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Biomedical subjects

G H Kang

Publications and source records attributed to G H Kang.

At least 19 recordsLinked to original sources
PubMed2007

Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features.

Promoter CpG island hypermethylation is an important carcinogenic event in prostate adenocarcinoma. Regardless of tissue type, human cancers have in common both focal CpG island hypermethylation and global genomic hypomethylation. The present study evaluated CpG island loci hypermethylation and LINE-1 and Alu repeat hypomethylation in prostate adenocarcinoma, analysed the relationship between them, and correlated these findings with clinicopathological features. We examined 179 cases of prostate adenocarcinoma and 30 cases of benign prostate hypertrophy for the methylation status of 22 CpG island loci and the methylation levels of LINE-1 and Alu repeats using methylation-specific polymerase chain reaction and combined bisulphite restriction analysis, respectively. The following 16 CpG island loci were found to display cancer-related hypermethylation: RASSF1A, GSTP1, RARB, TNFRSF10C, APC, BCL2, MDR1, ASC, TIG1, RBP1, COX2, THBS1, TNFRSF10D, CD44, p16, and RUNX3. Except for the last four CpG island loci, hypermethylation of each of the remaining 12 CpG island loci displayed a close association with one or more of the prognostic parameters (ie preoperative serum prostate specific antigen level, Gleason score sum, and clinical stage). Prostate adenocarcinoma with hypermethylation of each of ASC, COX2, RARB, TNFRSF10C, MDR1, TIG1, RBP1, NEUROG1, RASSF1A, and GSTP1 showed a significantly lower methylation level of Alu or LINE-1 than prostate adenocarcinoma without hypermethylation. In addition, hypomethylation of Alu or LINE-1 was closely associated with one or more of the above prognostic parameters. These data suggest that in tumour progression a close relationship exists between CpG island hypermethylation and the hypomethylation of repetitive elements, and that CpG island hypermethylation and DNA hypomethylation contribute to cancer progression.

Adenocarcinoma↗
PubMed2005

Protein C and/or S deficiency presenting as peripheral arterial insufficiency.

Although protein C and/or S deficiency has frequently been associated with venous thromboembolic events, instances of arterial thromboses have been reported. However, the exact incidence of protein C and/or S deficiency in patients with peripheral arterial insufficiency has not been established. Furthermore, given the lack of adequate studies to define the natural history and angiographic findings of these patients, the treatment has not been well delineated. Therefore, we conducted a prospective study to investigate the prevalence, characteristic angiographic findings and optimal treatments in patients with peripheral arterial insufficiency associated with protein C and/or S deficiency. Between September 2000 and August 2004, 133 patients who presented with peripheral arterial insufficiency underwent hypercoagulability tests before the initiation of any treatments. Of these, 11 patients (8.3%) with protein C and/or S deficiency were included in this study. There were nine males and two females. The ages ranged from 38 years to 72 years (mean 57 years). All patients showed characteristic angiographic findings: long segment thrombotic occlusion of a main peripheral artery without evidence of atherosclerosis or with mild atherosclerotic changes in the aorta and other major arterial trees. Surgical or endovascular procedures were performed in nine patients: bypass graft in four, thrombectomy in four and catheter-directed thrombolysis in one. Conservative treatment with full anticoagulation was performed in two patients. All patients received pre- and post-operative anticoagulation. Except for one amputated case, clinical and vascular laboratory improvements were achieved in 10 patients. Mean follow-up period was 21 months (range 4-45 months). However, one patient, in whom re-vascularization surgery was performed successfully, discontinued warfarin therapy himself at 10 months after surgery, graft occlusion and limb loss occurred at 30 months after surgery. This initial experience suggests that protein C and/or S deficiency may be an independent risk factor for peripheral arterial insufficiency. Patients who present with peripheral arterial insufficiency and protein C and/or S deficiency demonstrate characteristic angiographic findings. Once the diagnosis of protein C and/or S deficiency is made, patients should be treated with life-long anticoagulation.

Adult↗
PubMed2004

DNA hypermethylation in gastric cancer.

BACKGROUND: Transcriptional silencing of tumour suppressor genes by DNA hypermethylation plays a crucial role in the progression of gastric cancer. Many genes involved in the regulation of cell cycle, tissue invasion, DNA repair and apoptosis have been shown to be inactivated by this type of epigenetic mechanism. RESULTS: Recent studies have demonstrated that DNA hypermethylation begins early in cancer progression, and in some cases, may precede the neoplastic process. Ageing is associated with DNA hypermethylation, and may provide a mechanistic link between ageing and cancer. Several reports have indicated that Epstein-Barr virus-related gastric cancer is associated with a high frequency of DNA hypermethylation, suggesting that viral oncogenesis might involve DNA hypermethylation with inactivation of tumour suppressor genes. Hypermethylation of hMLH1 with the resulting loss of its expression is known to cause microsatellite instability, which reflects genomic instability associated with defective DNA mismatch repair genes in the tumour. CONCLUSIONS: In conclusion, recent studies demonstrate that DNA hypermethylation is a crucial mechanism of inactivation of tumour suppressor genes in gastric cancer. A better understanding of DNA hypermethylation will provide us with new opportunities in the diagnosis and therapy of gastric cancer.

Cadherins↗
PubMed2001

CpG island methylation in premalignant stages of gastric carcinoma.

There are limited reports on methylation analysis of the premalignant lesions of gastric carcinoma thus far. This is despite the fact that gastric carcinoma is one of the tumors with a high frequency of CpG island hypermethylation. To determine the frequency and timing of hypermethylation during multistep gastric carcinogenesis, non-neoplastic gastric mucosa (n = 118), adenomas (n = 61), and carcinomas (n = 64) were analyzed for their p16, human Mut L homologue 1 (hMLH1), death-associated protein (DAP)-kinase, thromobospondin-1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP-3) methylation status using methylation-specific PCR. Three different classes of methylation behaviors were found in the five tested genes. DAP-kinase was methylated at a similar frequency in all four stages, whereas hMLH1 and p16 were methylated in cancer samples (20.3% and 42.2%, respectively) more frequently than in intestinal metaplasia (6.3% and 2.1%, respectively) or adenomas (9.8% and 11.5%, respectively). However, hMLH1 and p16 were not methylated in chronic gastritis. THBS-1 and TIMP-3 were methylated in all stages but showed a marked increase in hypermethylation frequency from chronic gastritis (10.1% and 14.5%, respectively) to intestinal metaplasia (34.7% and 36.7%, respectively; P < 0.05) and from adenomas (28.3% and 26.7%, respectively) to carcinomas (48.4% and 57.4%, respectively: P < 0.05). The hMLH1, THBS1, and TIMP-3 hypermethylation frequencies were similar in both intestinal metaplasia and adenomas, but the p16 hypermethylation frequency tended to be higher in adenomas (11.5%) than in intestinal metaplasia (2.1%; P = 0.073). The average number of methylated genes was 0.6, 1.1, 1.1, and 2.0 per five genes per sample in chronic gastritis, intestinal metaplasia, adenomas, and carcinomas, respectively. This shows a marked increase in methylated genes from non-metaplastic mucosa to intestinal metaplasia (P = 0.001) as well as from premalignant lesions to carcinomas (P = 0.002). These results suggest that CpG island hypermethylation occur early in multistep gastric carcinogenesis and tend to accumulate along the multistep carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Source of errors in the evaluation of early rectal cancer by endoluminal ultrasonography.

PURPOSE: Although preoperative evaluation of early rectal cancers can be done by endoluminal sonography and by means of colonoscopic findings, it is still controversial whether endoluminal sonography can effectively discriminate mucosal from submucosal lesions. This study was performed to verify objective causes of errors in the evaluation of early rectal cancer (T0/1) using a review of videotaped endoluminal sonography images. METHODS: Eighty-nine patients with suspected early rectal cancer on endoluminal sonography were included. Two different scanners with appropriate probes were used according to tumor location, i.e., transrectal ultrasonography was used to scan up to 8 cm of the rectum above the anal verge, whereas endoscopic ultrasonography was used to assess higher lesions. Endoluminal sonography images were correlated with histologic infiltration and were reevaluated carefully to identify sources of errors. RESULTS: Sensitivity and specificity were 83.1 and 96.5 percent, respectively, for tumor staging, whereas sensitivity was very low compared with specificity (16.7 vs. 90.2 percent) for metastatic lymph nodes. Endoluminal sonography images showed irregularity of the underlying tumor border (P < 0.01) and hypoechoic blurring or cutoff of the inner and outer hypoechoic layers (P < 0.001), all of which closely correlated with histologic infiltration of tumor cells. Overstaging occurred more than twice as often as understaging in tumor reevaluation (14 vs. 5 occurrences). In contrast to tumors, lymph nodes showed a similar amount of both overstaging (four cases) and understaging (five cases). The sources of errors were summarized as five types: false instrumentation, interpretive errors, anatomic defects, imaging failure, and inevitable errors. CONCLUSIONS: Because false instrumentation, interpretive errors, and anatomic defects were considered preventable, 23 (82.1 percent) of the 28 errors might have been avoided. Therefore, a clear image by endoluminal sonography can effectively distinguish mucosal from submucosal lesions in early rectal cancer.

Diagnosis, Differential↗
PubMed2001

Mutations at the APC exon 15 in the colorectal neoplastic tissues of serial array.

Although the APC protein is known to participate in cellular proliferation and apoptosis, APC mutations have been thought to play a major role in the early stage of colorectal tumorigenesis. The somatic APC mutation of exon 15 was assessed to determine its impact on various stages of colorectal tumorigenesis. The colorectal neoplastic tissues of serial array studied included sporadic adenomas (group 1, n = 36), adenomas (group 2, n = 33), and carcinomas (group 3, n = 32) in the synchronous adenoma and carcinoma as well as sporadic carcinomas (group 4, n = 36). Aberrant DNA was detected by protein truncation test and confirmed by direct sequencing. The mutation prevalence was 36.1% in group 1, 45.5% in group 2, 59.4% in group 3, and 41.7% in group 4 with no differences among the groups. Among the 18 patients with synchronous adenoma and carcinoma, 9 had mutation in their adenomas and 12 in their carcinomas. The mutation loci and patterns did not differ in adenomas and carcinomas. Mutations in the mutation cluster region (MCR) were much more frequent than in the preceding region of MCR, i.e., 85.7% vs. 14.3%. The mutation prevalence of villous adenomas appeared greater than that of tubular adenoma (3/21 vs. 3/4). Predominant pathogenic mutations at MCR suggest that the APC mutation is implicated in all stages of colorectal tumorigenesis.

Adenocarcinoma↗
PubMed2001

Methylation of the hMLH1 promoter in multiple gastric carcinomas with microsatellite instability.

Hypermethylation of the hMLH1 promoter is observed in the majority of sporadic gastric carcinomas with high frequency microsatellite instability (MSI), and it contributes to the genesis of MSI-positive gastric carcinoma. Multiple gastric carcinoma is known to have a higher frequency of MSI positivity than single gastric carcinoma. However, the molecular basis of MSI in these tumors remains obscure. We investigated the role of hMLH1 promoter hypermethylation in the genesis of multiple gastric carcinoma with MSI. We analyzed 33 tumors from 15 patients with multiple gastric carcinoma (12 double tumors and three triple tumors) for MSI, expression of hMLH1 and hMSH2, and hypermethylation of hMLH1 and hMSH2 promoters. High frequency MSI was found in seven out of 33 tumors (21%) in five out of 15 patients (33%). All of the tumors with high frequency MSI had a lack of hMLH1 expression, with the presence of hMSH2 expression, while all the tumors with no MSI or low frequency MSI were positive for both hMLH1 and hMSH2. All of the tumors with no expression of hMLH1 had hMLH1 hypermethylation, whereas hMLH1 hypermethylation was observed in two out of 26 (8%) tumors with no or low frequency MSI. None of the tumors showed hMSH2 hypermethylation. These results suggest that epigenetic changes in the hMLH1 promoter account for the genesis of multiple gastric carcinoma with high frequency MSI.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Pelioid-type hepatocellular carcinoma masquerading as a hepatic hemangioma on technetium-99m red blood cell scintigraphy.

Technetium-99m red blood cell (RBC) scintigraphy is a very specific method to differentiate a hemangioma from other hepatic masses. The authors report a case of hepatocellular carcinoma that showed a focal area of increased uptake on Tc-99m RBC SPECT in a 60-year-old man. Dynamic computed tomography and angiography revealed features of both hemangioma and hepatocellular carcinoma. Pathologic examination showed that the portion of the hepatocellular carcinoma that showed increased uptake on Tc-99m RBC scintigraphy had peliosis, which is the likely cause of the radiotracer avidity.

Carcinoma, Hepatocellular↗
PubMed2001

Kaposi's sarcoma occurring during short-term dialysis: report of two cases.

Kaposi's sarcoma (KS) appears to develop in association with kidney transplantation, but unlikely with dialysis. We report two cases of classic KS that occurred in patients receiving short-term (less than 3 yr) dialysis. They have been suffering from chronic renal failure due to tuberculosis and diabetes mellitus, respectively. Several to multiple, reddened-violaceous patches, plaques and nodules were found on the hand and the lower extremities. Laboratory studies showed no evidence suggesting immunosuppressed state and there was no history of taking immunosuppressive agents. The biopsies of the two cases revealed proliferation of spindle-shaped cells focally arranged in bundles and multiple dilated vascular spaces outlined by an attenuated endothelium with intravascular and extravasated erythrocytes. The specimens expressed positivity with CD34 antigen. Human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) was detected in one case by polymerase chain reaction method.

Aged↗
PubMed2001

Papillary immature metaplasia of the uterine cervix: a report of 5 cases with an emphasis on the differential diagnosis from reactive squamous metaplasia, high-grade squamous intraepithelial lesion and papillary squamous cell carcinoma.

Papillary immature metaplasia (PIM) is a distinctive exophytic lesion of the uterine cervix and shares some histologic and cytologic features with ordinary squamous metaplasia (SM), atypical immature squamous metaplasia (AIM), high-grade squamous intraepithelial neoplasia (HSIL) and papillary squamous cell carcinoma (PSC). PIM has been suggested to be a subset of condyloma associated with low-risk type human papilloma virus (HPV), however, the etiologic role of HPV and biologic behavior of the disease are still elusive. We compared the clinical and histopathological findings, immunohistochemical expression of Ki-67 and p53 protein, and HPV typing of 5 cases of PIM with SM (n=9), HSIL (n=6), and PSC (n=4) to know the helpful features for the differential diagnosis. Histologically, all 5 cases showed a papillary proliferation of immature metaplastic cells involving the proximal transformation zone and endocervix. On HPV typing by polymerase chain reaction-restriction fragment length polymorphism, 2 out of 5 PIM were confirmed to have HPV 6 or HPV 11, while 2 out of 4 PSC were proved having HPV 31 and HPV 16 each. Ki-67 labeling index and mitotic index of PIM were significantly lower than those of HSIL or PSC. There were no significant differences of Ki-67 labeling index and mitotic index between PIM and SM. The expression of p53 varied among the groups and thus it was not helpful for the differential diagnosis.

Adult↗
PubMed2000

Applicability of carcinoembryonic antigen-specific monoclonal antibodies to radioimmunoguided surgery for human colorectal carcinoma.

Two carcinoembryonic antigen (CEA)-specific monoclonal antibodies (MAbs), PR1A3 and T84.66, were tested to determine whether they could accurately localize colorectal carcinoma and therefore be applicable in radioimmunoguided surgery (RIGS). Twenty-one tumors by three human colorectal carcinoma cell lines with various levels of CEA expression (KM-12c, C75, and Clone A) were successfully implanted in the intra-abdominal organs of 15 nude mice. The tumors was localized using a portable radioisotope detector (Neoprobe 1000) 48 h after injection of radiolabeled MAbs (10 mCi/mouse) when the precordial counts were <20 per 2 s. Histopathological identification of radiolabeled MAbs were also performed using immunohistochemistry and microautoradiography. Radioactivity counted on a portable radioisotope detector correlated well with that on a gamma counter. The distribution in the blood was significantly greater than in other organs (P < 0.001). Localization indices of the tumor in various organs was from 1.1 to 8.5 in the PR1A3-pretreated mice and 3.0 to 8.6 in the T84.66-pretreated mice. Silver grains and immune staining were distributed in the tumor cells of the PR1A3-pretreated mice, whereas they were in the necrotic debris as well as the tumor cells of the T84.66-pretreated mice. There were significantly more silver grains in the liver in the T84.66-pretreated mice than in the PR1A3-pretreated mice (P = 0.004). The sensitivity and specificity of tumor localization by RIGS were 71.4 and 91.4% in the PR1A3-pretreated mice, whereas they were 60 and 76% in the T84.66-pretreated mice. A study using specific anti-CEA MAbs suggested PR1A3 as an efficient immune probe for RIGS in colorectal carcinoma with a low rate of false-positive detection.

Animals↗
PubMed2000

Efficiency of combined colonoscopy and computed tomography for diagnosis of colonic actinomycosis: a retrospective evaluation of eight consecutive patients.

The preoperative diagnosis of colonic actinomycosis is accurate in fewer than 20% of patients. Colonoscopy and computed tomography (CT) findings were analyzed to ascertain their diagnostic value and their role in determining therapeutic modality and outcome. Before and after treatment we retrospectively evaluated eight consecutive patients with colonic actinomycosis, all of whom were women with a previous history of intrauterine contraceptive device use. Median follow-up period was 20 months (7-57). Localized nodules were found in all cases by colonoscopy; half of these nodules included umbilication at the apex. The colonic mucosa demonstrated normal to moderate inflammation as well as hyperemia and edema. Mucosal ulceration was found in only one case. All cases showed some degree of stenosis. These findings differ from those in other inflammatory or neoplastic diseases of the colon. Abdominopelvic CT revealed extramural involvement of heterogeneous lesions all cases. Contrast enhancement also indicated severe thickening of the colonic wall (7-20 mm) with focal and dense enhancement in six cases. Seven of eight patients required surgery for diagnostic or therapeutic purposes. Complete resolution was determined using both colonoscopy and CT. As more than half of these cases could have been safely managed using an adequate antibiotic treatment, diagnostic studies indicating a high likelihood of colonic actinomycosis should be evaluated to avoid unnecessary surgeries carried out for diagnostic purposes. A combination of colonoscopy and CT appears to be important for both diagnosis and management because of their compensatory findings of mucosal and extramucosal lesions, respectively.

Actinomycosis↗
PubMed2000

Correlation of p16 hypermethylation with p16 protein loss in sporadic gastric carcinomas.

Hypermethylation of p16 has been detected frequently in a variety of cancer cells and is known to repress the level of p16 transcription. In human gastric carcinoma (GC) cells, p16 protein loss has often been detected, but genetic alterations of p16 are infrequent. To investigate the molecular mechanism of p16 gene inactivation in gastric carcinogenesis, we examined the methylation status of p16 in GC using methylation-specific PCR. Thirty-seven of eighty-eight (42%) GC showed p16 hypermethylation. Immunohistochemical analysis of 41 cases of GC showed a complete loss of p16 immunoreactivity in 19 of 22 (86%) methylation-positive cases, but in only 2 of 19 (11%) methylation-negative cases. Of 88 GC, 21 cases were previously identified as having microsatellite instability (MSI). Interestingly, 13 of 21 (62%) MSI-positive tumors and 24 of 67 (36%) MSI-negative tumors had hypermethylation on p16. The relatively high frequency of hypermethylation on p16 and the strong correlation between the immunoreactivity and methylation patterns suggest that methylation is an important mechanism for p16 gene inactivation in GC.

Base Sequence↗
PubMed2000

Cholangioscopic findings in bile duct tumors.

BACKGROUND: Cholangioscopy has been used in the treatment of bile duct stones and the diagnosis of various bile duct tumors. However, the cholangioscopic characteristics of the various types of bile duct tumors have not been clearly described. We analyzed the results of cholangioscopic examinations and classified the findings according to tumor histology. METHODS: Cholangioscopic findings from 111 patients with benign or malignant bile duct tumors were reviewed. The mucosal changes, the presence of neovascularization, and the patterns of luminal narrowing were analyzed and compared with the histologic diagnosis. RESULTS: Bile duct adenocarcinoma can be classified into 3 different types according to the cholangioscopic findings: nodular, papillary, and infiltrative. Bile duct adenoma, hepatocellular carcinoma and other types of bile duct cancer such as mucin-hypersecreting cholangiocarcinoma, biliary cystadenocarcinoma, and squamous cell carcinoma also presented unique cholangioscopic characteristics. CONCLUSIONS: Bile duct tumors exhibit characteristic cholangioscopic findings and cholangioscopy seems to be useful for differential diagnosis.

Bile Duct Neoplasms↗
PubMed2000

Smooth muscle distribution in the extrahepatic bile duct: histologic and immunohistochemical studies of 122 cases.

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.

Bile Ducts, Extrahepatic↗
PubMed2000

Fibrous dysplasia with barely increased uptake on bone scan: a case report.

Fibrous dysplasia, in general, appears as an area of markedly increased uptake on bone scintigraphy. Therefore, the possibility of fibrous dysplasia is likely to be excluded when the lesion shows no or slightly increased uptake. The authors report a case of incidentally detected fibrous dysplasia that appeared as slightly increased uptake on bone scintigraphy and was found to harbor a bone infarction along with typical fibrous dysplasia by pathologic examination of a specimen sampled by curettage. Barely increased bone uptake in fibrous dysplasia may be associated with decreased vascularity and osteoblast activity of the lesion as a result of concurrent bone infarction. The authors suggest that not every case of fibrous dysplasia appears as an area of intensely increased uptake on a bone scan. Clinicians should be cautious in interpreting bone scans of radiographically indicated fibrous dysplasia.

Diphosphonates↗