1.Microsatellite Instability Is Associated with the Clinicopathologic Features of Gastric Cancer in Sporadic Gastric Cancer Patients.
Shin Hyuk KIM ; Byung Kyu AHN ; Young Su NAM ; Joo Youn PYO ; Young Ha OH ; Kang Hong LEE
Journal of Gastric Cancer 2010;10(4):149-154
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
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Humans
;
Microsatellite Instability
;
Microsatellite Repeats
;
Stomach Neoplasms
;
Succinimides
2.Qualitative and quantitative evaluation of root injury risk potentially burdening insertion of miniscrew implants.
Joanna ANTOSZEWSKA ; Paulina TRZESNIEWSKA ; Beata KAWALA ; Bjorn LUDWIG ; Hyo Sang PARK
Korean Journal of Orthodontics 2011;41(2):112-120
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
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Evaluation Studies as Topic
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Jaw
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Maxillary Sinus
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Molar
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Succinimides
3.Loss of Heterozygosity on Chromosome 15q15 Near Thrombospondin-1 Gene in Breast Carcinomas.
Jeana KIM ; Kyoung Mee KIM ; Heejeong LEE ; Kyungji LEE ; Mun Gan RHYU ; Anhi LEE ; Seok Jin KANG ; Kyo Young LEE
Korean Journal of Pathology 2009;43(3):221-230
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
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Breast
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Breast Neoplasms
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Loss of Heterozygosity
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Microsatellite Instability
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Microsatellite Repeats
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Neoplasm Metastasis
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Succinimides
4.Genetic Instability in Gastric Epithelial Neoplasias Categorized by the Revised Vienna Classification.
Woo Chul CHUNG ; Sung Hoon JUNG ; Kang Moon LEE ; Chang Nyol PAIK ; Jae Wuk KWAK ; Ji Han JUNG ; Jin Young YOO ; Min Kyoung LEE ; In Sik CHUNG
Gut and Liver 2010;4(2):179-185
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
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Chromosome Aberrations
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Genes, Tumor Suppressor
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Loss of Heterozygosity
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Microsatellite Instability
;
Microsatellite Repeats
;
Succinimides
5.Regression of Hyperplastic Gastric Polyp after Helicobacter pylori Eradication.
Sang Ah LIM ; Jae Won YUN ; Daewoong YOON ; Wonjae CHOI ; Seung Han KIM ; Jung Wan CHOE ; Mi Na KIM ; Eun Joo KANG ; Jong Jae PARK ; Moon Kyung JOO ; Beom Jae LEE ; Young Tae BAK ; Sang Woo LEE ; Jong Tae PARK
Korean Journal of Gastrointestinal Endoscopy 2011;42(2):74-82
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
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Helicobacter
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Helicobacter pylori
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Humans
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Incidence
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Polyps
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Stomach
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Succinimides
;
Surgical Instruments
6.Markers for Screening Lynch Syndrome Are Reliable and Useful for Identifying the Specimen Mislabeling.
Sun Ju BYEON ; Jiwoon CHOI ; Kyung Han NAM ; Bo Gun JANG ; Hee Eun LEE ; Min A KIM ; Woo Ho KIM
Korean Journal of Pathology 2012;46(2):131-136
BACKGROUND: During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. METHODS: We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). RESULTS: The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR<100. In addition, there were 153 cases (60.5%) of LR ranging from 100 to 10,000 and 100 cases (39.5%) of LR>10,000. Furthermore, the combined probability of identity was 9.23x10(-4) and the combined power of exclusion was 0.99908. CONCLUSIONS: Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.
Biometric Identification
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Colonic Neoplasms
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Colorectal Neoplasms, Hereditary Nonpolyposis
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Gene Frequency
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Humans
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Mass Screening
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Microsatellite Instability
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Microsatellite Repeats
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Pathology, Surgical
;
Succinimides
7.Transfection of hypertrophic cardiac myocytes in vitro with (99)Tc(m)-labeled antisense miR208b oligonucleotide.
Jing WANG ; Huijuan FENG ; Yangwei OU ; Yungang SUN ; Juqing WU ; Pan CHEN
Journal of Southern Medical University 2015;35(9):1316-1319
OBJECTIVETo test the efficiency of transfecting (99)Tc(m)-labeled anti-miR208b oligonucleotide into early hypertrophic cardiac myocytes in vitro.
METHODSThe anti-oligonucleotide targeting miR208b (AMO) was synthesized and modified with LNA followed by conjugation with N-hydroxysuccinimidyl S-acetyl-meraptoacetyl triglycine (NHS-MAG3) and radiolabeling with (99)Tc(m). NHS-MAG3-LNA-AMO and labeled AMO were purified with Sep-Pak C18 column chromatography, and the former was examined for UV absorption at the 260 nm using Gene Quant DNA/RNA calculator. The labeling efficiency, radiochemical purity, stability and molecular hybridization activity were analyzed. An angiotensin II-induced cell model of hypertrophic cardiac myocytes was transfected with (99)Tc(m)-NHS-MAG3-LNA-AMO via liposome, and the relative expression of miRNA208b and retention ratio of the labeled AMO in early hypertrophic cells were determined.
RESULTSThe labeling efficiency and radiochemical purity of the labeled AMO after purification exceeded 84% and 86%, respectively. The radio- chemical purities of the labeled AMO incubated in serum and normal saline for 12 h were both higher than 80%, and the labeled AMO showed a capacity to hybridize with the target gene. In the hypertrophic model of cardiac myocytes, the retention ratio of labeled AMO at 6 h was higher than 20%.
CONCLUSIONThe (99)Tc(m)-labeled antisense probe can be efficiently transfected into hypertrophic cardiac myocytes in vitro, which provides an experimental basis for subsequent radionuclide imaging studies.
Humans ; Isotope Labeling ; Liposomes ; MicroRNAs ; genetics ; Myocytes, Cardiac ; Oligonucleotides ; Oligonucleotides, Antisense ; Oligopeptides ; Radiopharmaceuticals ; Silicon Dioxide ; Succinimides ; Transfection
8.Effect of platelet CD42a modification by mPEG-SPA with different molecular masses.
Yin-ze ZHANG ; Wen XIONG ; Zhen LI ; Chao-peng SHAO ; Tian-jun LI ; Feng ZHAO ; Bao-cheng YANG
Journal of Southern Medical University 2007;27(3):392-393
OBJECTIVETo observe the effect platelet antigen modification by mPEG-SPA with different molecular masses.
METHODSPlatelet CD42a was modified by 5 kD and 20 kD mPEG-SPA, respectively, and the fluorescence intensity of CD42a was detect by flow cytometry and the three-dimensional structure of CD42a simulated to analyze the distribution of lysine in CD42a molecule.
RESULTSAfter platelet CD42a modification by 5 kD and 20 kD mPEG-SPA, the fluorescence intensity of CD42a decreased sharply by 85.54% and 88.65%, respectively, and multiple lysine regions were identified on the surface of CD42a molecule.
CONCLUSIONBoth 5 kD and 20 kD mPEG-SPA allow useful modification of platelet CD42a, but 20 kD mPEG-SPA is more advantageous than 5 kD mPEG-SPA.
Blood Platelets ; chemistry ; Humans ; Molecular Weight ; Platelet Glycoprotein GPIb-IX Complex ; chemistry ; Polyethylene Glycols ; chemistry ; Succinimides ; chemistry
9.Mutation and Expression of DNA2 Gene in Gastric and Colorectal Carcinomas.
Sung Hak LEE ; Yoo Ri KIM ; Nam Jin YOO ; Sug Hyung LEE
Korean Journal of Pathology 2010;44(4):354-359
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
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Colonic Neoplasms
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Colorectal Neoplasms
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DNA Repair
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Frameshift Mutation
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Immunohistochemistry
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Microsatellite Instability
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Stomach Neoplasms
;
Succinimides
;
Zinc Oxide
10.Clinicopathological Characteristics of Colorectal Cancer according to Microsatellite Instability.
Ki Tae SUK ; Hyun Soo KIM ; Jin Hyung LEE ; Bo Ra KIM ; Moon Young KIM ; Jae Woo KIM ; Soon Koo BAIK ; Sang Ok KWON ; Yosep CHONG ; Mee Yon CHO
Intestinal Research 2009;7(1):14-21
BACKGROUND/AIMS: Microsatellite instability (MSI) is associated with mutations in the DNA mismatch repair system and accounts for 10-15% of all cases of sporadic colorectal cancer (CRC). However, the characteristics and role of MSI as a marker for predicting the prognosis and therapeutic effect on CRC remain unclear. METHODS: Between June 2003 and December 2007, 259 patients (males, 159 [61%]; age, 63 [+/-11] years) who underwent surgery for CRC were retrospectively enrolled. The clinicopathologic characteristics of patients with high-frequency MSI (MSI-H) CRC were reviewed and compared to patients with low-frequency MSI or microsatellite stable CRC. The patient characteristics and MSI-related data were recorded for the following variables: gender, age, clinicopathologic findings, chemotherapy response, recurrence, and survival. RESULTS: MSI-H CRC was diagnosed in 30 patients (12%), low-frequency MSI CRC was diagnosed in 10 patients (4%), and microsatellite stable CRC in was diagnosed in 219 patients (84%). The MSI-H group exhibited the following characteristics: large size, right colon location, positive response to chemotherapy, low recurrence, longer survival, less neural invasion, poor differentiation, diffuse lymphoid reaction, and mucin pool formation. However, in the chemotherapy group (n=180), MSI-H was not a marker of longer survival. Based on Cox-regression analysis, stage IV CRC (OR=6.66; 95% CI, 2.24-53.00), MSI-H (OR=0.17; 95% CI, 0.04-0.73), and a positive response to chemotherapy (OR=0.02; 95% CI, 0.01-0.11) were related to mortality. CONCLUSIONS: MSI-H CRC had less neural invasion and diffuse lymphoid reaction. Further studies regarding the relationship between those pathologic findings and survival are needed.
Colon
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Colorectal Neoplasms
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DNA Mismatch Repair
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Humans
;
Microsatellite Instability
;
Microsatellite Repeats
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Mucins
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Prognosis
;
Recurrence
;
Retrospective Studies
;
Succinimides