81 results on '"Seong CM"'
Search Results
2. A243 VTD Followed by MPT Demonstrates High Response Rates for High-Risk Patients with Multiple Myeloma
- Author
-
Eom, HS, primary, Kim, YK, additional, Chung, J, additional, Kim, K, additional, Kim, H, additional, Lee, DS, additional, Jin, J, additional, Do, YR, additional, Oh, S, additional, Suh, C, additional, Seong, CM, additional, Kim, CS, additional, and Lee, JH, additional
- Published
- 2009
- Full Text
- View/download PDF
3. Sequential vincristine, adriamycin, dexamethasone (VAD) followed by bortezomib, thalidomide, dexamethasone (VTD) as induction, followed by high-dose therapy with autologous stem cell transplant and consolidation therapy with bortezomib for newly diagnosed multiple myeloma: results of a phase II trial.
- Author
-
Kim HJ, Yoon SS, Lee DS, Sohn SK, Eom HS, Lee JL, Chung JS, Kim K, Suh C, Won JH, Kim JS, Park JS, Kang HJ, Seong CM, Kim CS, Lee SJ, and Lee JH
- Published
- 2012
4. Redox-Neutral Decarboxylative and Desulfonylative C(sp 3 ) Trifluoromethylation: Method Development and Mechanistic Inquiry.
- Author
-
Seong CM and Roberts CC
- Abstract
Sodium triflinate (CF
3 SO2 Na) is an inexpensive bench-stable radical CF3 source that is often activated by external oxidants such as peroxides. However, despite the commercial accessibility of CF3 SO2 Na, the salt has never been applied to decarboxylative trifluoromethylation due to challenges in controlled cross-radical coupling. We report a redox-neutral approach to decarboxylative C(sp3 ) trifluoromethylation of carboxylic acid derivatives. Mechanistic inquiry is performed to address the limitations in scope.- Published
- 2023
- Full Text
- View/download PDF
5. Redox Inversion: A Radical Analogue of Umpolung Reactivity for Base- and Metal-Free Catalytic C(sp 3 )-C(sp 3 ) Coupling.
- Author
-
Seong CM, Ansel AQ, and Roberts CC
- Abstract
The construction of alkyl-alkyl bonds is a powerful tool in organic synthesis. Redox inversion, defined as switching the donor/acceptor profile of a functional group to its acceptor/donor profile, is used for C(sp
3 )-C(sp3 ) coupling. We report a photocatalytic coupling of carboxylic acids to form bibenzyls through a radical-radical coupling. Mechanistic insight is gained through control reactions. This unexplored redox-opposite relationship between a carboxylic acid and its redox-active ester is implemented in catalysis.- Published
- 2023
- Full Text
- View/download PDF
6. Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia.
- Author
-
Park YH, Kim DY, Mun YC, Cho EK, Lee JH, Jo DY, Kim I, Yoon SS, Park SY, Kim B, Bang SM, Kim H, Min YJ, Park JH, Seo JJ, Moon HN, Lee MH, Kim CS, Lee WS, Chong SY, Oh D, Zang DY, Lee KH, Hyun MS, Kim HS, Kim SH, Kwon H, Kim HJ, Park KT, Bae SH, Ryoo HM, Choi JH, Ahn MJ, Yoon HJ, Nam SH, Kim BS, and Seong CM
- Subjects
- Anthracyclines adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Arsenic Trioxide adverse effects, Cytarabine adverse effects, Follow-Up Studies, Humans, Idarubicin adverse effects, Recurrence, Remission Induction, Treatment Outcome, Tretinoin adverse effects, Leukemia, Promyelocytic, Acute diagnosis, Leukemia, Promyelocytic, Acute drug therapy, Leukemia, Promyelocytic, Acute genetics
- Abstract
Background/aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL)., Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up., Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis., Conclusion: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.
- Published
- 2022
- Full Text
- View/download PDF
7. Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.
- Author
-
Ahn SY, Son SK, Lee GH, Kim I, Cheong JW, Lee WS, Kim BS, Jo DY, Jung CW, Seong CM, Lee JH, Yuh YJ, Kim MK, Ryoo HM, Park MR, Cho SH, Kim HG, Zang DY, Park J, Kim H, Lee S, Kim SH, Chang MH, Lee HS, Choi CW, Kwon J, Lim SN, Oh SJ, Joo I, and Kim DW
- Abstract
Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea., Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response., Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients)., Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.
- Published
- 2022
- Full Text
- View/download PDF
8. Comprehensive DNA repair gene expression analysis and its prognostic significance in acute myeloid leukemia.
- Author
-
Park S, Kim YJ, Huh HJ, Chung HS, Lee M, Park YM, Mun YC, Seong CM, and Huh J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Cytogenetic Analysis, Disease Management, Disease Susceptibility, Female, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute therapy, Male, Middle Aged, Prognosis, Survival Analysis, Treatment Outcome, Young Adult, Biomarkers, Tumor, DNA Repair, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Transcriptome
- Abstract
Background: Deficiency in DNA damage response (DDR) pathway and accumulation of DNA damage increases mutation rates resulting in genomic instability and eventually increases the risk of cancer. The aim of our study was to investigate expressions of DNA repair genes as new prognostic biomarkers in acute myeloid leukemia (AML)., Methods: We utilized The Cancer Genome Atlas AML project (TCGA-LAML cohort, 15 acute promyelocytic leukemia (APL) and 155 non-APL AML) for the expression data of DNA repair genes. For validation, clinical samples (Ewha study group, 9 APL and 72 non-APL AML patients) were analyzed for the expression of 22 DNA repair genes using a custom RT
2 Profiler PCR Array., Results: APL patients presented significantly lower expression of DNA repair genes than non-APL AML patients in both study groups. Among non-APL AML patients, high expression levels of PARP1 , XRCC1 , and RAD51 were associated with poor overall survival (OS) probability in both study groups. Furthermore, Cox regression analysis showed that increased expression levels of PARP1 , XRCC1 , RAD51, BRCA1 and MRE11A could be independent risk factors for OS in the Ewha study group. Among non-APL patients of the Ewha study group, the OS probability of DDR-overexpressed group with at least one gene or more showing Z score greater than 1.5 was poorer than that of DDR non-overexpressed group., Conclusion: In the current study, the DNA repair gene expression profile of APL patients was different from that of non-APL AML patients. Overexpression of DNA repair genes could be a poor prognostic biomarker in non-APL AML.- Published
- 2021
- Full Text
- View/download PDF
9. Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species.
- Author
-
Mun YC, Ahn JY, Yoo ES, Lee KE, Nam EM, Huh J, Woo HA, Rhee SG, and Seong CM
- Subjects
- Apoptosis drug effects, Cell Line, Tumor, Humans, Leukemia, Promyelocytic, Acute metabolism, Leukemia, Promyelocytic, Acute pathology, Reactive Oxygen Species metabolism, Transfection, Antineoplastic Agents pharmacology, Arsenic Trioxide pharmacology, Leukemia, Promyelocytic, Acute drug therapy, Mitochondria metabolism, Peroxiredoxin III metabolism
- Abstract
NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2', 7'-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX
TM Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO2 (Cysteine sulfinic acid, Cys-SO2 H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time-dependent manner. Increased SO2 form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post-ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO-treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.- Published
- 2020
- Full Text
- View/download PDF
10. GATA1 Expression in BCR/ABL1-negative Myeloproliferative Neoplasms.
- Author
-
Yang N, Park S, Cho MS, Lee M, Hong KS, Mun YC, Seong CM, Huh HJ, and Huh J
- Subjects
- Alleles, Bone Marrow metabolism, Bone Marrow pathology, Cytogenetic Analysis, Fusion Proteins, bcr-abl genetics, Gene Expression, Humans, Immunohistochemistry, Janus Kinase 2 genetics, Myeloproliferative Disorders genetics, Polymorphism, Single Nucleotide, Primary Myelofibrosis diagnosis, Primary Myelofibrosis genetics, Severity of Illness Index, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential genetics, GATA1 Transcription Factor metabolism, Myeloproliferative Disorders diagnosis
- Abstract
Background: This study aimed to determine GATA1 expression levels to better characterize subgroups in BCR/ABL1-negative myeloproliferative neoplasms (MPNs)., Methods: This study enrolled 49 patients diagnosed as having BCR/ABL1-negative MPN on the basis of the 2016 World Health Organization classification : nine polycythemia vera (PV), 17 essential thrombocythemia (ET), 12 prefibrotic primary myelofibrosis (prePMF), and 11 overt primary myelofibrosis (PMF). Relevant clinical and laboratory data were retrieved from the medical records. The molecular analysis of CALR and MPL mutations and quantification of JAK2 V617F allele burden were performed. GATA1 expression was assessed by an immunohistochemical assay on bone marrow biopsy. GATA1 expression was analyzed serially in 18 patients., Results: GATA1 expression decreased significantly in PMF compared with that in other subtypes, while no statistical difference was identified between ET and prePMF. GATA1 expression did not differ according to the mutation profiles or the allele burden of JAK2 V617F, but it decreased significantly in patients with overt fibrosis or leukemic transformation., Conclusions: Our results suggest that GATA1 expression is significantly low in PMF and decreases with progressive fibrosis and possibly with leukemic transformation, although our attempt to accurately distinguish between subgroups using GATA1 immunohistochemical approach did not achieve statistical significance. A large patient cohort with long term follow-up is required to evaluate the prognostic value of GATA1 expression., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)
- Published
- 2018
- Full Text
- View/download PDF
11. Clinicopathological Characteristics of Hyperdiploidy with High-Risk Cytogenetics in Multiple Myeloma.
- Author
-
Yang N, Mun YC, Seong CM, Huh HJ, and Huh J
- Subjects
- Aged, Aged, 80 and over, Bone Marrow Cells metabolism, Chromosome Aberrations, Diploidy, Female, Humans, In Situ Hybridization, Fluorescence, Interphase, Karyotyping, Male, Metaphase, Middle Aged, Multiple Myeloma genetics, Multiple Myeloma mortality, Risk Factors, Trisomy, beta 2-Microglobulin analysis, Bone Marrow Cells cytology, Multiple Myeloma pathology
- Abstract
In multiple myeloma (MM), hyperdiploidy (HD) is known to impart longer overall survival. However, it is unclear whether coexistent HD ameliorates the adverse effects of known high-risk cytogenetics in MM patients. To address this issue, we investigated the clinicopathological characteristics of HD with high-risk cytogenetics in MM. Ninety-seven patients with MM were included in the study. For metaphase cytogenetics (MC), unstimulated cells from bone marrow aspirates were cultured for either 24 or 48 hours. To detect HD by interphase fluorescence in situ hybridization (iFISH), we assessed trisomies of chromosomes 5, 7, 9, 11, 15, and 17. Of the 97 MM patients, 40 showed HD. The frequency of co-occurrence of HD and high-risk cytogenetics was 14% (14/97). When the clinicopathological characteristics were compared between the two groups of HD with high-risk cytogenetics vs. non-HD (NHD) with high-risk cytogenetics, the level of beta 2 microglobulin and stage distribution significantly differed (P=0.020, P=0.032, respectively). This study shows that some of the clinicopathological characteristics of MM patients with high-risk cytogenetics differ according to HD or NHD status., Competing Interests: No potential conflicts of interest relevant to this article were reported., (© The Korean Society for Laboratory Medicine.)
- Published
- 2018
- Full Text
- View/download PDF
12. Prognostic Impact of IPSS-R and Chromosomal Translocations in 751 Korean Patients with Primary Myelodysplastic Syndrome.
- Author
-
Suh KJ, Cheong JW, Kim I, Kim HJ, Shin DY, Koh Y, Yoon SS, Min YH, Ahn JS, Kim YK, Lee YG, Lee JO, Bang SM, Mun YC, Seong CM, Park Y, Kim BS, Hong J, Park J, Lee JH, Kim SY, and Lee HG
- Subjects
- Antineoplastic Agents therapeutic use, DNA Methylation drug effects, Female, Humans, Male, Middle Aged, Multivariate Analysis, Myelodysplastic Syndromes drug therapy, Prognosis, Proportional Hazards Models, Republic of Korea, Retrospective Studies, Risk Factors, Severity of Illness Index, Translocation, Genetic drug effects, Treatment Outcome, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Translocation, Genetic genetics
- Abstract
Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06-2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06-2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
- Full Text
- View/download PDF
13. Calreticulin mRNA expression and clinicopathological characteristics in acute myeloid leukemia.
- Author
-
Park S, Huh HJ, Mun YC, Seong CM, Chung WS, Chung HS, and Huh J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Calreticulin metabolism, Child, Cytogenetic Analysis, Female, Gene Expression Profiling, Hematologic Diseases epidemiology, Hematologic Diseases genetics, Hematologic Diseases metabolism, Hematologic Diseases physiopathology, Humans, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute metabolism, Male, Middle Aged, RNA, Messenger metabolism, Retrospective Studies, Young Adult, Calreticulin analysis, Calreticulin genetics, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute physiopathology, RNA, Messenger analysis, RNA, Messenger genetics
- Abstract
Calreticulin, encoded by CALR, is a multifunctional protein with roles in calcium homeostasis and chaperoning molecular processes. This study aimed to evaluate calreticulin mRNA expression levels in acute myeloid leukemia (AML) compared with other hematologic malignancies, and to investigate the clinicopathological characteristics associated with expression in AML patients. The study group included 43 patients diagnosed with AML, 57 with other hematologic malignancies, and 21 benign hematologic conditions. CALR mRNA quantification using real-time polymerase chain reaction revealed it to be significantly higher in AML compared with other hematologic malignancies (P < 0.0001). There was no difference in CALR mRNA expression between AML subgroups by karyotype (P = 0.3201). No differences were found in age, white blood cell counts, platelet counts, bone marrow blast percentage, calcium, lactate dehydrogenase or CD34 expression rate between the high and low CALR groups (CALR mRNA ≥ 1.2 fold and <1.2 fold, respectively), although hemoglobin and sex differences were observed. Although statistically not significant, there was a trend that Relapse rate was lower (54.5% vs. 84.6%) (P = 0.1063) and disease-free survival was longer (22 months vs. 7 months) (P = 0.0784) in low CALR group, whereas overall survival was similar between the two groups (11 months and 8 months). The clinical relevance of CALR expression in AML remains to be clarified in a larger cohort., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
14. Genomic aberrations of myeloproliferative and myelodysplastic/myeloproliferative neoplasms in chronic phase and during disease progression.
- Author
-
Hahm C, Huh HJ, Mun YC, Seong CM, Chung WS, and Huh J
- Subjects
- Aged, Aged, 80 and over, DNA Copy Number Variations, Disease Progression, Female, Follow-Up Studies, Humans, Janus Kinase 2 genetics, Male, Middle Aged, Mutation, Neoplasm Staging, Polymorphism, Single Nucleotide, Retrospective Studies, Chromosome Aberrations, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Myelodysplastic-Myeloproliferative Diseases genetics, Myelodysplastic-Myeloproliferative Diseases pathology, Myeloproliferative Disorders genetics, Myeloproliferative Disorders pathology
- Abstract
Introduction: Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) may transform into secondary myelofibrosis (MF) or evolve into acute myeloid leukemia (AML). The genetic mechanisms underlying disease progression in MPN and MDS/MPN patients remain unclear. The purpose of this study was to investigate sequential genomic aberrations identified by single nucleotide polymorphism array (SNP-A)-based karyotyping that can detect cryptic aberrations or copy neutral loss of heterozygosity (CN-LOH) in the chronic phase and during disease progression of MPN and MDS/MPN patients., Methods: The study group included 13 MPN and four MDS/MPN patients (seven polycythemia vera (PV); four essential thrombocythemia (ET); two MPN-unclassifiable (MPN-U); one chronic myelomonocytic leukemia (CMML); one atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML); and two MDS/MPN-unclassifiable (MDS/MPN-U)). Among them, five patients (two PV, two MPN-U, and one MDS/MPN-U) progressed to MF and three patients (one CMML, one aCML, and one MDS/MPN-U) transformed to AML. The median follow-up period was 70 months (range, 7-152). Whole-genome SNP-A (SNP 6.0; Affymetrix, Santa Clara, CA, USA)-based karyotyping and JAK2 mutation analysis were performed according to the manufacturer's instructions., Results: SNP-A showed 19 kinds of genomic aberrations, including seven gains, eight deletions, and four CN-LOH. CN-LOH of 9p involving JAK2 was the most common aberration, followed by 5q deletion and 9p gain. The incidence of genomic changes identified by SNP was not different in patients with disease progression (75%), compared with those without disease progression (56%) (P = 0.4). However, when excluding 9p CN-LOH, the incidence of genomic changes was significantly higher in patients with disease progression than in patients without disease progression (63% and 0%, respectively, P = 0.01). Among eight patients with disease progression, two patients (two MPN-U) showed abnormal SNP-A results, whereas metaphase cytogenetics (MC) analysis showed normal results at diagnosis and during follow-up. In nine patients without disease progression, SNP-A did not show any genomic aberrations except for 9p CN-LOH. In three patients (one PV, one aCML, and one MDS/MPN-U), clonal evolutions were identified by both MC and SNP-A according to disease progression. One PV patient who progressed to MF at 45 months after diagnosis showed sequential genomic changes from 9p CN-LOH to 9p gain by SNP-A. Results of JAK2 mutation analysis were variable depending on the patient. Most of the patients with 9p CN-LOH or 9p gain showed more than 50% of the JAK2 mutant alleles. In one patient (MDS/MPN-U) evolving to AML, the number of JAK2 mutant alleles decreased according to disease progression., Conclusion: This study suggests sequential genomic changes identified by SNP-A may be associated with disease progression., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2015
- Full Text
- View/download PDF
15. Submicroscopic deletions of immunoglobulin heavy chain gene (IGH) in precursor B lymphoblastic leukemia with IGH rearrangements.
- Author
-
Huh J, Mun YC, Yoo ES, Seong CM, and Chung WS
- Subjects
- Adult, Child, Female, Humans, In Situ Hybridization, Fluorescence, Infant, Male, Middle Aged, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Young Adult, Gene Deletion, Gene Rearrangement, Immunoglobulin Heavy Chains genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
- Published
- 2015
- Full Text
- View/download PDF
16. Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.
- Author
-
Cheong JW, Kim HJ, Lee KH, Yoon SS, Lee JH, Park HS, Kim HY, Shim H, Seong CM, Kim CS, Chung J, Hyun MS, Jo DY, Jung CW, Sohn SK, Yoon HJ, Kim BS, Joo YD, Park CY, and Min YH
- Subjects
- Adult, Aged, Deferasirox, Female, Ferritins blood, Humans, Liver drug effects, Male, Middle Aged, Prospective Studies, Anemia, Aplastic therapy, Benzoates therapeutic use, Iron metabolism, Iron Overload drug therapy, Liver metabolism, Myelodysplastic Syndromes therapy, Transfusion Reaction, Triazoles therapeutic use
- Abstract
Background: Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA)., Study Design and Methods: This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA., Results: A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline., Conclusions: This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented., (© 2013 AABB.)
- Published
- 2014
- Full Text
- View/download PDF
17. Topoisomerase II alpha and microtubule-associated protein-tau as a predictive marker in axillary lymph node positive breast cancer.
- Author
-
Won HS, Lee KE, Sung SH, Choi MY, Jo JY, Nam EM, Mun YC, Seong CM, and Lee SN
- Subjects
- Adult, Aged, Aged, 80 and over, Anthracyclines administration & dosage, Axilla, Breast Neoplasms drug therapy, Breast Neoplasms enzymology, Breast Neoplasms surgery, Breast Neoplasms, Male chemistry, Breast Neoplasms, Male pathology, Carcinoma, Ductal, Breast chemistry, Carcinoma, Ductal, Breast pathology, Carcinoma, Lobular chemistry, Carcinoma, Lobular pathology, Carcinoma, Medullary chemistry, Carcinoma, Medullary pathology, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Poly-ADP-Ribose Binding Proteins, Predictive Value of Tests, Retrospective Studies, Taxoids administration & dosage, Treatment Outcome, Up-Regulation, Antigens, Neoplasm analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor analysis, Breast Neoplasms chemistry, Breast Neoplasms pathology, DNA Topoisomerases, Type II analysis, DNA-Binding Proteins analysis, Lymph Nodes pathology, tau Proteins analysis
- Abstract
Aims and Background: The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy., Methods and Study Design: Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry., Results: Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy., Conclusions: We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.
- Published
- 2014
- Full Text
- View/download PDF
18. ETV6/RUNX1 rearrangement identified by RT-PCR without evidence on FISH.
- Author
-
Hahm C, Han SH, Mun YC, Seong CM, Chung WS, and Huh J
- Subjects
- Base Sequence, Child, Preschool, DNA Mutational Analysis, DNA, Neoplasm genetics, False Negative Reactions, Female, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Molecular Sequence Data, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Reverse Transcriptase Polymerase Chain Reaction, Core Binding Factor Alpha 2 Subunit genetics, Oncogene Proteins, Fusion genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Published
- 2014
- Full Text
- View/download PDF
19. Comparative analysis between azacitidine and decitabine for the treatment of myelodysplastic syndromes.
- Author
-
Lee YG, Kim I, Yoon SS, Park S, Cheong JW, Min YH, Lee JO, Bang SM, Yi HG, Kim CS, Park Y, Kim BS, Mun YC, Seong CM, Park J, Lee JH, Kim SY, Lee HG, Kim YK, and Kim HJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antimetabolites adverse effects, Azacitidine adverse effects, Bone Marrow Examination, Decitabine, Disease-Free Survival, Female, Humans, Infection Control, Kaplan-Meier Estimate, Karyotyping, Male, Middle Aged, Myelodysplastic Syndromes classification, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Neutropenia chemically induced, Research Design, Retrospective Studies, Risk Assessment, Treatment Outcome, Young Adult, Antimetabolites therapeutic use, Azacitidine analogs & derivatives, Azacitidine therapeutic use, Myelodysplastic Syndromes drug therapy
- Abstract
The present study aimed to directly compare the efficacy and safety of azacitidine and decitabine in patients with myelodysplastic syndromes (MDS). We compared the overall response rate (ORR) (complete responses, partial responses, marrow complete responses, and haematological improvements), overall survival (OS), event-free survival (EFS), time to leukaemic transformation, and adverse outcomes between azacitidine and decitabine. To minimize the effects of treatment selection bias in this observational study, adjustments were made using the propensity-score matching method. Among 300 patients, 203 were treated with azacitidine and 97 with decitabine. Propensity-score matching yielded 97 patient pairs. In the propensity-matched cohort, there were no significant differences between the azacitidine and decitabine groups regarding ORR (44% vs. 52%), OS (26 vs. 22.9 months), EFS (7.7 vs. 7.0 months), and rate of leukaemic transformation (16% vs. 22% at 1 year). In patients ≥ 65 years of age, survival was significantly better in the azacitidine group (P = 0.017). Patients who received decitabine experienced more frequent episodes of grade 3 or 4 cytopenia and infectious episodes. We found that azacitidine and decitabine showed comparable efficacy. Among patients ≥ 65 years of age, survival was significantly better in the azacitidine group (ClinicalTrials.gov Identifier: NCT01409070)., (© 2013 Blackwell Publishing Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
20. Loss of CD26 protease activity in recipient mice during hematopoietic stem cell transplantation results in improved transplant efficiency.
- Author
-
Yoo E, Paganessi LA, Alikhan WA, Paganessi EA, Hughes F, Fung HC, Rich E, Seong CM, and Christopherson KW 2nd
- Subjects
- Animals, Biomarkers metabolism, Cell Movement physiology, Dipeptidyl Peptidase 4 deficiency, Dipeptidyl-Peptidase IV Inhibitors administration & dosage, Flow Cytometry, Hematopoiesis physiology, Mice, Mice, Congenic, Mice, Inbred C57BL, Oligopeptides administration & dosage, Cell Movement drug effects, Dipeptidyl Peptidase 4 metabolism, Dipeptidyl-Peptidase IV Inhibitors pharmacology, Hematopoiesis drug effects, Hematopoietic Stem Cell Transplantation methods, Oligopeptides pharmacology
- Abstract
Background: A firm understanding of the biology of hematopoietic stem and progenitor cell (HSC/HPC) trafficking is critical to improve transplant efficiency and immune reconstitution during hematopoietic stem cell transplantation (HSCT). Our earlier findings suggested that suppression of CD26 (dipeptidyl peptidase IV) proteolytic activity in the donor cell population can be utilized as a method for increasing transplant efficiency. However, factors in the recipient should not be overlooked, given the potential for the bone marrow (BM) microenvironment to regulate HSCT., Study Design and Methods: We first evaluated CD26 expression and then investigated the effects of the CD26 inhibitor diprotin A and the absence of CD26 (CD26-/-) in recipient mice on HSC/HPC homing and engraftment using an in vivo congenic mouse model of HSCT., Results: A significant increase in donor cell engraftment into the peripheral blood (PB), and to a lesser extent homing into the BM, was observed in CD26-/- mice or CD26 inhibitor-treated mice. Increased PB engraftment of CD26-/- mice was significant at 3 and 6 months, but not 1 month, after transplant. It was noted that the increased homing was statistically greater with donor cell manipulation (CD26-/- donor cells) than with recipient manipulation (CD26-/- recipient mice). Conversely, donor and recipient manipulation both worked well to increase PB engraftment at 6 months., Conclusion: These results provide preclinical evidence of CD26, in the HSCT recipient, as a major regulator of HSC/HPC engraftment with minor effects on HSC/HPC homing and suggest the potential use of CD26 inhibitors in HSCT patients to improve transplant efficiency., (© 2012 American Association of Blood Banks.)
- Published
- 2013
- Full Text
- View/download PDF
21. Acute promyelocytic leukemia with a rare PML exon 4/ RARA exon 3 fusion transcript variant.
- Author
-
Oh SJ, Park TS, Lee JY, Mun YC, Seong CM, Marschalek R, Meyer C, Chung WS, and Huh J
- Subjects
- Adult, Humans, Leukemia, Promyelocytic, Acute metabolism, Leukemia, Promyelocytic, Acute pathology, Male, Oncogene Proteins, Fusion metabolism, RNA, Messenger metabolism, RNA, Neoplasm metabolism, Exons, Leukemia, Promyelocytic, Acute genetics, Oncogene Proteins, Fusion genetics, RNA, Messenger genetics, RNA, Neoplasm genetics
- Published
- 2013
- Full Text
- View/download PDF
22. Single nucleotide polymorphism array-based karyotyping in acute myeloid leukemia or myelodysplastic syndrome with trisomy 8 as the sole chromosomal abnormality.
- Author
-
Hahm C, Mun YC, Seong CM, Han SH, Chung WS, and Huh J
- Subjects
- Adult, Aged, 80 and over, Chromosomes, Human, Pair 8 genetics, Female, Humans, Leukemia, Myeloid, Acute diagnosis, Loss of Heterozygosity, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Retrospective Studies, Abnormal Karyotype, Leukemia, Myeloid, Acute genetics, Myelodysplastic Syndromes genetics, Polymorphism, Single Nucleotide, Trisomy genetics
- Abstract
The clinical heterogeneity of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with trisomy 8 as the sole abnormality may result from cytogenetically undetectable genetic changes. The purpose of this study was to identify hidden genomic aberrations not detected by metaphase cytogenetics (MC) using high-resolution single nucleotide polymorphism array (SNP-A)-based karyotyping in AML/MDS patients with a sole trisomy 8. The study group included 8 patients (3 AML and 5 MDS) and array-based karyotyping was done using whole-genome SNP-A (SNP 6.0 and SNP 2.7M). By SNP-A, additional genomic aberrations not detected by MC were identified in 2 patients: 1 AML patient exhibited a copy-neutral loss of heterozygosity (CN-LOH) of 3q21.1-q29 and 11q13.1-q25 and the other patient with MDS (refractory cytopenia with unilineage dysplasia) had CN-LOH of 2p25.3-p15. In particular, the latter patient progressed to AML 18 months after the diagnosis. In 3 patients, aberrations in addition to trisomy 8 were not identified by SNP-A. In the remaining 3 patients, SNP-A could not detect trisomy 8, while trisomy 8 was found in 25-67% of metaphase cells by MC. This study suggests that additional genomic aberrations may in fact be present even in cases of trisomy 8 as sole abnormality by MC, and SNP-A could be a useful karyotyping tool to identify hidden aberrations such as CN-LOH., (Copyright © 2012 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF
23. Additional genomic aberrations identified by single nucleotide polymorphism array-based karyotyping in an acute myeloid leukemia case with isolated del(20q) abnormality.
- Author
-
Hahm C, Mun YC, Seong CM, Chung WS, and Huh J
- Subjects
- Adult, Antineoplastic Agents therapeutic use, Chromosome Deletion, Cytogenetic Analysis, Humans, Karyotyping, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Loss of Heterozygosity, Male, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Chromosomes, Human, Pair 20, Leukemia, Myeloid, Acute diagnosis
- Abstract
Prognosis is known to be better in cases with isolated chromosomal abnormalities than in those with complex karyotypes. Accordingly, del(20q) as an isolated abnormality must be distinguished from cases in which it is associated with other chromosomal rearrangements for a better stratification of prognosis. We report a case of an isolated del(20q) abnormality with additional genomic aberrations identified using whole-genome single nucleotide polymorphism array (SNP-A)-based karyotyping. A 39-yr-old man was diagnosed with AML without maturation. Metaphase cytogenetic analysis (MC) revealed del(20)(q11.2) as the isolated abnormality in 100% of metaphase cells analyzed, and FISH analysis using D20S108 confirmed the 20q deletion in 99% of interphase cells. Using FISH, other rearrangements such as BCR/ABL1, RUNX1/RUNX1T1, PML/RARA, CBFB/MYH11, and MLL were found to be negative. SNP-A identified an additional copy neutral loss of heterozygosity (CN-LOH) in the 11q13.1-q25 region. Furthermore, SNP-A allowed for a more precise definition of the breakpoints of the 20q deletion (20q11.22-q13.31). Unexpectedly, the terminal regions showed gain on chromosome 20q. The patient did not achieve complete remission; 8 months later, he died from complications of leukemic cell infiltrations into the central nervous system. This study suggests that a presumably isolated chromosomal abnormality by MC may have additional genomic aberrations, including CN-LOH, which could be associated with a poor prognosis. SNP-A-based karyotyping may be helpful for distinguishing true isolated cases from cases in combination with additional genomic aberrations not detected by MC.
- Published
- 2012
- Full Text
- View/download PDF
24. ABL1 deletion without BCR/ABL1 rearrangement is originated from a large-sized 9q deletion.
- Author
-
Huh J, Mun YC, Seong CM, and Chung WS
- Subjects
- Adult, Alleles, Chromosomes, Human, Pair 20 genetics, Chromosomes, Human, Pair 9 genetics, Gene Rearrangement, Humans, Interphase, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology, Proto-Oncogene Proteins c-ets genetics, Repressor Proteins genetics, ETS Translocation Variant 6 Protein, Gene Deletion, Genes, abl, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Published
- 2012
- Full Text
- View/download PDF
25. Ring chromosome 5 in acute myeloid leukemia defined by whole-genome single nucleotide polymorphism array.
- Author
-
Huh J, Mun YC, Chung WS, and Seong CM
- Subjects
- Chromosome Deletion, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Leukemia, Myeloid, Acute genetics, Male, Metaphase, Middle Aged, Oligonucleotide Array Sequence Analysis, Chromosomes, Human, Pair 5, Leukemia, Myeloid, Acute diagnosis, Polymorphism, Single Nucleotide, Ring Chromosomes
- Abstract
Chromosomes forming a corresponding ring cannot be clearly defined by conventional cytogenetics or FISH. Karyotypic analyses using whole-genome single nucleotide polymorphism arrays (SNP-A) may result in the identification of previously cryptic lesions and allow for more precise definition of breakpoints. We describe a case of AML with metaphase cells bearing -5, del(11)(q22), and +r. With SNP-A, a 5p-terminal deletion (11 megabases [Mb]), a 5q-terminal deletion (27 Mb), an 11q-interstitial deletion (29 Mb), and a 21q gain (3 Mb) were identified. Therefore, the G-banded karyotype was revised as 46, XY, r(5)(p15. 2q33.2), del(11)(q14.1q23.2), dup(21)(q22.13q22.2)[18]/46,XY[2]. SNP-A could be a powerful tool for characterizing ring chromosomes in which the involved chromosomes or bands cannot be precisely identified by conventional cytogenetics or FISH.
- Published
- 2012
- Full Text
- View/download PDF
26. Single nucleotide polymorphism array-based karyotyping shows sequential genomic changes from monosomy to copy-neutral loss of heterozygosity of chromosome 7 and 20q deletion within a balanced translocation t(14;20) in AML.
- Author
-
Huh J, Mun YC, Seong CM, and Chung WS
- Subjects
- Chromosome Banding, Clonal Evolution, Female, Humans, Karyotype, Karyotyping, Leukemia, Myeloid, Acute diagnosis, Loss of Heterozygosity, Middle Aged, Monosomy, Polymorphism, Single Nucleotide, Sequence Deletion, Chromosomes, Human, Pair 20, Chromosomes, Human, Pair 7, Leukemia, Myeloid, Acute genetics, Translocation, Genetic
- Abstract
Single nucleotide polymorphism array (SNP-A)-based karyotyping can identify copy-neutral loss of heterozygosity (CN-LOH) as well as cryptic lesions not detected by metaphase cytogenetics. We report serial genetic studies on a patient diagnosed with chronic myelomonocytic leukemia who progressed to acute leukemia. Monosomy 7 was predominantly found at diagnosis, but clones changed to CN-LOH of chromosome 7 with disease progression. Furthermore, subclones with genomic aberrations of 3q gain, 1p CN-LOH, and trisomy 12 newly appeared, suggesting that they were also involved in the transformation process. Additionally, by SNP-A, a presumably balanced translocation, t(14;20), identified by metaphase cytogenetics, was shown to result in an unbalanced 20q deletion at the breakpoint. The sequential changes identified by SNP-A may provide a better understanding of the mechanism of clonal evolution., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
27. Various patterns of IgH deletion identified by FISH using combined IgH and IgH/CCND1 probes in multiple myeloma and chronic lymphocytic leukemia.
- Author
-
Hwang Y, Lee JY, Mun YC, Seong CM, Chung WS, and Huh J
- Subjects
- Aged, Chromosomes, Human, Pair 14 genetics, Cyclin D1 genetics, Female, Humans, Male, Middle Aged, Translocation, Genetic, Gene Deletion, Immunoglobulin Heavy Chains genetics, In Situ Hybridization, Fluorescence, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Multiple Myeloma genetics
- Abstract
Introduction: Interphase fluorescence in situ hybridization (FISH) can identify submicroscopic deletions adjacent to the breakpoints of rearrangements undetected by conventional cytogenetics. In this study, the characteristics and frequency of the IgH deletion identified by interphase FISH were investigated in patients with multiple myeloma (MM) and chronic lymphocytic leukemia (CLL)., Methods: The study group included 29 patients with MM and eight patients with CLL. Interphase FISH was performed with the IgH dual color, break-apart rearrangement probe and the IgH/CCND1 dual color, dual fusion translocation probe., Results: The IgH deletion was found in 14% (4/29) of patients with MM and 13% (1/8) of the patients with CLL. Four patients had deletions of the whole or variable region of IgH on the native chromosome 14, whereas one patient had a deletion of the IgH variable region on a der(11)t(11;14). In two patients, the IgH break-apart FISH showed both patterns with and without IgH deletions. In cases showing the same pattern by IgH break-apart FISH, the IgH/CCND1 FISH showed different patterns, and vice versa., Conclusion: A variety of patterns of the IgH deletion were identified by interphase FISH using IgH break-apart and IgH/CCND1 probes in patients with MM and CLL. The results of this study suggest that the integrated information obtained with IgH break-apart and IgH/CCND1 FISH was needed to interpret FISH results unambiguously., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2011
- Full Text
- View/download PDF
28. 1-(Arylsulfonyl)-2,3-dihydro-1H-quinolin-4-one derivatives as 5-HT(6) serotonin receptor ligands.
- Author
-
Park CM, Choi JI, Choi JH, Kim SY, Park WK, and Seong CM
- Subjects
- Animals, Cell Line, Humans, Ligands, Models, Molecular, Protein Binding, Structure-Activity Relationship, Quinolones chemistry, Quinolones pharmacology, Receptors, Serotonin metabolism, Serotonin Antagonists chemistry, Serotonin Antagonists pharmacology
- Abstract
Piperazinyl derivatives of 1-(arylsulfonyl)-2,3-dihydro-1H-quinolin-4-ones have been identified with high binding affinities for 5-HT(6) receptor. In particular, 2-methyl-5-(N-methyl-piperazin-1-yl)-1-(naphthalene-2-sulfonyl)-2,3-dihydro-1H-quinolin-4-one (8g) exhibits high binding affinity toward 5-HT(6) (IC(50)=8nM) receptor with good selectivity over other serotonin and dopamine receptors., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
29. [Variant Philadelphia chromosome identified by interphase fluorescence in situ hybridization (FISH) without evidence on G-banded karyotyping and metaphase FISH].
- Author
-
Kim MK, Mun YC, Seong CM, Chung WS, and Huh J
- Subjects
- Adult, Chromosomes, Human, Pair 22, Chromosomes, Human, Pair 9, Humans, Interphase, Karyotyping, Leukemia diagnosis, Leukemia genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Male, Metaphase, Middle Aged, Phenotype, Translocation, Genetic, In Situ Hybridization, Fluorescence methods, Philadelphia Chromosome
- Abstract
A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46,XY,t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[5]/46,XY[3]. Interphase FISH revealed nuc ish(ABL1,BCR) × 3(ABL1 con BCR × 2)[329/450]/(ABL1,BCR) × 4(ABL1 con BCR × 3)[5/450]/(AL1,BCR) × 3(ABL1 con BCR × 1)[44/450]. Metaphase FISH showed ish (9;22)(ABL1+,BCR1+;BCR+,ABL+)[22]/der(22)(BCR+,ABL1+)[3]. The other case was that of a 31-yr-old male patient diagnosed with CML in the blastic phase. G-banded karyotyping of all 20 metaphase cells showed 47,XYYc,dup(1)(q21q32),del(7)(p11.2),t(9;22)(q34;q11.2). Interphase FISH revealed nuc ish(ABL1,BCR) × 3(ABL1 con BCR × 2)[254/600]/(ABL1,BCR) × 3(ABL1 con BCR × 1)[191/600]. Metaphase FISH showed ish t(9;22)(ABL1+,BCR+;BCR+,ABL1+)[16]. These results suggest that typical t(9;22) and variant Ph may coexist in the same patient, and interphase FISH may facilitate the detection of the variant Ph that cannot be detected by G-banded karyotyping alone.
- Published
- 2010
- Full Text
- View/download PDF
30. Unsorted human adipose tissue-derived stem cells promote angiogenesis and myogenesis in murine ischemic hindlimb model.
- Author
-
Kang Y, Park C, Kim D, Seong CM, Kwon K, and Choi C
- Subjects
- Adult, Animals, Biomarkers metabolism, Cell Differentiation, Cells, Cultured, Culture Media, Disease Models, Animal, Endothelial Cells metabolism, Female, Hindlimb, Humans, Ischemia metabolism, Ischemia pathology, Ischemia physiopathology, Male, Mice, Mice, Inbred C57BL, Mice, Nude, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Muscular Atrophy pathology, Muscular Atrophy prevention & control, Necrosis, Perfusion Imaging, Phenotype, Subcutaneous Fat, Abdominal metabolism, Time Factors, Endothelial Cells transplantation, Ischemia surgery, Muscle Development, Muscle, Skeletal blood supply, Muscle, Skeletal physiopathology, Neovascularization, Physiologic, Stem Cell Transplantation, Subcutaneous Fat, Abdominal cytology
- Abstract
We examined the protective effect of unsorted human adipose tissue-derived stem cells (hADSCs) with a short-term culture in endothelial differentiation medium on tissue repair after ischemic injury. hADSCs were isolated from human subcutaneous adipose tissue and cultured in vitro in endothelial differentiation medium for 2wks before transplantation. Cultured hADSCs showed a typical mesenchymal stromal cell-like phenotype, positive for endothelial-specific markers including VE-cadherin, Flt-1, eNOS, and vWF but not CD31. Two hours after ligation of the femoral artery and vein, mice were injected with the unselected hADSCs locally near the surgery site and tested for tissue perfusion and repair. Tissue perfusion rates of the ischemic limbs were significantly higher in the group treated with hADSCs compared with those of the control mice as early as post-operative day 3 (median 195.3%/min; interquartile range, 82.0-321.1 vs. median 47.1%/min; interquartile range, 18.0-58.7; p=0.001 by Friedman two-way analysis). Subsequently, the mice treated with hADSC showed better prognosis at 4wks after surgery, and the histological analysis revealed increased vascular density and reduced muscle atrophy in the hADSC-transplanted limbs. Moreover, hADSC-treated muscle contained differentiated myocytes positive for human NF-κB and myogenin antigen. These results collectively indicate that unsorted hADSCs after a 2-wk-in vitro culture have a therapeutic potential in ischemic tissue injury via inducing both angiogenesis and myogenesis., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
31. Clinical utility of FISH analysis in addition to G-banded karyotype in hematologic malignancies and proposal of a practical approach.
- Author
-
Kwon WK, Lee JY, Mun YC, Seong CM, Chung WS, and Huh J
- Abstract
Background: Fluorescence in situ hybridization (FISH) analysis can provide important information in the management of patients with hematologic malignancies. However, FISH performed in addition to G-banded karyotype can be labor-intensive and expensive. The aim of this study was to evaluate whether FISH gives additional information in the setting of adequate conventional cytogenetics in cases of hematologic malignancies., Methods: Bone marrow aspirates were obtained from 135 patients at diagnosis (56 AML, 32 MDS, 20 ALL, and 27 MM) between 2005 and 2010. Interphase FISH was performed using the following probes: BCR/ABL1, AML1/ETO, PML/RARA, CBFB, MLL, EGR1, CEP8, and D7S486 for AML; CEP8, D20S108, EGR1, and D7S486 for MDS; BCR/ABL1, MLL, CDKN2A (p16), ETV6, and 6q21/c-myc for ALL; IgH, TP53, D13S25, IgH/CCND1, IgH/MAF, IgH/FGFR3, and 1q21/8p21 for MM. We compared the results of FISH with the corresponding aberrations identified by G-banded karyotype., Results: Additional genetic aberrations detected by FISH (which were not identified by G-banded karyotype) were 4%, 9%, 50%, and 67% in AML, MDS, ALL, and MM, respectively. In ALL, CDKN2A and ETV6 FISH revealed additional genetic aberrations in 33% and 28% of cases, respectively. In MM, FISH was of benefit in detecting IgH, D13S25, TP53, and 1q21 rearrangements, not detected by G-banded karyotype (31%, 36%, 20%, and 40%, respectively)., Conclusion: These results suggest that performing FISH in addition to G-banded karyotype may contribute little additional genetic information in AML and MDS, whereas routine FISH analysis appears to be an efficient screening method in ALL and MM.
- Published
- 2010
- Full Text
- View/download PDF
32. Synthesis and SAR of (piperazin-1-yl-phenyl)-arylsulfonamides: a novel series of atypical antipsychotic agents.
- Author
-
Park CM, Kim SY, Park WK, Choi JH, and Seong CM
- Subjects
- Antipsychotic Agents chemical synthesis, Piperazines chemistry, Receptors, Serotonin classification, Receptors, Serotonin drug effects, Structure-Activity Relationship, Sulfonamides chemical synthesis, Antipsychotic Agents chemistry, Antipsychotic Agents pharmacology, Sulfonamides chemistry, Sulfonamides pharmacology
- Abstract
(Piperazin-1-yl-phenyl)-arylsulfonamides were synthesized and identified to show high affinities for both 5-HT(2C) and 5-HT(6) receptors. Among them, naphthalene-2-sulfonic acid isopropyl-[3-(4-methyl-piperazin-1-yl)-phenyl]-amide (6b) exhibits the highest affinity towards both 5-HT(2C) (IC(50)=4 nM) and 5-HT(6) receptors (IC(50)=3 nM) with good selectivity over other serotonin (5-HT(1A), 5-HT(2A), and 5-HT(7)) and dopamine (D(2)-D(4)) receptor subtypes. In 5-HT(2C) and 5-HT(6) receptor functional assays, this compound showed considerable antagonistic activity for both receptors., (Copyright 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
33. Bortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates: results of the Korean Multiple Myeloma Working Party (KMMWP).
- Author
-
Eom HS, Kim YK, Chung JS, Kim K, Kim HJ, Kim HY, Jin JY, Do YR, Oh SJ, Suh C, Seong CM, Kim CS, Lee DS, and Lee JH
- Subjects
- Aged, Boronic Acids administration & dosage, Bortezomib, Dexamethasone administration & dosage, Female, Hematopoietic Stem Cell Transplantation, Humans, Korea epidemiology, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma epidemiology, Multiple Myeloma pathology, Neoadjuvant Therapy methods, Prednisolone administration & dosage, Pyrazines administration & dosage, Thalidomide administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Multiple Myeloma drug therapy
- Abstract
Bortezomib (VELCADE), thalidomide and dexamethasone (VTD), as well as melphalan, prednisolone, and thalidomide (MPT) therapy, are highly effective in patients with multiple myeloma. We evaluated the responses and survival times of 35 patients treated with VTD followed by MPT. All patients were newly diagnosed and non-transplantation candidates. Patients received six cycles of VTD, which were followed by eight cycles of MPT. Approximately 97% of patients exhibited early responses to therapy, as early as the second cycle of VTD. Thirty percent of the responses were high quality, which was defined as a complete response (CR), a near-CR or a very good partial response. High-risk patients were defined as patients with any of the following aberrations: del(13), t(4;14), or del(17p). The remaining patients were defined as standard risk. Eleven high-risk patients showed 100% response rates, including 91% high-quality responses. In contrast, 13 standard-risk patients exhibited 92% response rates, including 61% high-quality responses. The overall 2-year survival rates were 60% in high-risk patients and 85% in standard-risk patients, which was not significantly different. As a first-line therapy, VTD followed by MPT has the potential to provide high-quality responses with durable remission among elderly and high-risk patients (clinicaltrials.gov identifier: NCT00320476).
- Published
- 2010
- Full Text
- View/download PDF
34. [Myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura].
- Author
-
Hwang Y, Huh JW, Mun YC, Seong CM, and Chung WS
- Subjects
- Adult, Bone Marrow Cells cytology, Cell Lineage, Chromosome Aberrations, Diagnosis, Differential, Female, Humans, Male, Megakaryocytes immunology, Megakaryocytes pathology, Middle Aged, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Purpura, Thrombocytopenic, Idiopathic genetics, Purpura, Thrombocytopenic, Idiopathic pathology, Retrospective Studies, Myelodysplastic Syndromes diagnosis, Purpura, Thrombocytopenic, Idiopathic diagnosis
- Abstract
Background: In patients with isolated thrombocytopenia, but without significant dysplasia, diagnosis of idiopathic thrombocytopenic purpura (ITP) rather than myelodysplastic syndrome (MDS) may be taken into account. It is important to make an accurate diagnosis because different treatments are used for ITP and MDS. The purpose of this study was to investigate the clinical and hematologic features of patients who were initially diagnosed as ITP but had cytogenetic abnormalities., Methods: We retrospectively reviewed cytogenetic studies of 100 patients who were diagnosed as ITP from 2004 to 2009 at Mokdong Hospital of Ewha Womans University based on clinical features and hematologic studies. Bone marrow pathology was re-evaluated based on 2008 WHO classification. Cytogenetic analysis was performed by 24-48 hr culture of bone marrow aspirates without using mitogens and 20 metaphases were analyzed., Results: Of the 100 patients diagnosed as ITP initially, three patients (3%) had cytogenetic abnormalities. They had no thrombocytopenia-related symptoms and thrombocytopenia was found accidentally. The numbers of megakaryocytes in bone marrow were increased and dysplasia was not found in megakaryocyte, erythroid, and myeloid cell lineages. The proportion of blasts was within normal limits. Clonal chromosomal abnormalities found were der(1;7)(q10;p10), add(9)(q12), or t(7;11)(p22;q12). Presumptive diagnosis of MDS or diagnosis of idiopathic cytopenia of undetermined significance (ICUS) was made according to 2008 WHO classification. During the follow up, disease progression was not found., Conclusions: In patients with suspected ITP, cytogenetic analysis should be done. If specific clonal chromosomal abnormality is found, presumptive diagnosis of MDS has to be considered and close follow up is needed.
- Published
- 2010
- Full Text
- View/download PDF
35. Proinflammatory cytokine IL-1beta stimulates IL-8 synthesis in mast cells via a leukotriene B4 receptor 2-linked pathway, contributing to angiogenesis.
- Author
-
Kim GY, Lee JW, Ryu HC, Wei JD, Seong CM, and Kim JH
- Subjects
- Cell Line, Fluorescent Antibody Technique, Gene Expression, Gene Expression Regulation physiology, Humans, NADPH Oxidase 1, NADPH Oxidases metabolism, Reactive Oxygen Species metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction physiology, Interleukin-1beta metabolism, Interleukin-8 biosynthesis, Mast Cells metabolism, Neovascularization, Physiologic physiology, Receptors, Leukotriene B4 metabolism
- Abstract
Recent studies have suggested that mast cells have critical roles in angiogenesis. However, the detailed mechanism by which mast cells contribute to angiogenesis is not yet clearly understood, especially in response to proinflammatory cytokines. In this study, we showed that the proinflammatory cytokine IL-1beta induces the synthesis of IL-8, a potent angiogenic factor, in human mast cells via the leukotriene B(4) receptor (BLT)2. We also characterized the BLT2 downstream signaling pathway and determined that BLT2-mediated IL-8 synthesis involves the upregulation of Nox1, a member of the NADPH oxidase family, Nox1-dependent reactive oxygen species generation and the subsequent activation of the redox-sensitive transcription factor NF-kappaB. For instance, knockdown of BLT2 and Nox1 with specific small interfering RNA, treatment with a specific BLT2 antagonist, LY255283, or treatment with a potential Nox inhibitor, diphenylene iodonium, suppressed IL-1beta-induced IL-8 synthesis. We found that the conditioned media collected from IL-1beta-treated human mast cell line HMC-1 had significantly enhanced angiogenic activity that could be dramatically attenuated by either small interfering RNA knockdown of BLT2 or treatment with neutralizing Ab to IL-8. Finally, the experiments were repeated using human primary cord blood-derived mast cells, and the results were clearly reproduced. Taken together, our results suggest that BLT2-Nox1-reactive oxygen species-dependent pathway plays a role in promoting the secretion of IL-8 from human mast cells in response to the proinflammatory cytokine IL-1beta, thus contributing to angiogenesis.
- Published
- 2010
- Full Text
- View/download PDF
36. A case of Wernicke's encephalopathy following fluorouracil-based chemotherapy.
- Author
-
Cho IJ, Chang HJ, Lee KE, Won HS, Choi MY, Nam EM, Mun YC, Lee SN, and Seong CM
- Subjects
- Acute Disease, Female, Humans, Magnetic Resonance Imaging, Middle Aged, Nasopharyngeal Neoplasms drug therapy, Nasopharyngeal Neoplasms radiotherapy, Thiamine therapeutic use, Thiamine Deficiency diagnosis, Wernicke Encephalopathy diagnosis, Antimetabolites, Antineoplastic adverse effects, Fluorouracil adverse effects, Thiamine Deficiency complications, Wernicke Encephalopathy chemically induced
- Abstract
The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.
- Published
- 2009
- Full Text
- View/download PDF
37. Acute fibrinous and organizing pneumonia following hematopoietic stem cell transplantation.
- Author
-
Lee SM, Park JJ, Sung SH, Kim Y, Lee KE, Mun YC, Lee SN, and Seong CM
- Subjects
- Acute Disease, Anti-Bacterial Agents therapeutic use, Biopsy, Cryptogenic Organizing Pneumonia etiology, Cryptogenic Organizing Pneumonia pathology, Fatal Outcome, Glucocorticoids administration & dosage, Hemoptysis etiology, Humans, Lung Diseases pathology, Male, Middle Aged, Pleural Effusion etiology, Pulse Therapy, Drug, Radiography, Thoracic, Respiratory Insufficiency etiology, Tomography, X-Ray Computed, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute surgery, Lung Diseases etiology
- Abstract
A 60-year-old man presented with cough, sputum, and dyspnea. He had a history of acute myeloid leukemia and hematopoietic stem cell transplantation with chronic renal failure. Chest CT scans showed miliary nodules and patchy consolidations. Histological examination revealed numerous fibrin balls within the alveoli and thickening of the alveolar septum, both of which are typical pathological features of acute fibrinous and organizing pneumonia (AFOP). We report the first case of AFOP following allogeneic hematopoietic stem cell transplantation.
- Published
- 2009
- Full Text
- View/download PDF
38. CD34, RAB20, PU.1 and GFI1 mRNA expression in myelodysplastic syndrome.
- Author
-
Huh HJ, Chae SL, Lee M, Hong KS, Mun YC, Seong CM, Chung WS, and Huh JW
- Subjects
- Adolescent, Adult, Aged, Anemia, Aplastic diagnosis, Child, Child, Preschool, DNA-Binding Proteins analysis, Diagnosis, Differential, Female, Humans, Infant, Male, Middle Aged, RNA, Messenger analysis, RNA, Messenger biosynthesis, Transcription Factors analysis, Young Adult, Antigens, CD34 biosynthesis, DNA-Binding Proteins biosynthesis, Myelodysplastic Syndromes diagnosis, Proto-Oncogene Proteins biosynthesis, Trans-Activators biosynthesis, Transcription Factors biosynthesis, rab GTP-Binding Proteins biosynthesis
- Abstract
Myelodysplastic syndrome (MDS) with hypocellular bone marrow (BM) is often difficult to distinguish from aplastic anemia (AA). Furthermore, the diagnosis of MDS with low blast counts and normal karyotype may be problematic. These issues highlight the need for a reliable marker for the diagnosis of MDS. This study was conducted to determine if changes of mRNA expression in any of the four selected genes would be useful markers for differentiation of hypoplastic MDS from AA, and MDS from benign disease, as well as to investigate whether mRNA expressions differ between MDS risk subgroups. Thirty-five patients diagnosed with MDS, 27 patients with AA and 17 patients with benign diseases were included. The CD34, RAB20, PU.1 and GFI1 mRNA levels were measured by real-time RT-PCR. The CD34 mRNA expressions in hypoplastic MDS were higher than those found in AA. PU.1 and GFI1 mRNA expressions were significantly lower in MDS with low blast counts and normal karyotype than those of benign disease. High-risk MDS showed higher CD34 expressions than those of low-risk MDS. This study suggests that measurement of CD34 and GFI1 mRNA expressions could be useful as a diagnostic and prognostic marker for MDS.
- Published
- 2009
- Full Text
- View/download PDF
39. Individual and common inhibitors of coronavirus and picornavirus main proteases.
- Author
-
Kuo CJ, Liu HG, Lo YK, Seong CM, Lee KI, Jung YS, and Liang PH
- Subjects
- Amino Acid Sequence, Computer Simulation, Conserved Sequence, Drug Evaluation, Preclinical, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases chemistry, Protein Binding, Protein Structure, Tertiary, Sequence Alignment, Structure-Activity Relationship, Coronavirus drug effects, Coronavirus enzymology, Peptide Hydrolases metabolism, Picornaviridae drug effects, Picornaviridae enzymology, Protease Inhibitors chemistry, Protease Inhibitors pharmacology
- Abstract
Picornaviruses (PV) and coronaviruses (CoV) are positive-stranded RNA viruses which infect millions of people worldwide each year, resulting in a wide range of clinical outcomes. As reported in this study, using high throughput screening against approximately 6800 small molecules, we have identified several novel inhibitors of SARS-CoV 3CL(pro) with IC(50) of low microM. Interestingly, one of them equally inhibited both 3C(pro) and 3CL(pro) from PV and CoV, respectively. Using computer modeling, the structural features of these compounds as individual and common protease inhibitors were elucidated to enhance our knowledge for developing anti-viral agents against PV and CoV.
- Published
- 2009
- Full Text
- View/download PDF
40. Characterization of phenotypically distinct B-cell subsets and receptor-stimulated mitogen-activated protein kinase activation in human cord blood B cells.
- Author
-
Ha YJ, Mun YC, Seong CM, and Lee JR
- Subjects
- Adult, Antigens, CD34 immunology, Antigens, CD34 metabolism, B-Lymphocyte Subsets immunology, Blotting, Western, Bone Marrow immunology, Bone Marrow metabolism, CD40 Antigens immunology, CD40 Antigens metabolism, CD5 Antigens immunology, CD5 Antigens metabolism, Enzyme Activation, Fetal Blood immunology, Flow Cytometry, Humans, Immunoglobulin M immunology, Immunoglobulin M metabolism, Lymphocyte Activation, Mitogen-Activated Protein Kinase Kinases immunology, Phenotype, Receptors, Antigen, B-Cell immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, B-Lymphocyte Subsets metabolism, Fetal Blood metabolism, Mitogen-Activated Protein Kinase Kinases metabolism, Receptors, Antigen, B-Cell metabolism
- Abstract
Human cord blood (CB) is a valuable source of hematopoietic stem cells, but clinical reports have indicated slow recovery of B-cell development and function after CB transplantation. To investigate the basis of these B-cell defects in reconstitution, we characterized B cells purified from CB. We compared B-cell receptor activation and B-cell subsets in CB, bone marrow (BM), and peripheral blood (PB). We found that in CB B cells activation of extracellular signal-regulated kinase (ERK) and p38 following ligation of CD40 but not of the B-cell antigen receptor (BCR) was inefficient. The patterns of expression of CD5, CD34, and CD40 in the B-cell population of CB were similar to those in PB rather than in BM. The B cells in CB contained an increased proportion of B cells expressing a high level of CD24 and a low proportion of B cells expressing CD27, pointing to the presence of circulating CD24high immature transitional and CD27(-) naive B cells. CD40-mediated activation of ERK and p38 was also minimal in these B cells of CB. These findings may account for the functional defects of B cells in transplanted CB.
- Published
- 2008
- Full Text
- View/download PDF
41. Synthesis and structure-activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: a novel series of 5-HT2C receptor antagonists.
- Author
-
Park CM, Kim SY, Park WK, Park NS, and Seong CM
- Subjects
- Amines chemistry, Animals, CHO Cells, Carboxylic Acids chemistry, Chemistry, Pharmaceutical methods, Cricetinae, Cricetulus, Drug Design, Humans, Indoles pharmacology, Inhibitory Concentration 50, Models, Chemical, Pyridines pharmacology, Receptor, Serotonin, 5-HT2C metabolism, Structure-Activity Relationship, Sulfonamides chemistry, Technology, Pharmaceutical methods, Amines chemical synthesis, Indoles chemical synthesis, Pyridines chemical synthesis, Serotonin 5-HT2 Receptor Antagonists
- Abstract
A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT(2C) receptor. Among them, 1H-indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide (15k) exhibits the highest affinity (IC(50)=0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT(1A), 5-HT(2A), and 5-HT(6)) and dopamine (D(2)-D(4)) receptors.
- Published
- 2008
- Full Text
- View/download PDF
42. A new HLA-A*33 variant, HLA-A*3314, identified in a Korean individual.
- Author
-
Lee KW, Huh JW, and Seong CM
- Subjects
- Asian People, Humans, Korea, Amino Acid Substitution, HLA-A Antigens genetics, Mutation, Missense
- Abstract
The sequence of human leukocyte antigen (HLA)-A*3314 is identical to that of HLA-A*330301 except for a single-nucleotide substitution at codon 49 (GCG-->GGG) resulting in an amino acid change from Ala to Gly.
- Published
- 2008
- Full Text
- View/download PDF
43. Prognostic significance of CD44s expression in biliary tract cancers.
- Author
-
Lee SM, Lee KE, Chang HJ, Choi MY, Cho MS, Min SK, Lee HK, Mun YC, Nam EM, Seong CM, and Lee SN
- Subjects
- Adult, Aged, Aged, 80 and over, Biliary Tract Neoplasms mortality, Female, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, Retrospective Studies, Survival Analysis, Biliary Tract Neoplasms metabolism, Glycoproteins biosynthesis, Hyaluronan Receptors biosynthesis
- Abstract
Background: CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers., Methods: Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed., Results: Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival., Conclusions: CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.
- Published
- 2008
- Full Text
- View/download PDF
44. Discovery of 3-aryl-3-methyl-1H-quinoline-2,4-diones as a new class of selective 5-HT6 receptor antagonists.
- Author
-
Seong CM, Park WK, Park CM, Kong JY, and Park NS
- Subjects
- Cell Line, Humans, Quinolines chemistry, Radioligand Assay, Receptors, Serotonin metabolism, Serotonin Antagonists chemistry, Serotonin Antagonists metabolism, Quinolines pharmacology, Receptors, Serotonin drug effects, Serotonin Antagonists pharmacology
- Abstract
A 5,7-dichloro-3-phenyl-3-methyl-quinoline-2,4-dione (11a) has been identified in a random screen as a lead for 5-HT(6) antagonist. During the lead optimization process, several analogs were synthesized and their biological activities were investigated. Within this series, several compounds display high binding affinity and selectivity for the 5-HT(6) receptor. In particular, 3-(4-hydroxyphenyl)-3-methyl-quinoline-2,4-dione (12f) exhibits high affinity (K(i)=12.3 nM) for 5-HT(6) receptor with good selectivity over other serotonin and dopamine (D(1)-D(4)) receptor subtypes. In a functional adenylyl cyclase stimulation assay, this compound exhibited considerable antagonistic activity (IC(50)=0.61 microM).
- Published
- 2008
- Full Text
- View/download PDF
45. Gene expression profile related to prognosis of acute myeloid leukemia.
- Author
-
Park MH, Cho SA, Yoo KH, Yang MH, Ahn JY, Lee HS, Lee KE, Mun YC, Cho DH, Seong CM, and Park JH
- Subjects
- Annexin A2 genetics, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Neoplastic, HL-60 Cells, Humans, Leukemia, Promyelocytic, Acute genetics, Prognosis, Protein Phosphatase 2 genetics, Up-Regulation, Gene Expression Profiling, Leukemia, Myeloid, Acute genetics, Oligonucleotide Array Sequence Analysis
- Abstract
Acute myeloid leukemia (AML) is a heterogeneous group of diseases with respect to biology and clinical course. Through genome-wide scanning, we can have an improvement of the diagnosis and assay system of AML. Microarray was performed for the identification of acute myeloid leukemia prognosis. We divided patients into two groups (good prognosis group, GPG and poor prognosis group, PPG) based on differences in the individual reactions to treatment. Gene expression profiles were analyzed using microarray. Among genes up-regulated at least two-fold and down-regulated at least 0.5-fold in HL-60, we chose three up-regulated genes (PPP2CA, ME3, and CCDN2) and three down-regulated genes (GLO1, ANXA2, and BMI1) and confirmed the expression of these six genes by RT-PCR. We created a leukemia-specific subclass microarray, based on the gene expression profiles. Clinical samples from the bone marrow of four patients were hybridized on this microarray. Among the genes selected by the microarray technology, NB4, silenced TRIB3 and overexpressed XRN2 were not differentiated in spite of treatment with ATRA. This indicates that XRN2 and TRIB3 play an important role in cell differentiation. These data provided an expression profile for the diagnosis and prognosis of AML patients and identified candidate genes that might allow the prognosis of AML through the relative comparison of the expression level of genes between GPG and PPG.
- Published
- 2007
46. Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation.
- Author
-
Yang DH, Lee JJ, Mun YC, Shin HJ, Kim YK, Cho SH, Chung IJ, Seong CM, and Kim HJ
- Subjects
- Adolescent, Adult, Biomarkers, Tumor genetics, CD56 Antigen genetics, Chromosomes, Human, Pair 21 genetics, Chromosomes, Human, Pair 8 genetics, Disease-Free Survival, Female, Humans, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Predictive Value of Tests, Recurrence, Remission Induction, Retrospective Studies, Survival Rate, Translocation, Genetic, Transplantation, Homologous, Antimetabolites, Antineoplastic administration & dosage, Biomarkers, Tumor biosynthesis, CD56 Antigen biosynthesis, Cytarabine administration & dosage, Gene Expression Regulation, Leukemic, Hematopoietic Stem Cell Transplantation mortality, Leukemia, Myeloid, Acute therapy
- Abstract
CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multidrug resistance, but its clinical and prognostic significance has not been clearly identified. This study examined CD56 expression in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs. 88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P = 0.02). The median duration of disease-free survival (DFS) was significantly shorter in the CD56+ (median, 12.2 +/- 6.4 months) than in the CD56- group (median, not reached) (P = 0.02). In addition, the median duration of survival differed significantly in the CD56+ group (median, 14.9 +/- 4.4 months) compared with the CD56- group (median, not reached) (P = 0.01). Of the fifteen transplanted patients who achieved CR, allogeneic HST was performed from their siblings. The median duration of DFS in the CD56+ patients was significantly shorter than the CD56- patients (median, 24.4 +/- 4.5 months vs. median, not reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS and survival for AML patients with t(8:21), including those patients who underwent transplantation.
- Published
- 2007
- Full Text
- View/download PDF
47. Early imatinib-mesylate-induced hepatotoxicity in chronic myelogenous leukaemia.
- Author
-
Kong JH, Yoo SH, Lee KE, Nam SH, Kwon JM, Lee SM, Chang HJ, Choi MY, Cho MS, Mun YC, Nam E, Lee SN, and Seong CM
- Subjects
- Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Benzamides, Bile Ducts pathology, Cytarabine administration & dosage, Drug Eruptions etiology, Hepatocytes pathology, Humans, Idarubicin administration & dosage, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Liver Function Tests, Male, Middle Aged, Piperazines administration & dosage, Piperazines therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyrimidines administration & dosage, Pyrimidines therapeutic use, Antineoplastic Agents adverse effects, Blast Crisis drug therapy, Chemical and Drug Induced Liver Injury etiology, Cholestasis, Intrahepatic chemically induced, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Piperazines adverse effects, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects
- Abstract
Imatinib mesylate is the first molecule of targeted therapy in chronic myelogenous leukaemia inhibiting constitutively activated BCR-ABL kinase. There are no long-term follow-up studies of large sample sizes to assess the toxicity of the use of imatinib mesylate over 10 years. Several cases of hepatotoxicity, including fatal liver failure, have been associated with the long-term use of imatinib mesylate. We report here on a patient who experienced immediate dominant cholestatic damage of the liver and mild hepatocyte damage during imatinib mesylate therapy. This differs from most reports showing dominantly acute hepatitis with necrosis associated with the use of imatinib mesylate., (Copyright 2007 S. Karger AG, Basel.)
- Published
- 2007
- Full Text
- View/download PDF
48. A multicenter retrospective analysis of adverse events in Korean patients using bortezomib for multiple myeloma.
- Author
-
Bang SM, Lee JH, Yoon SS, Park S, Min CK, Kim CC, Suh C, Sohn SK, Min YH, Lee JJ, Kim K, Seong CM, Yoon HJ, Cho KS, Jo DY, Lee KH, Lee NR, and Kim CS
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Asian People, Boronic Acids administration & dosage, Bortezomib, Dexamethasone administration & dosage, Dexamethasone adverse effects, Female, Humans, Korea, Male, Middle Aged, Multiple Myeloma complications, Multiple Myeloma mortality, Pyrazines administration & dosage, Retrospective Studies, Stem Cell Transplantation mortality, Thalidomide administration & dosage, Thalidomide adverse effects, Transplantation, Autologous, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Boronic Acids adverse effects, Multiple Myeloma therapy, Pyrazines adverse effects
- Abstract
The proteasome inhibitor bortezomib has demonstrated clinical activity in patients with multiple myeloma (MM). Adverse events, including thrombocytopenia and peripheral neuropathy, have affected 30% to 60% of patients overall, and interrupted therapy in 10% to 20%. No prior toxicity data are available for Asian patients who have used bortezomib for MM. We used National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, to review the clinical records of patients with an MM diagnosis from 25 centers in Korea. The included patients were treated with bortezomib alone or in combination with other agents, including thalidomide. Ninety-five MM patients were treated. The patients had a median age of 60 years (range, 42-77 years). The median number of previous treatments was 3 (range, 0-10), and 39% of the patients had been treated with 4 or more major classes of agents, including thalidomide (67%), and autologous stem cell transplantation (51%). Regimens included bortezomib only in 38 patients (40%), bortezomib plus dexamethasone in 34 patients (36%), and bortezomib plus a thalidomide-containing regimen in 23 patients (24%). The analysis of patient response to therapy revealed a complete response (CR) or a near-CR in 31 patients (33%) and a partial response in 30 patients (32%), for an objective response rate of 65% in 93 patients. The most common adverse events reported were thrombocytopenia (47%), sensory neuropathy (42%), anemia (31%), and leukopenia (31%). Thirteen patients (14%) stopped therapy because of adverse events (neuropathy, 8; infection, 4; diarrhea, 1). Neuropathy greater than grade 2 was more frequent in patients who received 4 or more prior therapy regimens (17/37) than in those who received 3 or fewer (14/58). In addition, therapy including thalidomide was significantly correlated with neuropathy of grades 1 to 3 (P = .001). We identified 6 therapy-related deaths (6%) within 20 days after the last dose of bortezomib. The causes of death were infection in 3 patients, disease progression in 2 patients, and suicide in 1 patient. The incidences of thrombocytopenia and neurotoxicity were similar; however, gastrointestinal toxicities were relatively low in Korean patients compared with those reported in Western studies. Significant neuropathy was associated with the number of prior regimens and combination with thalidomide. These findings provide useful information for clinicians and patients using bortezomib.
- Published
- 2006
- Full Text
- View/download PDF
49. A prospective randomized study on the mobilization of CD34+ cells comparing continuous intravenous vs subcutaneous administration of rhG-CSF in normal donors.
- Author
-
Lee KE, Mun YC, Nam SH, Kwon JM, Lee SM, Lee MA, Yoo ES, Ahn JY, Kim JH, and Seong CM
- Subjects
- Adolescent, Adult, Cell Separation, Female, Flow Cytometry, Humans, Immunophenotyping, Kinetics, Male, Middle Aged, Models, Statistical, Phenotype, Prospective Studies, Recombinant Proteins, Time Factors, Antigens, CD34 biosynthesis, Granulocyte Colony-Stimulating Factor administration & dosage, Hematopoietic Stem Cell Mobilization methods, Infusions, Intravenous methods, Injections, Subcutaneous methods
- Abstract
The efficacy of mobilizing peripheral blood progenitor cells (PBPC) with continuous intravenous (c.i.v.) administration of rhG-CSF was randomly compared to subcutaneous (s.c.) administration, in 15 normal donors in each arm of the study for 6 days. The percentage and absolute numbers of CD34+ cells in the c.i.v. and s.c. groups increased maximally at day 3 and 5, respectively, when compared with the steady-state (day 0) level. Peak CD34+ cell levels were achieved on day 3 in the c.i.v. group, with more rapid results than in the s.c. group (49.3/microl vs 35.9/microl, P=0.043). Plasma rhG-CSF levels declined progressively during mobilization in each group as the WBC increased. The serum level of rhG-CSF did not correlate with CD34+ cell counts in the peripheral blood. Toxicity profiles in the c.i.v. and s.c. groups were similar. Each regimen was effective in successfully mobilizing the target CD34 cell number.
- Published
- 2005
- Full Text
- View/download PDF
50. Gefitinib trial in a fanconi's anemia patient with multiple squamous cell carcinomas and hepatocellular carcinoma.
- Author
-
Jung HS, Byun GW, Lee KE, Mun YC, Nam SH, Kwon JM, Lee SN, Im SA, Seong CM, and Lee SN
- Abstract
FA (Fanconi's Anemia) is an autosomal recessive disorder that is characterized by pancytopenia with bone marrow hypoplasia, diverse congenital abnormalities and an increased predisposition towards malignancy. The mainstay of the treatment for these cancers has been surgery, because of the hypersensitive reactions of FA patients to DNA cross- linking agents or radiation. Therefore, there has been no effective therapy for advanced squamous cell carcinoma. We report here on a patient suffering from advanced multiple squamous cell carcinoma and hepatocellular carcinoma along with an FA, and this patient was treated with gefitinib.
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.