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1.
Article in English | WPRIM | ID: wpr-898226

ABSTRACT

Background@#Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). @*Methods@#A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. @*Results@#Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. @*Conclusion@#The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

2.
Article in English | WPRIM | ID: wpr-890522

ABSTRACT

Background@#Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). @*Methods@#A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome. @*Results@#Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group. @*Conclusion@#The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

3.
Chonnam Medical Journal ; : 99-103, 2019.
Article in English | WPRIM | ID: wpr-763277

ABSTRACT

Breast cancer is the second most common cancer in Korean women. Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast cancer and are detected in 15–20% of hereditary breast cancer. We investigated the BRCA1 and BRCA2 mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of BRCA1 and BRCA2 in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The BRCA1/2 mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons.


Subject(s)
BRCA1 Protein , BRCA2 Protein , Breast Neoplasms , Breast , Exons , Female , Genes, BRCA2 , Germ-Line Mutation , Humans , Korea , Mutation Rate , Polymorphism, Single Nucleotide
4.
Chonnam Medical Journal ; : 31-35, 2018.
Article in English | WPRIM | ID: wpr-787260

ABSTRACT

We aimed to evaluate the prevalence of familial hypercholesterolaemia (FH) in a subject with hypercholesterolaemia from two population-based cohorts in South Korea. A total of 283 subjects with total cholesterol levels of 290 mg/dL (7.5 mmol/L) or higher were selected from the Namwon and Dong-gu Studies. We used next generation sequencing (NGS) to detect mutations in low-density lipoprotein receptors (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. We have confirmed 17 different mutations of the LDLR, APOB and PCSK9 in 23 subjects (8.1%). Eleven LDLR variants and one APOB variant have been previously reported. One LDLR and two PCSK9 rare variants were identified in the variants database, but not in the FH mutation database. Two novel LDLR variants were found, p.Leu680Val, and p.Thr734Phe. No LDLR, APOB or PCSK9 deletions nor insertions were found. When the subjects were restricted to 110 subjects with a total cholesterol ≥310 mg/dL, only 10 variants were found in the 10 subjects (9.1%). These results suggest that given the low prevalence of FH mutations in subjects with high total cholesterol levels, NGS-based testing for a population-based approach to FH detection may not be cost-effective.


Subject(s)
Apolipoproteins , Apolipoproteins B , Cholesterol , Cohort Studies , High-Throughput Nucleotide Sequencing , Hyperlipoproteinemia Type II , Korea , Prevalence , Proprotein Convertases , Receptors, Lipoprotein
5.
Article in English | WPRIM | ID: wpr-714823

ABSTRACT

BACKGROUND: We investigated the association between pentraxin 3 (PTX3), a novel inflammatory marker, and bone mineral density (BMD) in the general Korean population. METHODS: We selected a sub-cohort of 1,440 subjects (757 men and 683 women) from participants in the community-based Dong-gu Study. The mean age was 66.0 ± 8.1 years for men and 63.7 ± 7.9 years for women. The plasma PTX3 levels were measured using an enzyme-linked immunosorbent assay, and BMD was measured in the femoral neck and lumbar spine using dual-energy X-ray absorptiometry. Linear regression analyses were used to evaluate the association between the plasma PTX3 levels and BMD. RESULTS: PTX3 was inversely associated with the BMD of the lumbar spine (P = 0.010) and femoral neck (P < 0.001) in men but not in women. For men, the association with the BMD of the femoral neck remained after adjustment for multiple comparison (P = 0.020). CONCLUSION: This study suggests that PTX3 levels might be inversely associated with BMD in elderly men.


Subject(s)
Absorptiometry, Photon , Aged , Bone Density , Enzyme-Linked Immunosorbent Assay , Female , Femur Neck , Humans , Linear Models , Male , Plasma , Spine
6.
Article in English | WPRIM | ID: wpr-129233

ABSTRACT

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.


Subject(s)
Alleles , Biomarkers , Cell Line , Cell Proliferation , Chemotherapy, Adjuvant , Colon , Colonic Neoplasms , Fluorouracil , Genotype , Humans , Leucovorin , Lymphocytes , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Receptor, Fibroblast Growth Factor, Type 4 , Signal Transduction
7.
Article in English | WPRIM | ID: wpr-129219

ABSTRACT

PURPOSE: Fibroblast growth factor receptor 4 (FGFR4) plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of FGFR4 polymorphism in patients with resected colon cancer, including the underlying mechanism. MATERIALS AND METHODS: FGFR4 polymorphism was characterized in patientswho received curative resection for stage III colon cancer. FGFR4-dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines. RESULTS: Among a total of 273 patients, the GG of FGFR4 showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele. CONCLUSION: The Arg388 allele of FGFR4 may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.


Subject(s)
Alleles , Biomarkers , Cell Line , Cell Proliferation , Chemotherapy, Adjuvant , Colon , Colonic Neoplasms , Fluorouracil , Genotype , Humans , Leucovorin , Lymphocytes , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Receptor, Fibroblast Growth Factor, Type 4 , Signal Transduction
8.
Article in English | WPRIM | ID: wpr-170079

ABSTRACT

PURPOSE: The purpose of this study is to investigate the role of fibroblast growth factor receptor 4 (FGFR4) polymorphism in esophageal cancer after chemoradiotherapy (CRT). MATERIALS AND METHODS: Peripheral blood samples from 244 patients treated with CRT for esophageal squamous cell carcinoma were assessed for the role of FGFR4 genotype on treatment response and survival. RESULTS: A total of 94 patients were homozygous for the Gly388 allele, and 110 were heterozygous and 40 homozygous for the Arg388 allele. No significant association was found between the FGFR4 genotype and clinicopathological parameters. However, patients carrying the Gly388 allele showed a better overall response rate than Arg388 carriers (p=0.038). In addition, Gly388 allele patients at an earlier stage showed better overall survival (OS) and progression-free survival than Arg388 carriers. Among these, the Gly388 allele showed significantly improved OS compared to Arg388 carriers in the lymph node (LN) metastasis group (p=0.042) compared to the no LN metastasis group (p=0.125). However, similar survival outcomes were observed for advanced-stage disease regardless of genotype. CONCLUSION: This result suggests that the role of FGFR4 Gly388 in treatment outcomes differs according to esophageal cancer stage. It showed a predictive role in the response of esophageal cancer patients to CRT with a better trend for OS in Gly388 than Arg388 carriers in the early stages. In particular, LN-positive early-stage patients carrying the Gly388 allele showed improved OS compared to those carrying Arg388.


Subject(s)
Alleles , Biomarkers , Carcinoma, Squamous Cell , Chemoradiotherapy , Disease-Free Survival , Esophageal Neoplasms , Genotype , Humans , Lymph Nodes , Neoplasm Metastasis , Receptor, Fibroblast Growth Factor, Type 4
9.
Chonnam Medical Journal ; : 59-63, 2016.
Article in English | WPRIM | ID: wpr-169469

ABSTRACT

Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population-based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD.


Subject(s)
Absorptiometry, Photon , Apolipoproteins E , Asians , Bone Density , Cohort Studies , Dataset , Female , Femur Neck , Genotype , Humans , Male , Polymorphism, Genetic , Spine
10.
Chonnam Medical Journal ; : 59-63, 2016.
Article in English | WPRIM | ID: wpr-788325

ABSTRACT

Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population-based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD.


Subject(s)
Absorptiometry, Photon , Apolipoproteins E , Asians , Bone Density , Cohort Studies , Dataset , Female , Femur Neck , Genotype , Humans , Male , Polymorphism, Genetic , Spine
11.
Article in English | WPRIM | ID: wpr-210702

ABSTRACT

We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C-reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C-reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway.


Subject(s)
Aged , Apolipoproteins E/genetics , C-Reactive Protein/metabolism , Female , Genetic Association Studies , Genotype , Humans , Inflammation/blood , Leukocyte Count , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Polymorphism, Single Nucleotide/genetics , Prospective Studies , Republic of Korea
12.
Article in English | WPRIM | ID: wpr-60722

ABSTRACT

The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (microM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea.


Subject(s)
Age Factors , Aged , Aging , Cohort Studies , Female , Folic Acid/blood , Genotype , Homocysteine/blood , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Reference Values , Republic of Korea , Sex Factors
13.
Article in English | WPRIM | ID: wpr-190497

ABSTRACT

BACKGROUND: Few studies have investigated the association between Apolipoprotein E (APOE) polymorphisms and chronic kidney disease (CKD) in the general population, and their results are inconsistent. METHODS: The current study population was composed of 9,033 subjects aged > or = 50 years who participated in the baseline survey of the Dong-gu Study, which was conducted in Korea between 2007 and 2010. APOE polymorphisms were identified by polymerase chain reaction, and the estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. RESULTS: Individuals with the APOE E2 allele had significantly lower total and low density lipoprotein cholesterol levels, those with the APOE E4 allele had lower high density lipoprotein (HDL) cholesterol levels, and those with the APOE E3 allele had lower log-triglyceride levels. Adjusting for covariates (sex, age, body mass index, smoking, systolic blood pressure, hypertension, diabetes, total cholesterol, HDL cholesterol, log-transformed triglycerides, and log-transformed albumin to creatinine ratio), mean eGFR was not significantly different among APOE alleles (E2, 69.4 mL/min/1.73 m2; E3, 69.5 mL/min/1.73 m2; E4, 69.4 ml/min/1.73 m2; P = 0.873). Additionally, the odds ratios (ORs) indicated that APOE polymorphisms were not independent risk factors for CKD (OR, 1.07; 95% confidence interval [CI], 0.91 to 1.26 for the E2 vs. E3 allele; OR, 1.01; 95% CI, 0.88 to 1.16 for the E4 vs. E3 allele). CONCLUSION: APOE polymorphisms were not associated with either eGFR or CKD in the general Korean population.


Subject(s)
Alleles , Apolipoproteins E , Apolipoproteins , Blood Pressure , Body Mass Index , Cholesterol , Cholesterol, HDL , Cholesterol, LDL , Creatinine , Surveys and Questionnaires , Diet , Glomerular Filtration Rate , Hypertension , Korea , Lipoproteins , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Genetic , Renal Insufficiency, Chronic , Risk Factors , Smoke , Smoking , Triglycerides
14.
Article in English | WPRIM | ID: wpr-25352

ABSTRACT

SUV39H1 is a histone 3 lysine 9 (H3K9)-specific methyltransferase that is important for heterochromatin formation and the regulation of gene expression. Chaetocin specifically inhibits SUV39H1, resulted in H3K9 methylation reduction as well as reactivation of silenced genes in cancer cells. Histone deacetylase (HDAC) inhibitors inhibit deacetylases and accumulate high levels of acetylation lead to cell cycle arrest and apoptosis. In this study, we demonstrated that treatment with chaetocin enhanced apoptosis in human leukemia HL60, KG1, Kasumi, K562, and THP1 cells. In addition, chaetocin induced the expression of cyclin-dependent kinase inhibitor 2B (p15), E-cadherin (CDH1) and frizzled family receptor 9 (FZD9) through depletion of SUV39H1 and reduced H3K9 methylation in their promoters. Co-treatment with chaetocin and HDAC inhibitor trichostatin A (TSA) dramatically increased apoptosis and produced greater activation of genes. Furthermore, this combined treatment significantly increased loss of SUV39H1 and reduced histone H3K9 trimethylation responses accompanied by increased acetylation. Importantly, co-treatment with chaetocin and TSA produced potent antileukemic effects in leukemia cells derived from patients. These in vitro findings suggest that combination therapy with SUV39H1 and HDAC inhibitors may be of potential value in the treatment of leukemia.


Subject(s)
Acetylation/drug effects , Adolescent , Adult , Aged , Apoptosis/drug effects , Cadherins/metabolism , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p15/metabolism , DNA Methylation/drug effects , Enzyme Inhibitors/therapeutic use , Frizzled Receptors/metabolism , Gene Expression Regulation/drug effects , HL-60 Cells , Histone Deacetylase Inhibitors/therapeutic use , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Histones/genetics , Humans , Hydroxamic Acids/therapeutic use , K562 Cells , Leukemia/drug therapy , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Piperazines/therapeutic use , Promoter Regions, Genetic , Young Adult
15.
Article in English | WPRIM | ID: wpr-202306

ABSTRACT

The purpose of this study was to examine the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and bone mineral density (BMD). Two large cohort studies were performed: the Dong-gu Study (3,621 men and 5,409 women) and the Namwon Study (3,703 men and 5,672 women). We assessed lumbar spine and femoral neck BMD by dual-energy X-ray absorptiometry. Genotypes were determined by real-time polymerase chain reaction. Multiple linear regression analysis was performed to evaluate the association between MTHFR C677T and BMD, adjusting for age, weight and height. The MTHFR C677T genotype frequencies for CC, CT, and TT genotypes were 34.5, 48.7, and 16.8%, respectively, in the Dong-gu Study and 33.6, 49.2, and 17.2%, respectively, in the Namwon Study. There are no significant differences between the MTHFR C677T genotype and the BMD at the lumbar spine and femoral neck in men or women in both cohorts.


Subject(s)
Absorptiometry, Photon , Aged , Alleles , Bone Density , Cohort Studies , Female , Femur Neck/diagnostic imaging , Gene Frequency , Genotype , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Polymorphism, Single Nucleotide
16.
Article in English | WPRIM | ID: wpr-123289

ABSTRACT

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Azacitidine/pharmacology , DNA Methylation/drug effects , DNA Modification Methylases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Female , Genes, Tumor Suppressor , Humans , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Young Adult
17.
Article in Korean | WPRIM | ID: wpr-761093

ABSTRACT

Benign paroxysmal positional vertigo (BPPV) of anterior semicircular canal (ASC) is the rarest variant of BPPV, which is thought to be due to the anatomically superior position of ASC during most activities. This type of BPPV is currently diagnosed by detecting positional down-beating nystagmus in the Dix-Hallpike test. A 62-year-old female presented with positional vertigo, especially when sitting up. No nystagmus was induced by both Dix-Hallpike tests, however, positional down-beating nystagmus was observed with the left torsional component when sitting up from both Dix-Hallpike positions and supine position. After the reverse Epley maneuver, up-beating nystagmus was newly observed in the left Dix-Hallpike test, which was compatible with BPPV of the left posterior semicircular canal. This patient was thought to suffer from canalithiasis of the left ASC.


Subject(s)
Female , Humans , Middle Aged , Semicircular Canals , Supine Position , Vertigo
18.
Article in English | WPRIM | ID: wpr-720125

ABSTRACT

BACKGROUND: All-trans retinoic acid (ATRA)/anthracycline chemotherapy is beneficial in newly diagnosed acute promyelocytic leukemia (APL); however, it is important to identify patients with high-risk disease to increase the cure rate. We investigated the outcome of ATRA/anthracycline chemotherapy and clinicobiological correlations of FLT3/ITD and NPM1 mutations in APL patients. METHODS: Induction therapy included oral ATRA (45 mg/m2/day) and idarubicin (12 mg/m2/day, intravenous, on days 2, 4, and 6). Patients achieving complete remission (CR) received 3 courses of ATRA combined with reinforced consolidation therapy. Mutations were analyzed using GeneScan and polymerasae chain reaction assays of bone marrow samples obtained from patients at diagnosis. RESULTS: Forty-five (84.9%) of 53 eligible patients achieved CR. The overall relapse rate was 8.9%, and the 3-year overall survival (OS) and leukemia-free survival (LFS) were 84.9+/-4.9% and 77.5+/-6.0%, respectively. The NPM1 mutation was not found in any patient, while the FLT3/ITD mutation was found in 10 (20.0%) patients. Of the FLT3/ITD+ patients, 80% belonged to the high-risk group, defined according to the presenting WBC and platelet counts. Among the patients who achieved CR, those who were FLT3/ITD+ had a higher relapse rate than those FLT3/ITD-. FLT3/ITD+ patients also had a significantly lower 3-year LFS than FLT3/ITD- patients. Multivariate analysis of the LFS showed that the FLT3/ITD mutation was independently associated with a shorter overall LFS, after adjusting for pretreatment risk stratification. CONCLUSION: This study investigated the clinical outcome of newly diagnosed APL patients treated with ATRA/anthracycline chemotherapy. Patients carrying the FLT3/ITD mutation had more aggressive clinical features and a poorer clinical outcome.


Subject(s)
Bone Marrow , Drug Therapy, Combination , Humans , Idarubicin , Leukemia, Promyelocytic, Acute , Lifting , Multivariate Analysis , Platelet Count , Prognosis , Recurrence , Treatment Outcome , Tretinoin
19.
Article in English | WPRIM | ID: wpr-721029

ABSTRACT

BACKGROUND: Nucleophosmin (NPM1) gene and fms-like tyrosine kinase 3 gene-internal tandem duplication (FLT3-ITD) mutations are the most frequent mutations in patients with cytogenetically normal (CN)-AML. We analyzed the prognostic impact of these mutations and their interactions in adults with CN-AML. METHODS: NPM1 mutation (NPM1mut) and FLT3-ITD mutation (FLT3-ITD+) were analyzed by GeneScan and PCR assays of bone marrow samples obtained from 121 adult patients with CN-AML (age< or =60 years at diagnosis). RESULTS: The incidence of FLT3-ITD+ was higher in the NPM1mut group than in the wild-type NPM1 gene (NPM1wt) group. The patients were divided according to their mutation status into the NPM1mut/FLT3-ITD (isolated NPM1mut), NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-, and NPM1wt/FLT3-ITD+ (isolated FLT3-ITD+) groups. The isolated NPM1mut group showed significantly better clinical outcomes in terms of relapse rate, 5-year relapse-free survival (RFS), and overall survival (OS) than the other groups. In contrast, the isolated FLT3-ITD+ group had a higher relapse rate and shorter RFS and OS than the other groups. The 5-year RFS rate was much higher among the patients who underwent allogeneic stem cell transplantation (alloSCT) than among those treated with high-dose cytarabine chemotherapy (HDAC) only as consolidation therapy in the isolated NPM1mut group and the NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD- group. CONCLUSION: Adult patients with CN-AML carrying isolated NPM1mut and isolated FLT3-ITD+ exhibit different clinical outcomes than those with NPM1mut/FLT3-ITD+ or NPM1wt/FLT3-ITD-. Although isolated NPM1mut leads to favorable clinical outcomes of CN-AML, the role of alloSCT in such patients remains to be considered.


Subject(s)
Adult , Bone Marrow , Cytarabine , fms-Like Tyrosine Kinase 3 , Humans , Incidence , Leukemia, Myeloid, Acute , Lifting , Nuclear Proteins , Polymerase Chain Reaction , Recurrence , Stem Cell Transplantation
20.
Article in English | WPRIM | ID: wpr-101488

ABSTRACT

This study examined the prevalence of oral microbes in the saliva of oncological patients and healthy subjects. PCR was used to assess the frequency of oral microbes including 3 cariogenic bacteria, 5 periodontopathic bacteria and 4 Candida species in the saliva of 104 oncological patients and 52 healthy subjects. Among these microorganims, Streptococcus mutans, Fusobacterium nucleatum and Candida albicans were most frequently detected in both groups. There were no significant differences in the prevalence of cariogenic bacteria between the patient and healthy groups, whereas significant differences in the frequency of Porphyromonas gingivalis and Tannerella forsythia were observed between the two groups (p < 0.05). The prevalence of all five periodontopathogens was higher in the healthy group than in the patient group. The prevalence of C. albicans in patients was significantly higher than that of healthy group (p < 0.05). In conclusion, there were significant differences in the prevalence of P. gingivalis, T. forsythia and C. albicans between the oncological patient group and healthy group.


Subject(s)
Bacteria , Candida , Candida albicans , Forsythia , Fusobacterium nucleatum , Humans , Polymerase Chain Reaction , Porphyromonas gingivalis , Prevalence , Saliva , Streptococcus mutans
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