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Biomedical subjects

W H Kim

Publications and source records attributed to W H Kim.

At least 19 recordsLinked to original sources

Study of an alpha track analysis and a fission track analysis for determining the hot particles contaminated with Pu and U isotopes.

A fission track analysis and alpha track analysis were developed to detect fissile particles such as uranium and plutonium isotopes as well as to identify particle-bound plutonium in contaminated soil or sediment. To record a reference point, a locator SEM grid electroplated with boron was used to obtain a recorded grid image on the Lexan or CR-39 detector. With the fission track technique, the track images of the grid coated with boron and the fissile nuclides on the CR-39 detector were clearly recorded so that the location of the fissile particles could be easily identified in the radio-contaminated soil matrix. With the alpha track technique, many of the hot particles in the BOMARC soil turned out to be contaminated with plutonium isotopes rather than uranium isotopes.

Alpha Particles↗

Expression of Lewis antigens and their precursors in gastric mucosa: relationship with Helicobacter pylori infection and gastric carcinogenesis.

Lewis (Le)-associated antigens are carbohydrates that are related biochemically to the ABO blood groups, and may have a role in Helicobacter pylori adherence. To evaluate their relationship to clinicopathological outcomes, gastric Le expression, including type 1 precursor, type 1 H, Le(a), Le(b), Le(x), Le(y) and sialylated Le(a) (CA19-9), was evaluated immunohistochemically in 233 gastric biopsy specimens obtained at routine gastroscopy. Expression was also investigated in gastric tissues showing chronic gastritis, intestinal metaplasia, and carcinoma from 42 patients with gastric cancer. A polymerase chain reaction was performed for H. pylori and the bacterial babA2 gene. We identified type 1 precursor expression in 34.3%, type 1 H in 55.8%, Le(a) in 44.2%, Le(b) in 82.0%, Le(x) in 44.2%, Le(y) 56.7%, and CA19-9 in 16.3% of the 233 gastric biopsy specimens. Expression of type 1 H, Le(b), and CA19-9 was significantly associated with H. pylori infection and histological features (p < 0.05), and expression of type 1 H was an independent predictive factor for H. pylori infection by multivariate logistic regression (p = 0.020). Positivity for the babA2 genotype correlated significantly with H. pylori infection and type 1 H expression in gastric biopsy specimens (p < 0.05). The babA2 genotype was more frequent in gastric mucosa from the gastric cancer patients than in gastric biopsy specimens from routine gastroscopy (p = 0.009). In the 42 gastric cancer patients, the frequency of type 1 precursor, Le(a), and Le(x) expression was significantly higher in intestinal metaplasia and carcinoma than in chronic gastritis (p < 0.05), but the frequency of type 1 H and Le(b) expression was significantly lower in intestinal metaplasia and carcinoma (p < 0.05). In conclusion, Le expression, especially that of type 1 H, was significantly associated with clinicopathological features. In gastric cancer patients, Le expression was altered in intestinal metaplasia and carcinoma in comparison with chronic gastritis.

Adhesins, Bacterial↗

Diagnostic yield of advanced colorectal neoplasia at colonoscopy, according to indications: an investigation from the Korean Association for the Study of Intestinal Diseases (KASID).

BACKGROUND AND STUDY AIMS: The factors that more accurately predict the detection of colorectal cancers and adenomas at colonoscopy are different. We conducted a prospective multicenter study to evaluate which indications were most closely associated with advanced colorectal neoplasm (CRN), including colorectal cancer, in a group of patients undergoing colonoscopy. PATIENTS AND METHODS: The 17 468 patients were enrolled in this study between July 2003 and March 2004, from 11 tertiary medical centers in Korea. They were recruited according to 11 itemized colonoscopic indications. The term "advanced adenoma" refers here to tubular adenomas of diameter of 11 mm or more, or to tubulovillous, villous, or severely dysplastic adenomas, irrespective of their size. Cancer was defined as the invasion of malignant cells beyond the muscularis mucosa. Advanced CRN was defined as advanced adenoma or invasive cancer. RESULTS: Advanced CRN was found in 1227/17 307 patients (1176 advanced adenomas plus 51 carcinomas, 7.1 %). According to univariate and multivariate analysis, the factors associated with advanced CRN included age >60 years (odds ratio (OR) 2.1, 95 % confidence interval (CI) 1.8 - 2.4, P < 0.0001), male gender (OR 2.1, 95 %CI 1.7 - 2.7, P < 0.0001), referral for colonoscopy from primary care physician (OR 3.1, 95 %CI 2.5 - 3.7, P < 0.0001), and several other indications (OR 1.8, 95 %CI 1.5 - 2.3, P < 0.001). The yield of colonoscopy for advanced CRN was lower (2.2 %) than expected in patients with iron-deficiency anemia (OR 0.5, 95 %CI 0.2 - 0.9, P = 0.03). CONCLUSIONS: Age, gender, and referral for colonoscopy from primary care physician constituted important independent predictors of advanced CRN in patients undergoing colonoscopy.

Adenoma↗

Prevalence of and risk factors for extracranial internal carotid artery stenosis in Korean Type 2 diabetic patients.

AIMS: The objectives of this study were to evaluate the prevalence of and risk factors for extracranial internal carotid artery stenosis in Type 2 diabetic patients. METHODS: This study included 406 patients aged 40-79 years with Type 2 diabetes (male 55.4%, female 44.6%). Both carotid arteries of each patient were examined by carotid duplex scanning. The duplex ultrasound criteria based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) measurement method were used for the identification of carotid stenosis. RESULTS: Extracranial internal carotid artery stenosis >or= 40% by velocity criteria was detected in 5.2% of the patients. The prevalence of carotid stenosis increased with advancing age: 1.0% at 40-49 years of age, 5.0% at 50-59 years, 7.3% at 60-69 years and 9.5% at 70-79 years. The degree of stenosis was > 70% in 42.9% of patients with stenosis, Bilateral stenosis was detected in 14% of patients. Of the patients with >or= 40% carotid stenosis, 33% had a decreased ankle-brachial index, 38% had a previous history of stroke, and only one patient (5%) had a documented history of coronary artery disease. Multivariate analysis, including variables determined to be significantly different by univariate analysis between patients with or without >or= 40% stenosis, indicated that age, systolic blood pressure and high-density lipoprotein (HDL)-cholesterol (inverse correlation) were independent risk factors associated with carotid stenosis. CONCLUSIONS: Carotid duplex scanning is a useful strategy in identifying carotid stenosis in older Type 2 diabetic patients with high systolic blood pressure, or low levels of HDL cholesterol. The early identification and subsequent appropriate management of carotid stenosis, particularly in this group of patients, may facilitate efforts to reduce the incidence of macrovascular complications.

Adult↗

Outcome after one-stage repair of tetralogy of Fallot.

AIM: The purpose of this study was to evaluate the outcome after one-stage repair of tetralogy of Fallot (TOF). METHODS: Between May 1997 and December 2002, 240 patients with a median age of 9 months (1 month-48 years) underwent one-stage repair of TOF. Closure of ventricular septal defect (VSD) was accomplished through the right atrium in 171 (71.3%) patients and through the right ventricle in 69 (28.7%) patients. For the reconstruction of the right ventricular outflow tract (RVOT), transannular repair was performed in 151 (62.9%) patients, and non-transannular repair was performed in 89 (37.1%) patients. Follow-up was complete, averaging 40+/-17.6 months (3 months-5.8 years). RESULTS: There were 2 (0.8%) operative deaths. Between early repair group (age under 6 months) and late repair group (age above 6 months), there were no differences in the method of RVOT reconstruction (transannular vs non-transannular) and the need for branch pulmonary artery angioplasty. Early repair group had more transventricular VSD closure than late repair group (46% vs 22%, P < 0.05). Duration of inotropic support and intensive care unit (ICU) stay were longer in the early repair group (P < 0.05). Five patients required reoperations due to RVOT obstruction (n = 3), and residual VSD (n = 2). Kaplan-Meier freedom from reoperation at 5 years was 98.3+/-1%. Nine patients underwent catheter intervention for branch pulmonary artery stenosis. Freedom from reintervention at 5 years was 95.4+/-1.5%. All survivors are currently asymptomatic. CONCLUSIONS: One-stage repair of TOF could be performed with low mortality and morbidity. Especially, early one-stage repair in symptomatic infant could be performed with low risk, eliminating the need for palliative procedures.

Abnormalities, Multiple↗

Sentinel node biopsy for cT1 and cT2a gastric cancer.

AIMS: To evaluate the feasibility and accuracy of sentinel node (SN) biopsy for gastric cancer. PATIENTS AND METHODS: One hundred patients with gastric cancer diagnosed as cT1 (n=80) or cT2a (n=20) were enrolled. Indocyanine green-stained SNs were analysed by hematoxylin and eosin staining (n=100) and by cytokeratin immunohistochemistry (n=50). RESULTS: SNs were identified in 94 of the 100 patients and the mean number of SNs was 4.4 (range, 1-12). Of these 94 patients, 14 patients had lymph node metastases. Two patients with T1 and one patient with T2 had metastases in non-SNs alone by hematoxylin and eosin staining (diagnostic accuracy =97.3% in T1 and 95.0% in T2). All three patients with a false negative result had a tumour, which was more than 4 cm in size and signet ring cell histology. In two of them, the tumour was located at lesser curvature. By immunohistochemical staining, three patients with T1 and one patient with T2 were found to have lymph node micrometastases in non-SNs alone among 45 patients (diagnostic accuracy =92.1% in T1, 85.7% in T2). CONCLUSION: SN biopsy using indocyanine green can be performed rapidly and easily with a high detection rate and accuracy in patients with T1 gastric cancer. However, it should be performed with caution for large tumours with a signet ring cell histology located at lesser curvature due to the possibility of a false negative result.

Adult↗

Primary colon lymphoma in Korea: a KASID (Korean Association for the Study of Intestinal Diseases) Study.

Although almost all primary colorectal lymphomas are of B-cell lineage in Western countries, primary colorectal T-cell lymphomas are not uncommon in the East. The aim of this study was to review the clinical characteristics and treatment outcomes of primary colorectal lymphomas, with special emphasis on the differences between T-cell and B-cell lymphomas. Ninety-five cases of primary colorectal lymphomas that satisfied Dawson's criteria were identified from the clinical databases of 13 university hospitals in Korea. The mean age at the time of presentation was 51.1 years and the male:female ratio was 64:31. The clinical information, including endoscopic and histological characteristics, was retrospectively analyzed. Of the primary colorectal lymphomas, 78 cases (82.1%) were of B-lineage and 17 cases (17.9%) were of T-cell lineage. Patients with T-cell lymphomas presented at a younger age than patients with B-cell lymphomas (42.8 vs 52.9 years, respectively; P = 0.016). The most common presenting symptom was abdominal pain (87.1%) for B-cell lymphomas, whereas hematochezia or night fever was more common for T-cell lymphomas (52.9% and 35.3%, respectively). The most common endoscopic type was fungating mass (54.0%) for B-cell lymphomas and ulcerative/ulcero-infiltrative lesions (80.0%) for T-cell lymphomas. Intussusception was more common in B-cell lymphomas than in T-cell lymphomas (30.8% vs 5.9%, respectively; P = 0.035), but perforation was more common in T-cell lymphomas than in B-cell lymphomas (23.5% vs 3.8%, respectively; P = 0.005). The prognosis was significantly worse for T-cell lymphomas than for B-cell lymphomas (P = 0.002). Primary colorectal T-cell lymphomas are characterized by multifocal ulcerative lesions in relatively young patients, a high rate of hematochezia, fever, or perforation, and a poor prognosis even for cases of localized disease.

Adolescent↗

Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non-germinal centre B-like diffuse large B-cell lymphomas.

AIMS: To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B-cell lymphomas (DLBCLs) of germinal centre (GC) and non-GC phenotypes. METHODS AND RESULTS: Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non-GC phenotype according to the immunohistochemical expression of bcl-6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non-GC phenotype (P = 0.004, P = 0.001, P < 0.001). Concurrent disruptions of the p16-Rb and p14-p53 pathways as represented by the immunoprofile of p16/p14/p53 (-/-/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (-/-/+) group versus 62 months in the other groups, P =0.0485]. CONCLUSIONS: The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non-GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (-/-/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.

Adolescent↗

Prognostic significance of the expression of Smad4 and Smad7 in human gastric carcinomas.

BACKGROUND: Transforming growth factor-beta (TGF-beta) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members. PATIENTS AND METHODS: To clarify the correlations between clinicopathologic profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method. RESULTS: Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour-node-metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors. CONCLUSION: Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas.

Adult↗

Alteration of E-cadherin-mediated adhesion protein is common, but microsatellite instability is uncommon in young age gastric cancers.

AIMS: Gastric adenocarcinoma in young patients has been considered to differ in many ways from gastric carcinoma in older patients. This study was designed to determine the clinicopathological features and molecular mechanisms. METHODS AND RESULTS: Based on 4123 patients of gastric cancer in Seoul National University Hospital, 135 patients (3.3%) were chosen by the age of 30 years or younger. Expression of E-cadherin, beta-catenin, p53 and Epstein-Barr virus (EBV) was analysed using the tissue array method in formalin-fixed paraffin-embedded specimens and microsatellite instability (MSI) was determined. As a control, 320 cases of older patients were compared. Gastric adenocarcinoma of young patients revealed significant female predominance, type IV gross type, proximal location, diffuse type and frequent lymph node metastasis. In-situ hybridization for EBV showed higher positivity in young patients (9/78, 11.5%) than in older ones, but not statistically significant. In EBV+ cases, p53 over-expression was significantly higher in young patients than older patients (P < 0.05). Alteration of E-cadherin or beta-catenin was significantly higher in younger patients than in older patients (P < 0.05). Overall survival was significantly poorer in younger patients than older ones. The frequency of MSI was rare (1.3%, P < 0.05) in young patients compared with older patients (9.3%). CONCLUSIONS: These data indicate that gastric adenocarcinoma of young patients has a poor prognosis, possesses aggressive histopathological features, exhibits reduced expression of E-cadherin and beta-catenin, and demonstrates lower MSI than tumours in older patients.

Adenocarcinoma↗

Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers.

Promoter hypermethylation of CpG islands in tumour suppressor genes can lead to transcriptional inactivation. To investigate the association between methylation and expression at O6-methylguanine-DNA methyltransferase, we performed methylation-specific PCR and immunohistochemistry in 149 gastric carcinomas. Promoter methylation was found in 14.1% of tumours and loss of expression was detected in 11.4% of tumours. To examine correlation between the O6-methylguanine-DNA methyltransferase expression and the clinical data, we investigated O6-methylguanine-DNA methyltransferase expression in 315 consecutive gastric carcinomas. A similar frequency of loss of O6-methylguanine-DNA methyltransferase expression was confirmed in these cases. The loss of O6-methylguanine-DNA methyltransferase expression was significantly associated with pTNM stage (P=0.037), tumour invasion (P=0.02), microsatellite instability (P=0.041) and overall survival (P=0.01). Among 11 gastric cancer cell lines, SNU-620 showed the loss of O6-methylguanine-DNA methyltransferase expression as well as promoter methylation. After treatment with 5-aza-2-deoxycytidine, a demethylating agent, SNU-620 re-expressed O6-methylguanine-DNA methyltransferase mRNA. In summary, we suggest that during gastric carcinogenesis, the loss of O6-methylguanine-DNA methyltransferase expression frequently occurs via the hypermethylation of the CpG islands of the promoter region, and that this is significantly associated with the clinicopathological characteristics.

Antimetabolites, Antineoplastic↗

Comprehensive analysis of promoter methylation and altered expression of hMLH1 in gastric cancer cell lines with microsatellite instability.

PURPOSE: Aberrant methylation of the promoter CpG island of hMLH1 is associated with gene silencing in colon cancer and gastric cancer with microsatellite instabilities (MSI). We analyzed the pattern of promoter methylation causing gene silencing. METHODS: Comprehensive analysis of hMLH1 promoter was performed by bisulfite genomic sequencing in human gastric cancer cell lines. Altered expression of hMLH1 was examined by the immunocytochemical staining method and RT-PCR, and microsatellite instability was examined using two representative mononucleotide repeat microsatellite markers, BAT-25 and BAT-26. RESULTS: As a result, MSI-positive gastric cancer cell lines were methylated extensively at the overall promoter region. MSI-negative gastric cancer cell lines - except in SNU-620 - were unmethylated completely at the overall promoter region including the more upstream region in contrast to colorectal cancer cell lines. Even though SNU-620 was methylated fully at the overall promoter region - except for partial methylation at the specific region (from -270 to -199) near the transcriptional start - hMLH1 protein was expressed. CONCLUSION: Our data suggest that the methylation density of a specific region plays an important role in gene inactivation of hMLH1 and that the methylation status of the more upstream promoter region and exon 1 start region are not essential for gene inactivation.

Adaptor Proteins, Signal Transducing↗

Comparison of two fibrin glues in anastomoses and skin closure.

To control intra-operative haemorrhage, fibrin glues are preferred by many surgeons because of their biological advantages and convenience of application. Manufacturers have developed a few kinds of fibrin glues with a little difference in their composition. This study was to compare the effectiveness of two commercially available fibrin glues; Greenplast (Green Cross P. D. Company, Yongin, Korea) and Tisseel (Baxter-Immuno AG, Vienna, Austria). They were applied experimentally to several kinds of surgery in dogs - renal vessel anastomosis, partial splenectomy, intestinal anastomosis and incision skin wound - and evaluated for their haemostatic and adhesive effects. When the two glues were applied in renal vessel anastomosis, the amount of haemorrhage in artery and vein decreased significantly. They also decreased the haemorrhage in partial splenectomy. At 10 min after application of the glues to an incision skin wound, the tensile strengths developed were significantly higher than that of control. The present study indicates that two-component fibrin glues have a haemostatic effect as a mechanical barrier in renal vessel anastomosis and an adhesive effect in the early stage of incision skin wound closure, and the two glues have similar effects with no complications.

Anastomosis, Surgical↗

Tracheal compression by elongated aortic arch in patients with congenitally corrected transposition of the great arteries.

We investigate the tracheal compression by aortic arch in patients with congenitally corrected transposition of the great arteries. Fourteen patients whose ascending aorta was connected to descending aorta on the contralateral side were divided into two groups according to the severity of tracheal compression on lateral angiogram: group 1 (stenosis > or = 50%, eight patients) and group 2 (stenosis < 50%, six patients). We compared the following variables between the groups: aortic size, lateral displacement of ascending aorta, retrosternal space, and contour of aortic arch. Spiral computed tomography (CT) was done in five patients of group 1. The ratio between measured and normal diameters of ascending aorta of group 1 was significantly larger than that of group 2 (1.57 +/- 0.14 compared to 1.19 +/- 0.26, p = 0.014). There was linear correlation between the tracheal compression and aortic size (r = 0.69, p = 0.001). The ascending aorta was positioned more laterally and the aortic arch was located more posteriorly in group 1. In four patients with decreased tracheal compression after surgery, aortic size decreased and the ascending aorta restored its anterior position. Spiral CT showed transversely oriented aortic arch and severe tracheal compression in the anteroposterior direction by aortic arch. The tracheal compression by aortic arch in corrected transposition is common when the descending aorta is located on the contralateral side of the ascending aorta. Aortic size, posterior position, elongation, and end-on appearance of the aortic arch are the useful predictors of tracheal compression.

Adolescent↗

Additive activation of hepatic NF-kappaB by ethanol and hepatitis B protein X (HBX) or HCV core protein: involvement of TNF-alpha receptor 1-independent and -dependent mechanisms.

Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)-mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB-inducing kinase (NIK), IkappaB kinase (IKK), or IkappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor a receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease.

Acetaldehyde↗

MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators.

BACKGROUND: Although mucin expressions appear to be correlated with prognoses in patients with various cancers, several studies have reported conflicting and inconclusive results on the prognostic significance of mucin expression in gastric carcinomas. METHODS: To clarify the correlations between clinicopathologic profiles and the patients' survival, the expression of MUC1, MUC2, MUC5AC, MUC6 mucins and the p53 protein were evaluated immunohistochemically in 300 consecutive gastric carcinomas using the tissue-array method. In addition, 59 gastric adenomas and 57 adenoma-associated carcinomas were investigated. RESULTS: MUC1 was expressed in 2 (3.4%) cases of gastric adenoma, and MUC2 in 19 (32.2%) cases of gastric adenoma, out of a total of 59 lesions. In consecutive gastric carcinomas, 24.3% of gastric carcinomas expressed MUC1, 27.3% expressed MUC2, 38.0% expressed MUC5AC and 12.7% expressed MUC6. The rate of MUC1 expression in gastric carcinomas was significantly higher than in associated gastric adenomas (P < 0.01). The patients with MUC1-positive carcinomas showed significantly poorer survival than those with MUC1-negative carcinomas. On the other hand, MUC2, MUC5AC and MUC6 expressions were not significantly associated with patient survival. Interestingly, combined evaluation revealed that the group with the MUC1-negative plus p53-negative expression pattern showed a better prognosis than the remaining cases. In contrast, the group with the MUC2-negative plus p53-positive pattern showed a worse prognosis. CONCLUSIONS: Mucin expression is altered in gastric adenoma and carcinoma, and MUC1 mucin expression is significantly associated with poorer outcome in gastric carcinomas. A MUC1-negative plus p53-negative pattern or a MUC2-negative plus p53-positive pattern may predict outcome in patients with gastric carcinomas.

Adenoma↗

Antimetastatic and antitumor effects of benzoquinonoid AC7-1 from Ardisia crispa.

An antimetastatic and cytostatic substance, termed AC7-1, was isolated from Ardisia crispa and identified as a benzoquinonoid compound, 2-methoxy-6-tridecyl-1,4-benzoquinone. It was originally characterized as the potent PAF (platelet-activating factor) receptor-binding antagonist with nonspecific antiplatelet effects on platelet aggregation induced by various agonists including PAF, ADP, thrombin and collagen. The nonspecific antiaggregatory properties of AC7-1 drew our interest given its possible relationship in integrin receptor-binding antagonistic activity. The integrin receptor plays an important role in metastasis and thrombosis as the cell surface transmembrane protein. Based on the aforementioned facts, the antimetastatic activities of AC7-1 were examined using various in vitro and in vivo metastasis assays. AC7-1 strongly blocked B16-F10 melanoma cell adhesion to extracellular matrix (ECM) and B16-F10 melanoma cell invasion. AC7-1 also remarkably inhibited pulmonary metastasis and tumor growth in vivo. AC7-1 inhibited B16-F10 melanoma cell adhesion to only specific synthetic peptides including RGDS. These findings suggest that antimetastatic activities of AC7-1 can be caused by blocking integrin-mediated adherence. We found AC7-1 to be a potential candidate for the development of a new antimetastatic drug.

Animals↗