PURPOSE: Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers. MATERIALS AND METHODS: Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used. RESULTS: MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer. CONCLUSIONS: MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.
Colorectal Neoplasms ; Humans ; Microsatellite Instability ; Microsatellite Repeats ; Stomach Neoplasms ; Succinimides

OBJECTIVE: Microscrew implants (MSIs) offer many advantages, but some complications are known to occur during their insertion. One of the most commonly reported complications is root injury. Our aim was to identify factors associated with root injury and to evaluate their qualitative and quantitative values. METHODS: Thirty-five orthodontists placed MSIs (AbsoAnchor(R), Dentos Co. Ltd, Daegu, Korea) in the upper jaw of typodonts, labially between the second premolar and the first molar, in low and high vertical positions. Root contacts were counted, and distances between MSI apices and roots were measured. Fear level of the orthodontists was surveyed before and after the experiment. Wilcoxon's test, chi-square test, and Mann-Whitney test were used for statistical analysis. RESULTS: Overall root contact rate of MSI insertion was 23.57%. The root contact rate was significantly higher in MSIs inserted at 90degrees (45.71%) than at 30degrees (1.43%). The distance between the dental root and MSI also increased significantly in MSIs inserted at 30degrees. Mean fear level before MSI insertion (4.6) significantly decreased after insertion (3.2); the causative factors were risk of injury to dental root and maxillary sinus or mandibular canal. CONCLUSIONS: Root injury is relatively rare, and oblique angulation reduces the risk of root and MSI contact.
Bicuspid ; Evaluation Studies as Topic ; Jaw ; Maxillary Sinus ; Molar ; Succinimides

BACKGROUND: Chromosome 15q15 near the thrombospondin-1 (THBS-1) gene may be associated with tumor progression and metastasis. To clarify the potential role of the15q15 region in progression of breast carcinoma, we investigated the loss of heterozygosity (LOH) and the microsatellite instability (MSI) status of chromosome 15q15. Methods : LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. METHODS: LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. RESULTS: Of 77 breast carcinomas containing the heterozygous alleles, 25 (32%) showed LOH in at least one microsatellite marker. Partial LOH and total LOH were detected in 14 (18.27%) and 11 (14.3%) cases. The total LOH were inversely correlated with node metastasis. A single LOH at D15S514 was inversely correlated with nuclear grade and a single LOH at the D15S129 allele was associated with increased expression of the THBS-1 gene. MSI-positive breast carcinomas detected in 14 (17%) cases showed no correlation with any clinicopathologic feature. CONCLUSIONS: These results indicate that loss of the chromosome 15q15 region delays the progression of breast carcinoma because the magnitude of LOH is large and involves the THBS-1 gene and additional genetic elements. The genes located on chromosome 15q15 probably play a tissue-type-dependent role in malignant growth of the tumor.
Alleles ; Breast ; Breast Neoplasms ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats ; Neoplasm Metastasis ; Succinimides

BACKGROUND/AIMS: The aim of this study was to determine the structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), at multiple tumor suppressor gene loci in gastric epithelial neoplasia categorized by the revised Vienna classification. METHODS: All tissue samples were excised by endoscopic mucosal resection. Sixty category 3 (low-grade adenoma) tissue samples and 51 category 4 samples (high-grade adenoma and intramucosal carcinoma with adenoma) were examined at the 7 sets of microsatellite loci linked to the tumor suppressor gene locus. RESULTS: For category 3 and 4 tissue samples, there were no differences in the frequencies of LOH-positive chromosomes or the extent of chromosomal loss. The Helicobacter-pylori (H. pylori)-positive rate was significantly higher in MSI-positive category 4 samples than in category 3 samples (p=0.04). The frequency of MSI positivity was significantly higher in category 4 samples than in category 3 samples (p=0.003). CONCLUSIONS: H. pylori infection is associated with genetic instability of the premalignant lesion. MSI occurs in the early stages of gastric carcinogenesis and its occurrence increases during malignant transformation. Detection of MSI in premalignant gastric lesions may be a surveillant of risk of malignant transformation.
Adenoma ; Chromosome Aberrations ; Genes, Tumor Suppressor ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats ; Succinimides

BACKGROUND/AIMS: Recent studies have suggested that the eradication of Helicobacter pylori (Hp) may lead to the regression of hyperplastic polyps (HPPs) in the stomach. We evaluated the sizes of HPPs after Hp eradication and we also compared the clinical parameters between the regression and non-regression groups. METHODS: We enrolled 187 patients who had HPPs in the stomach. The polyps were measured by using biopsy forceps, and the endoscopically observed changes of the polyps were assessed by two endoscopists. RESULTS: Total regression was observed in 68 patients of the eradicated group and in 6 patients in the non-eradicated group (42.5% vs. 22.2%, respectively, p<0.05). The non regression rate was significantly higher for the non-eradicated group than that for the eradicated group (33% vs. 10%, respectively, p<0.05). Comparing between the regression and non-regression groups, the incidence of polyps that were smaller than 10 mm in size and sessile was significantly higher in the regression group. Hp eradication was the only significant predictor of regression. CONCLUSIONS: Hp eradication could be a therapeutic option for Hp positive-hyperplastic gastric polyps, and especially for those that are less than 10 mm in size and sessile.
Biopsy ; Helicobacter ; Helicobacter pylori ; Humans ; Incidence ; Polyps ; Stomach ; Succinimides ; Surgical Instruments

PURPOSE: The aim of this study was to determine whether insulin resistance may be present and to analyze factors affecting the development of insulin resistance in children and adolescents born small for gestational age (SGA). METHODS: This study includes 24 children and 18 SGA adolescents and 13 children and 14 control adolescents. All patients underwent a standard, 2-hour oral glucose tolerance test (OGTT). Serum levels of fasting blood sugar, insulin, leptin, adiponectin, homeostasis model assessment-insulin resistance (HOMA- IR), quantitative insulin sensitivity check index (QUICKI), insulin sensitivity index (ISI), mean serum insulin (MSI) and mean serum glucose (MSG) were evaluated. RESULTS: The insulin responses at 30 min and 120 min after glucose load were significantly higher in pubertal SGA than control groups (P<0.05). Impaired glucose tolerance was found from 2 subjects (8.7 %) in prepubertal SGA group and from 3 subjects (15.0%) in pubertal SGA group. None of the patients had developed type 2 diabetes. MSI levels during OGTT were higher in pubertal SGA than in control. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group (9.04+/-4.51 vs. 18.83+/-11.65 microgram/mL, P<0.05). Adiponectin level was correlated with HOMA-IR, QUICKI and ISI (r=-0.37, r=0.32, r=0.51, respectively, P<0.05). CONCLUSION: Adiponectin level was correlated with HOMA-IR, QUICKI and ISI. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group. We suggest the check of insulin resistance using HOMA-IR, QUICKI, ISI and adiponectin is important for the prevention of metabolic syndrome (MS) in adolescents born SGA.
Adiponectin ; Adolescent ; Blood Glucose ; Child ; Fasting ; Gestational Age ; Glucose ; Glucose Tolerance Test ; Homeostasis ; Humans ; Infant ; Insulin ; Insulin Resistance ; Leptin ; Succinimides

PURPOSE: The aim of this study was to investigate the immunomodulatory effects of canine periodontal ligament stem cells on allogenic and xenogenic immune cells in vitro. METHODS: Mixed cell cultures consisting of canine stem cells (periodontal ligament stem cells and bone marrow stem cells) and allogenic canine/xenogenic human peripheral blood mononuclear cells (PBMCs) were established following the addition of phytohemagglutinin. The proliferation of PBMCs was evaluated using the MTS assay. The cell division of PBMCs was analyzed using the CFSE assay. The apoptosis of PBMCs was assessed using the trypan blue uptake method. RESULTS: Periodontal ligament stem cells and bone marrow stem cells inhibited the proliferation of allogenic and xenogenic PBMCs. Both periodontal ligament stem cells and bone marrow stem cells suppressed the cell division of PBMCs despite the existence of a mitogen. No significant differences in the percentages of apoptotic PBMCs were found among the groups. CONCLUSIONS: Canine periodontal ligament stem cells have an immunomodulatory effect on allogenic and xenogenic PBMCs. This effect is not a product of apoptosis of PBMCs but is caused by the inhibition of cell division of PBMCs.
Apoptosis ; Bone Marrow ; Cell Culture Techniques ; Cell Division ; Diminazene ; Fluoresceins ; Humans ; Immunomodulation ; Ligaments ; Periodontal Ligament ; Stem Cells ; Succinimides ; Trypan Blue

PURPOSE: Hepatocellular carcinoma (HCC) shows various molecular and genetic alterations in its development and progression. Recently, microsatellite instability (MSI) and the loss of heterozygosity (LOH), have been postulated as useful prognostic factors in many malignant tumors. LOH is related to the allelic loss of various tumor suppressor genes, however, MSI has been found to be the result of a mismatched DNA pairing. Our objectives were to evaluate MSI and p53 gene LOH and to correlate this to clinicopathological factors. METHODS: MSI analysis was performed by using polymerase chain reaction with 5 microsatellite markers (BAT25, BAT26, D2S123, D5S346 and D17S250 recommended in the 1998 NCI International Workshop) on 50 surgically resected tumors. p53 LOH was detected with 4 markers (D17S796, TP53, D17S5, D17S513). RESULTS: MSI and p53 LOH were detected in 30% and 66%, respectively. 18% of HCCs exhibited MSI in 5 NCI-recommended markers and 18% of HCCs demonstrated MSI in 4 p53 markers. MSI was mostly detected in BAT25 and BAT26 markers. MSI was more frequently detected in tumor grade I, small HCC, and non-lymphovascular group. For the most part, p53 LOH was detected by D17S513 marker (38.1%). p53 LOH results were correlated with higher tumor grade and invasiveness. LOH-High group showed a significant correlation with advanced HCCs and lymphovascular invasion. There was no demonstrated correlation between MSI and p53 LOH was not demonstrated. CONCLUSION: These results suggest that MSI may be involved to some extent in hepatocarcinogenesis and tumor invasion. Also MSI and p53 gene LOH may be a useful clinical indicator in determining the prognosis among patients with HCC.
Carcinoma, Hepatocellular ; DNA ; Genes, p53 ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Microsatellite Instability ; Microsatellite Repeats ; Polymerase Chain Reaction ; Prognosis ; Succinimides

BACKGROUND: Deregulation of DNA repair and replication are involved in cancer development. DNA2 is a nuclease/helicase that plays roles in DNA repair and replication. The aim of this study was to explore DNA2 mutation and DNA2 protein expression in gastric cancers (GCs) and colorectal cancers (CRCs). METHODS: We analyzed two mononucleotide repeats in DNA2 in 27 GCs with high microsatellite instability (MSI-H), 34 GCs with stable MSI (MSS), 29 CRCs with MSI-H and 35 CRCs with MSS by single-strand conformation polymorphism. We also analyzed DNA2 expression in GCs and CRCs either with MSI-H or MSS. RESULTS: We found DNA2 mutations in two GCs (7.1%) and two CRCs with MSI-H (6.9%), but not in cancers with MSS. The mutations consisted of three cases of a c.2593delT and one of a c.2592_2593delTT, which would result in premature stopping of amino acid synthesis (p.Ser865Hisfsx6 and p.Ser865Thrfsx20, respectively). DNA2 expression was observed in 16 (80%) of the GCs and 15 (75%) of the CRCs with MSI-H, but all of the cancers with DNA2 frameshift mutations were weak or negative for DNA2. CONCLUSIONS: Our data indicate that DNA2 mutation and loss of DNA2 expression occur in GCs and CRCs, and suggest that these alterations may contribute to cancer pathogenesis by deregulating DNA repair and replication.
Calcium Hydroxide ; Colonic Neoplasms ; Colorectal Neoplasms ; DNA Repair ; Frameshift Mutation ; Immunohistochemistry ; Microsatellite Instability ; Stomach Neoplasms ; Succinimides ; Zinc Oxide

PURPOSE: Microsatellite instability-high (MSI-H) colorectal cancer (CRC) displays a well-described distinct phenotype, but the true biological significance of MSI-low (L) is still uncertain. To clarify the significance of this MSI-L, we studied the differences between patients with CRC with MSI-H, MSI-L, and microsatellite stability (MSS). METHODS: A total of 723 consecutive patients (429 males and 294 females) who had undergone resections between September 2002 and August 2007 were studied. We analyzed the clinicopathological features, the MSI statuses, and the prognoses of the 723 CRC patients. RESULTS: MSI-H was observed in 54 (7.5%), MSI-L in 27 (3.7%), and MSS in 642 (88.8%) of the 723 colorectal cancer patients. MSI-L and MSS CRC share similar clinicopathological features. A univariate analysis showed no significant differences in overall survival between MSI-L, MSS, and MSI-H. In the multivariate Cox regression analysis, MSI-L was significantly (P=0.036) associated with poorer prognosis compared with MSS tumors, after adjustment for factors previous shown to be associated with the survival based on potentially relevant variables. CONCLUSION: In conclusion, the current study showed no difference in the clinicopathological features of MSI-L versus MSS CRCs. However, in the multivariate analysis, patients with MSI-L CRCs had significantly poorer overall survival. Finally, these findings support the existence of MSI-L CRCs as a distinct category. Thus, further studies are required to explore possible reasons for the adverse prognosis associated with MSI-L cancers.
Calcium Hydroxide ; Colorectal Neoplasms ; Humans ; Male ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Phenotype ; Prognosis ; Succinimides ; Zinc Oxide