[show abstract][hide abstract] ABSTRACT: Endoscopic resection has become standard therapy for selected patients with early gastric carcinoma (EGC). However, the preoperative diagnostic accuracy for excluding submucosal (SM) invasion is not precise. Moreover, histologic features predicting SM invasion in gastric carcinomas (SMiGC) have not been studied extensively.
Pre-treatment gastric biopsies from 60 patients with SM invasion who underwent endoscopic resection were reviewed and compared to 58 biopsies of lesions confirmed to be intramucosal carcinomas (IMC). For validation of the results, an independent cohort consisting of 616 gastric biopsies confirmed as EGC were analyzed. For statistical analyses, chi-square test, Fisher's exact test and multiple logistic progression tests were used.
In the biopsy specimens of patients with SMiGCs, differentiated histology, poorly differentiated component, wisps of muscularis mucosa, tumor cribriforming, papillary architecture, desmoplasia and intraglandular eosinophilic necrotic debris (IEND) were observed in 96.7%, 36.7%, 16.7%, 16.7%, 23.3%, 40%, and 46.7% of cases, respectively, while the same features were observed in 100%, 5.2%, 0%, 1.7%, 5.2%, 19%, and 22.4% of biopsies with IMC. In multivariate analyses, poorly differentiated component [odds ratio (OR), 9.59, p = 0.002], IEND [OR, 6.23, p = 0.012], tumor cribriforming [OR, 4.66, p = 0.03] and papillary architecture [OR, 5.52, p = 0.018] were significantly associated with the detection of SM invasion. In the validation cohort, poorly differentiated component (p = 0.003) and papillary architecture (p = 0.008) remained significant.
Poorly differentiated component and papillary architecture are significant histopathologic predictors of SM invasion in pretreatment gastric biopsies of lesions considered for endoscopic therapy. Additional prospective studies are warranted to confirm our findings.Virtual slide: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1588557731103084.
[show abstract][hide abstract] ABSTRACT: The impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubicin, vincristine, and prednisone for newly diagnosed diffuse large B-cell lymphoma (DLBCL) and for whom data were available regarding pretreatment nutritional status. Nutritional status at diagnosis was assessed by triceps skin fold (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI), serum albumin, prealbumin, and transferrin. For patients aged 60 yr and older, poor performance and higher tumor burden were associated with malnourishment represented by albumin <3.5 g/dL, prealbumin < 17 g/dL, and transferrin <170 mg/L. Lower BMI (<20), serum albumin, prealbumin, and transferrin were identified as risk factors for febrile neutropenia in univariate analysis, but not in multivariate analysis. In the univariate analysis for OS, all nutritional parameters except MAMC showed a significant association with survival. However, BMI was the only parameter that was independently prognostic for OS in the multivariate analysis (P = 0.031; hazards ratio = 3.32). Nutritional insufficiency encountered in DLBCL patients might influence the occurrence of treatment-related toxicity and poor survival outcome of patients.
Nutrition and Cancer 01/2014; · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Paclitaxel and gemcitabine (PG) combination chemotherapy is effective as a maintenance chemotherapeutic regimen in metastatic breast cancer (MBC) patients because it increases progression-free survival (PFS), which increases overall survival (OS). The primary purpose of our study was to investigate the association between genetic polymorphisms in the genes involved in PG pathways and clinical outcomes in MBC patients treated with PG chemotherapy.
A total of 324 MBC patients were enrolled in this prospective multicenter trial of PG as the first-line chemotherapy. Eighty-five of the 324 patients from two institutes were available for analysis of single nucleotide polymorphisms (SNPs). Germline DNA was extracted from peripheral blood mononuclear cells. Thirty-eight SNPs in 15 candidate genes selected from pathways that may influence the metabolism and transport of, or sensitivity, to PG were analysed.
The median PFS and OS of all 324 patients were 8.7months (95% confidence interval [CI]: 7.5-9.6months) and 26.9months (95% CI: 23.6-30.1months), respectively. An SNP in SLC28A3 (rs7867504, C/T) was associated with OS (CC or CT versus TT: 37 versus 21months, p=0.027, hazard ratio [HR] 2.6, 95% CI: 1.1-6.3). SLC29A1 GA haplotype had a significantly shorter OS (p=0.030, HR 3.391, 95% CI: 1.13-10.19). RRM1 (ribonucleotide reductase large subunit M1) SNP (rs9937), and haplotypes ATAA and ATGA were significantly associated with neurotoxicity.
Genetic polymorphisms in SLC28A3, SLC29A1 and RRM1 can influence the clinical outcome of MBC patients treated with PG chemotherapy. Further studies on the functional mechanisms relating to these germline polymorphisms in these genes are warranted.
European journal of cancer (Oxford, England: 1990) 12/2013; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although peripherally-inserted central catheter (PICC) insertion is commonly performed under fluoroscopic guidance, few reports have addressed performance and dosimetry when PICC is inserted under C-arm fluoroscopy.
To evaluate the risk factors of radiation dose in performing PICC insertion using flat panel detector-based mobile C-arm fluoroscopy and a conventional angiography machine.
Ninety-eight patients underwent the PICC procedure using conventional angiography equipment (n=49) or flat panel detector-based mobile C-arm fluoroscopy (n=49). Data were prospectively analyzed from July to November 2012. Dose-area product (DAP), tube voltage, tube current, fluoroscopy time, and image quality measured on a 5-point scale were estimated and compared using appropriate statistical tests.
There were no significant differences in tube voltage, fluoroscopy time, and image quality between conventional angiography and mobile C-arm fluoroscopy. DAP, mean arm tube current, and tube current in chest fluoroscopy were significantly lower in mobile C-arm fluoroscopy than using the conventional angiography machine (P <0.05). Multivariate analysis identified tube current in chest fluoroscopy, arm tube current, and fluoroscopy equipment as significant risk factors for elevated radiation dose in PICC insertion.
PICC insertion can be performed using flat panel detector-based mobile C-arm fluoroscopy instead of a conventional angiography machine. Image quality and fluoroscopy time were not different between the two systems and the use of C-arm fluoroscopy significantly reduced radiation dose.
[show abstract][hide abstract] ABSTRACT: Single nucleotide polymorphisms (SNP) are inter-individual genetic variations that could explain inter-individual differences of response/survival to chemotherapy. The present study was performed to build up a risk model for survival in 247 patients with acute myeloid leukaemia (AML) with normal karyotype (AML-NK). Genome-wide Affymetrix SNP array 6.0 was used for genotyping in discovery set (n = 118). After identifying significant SNPs for overall survival (OS) in single SNP analysis, a risk model was constructed. Out of 632 957 autosomal SNPs analysed, finally four SNPs (rs2826063, rs12791420, rs11623492 and rs2575369) were introduced into the risk model. The model could stratify the patients according to their OS in discovery set (P = 1·053656 × 10−4). Replication was performed using Sequenom platform for genotyping in the validation cohort (n = 129). The model incorporated with clinical and four SNP risk score was successfully replicated in a validation set (P = 5·38206 × 10−3). The integration of four SNPs and clinical factors into the risk model showed higher area under the curve (AUC) reults than in the model incorporating only clinical or only four SNPs, suggesting improved prognostic stratification power by combination of four SNPs and clinical factors. In conclusion, a genome-wide SNP-based risk model in 247 patients with AML-NK can identify a group of high risk patients with poor survival.
British Journal of Haematology 10/2013; 163(1):62-71. · 4.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324-2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227-2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.Modern Pathology advance online publication, 28 June 2013; doi:10.1038/modpathol.2013.108.
[show abstract][hide abstract] ABSTRACT: Background:Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms.Methods:In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination.Results:The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases (P < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group (P < .001, odds ratio = 1.90, 95% confidence interval, 1.45-2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group (P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (P = .04, regression coefficient = 0.89, and median regression).Conclusion:The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.
Journal of Geriatric Psychiatry and Neurology 06/2013; · 3.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: We were not aware of a well-validated patellofemoral joint-specific scoring system. We performed this study to develop and validate a scoring system (Samsung Medical Center [SMC] patellofemoral scoring system) suitable for the evaluation of patellofemoral joint status.
We recruited 179 individuals consisting of a study group of 123 patients with anterior knee pain but without pain in another part of the knee, twenty-eight patients with knee pain other than anterior knee pain (group A), and twenty-eight healthy volunteers without knee pain (group B). Items in the development of the scoring system that showed a significant difference between the study group and group A and between the study group and the group B were selected. Test-retest reliability was measured by intraclass correlation coefficient, internal consistency was measured by the Cronbach alpha, content validity was assessed by ceiling and floor effects, and construct validity was determined by the association of the Feller scores and the SMC patellofemoral scores.
After the item verification process, seventeen items (eight items for patellofemoral pain and nine items for patellofemoral function) were selected. Test-retest reliability for overall SMC patellofemoral scores showed excellent reliability (intraclass correlation coefficient, 0.85), and internal consistency was excellent (Cronbach alpha, 0.97). Floor and ceiling effects were acceptable (<30%) for all the items of the SMC patellofemoral scoring system, except one: sitting down on a chair, in the patellofemoral function score. The SMC patellofemoral scores showed moderate correlation with the Feller scores (ρ = -0.45).
The SMC patellofemoral score is a novel scoring system that distinguishes patients with anterior knee pain or patellofemoral dysfunction from patients with knee pain or dysfunction arising from other knee problems, and from those without knee pain. The reliability and validity of the SMC patellofemoral scoring system were verified in the present study.
The Journal of Bone and Joint Surgery 04/2013; 95(7):620-6. · 3.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD).
Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences.
Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives.
BDNF genotyping may be informative for anticipating chronicity in major depression.
[show abstract][hide abstract] ABSTRACT: Acute hepatic failure (AHF) is one of the most serious complications of transcatheter arterial chemoembolization (TACE). The aims of this study were to investigate risk factors of AHF after TACE and to establish a predictive model for AHF.
In the evaluation set, a total of 820 patients who underwent TACE as a first treatment for hepatocellular carcinoma were included. The demographic, laboratory, radiological and treatment-related factors were analysed to identify risk factors for AHF after TACE and a predictive model was established using the identified risk factors. In the validation set, a different cohort of 438 patients was included to validate the predictive model.
The incidence of post-TACE AHF was 15.1% (124/820). Multivariate analysis revealed that presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and log alpha-foetoprotein levels, and low albumin and sodium levels were independent risk factors. A mathematical model was established using these independent risk factors, and the area under the receiver operating characteristic curve of the model was 0.773 (95% confidence interval, 0.726-0.820). The cut-off value of 9 had a sensitivity of 78.2%, a specificity of 72.3%, a positive likelihood ratio of 2.82, a negative likelihood ratio of 0.30, a positive predictive value of 28.9% and a negative predictive value of 95.8%.
The risk factors of post-TACE AHF were presence of portal vein thrombosis, high aspartate aminotransferase, bilirubin, and alpha-foetoprotein levels, and low serum albumin and sodium levels. A mathematical model to predict post-TACE AHF was established.
Liver international: official journal of the International Association for the Study of the Liver 02/2013; 33(2):197-202. · 3.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC), whereas the prognosis of patients with advanced gastric cancer (AGC) remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes) and AGCs (3104 genes). A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010). The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.
PLoS ONE 01/2013; 8(12):e82770. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites.Modern Pathology advance online publication, 14 December 2012; doi:10.1038/modpathol.2012.205.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. METHODS: Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC) were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS) score. RESULTS: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trials was substantially higher in patients who had a higher level of education (p<0.001), were married (p=0.004), and had a higher economic status (p=0.001). However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%). Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p<0.001). CONCLUSIONS: This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.
BMC Cancer 12/2012; 12(1):594. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle.
Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin.
The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects.
The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.
[show abstract][hide abstract] ABSTRACT: Response to drug treatment of major depression is variable and biomarkers of response are needed. Cyclic AMP response element binding protein (CREB) is considered a key mediator of antidepressant drug effect. We studied CREB in T-lymphocytes as a potential predictor of response to a selective serotonin reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot and electrophoretic mobility shift assays, at baseline and after 6 wk treatment. Thirty-four healthy controls were also studied. The rate of response was 36 of 69 cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed group compared to controls (p = 0.044 and p<0.001, respectively). Baseline tCREB values in responders were significantly reduced in comparison to non-responders and to controls. After 6 wk treatment, median values of change of all CREB measures were greater in responders (36) than in non-responders (33; p<0.001 for tCREB, p = 0.003 for pCREB, and p=0.072 for CRE-DNA binding). Similar but less robust changes in CREB variables distinguished remitters from non-remitters. The optimum value of baseline tCREB predicted response with a positive predicted value of 0.778 [21/27; 95% confidence intervals (CI) 0.621-0.935], negative predictive value of 0.643 (27/42; 95% CI 0.498-0.788) and accuracy of 0.695 (48/69; 95% CI 0.586-0.804). Patients with low baseline tCREB had a significantly greater rate of response (78%) than patients with high baseline tCREB (36%), p < 0.001. Moreover, the greatest changes in tCREB with treatment were observed in subjects who did respond. This preliminary study suggests that T-lymphocytic CREB biomarkers are reduced in depressed patients and may assist in the prediction of response to SSRI drugs in depression.
The International Journal of Neuropsychopharmacology 11/2012; · 5.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) accounts for 95% of pancreatic cancers. CA19-9 is not widely used for screening PDAC due to its low sensitivity. Here, we studied the clinical usefulness of cathepsin D, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) for screening patients with PDAC. A total of 248 patients with PDAC and 216 control subjects were recruited (109 PDAC patients and 70 controls in the training set and 139 PDAC patients and 146 controls in the validation set). We measured serum levels of cathepsin D, TIMPs (-1, -3 and -4), and MMPs (-1, -7, -8 and -9) using fluorokine MAP multiplex kits. The concentrations of cathepsin D and MMP-7 were significantly higher in PDAC subjects than control subjects. In the training set, the diagnostic sensitivity and AUC of the panel of CA19-9, cathepsin D, and MMP-7 for PDAC were increased to 88% and 0.900, compared to 74% and 0.835 of CA19-9 single marker at 80% specificity. The sensitivity using cut-off value of biomarker panel was significantly increased in the validation set as well as training set. Our findings indicate that a serum biomarker panel consisting of CA19-9, cathepsin D, and MMP-7 may provide the most effective screening test currently feasible for PDAC.
[show abstract][hide abstract] ABSTRACT: RATIONALE: Serotonin transporter (5-HTT) gene polymorphisms are linked with antidepressant response to selective serotonin reuptake inhibitor drugs (SSRIs), though the favorable allelic variant differs by ethnic group (Caucasian versus Korean or Japanese). In Caucasian patients, response also is linked to measures of platelet 5-HTT function. OBJECTIVES: Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients. METHODS: We enrolled 99 patients with major depression and 48 control subjects. For statistical power, both samples were enriched with the l/l 5-HTTLPR polymorphism, which is uncommon in Koreans. Patients were treated with fluoxetine or sertraline. Response was assessed at 6 weeks. Subjects were genotyped for s/l polymorphism in the 5-HTT promoter region (5-HTTLPR). Platelet 5-HTT activity was determined as maximal uptake rate (Vmax) and affinity constant (Km). RESULTS: Response was differentially associated with the s allele of 5-HTTLPR, which also was significantly associated with Vmax. These associations are opposite to those reported in Caucasian populations. Responders had significantly higher Vmax and Km than nonresponders. In Koreans as well as Caucasians, high Vmax is related to antidepressant response to SSRIs, though the 5-HTTLPR polymorphism associations with both response and function differ by ethnicity. CONCLUSIONS: Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.
[show abstract][hide abstract] ABSTRACT: DNA repair machinery may contribute to the mechanism of the action in imatinib. We examined the association between the single nucleotide polymorphism (SNP) markers involved in the DNA repair enzyme pathway (ERCC1/2/4/5, XRCC1/2/4/5) and the clinical outcomes following an imatinib therapy in chronic phase chronic myeloid leukemia (CML) patients. A total of 169 Korean patients were included. Of the 19 SNPs from these patients, those with the TT genotype of ERCC1 (rs11615) showed a higher probability of achieving major cytogenetic response [P = 0.002, HR 5.14 (95 % CI 1.83-14.43)], complete cytogenetic response [P = 0.012, HR 3.47 (95 % CI 1.31-9.17)], and major molecular response [P = 0.001, HR 5.71 (95 % CI 2.13-15.30)] than those with CC or CT genotypes. This suggests that SNP markers on ERCC1 may predict the response to imatinib therapy, which proposes the potential involvement of the DNA repair machinery in the mechanism of imatinib action in chronic phase CML.
International journal of hematology 07/2012; 96(3):327-33. · 1.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Non alcoholic fatty liver disease (NAFLD) is associated with increased risk of type 2 diabetes and chronic liver disease but identifying patients who have NAFLD without resorting to expensive imaging tests is challenging. In order to help identify people for imaging investigation of the liver who are at high risk of NAFLD, our aim was to: a) identify easily measured risk factors at baseline that were independently associated with incident fatty liver at follow up, and then b) to test the diagnostic performance of thresholds of these factors at baseline, to predict or to exclude incident fatty liver at follow up. METHODS: 2589 people with absence of fatty liver on ultrasound examination at baseline were reexamined after a mean of 4.4 years in a Korean occupational cohort study. Multi-variable logistic regression analyses were used to identify baseline factors that were independently associated with incident fatty liver at follow up. The diagnostic performance of thresholds of these baseline factors to identify people with incident fatty liver at follow-up was assessed using receiver operating characteristic (ROC) curves. RESULTS: 430 incident cases of fatty liver were identified. Several factors were independently associated with incident fatty liver: increased triglyceride (per mmol/l increase) OR 1.378 [95%CIs 1.179, 1.611], p < 0.0001; glucose (per mmol/l increase) OR 1.215 [95%CIs 1.042, 1.416], p = 0.013; waist (per cm increase) OR 1.078 [95%CIs 1.057, 1.099], p < 0.001; ALT (per IU/L increase) OR 1.009 [95%CIs 1.002, 1.017], p = 0.016; and platelets (per 1x109/L increase) OR 1.004 [1.001, 1.006], p = 0.001; were each independently associated with incident fatty liver. Binary thresholds of the five factors were applied and the area under the ROC curve for incident fatty liver was 0.75 (95%CI 0.72-0.78) for the combination of all five factors above these thresholds. CONCLUSION: Simple risk factors that overlap considerably with risk factors for type 2 diabetes allow identification of people at high risk of incident fatty liver at who use of hepatic imaging could be targeted.