinomas with replication error (RER) do not harbor mutations of the hMLH1 and hMSH2 genes that account for about 70% of hereditary nonpolyposis colon cancer. Despite the absence of mutations of the hMLH1 gene, the majority of RER-positive sporadic colorectal carcinomas lack hMLH1 protein expression, which have been reported to be related to hypermethylation of the promoter region of hMLH1 gene. High frequency of microsatellite instability (MSI) has been observed in about 15% of sporadic gastric carcinomas. The relationship of tumor MSI, methylation of promoter regions of hMLH1 or hMSH2, and expression of corresponding gene products has not been studied in gastric carcinomas as thoroughly as in colorectal carcinomas. We explored the relationship between methylation of hMLH1 or hMSH2 promoter regions and its protein expression in both RER-positive and RER-negative gastric carcinomas. Of 93 cases, 20 cases comprised the RER+ group (MSI-H tumors) and the remainder comprised the RER- group (7 cases, MSI-L; 66 cases, MSS). By immunohistochemistry absence of hMLH1 protein expression was limited entirely to the RER+ group (20 of 20, 100%). All 93 cases showed hMSH2 protein expression. Nineteen (95%) of 20 RER+ tumors harbored hypermethylation of the hMLH1 promoter region whereas only four cases (5.5%) of the 73 RER- tumors did. Hypermethylation of the hMSH2 promoter region was not observed in either the RER+ group or the RER- group. These results suggest that hypermethylation of the hMLH1 promoter region may be the principal mechanism of gene inactivation in sporadic gastric carcinomas with a high frequency of MSI.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Development of intracytoplasmic lumens in a colon cancer cell line cultured on a non-adhesive surface.

Cell-matrix interactions have important effects on phenotypic features, such as morphology, differentiation and cell growth. Several papers have suggested that when cell-matrix interactions are interrupted, cells grow as multicellular spheroids and eventually undergo apoptosis. We found that when ET(-), a laminin non-adherent colon cancer cell line, was cultured on poly-2-hydroxyethyl methacrylate (HEMA) coated plastic, the cells floated as cellular aggregates of spheroids or as single cells. Some of the single cells contained a very large intracytoplasmic lumen (ICL) and appeared similar to signet ring cells. These ICL were lined by a layer of short microvilli. The number of the cell did not increased cells when cultured on poly-HEMA. Another type of single cells, usually without ICL, demonstrated the characteristics of apoptotic cells by histologic examination. Acridine orange staining, flow cytometry and electron microscopy confirmed the apoptotic nature of those cells. In immunohistochemical staining for proliferating cell nuclear antigen, spheroids of cells and single cells with ICL were immunoreactive, while most of the single cells without ICL were negative. These results suggest that multicellular aggregation and formation of ICL were induced by the adaptation of ET(-) colon cancer cells in a harmful environment caused by reduced adhesiveness, and these changes might be related to cell survival.

Acridine Orange↗
PubMed1999

Clinicopathologic characteristics of replication error-positive gastric carcinoma.

Microsatellite instability (MI), an expansion or contraction of microsatellites, is a manifestation of replication errors (RERs) that is recognized as performing an important role in carcinogenesis in a proportion of gastric carcinomas. We analyzed 96 cases of sporadic gastric carcinomas for the occurrence of MI in BAT-26 and other six microsatellite loci. Gastric carcinomas with BAT-26 alteration demonstrated a higher proportion of unstable loci in other examined microsatellites than did gastric carcinomas without BAT-26 alteration. We classified gastric carcinomas with BAT-26 alteration as RER+ and compared the RER status with their clinicopathologic features. Ten (10.4%) of 96 gastric carcinomas showed RERs: 2 (7.7%) of 26 early gastric carcinomas and 8 (11.4%) of 70 advanced gastric carcinomas were RER+. RER+ gastric carcinomas were significantly associated with older age, elevated gross type (Borrmann Type 2 or EGC IIa), expanding growth pattern (Ming's classification), and minimal desmoplasia. Although statistically not significant, RER+ gastric carcinomas showed more frequent intestinal type (Lauren's classification), more antral involvement, and lower lymph node metastasis than did RER- gastric carcinomas. There was no association between RER status and intratumoral lymphocyte infiltration or histologic differentiation. In conclusion, RER+ gastric carcinomas demonstrated distinct clinicopathologic features, and BAT-26 was a useful marker for assessing the RER status of gastric carcinomas.

Adult↗
PubMed1998

p53 mutation and overexpression in hepatocellular carcinoma and dysplastic nodules in the liver.

In hepatocarcinogenesis, both de novo and multistep pathways have been suggested and in the latter a dysplastic nodule is the proposed precancerous lesion. In this study, we tried to ascertain whether or not the p53 gene is altered in low-grade/high-grade dysplastic nodules (LDN/HDN) and to determine the role of p53 alteration in multistep hepatocarcinogenesis. Eight hepatocellular carcinomas (HCCs), 9 HDNs, 17 LDNs and 25 cirrhotic nodules (LCs) were examined by polymerase chain reaction-single strand conformation polymorphism/direct sequencing and immunohistochemical staining for p53. Four of the 8 HCCs (50%) revealed p53 overexpression and 2 (25%) had missense mutations. Four of the 9 HDNs (44%) showed weak and/or focal p53 overexpression but none had mutation in the exons examined. Neither p53 overexpression nor mutation was found in 17 LDNs and 25 LCs. These results suggest that p53 mutation might be an unusual event in precancerous lesions of multistep hepatocarcinogenesis (DN-HCC sequence) and may play a less crucial part than in colorectal carcinogenesis.

Aged↗
PubMed1998

Alpha-fetoprotein-producing gastric carcinoma presenting focal hepatoid differentiation in metastatic lymph nodes.

Hepatoid adenocarcinoma (HA) is a rare variant of adenocarcinoma of the stomach, which is clinically characterized by increased level of serum alpha-fetoprotein (AFP) and poor prognosis. Microscopic findings include both adenocarcinomatous and hepatoid elements. A case of gastric adenocarcinoma with focal hepatoid differentiation confined within the metastatic lymph nodes occurred in a 55-year-old woman, who developed an advanced gastric carcinoma composed entirely of a typical papillo-tubular adenocarcinoma. Metastatic tumors were present in 8 of 13 perigastric lymph nodes, and 3 of these showed medullary and trabecular tumour growth reminiscent of hepatocellular carcinoma with immunohistochemical positivity for AFP. Preoperative serum AFP was 630 ng/ml and dropped to 76 ng/ml 2 weeks after the operation. Microscopic and immunohistochemical studies on the entire primary tumour tissue failed to demonstrate a focus of hepatoid or an AFP-positive area. This suggests that elevation of serum AFP may be reflected by focal hepatoid differentiation only in the metastatic lymph nodes, requiring extensive evaluation of the metastatic tumour in regional lymph nodes in the case of AFP-producing gastric carcinoma.

Adenocarcinoma↗
PubMed1998

Zinc deficiency manifested by dermatitis and visual dysfunction in a patient with Crohn's disease.

We report a case of Crohn's disease with low serum zinc concentration in a 26-year-old woman. She demonstrated acrodermatitis enteropathica and decreased visual acuity during total parenteral nutrition. Subsequent intravenous zinc supplementation resulted in alleviation of the skin lesions and improvement of visual acuity. This case supports the notion that depressed serum zinc in Crohn's disease may cause clinical manifestations, such as acrodermatitis enteropathica and retinal dysfunction, which may be correctable with zinc supplementation.

Acrodermatitis↗