25 results on '"Ji, Min-Woo"'
Search Results
2. Digitalized Control Algorithm of Bridgeless Totem-Pole PFC with a Simple Control Structure Based on the Phase Angle
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Lee, Gi-Young, primary, Park, Hae-Chan, additional, Ji, Min-Woo, additional, and Kim, Rae-Young, additional
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- 2023
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3. Attentional bias for high-calorie food cues by the level of hunger and satiety in individuals with binge eating behaviors
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Ji-Min Woo, Gi-Eun Lee, and Jang-Han Lee
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binge eating ,hunger and satiety ,food cues ,incentive salience ,attentional bias ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
IntroductionThe abnormal hyperreactivity to food cues in individuals with binge eating behaviors could be regulated by hedonic or reward-based system, overriding the homeostatic system. The aim of the present study was to investigate whether attentional bias for food cues is affected by the level of hunger, maintaining the normal homeostatic system in individuals with binge eating behaviors.MethodsA total of 116 female participants were recruited and divided into four groups: hungry-binge eating group (BE) (n = 29), satiated BE (n = 29), hungry-control (n = 29), satiated control (n = 29). While participants completed a free-viewing task on high or low-calorie food cues, visual attentional processes were recorded using an eye tracker.ResultsThe results revealed that BE group showed longer initial fixation duration toward high-calorie food cues in both hunger and satiety condition in the early stage, whereas the control group showed longer initial fixation duration toward high-calorie food cues only in hunger conditions. Moreover, in the late stage, the BE group stared more at the high-calorie food cue, compared to control group regardless of hunger and satiety.DiscussionThe findings suggest that automatic attentional bias for food cues in individuals with binge eating behaviors occurred without purpose or awareness is not affected by the homeostatic system, while strategic attention is focused on high-calorie food. Therefore, the attentional processing of food cues in binge eating group is regulated by hedonic system rather than homeostatic system, leading to vulnerability to binge eating.
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- 2023
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4. Characterization of Newly Recorded Talaromyces veerkampii Isolated from Field Soil in Korea based on Morphology and Multigene Sequence Analysis
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Mahesh Adhikari, Hyun Seung Kim, Hyo Bin Park, Ki Young Kim, In Kyu Lee, Eun Jeong Byeon, Ji Min Woo, Hyang Burm Lee, and Youn Su Lee
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ascomycota ,characteristics ,description ,talaromyces veerkampii ,Biology (General) ,QH301-705.5 - Abstract
A fungal isolate belonging to the phylum Ascomycota was isolated and identified as Talaromyces veerkampii in 2017 during a survey of fungal diversity in field soils in Korea. This fungal isolate was identified and described based on macro- and micromorphological and molecular characterization. The identification was also based on partial 18S-ITS1-5.8S-ITS2-28S rDNA and calmodulin (CaM)-encoding gene sequencing data. Talaromyces veerkampii has not been previously reported in Korea. Thus, we report here a newly discovered species from soil in Korea along with its morphological and molecular characteristics.
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- 2022
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5. Morphological and Molecular Characterization of the Newly Reported Penicillium pimiteouiense from Field Soil in Korea
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Mahesh Adhikari, Hyun Seung Kim, Hyo Bin Park, Ki Young Kim, In Kyu Lee, Eun Jeong Byeon, Ji Min Woo, Hyang Burm Lee, and Youn Su Lee
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β-tubulin ,calmodulin ,discovery ,penicillium ,phylogeny ,Biology (General) ,QH301-705.5 - Abstract
Penicilliumpimiteouiense was discovered in South Korea during an investigation of fungal communities in soil collected from the Gyeongsangbuk-do province. In this study, we performed molecular analysis of this fungal isolate using internal transcribed spacer rDNA, β-tubulin, and Calmodulin gene sequences. We also performed morphological analysis using five agar media, potato dextrose, oatmeal, malt extract, czapek yeast extract, and yeast extract sucrose. In this study, the molecular and morphological analyses of P. pimiteouiense with detailed descriptions and figures has been carried out.
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- 2022
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6. Improving catalytic activity of the Baeyer–Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of (Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid
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Ji-Min Woo, Eun-Yeong Jeon, Eun-Ji Seo, Joo-Hyun Seo, Dong-Yup Lee, Young Joo Yeon, and Jin-Byung Park
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Medicine ,Science - Abstract
Abstract Baeyer–Villiger monooxygenases (BVMOs) can be used for the biosynthesis of lactones and esters from ketones. However, the BVMO-based biocatalysts are not so stable under process conditions. Thereby, this study focused on enhancing stability of the BVMO-based biocatalysts. The biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid by the recombinant Escherichia coli expressing the BVMO from Pseudomonas putida and an alcohol dehydrogenase from Micrococcus luteus was used as a model system. After thorough investigation of the key factors to influence stability of the BVMO, Cys302 was identified as an engineering target. The substitution of Cys302 to Leu enabled the engineered enzyme (i.e., E6BVMOC302L) to become more stable toward oxidative and thermal stresses. The catalytic activity of E6BVMOC302L-based E. coli biocatalysts was also greater than the E6BVMO-based biocatalysts. Another factor to influence biocatalytic performance of the BVMO-based whole-cell biocatalysts was availability of carbon and energy source during biotransformations. Glucose feeding into the reaction medium led to a marked increase of final product concentrations. Overall, the bioprocess engineering to improve metabolic stability of host cells in addition to the BVMO engineering allowed us to produce (Z)-11-(heptanoyloxy)undec-9-enoic acid to a concentration of 132 mM (41 g/L) from 150 mM ricinoleic acid within 8 h.
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- 2018
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7. Substrate-binding Site Engineering of Candida antarctica Lipase B to Improve Selectivity for Synthesis of 1-monoacyl-sn-glycerols
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Ji-Min Woo, Young-Seo Kang, Sun-Mee Lee, Seongsoon Park, and Jin-Byung Park
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Biomedical Engineering ,Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Published
- 2022
8. A uniform conditioning regimen of busulfan, fludarabine, and antithymocyte globulin for allogeneic haematopoietic cell transplantation from haploidentical family, matched sibling, or unrelated donors-A single-centre, prospective, explorative study
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Yunsuk Choi, Eun‐Ji Choi, Han‐Seung Park, Jung‐Hee Lee, Je‐Hwan Lee, Young‐Shin Lee, Young‐A Kang, Mijin Jeon, Ji Min Woo, Hyeran Kang, Seunghyun Baek, Su Mi Kim, Chae‐Eun Bong, and Kyoo‐Hyung Lee
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Hematology - Abstract
In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.
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- 2022
9. Engineering of a bacterial outer membrane vesicle to a nano-scale reactor for the biodegradation of β-lactam antibiotics
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Ji-Min Woo, Myeong-Yeon Kim, Ji-Won Song, Yoonjin Baeg, Hye-Jin Jo, Sun-Shin Cha, and Jin-Byung Park
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Bacterial Outer Membrane ,Escherichia coli ,Bioengineering ,General Medicine ,beta-Lactams ,Applied Microbiology and Biotechnology ,Biotechnology ,Anti-Bacterial Agents ,Bacterial Outer Membrane Proteins - Abstract
Bacterial outer membrane vesicles (OMVs) are small unilamellar proteoliposomes, which are involved in various functions including cell to cell signaling and protein excretion. Here, we have engineered the OMVs of Escherichia coli to nano-scaled bioreactors for the degradation of β-lactam antibiotics. This was exploited by targeting a β-lactamase (i.e., CMY-10) into the OMVs of a hyper-vesiculating E. coli BL21(DE3) mutant. The CMY-10-containing OMVs, prepared from the E. coli mutant cultures, were able to hydrolyze β-lactam ring of nitrocefin and meropenem to a specific rate of 6.6 × 10
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- 2022
10. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.
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Ji-Min Woo, Ji-Won Kim, Ji-Won Song, Lars M Blank, and Jin-Byung Park
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Medicine ,Science - Abstract
The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.
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- 2016
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11. Incidence, Management, and Prognosis of Graft Failure and Autologous Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation
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Han Seung Park, Young Shin Lee, Eun-Ji Choi, Young-Ah Kang, Ji Min Woo, Je-Hwan Lee, Jun-Hong Park, Jung-Hee Lee, Mijin Jeon, Hyeran Kang, and Kyoo Hyung Lee
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Autologous Reconstitution ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Transplantation, Homologous ,Cumulative incidence ,030212 general & internal medicine ,Oncology & Hematology ,Primary Graft Failure ,Treatment Failure ,Aplastic anemia ,Survival rate ,Survival analysis ,Aged ,Acute leukemia ,business.industry ,Reduced-intensity Conditioning ,Mortality rate ,Secondary Graft Failure ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,medicine.disease ,Transplantation ,Leukemia, Myeloid, Acute ,Original Article ,Female ,business - Abstract
Background This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000–September 2017) at our center. Results Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34+ cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis., Graphical Abstract
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- 2021
12. Effect of a ga-doped ZnO thin film with a ZTO buffer layer fabricated by using pulsed DC magnetron sputter for dye-sensitized solar cells
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Song, Sang-Woo, Lee, Kyung-Ju, Roh, Ji-Hyung, Park, On-Jeon, Kim, Hwan-Sun, Moon, Byung-Moo, and Ji, Min-Woo
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- 2014
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13. Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Allogeneic Hematopoietic Cell Transplantation for Higher-Risk Myelodysplastic Syndrome
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Han-Seung Park, Ji Min Woo, Young-Shin Lee, Je-Hwan Lee, Mijin Jeon, Jung-Hee Lee, Eun-Ji Choi, Hyeran Kang, Kyoo Hyung Lee, and Young-Ah Kang
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Oncology ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Post transplantation cyclophosphamide ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Transplantation ,Graft-versus-host disease ,Internal medicine ,medicine ,business - Abstract
Introduction: Allogeneic hematopoietic cell transplantation is an only potentially curative option for patients with higher-risk myelodysplastic syndrome (MDS). Owing to the advances in treatment strategies including reduced intensity conditioning, graft-versus-host disease (GVHD) prevention and supportive care, more elderly patients or those with comorbidities can proceed to allogeneic HCT. However, the long-term survival rate following allogeneic HCT is reported to be less than 50%, and non-relapse mortality (NRM) rate is still high reaching upto 30%. In this study, we aimed to evaluate the feasibility of using post-transplantation cyclophosphamide (PTCy) as a GVHD prophylaxis in allogeneic HCT for higher-risk MDS patients. We also compared the post-transplantation outcomes of PTCy group and those of historical control who received HCT using anti-thymocyte globulin (ATG). Methods: Patients with higher-risk MDS or MDS/myeloproliferative neoplasm (MPN) with bone marrow blast ≥ 5% were included in this study. Higher-risk MDS was defined by MDS with International Prognostic Scoring System >1.0 or bone marrow blast ≥ 5% at any time points before HCT. Conditioning regimen consists of busulfan (4-days for patients aged Results: Ninety-two and 144 patients received allogeneic HCT using PTCy and ATG, respectively. The median overall survival were 47.9 and 44.0 months, respectively (P=.383). Cumulative incidence of total and grade II-IV acute GVHD in PTCy and ATG group were 19.6% vs. 37.5% (P=.002), and 2.6% vs. 21.7% (P Conclusion: Allogeneic HCT using PTCy as GVHD prophylaxis in higher-risk MDS seems feasible in terms of low rate of acute GVHD and relapse incidence. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board; AbbVie: Honoraria, Other: Advisory board.
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- 2021
14. Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus
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Hyoun-Ah Kim, Ju-Yang Jung, Wook-Young Baek, Chang-Hee Suh, and Ji-Min Woo
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0301 basic medicine ,Adult ,Male ,Cyclophosphamide ,lcsh:Medicine ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Systemic lupus erythematosus ,immune system diseases ,Genotype ,Republic of Korea ,Medicine ,Humans ,Lupus Erythematosus, Systemic ,Genetic Predisposition to Disease ,Allele ,lcsh:Science ,skin and connective tissue diseases ,Genetic association study ,030203 arthritis & rheumatology ,Multidisciplinary ,medicine.diagnostic_test ,biology ,integumentary system ,business.industry ,Haplotype ,lcsh:R ,Milk Proteins ,Healthy Volunteers ,030104 developmental biology ,Gene Expression Regulation ,Haplotypes ,Erythrocyte sedimentation rate ,Case-Control Studies ,Immunology ,Antigens, Surface ,biology.protein ,lcsh:Q ,Female ,Antibody ,MFGE8 ,business ,medicine.drug - Abstract
Systemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.
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- 2019
15. Androgen therapy for patients with lower‐risk myelodysplastic syndrome and significant cytopenia: a retrospective study
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Young-Shin Lee, Mijin Jeon, Kyoo-Hyung Lee, Ji Min Woo, Hyeran Kang, Je-Hwan Lee, Miee Seol, Young-Ah Kang, Han-Seung Park, Eun-Ji Choi, and Jung-Hee Lee
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,medicine.drug_class ,Lower risk ,Young Adult ,medicine ,Humans ,Young adult ,Aged ,Retrospective Studies ,Aged, 80 and over ,Danazol ,Cytopenia ,business.industry ,Retrospective cohort study ,Hematology ,Middle Aged ,medicine.disease ,Androgen ,Thrombocytopenia ,Treatment Outcome ,Oxymetholone ,Androgen Therapy ,Myelodysplastic Syndromes ,Androgens ,Female ,business ,medicine.drug - Published
- 2019
16. Comparison of anthracyclines used for induction chemotherapy in patients with FLT3 -ITD-mutated acute myeloid leukemia
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Miee Seol, Juhyun Moon, Eun-Hye Hur, Young-Shin Lee, Kyoo-Hyung Lee, Eun-Ji Choi, Jung-Hee Lee, Han-Seung Park, Je-Hwan Lee, Yeon Hee Kim, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Bon-Kwan Goo, and Sun-Hye Ko
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Anthracycline ,Daunorubicin ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Idarubicin ,Aged ,Retrospective Studies ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Induction chemotherapy ,Myeloid leukemia ,Induction Chemotherapy ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Leukemia, Myeloid, Acute ,Leukemia ,Regimen ,030104 developmental biology ,fms-Like Tyrosine Kinase 3 ,030220 oncology & carcinogenesis ,Mutation ,Cytarabine ,Female ,business ,medicine.drug - Abstract
This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m2/d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2/d × 3d; n = 51), or idarubicin (IDA; 12 mg/m2/d × 3d; n = 33) in combination with cytarabine (100–200 mg/m2/d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m2/d) or IDA (8 or 12 mg/m2/d) in addition to 5 days of cytarabine. Complete remission (CR) rates were 77.3%, 56.9%, and 69.7% for HD-DN, SD-DN, and IDA, respectively (P = 0.101; HD-DN vs. SD-DN, P = 0.036; HD-DN vs. IDA, P = 0.453; IDA vs. SD-DN, P = 0.237). The HD-DN showed higher overall survival (OS) and event-free survival (EFS) than SD-DN and IDA: the differences between HD-DN and SD-DN (P = 0.009 for OS and P = 0.010 for EFS) were statistically significant. Results of in vitro studies using FLT3-ITD-mutated cell lines supported these findings. In conclusion, HD-DN improved the CR rate, OS, and EFS of FLT3-ITD-mutated AML patients. HD-DN also tended to yield better outcomes than IDA, though the difference was not significant. The superiority of HD-DN over IDA should be confirmed in future studies.
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- 2018
17. Machine Learning-Based Approach to Predict Survival after Allogeneic Hematopoietic Cell Transplantation in Hematologic Malignancies
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Je-Hwan Lee, Han-Seung Park, Eun-Ji Choi, Jung-Hee Lee, Kyoo Hyung Lee, Ji Min Woo, Young-Shin Lee, Hyeran Kang, Young-Ah Kang, Mijin Jeon, and Jun-Hong Park
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Acute leukemia ,Receiver operating characteristic ,business.industry ,Donor selection ,Immunology ,Cell Biology ,Hematology ,Logistic regression ,medicine.disease ,Machine learning ,computer.software_genre ,Biochemistry ,Confidence interval ,Transplantation ,Medicine ,Artificial intelligence ,business ,computer ,Myeloproliferative neoplasm ,Multiple myeloma - Abstract
Background Allogeneic hematopoietic cell transplantation (HCT) has been more widely applicable to the patients with hematologic malignancies owing to the increased donor availability, advances in conditioning regimen, prevention of transplantation-related toxicities, and general supportive care. However, there is no comprehensive and uniform approach for decision making which incorporates transplantation-related factors including patients and donor selection, conditioning intensity, or prevention of graft-versus-host disease (GVHD). In this regard, we aimed to establish and validate a machine learning-based predictive model for survival after allogeneic HCT in hematologic malignancies. Method Data from 2,011 patients with hematologic malignancies (1,464 acute leukemia, 296 myelodysplastic syndrome, 100 chronic myeloid leukemia, 45 myeloproliferative neoplasm, 85 lymphoma, and 21 multiple myeloma) who received allogeneic HCT between December 1993 and December 2019 at the Asan Medical Center were retrospectively analyzed. Results The median overall and event-free survival of total patients were 4.2 year (95% confidence interval [CI], 2.9-5.4) and 1.5 year (95% CI, 1.1-1.8), respectively. To predict post-transplantation survival, the patients were classified into "survived more than 5 years" and "died before 5 years". Among four major machine learning models (random forest [RF], support vector machine, logistic regression, and feed forward neural network), we selected RF method according to the predictive power of each algorithm. Using the RF machine learning algorithm, we developed a post-transplantation survival predicting model with the training cohort of 1,408 patients (70%) and tested it with the validation cohort of 603 patients (30%). Of >200 variables, 33 were selected using recursive feature elimination, and the estimated area under the receiver operator characteristic curve and accuracy of the model was 0.812 and 0.73, respectively. We then evaluated the robustness of predictive power of the model using 10-fold cross-validation in validation cohort. In addition, risk scores were calculated from each patient in the validation cohort, and there was an agreement between the estimated predicted risk and observed risk. Conclusion In conclusion, the machine learning-based prediction model seems feasible assuming post-transplantation survival outcomes in hematologic malignancies. Our findings could be helpful for clinicians to select more appropriate donor in terms of age or type of human leukocyte antigen mismatch, conditioning regimen, and GVHD prophylaxis. Disclosures Lee: Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Lee:Hanmi: Research Funding.
- Published
- 2020
18. Multi-level engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalysts for the production of C9 chemicals from oleic acid
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Eun Ji Seo, Young Joo Yeon, Ji Min Woo, Sungho Jang, Gyoo Yeol Jung, Chae Won Kang, and Jin Byung Park
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0106 biological sciences ,Population ,Bioengineering ,medicine.disease_cause ,01 natural sciences ,Applied Microbiology and Biotechnology ,Mixed Function Oxygenases ,03 medical and health sciences ,chemistry.chemical_compound ,Biotransformation ,Bacterial Proteins ,010608 biotechnology ,medicine ,Escherichia coli ,education ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,education.field_of_study ,Pseudomonas putida ,Fatty Acids ,Fatty acid ,Monooxygenase ,Oleic acid ,Biochemistry ,chemistry ,Metabolic Engineering ,Biocatalysis ,Fermentation ,Biotechnology ,Oleic Acid - Abstract
Whole-cell biotransformation is one of the promising alternative approaches to microbial fermentation for producing high-value chemicals. Baeyer–Villiger monooxygenase (BVMO)-based Escherichia coli biocatalysts have been engineered to produce industrially relevant C9 chemicals, such as n-nonanoic acid and 9-hydroxynonanoic acid, from a renewable long-chain fatty acid. The key enzyme in the biotransformation pathway (i.e., BVMO from Pseudomonans putida KT2440) was first engineered, using structure modeling-based design, to improve oxidative and thermal stabilities. Using a stable and tunable plasmid (STAPL) system, E. coli host cells were engineered to have increased plasmid stability and homogeneity of the recombinant E. coli population, as well as to optimize the level of BVMO expression. Multi-level engineering of the key enzyme in host cells, allowed recombinant E. coli expressing a fatty acid double-bond hydratase, a long-chain secondary alcohol dehydrogenase, and the engineered BVMO from P. putida KT2440 (i.e., E6BVMO_C302L/M340L), to ultimately produce C9 chemicals (i.e., n-nonanoic acid and 9-hydroxynonanoic acid) from oleic acid, with a yield of up to 6 mmoL/g dry cells. This yield was 2.4-fold greater than the yield in the control strain before engineering. Therefore, this study will contribute to the development of improved processes for the biosynthesis of industrially relevant medium chain fatty acids via whole-cell biocatalysis.
- Published
- 2019
19. Decitabine Versus Intensive Chemotherapy for Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia
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Ji Min Woo, Miee Seol, Je-Hwan Lee, Kyoo Hyung Lee, Eun-Ji Choi, Jung-Hee Lee, Han-Seung Park, Young-Ah Kang, Mijin Jeon, and Young-Shin Lee
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Oncology ,Male ,Cancer Research ,Time Factors ,Biochemistry ,0302 clinical medicine ,hemic and lymphatic diseases ,Gene Duplication ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Infusions, Intravenous ,Aged, 80 and over ,Remission Induction ,Age Factors ,Cytarabine ,Myeloid leukemia ,Hematology ,Prognosis ,Chemotherapy regimen ,Leukemia ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Immunology ,Decitabine ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Idarubicin ,Humans ,Aged ,Retrospective Studies ,business.industry ,Surrogate endpoint ,Daunorubicin ,Cell Biology ,DNA Methylation ,medicine.disease ,Hypomethylating agent ,fms-Like Tyrosine Kinase 3 ,business ,030215 immunology ,Follow-Up Studies - Abstract
Background Elderly patients with acute myeloid leukemia (AML) has generally poor prognosis prognosis in accordance with their unfavorable clinical and biologic features. Hypomethylating agents have shown potential in the treatment of AML as well as myelodysplastic syndrome (MDS). In this retrospective study, we compared the outcomes of elderly AML patients according to induction treatment options: decitabine versus intensive chemotherapy. We also tried to identify specific subsets of patients who are most likely to benefit from decitabine or intensive chemotherapy. Methods This study included elderly patients aged 65 years or older who received induction treatment with decitabine or intensive chemotherapy for newly diagnosed AML at a single institute. The endpoints for this study were overall survival (OS), response, and event-free survival (EFS). Response included complete remission (CR), CR with incomplete hematologic recovery (CRi), and CR with partial hematologic recovery (CRh). Results A total of 107 patients, decitabine for 75 and intensive chemotherapy for 32, were analyzed. Decitabine was given as 20 mg/m2/day for 5 days every 4 weeks. Median 5 courses (range, 1-43) were delivered to the patients and 16 patients were still on decitabine treatment at the time of analysis. Intensive chemotherapy regimens included cytarabine plus daunoruribin (n=21) or idarubicin (n=10), and hyper-CVAD (n=1): 25 patients received one course and 7 received two courses for induction treatment. The rate for CR + CRi + CRh (CRR) was 38.6% (39 of 101 assessable patients). With a median follow-up duration of 14.8 months (95% confidence interval [CI], 12.0-22.8) among surviving patients, 79 patients died and 22 relapsed. The median OS and EFS were 12.3 months (95% CI, 10.0-14.7) and 4.1 months (95% CI, 2.5-5.7), respectively. Decitabine showed lower CRR (26.1% vs. 65.6, P Conclusion Decitabine showed similar OS to intensive chemotherapy despite of lower response rate in elderly AML patients. Clinical outcomes of specific subgroups seemed to be different according to induction treatment options. Further studies are warranted for selection of optimal treatment options for elderly AML patients. Disclosures No relevant conflicts of interest to declare.
- Published
- 2018
20. Improving catalytic activity of the Baeyer–Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of (Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid
- Author
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Eun Yeong Jeon, Young Joo Yeon, Jin Byung Park, Eun Ji Seo, Dong-Yup Lee, Joo-Hyun Seo, and Ji Min Woo
- Subjects
0301 basic medicine ,Stereochemistry ,Protein Conformation ,Science ,Ricinoleic acid ,Sequence Homology ,Article ,Mixed Function Oxygenases ,Metabolic engineering ,03 medical and health sciences ,chemistry.chemical_compound ,Biotransformation ,Escherichia coli ,Amino Acid Sequence ,Alcohol dehydrogenase ,Multidisciplinary ,biology ,Pseudomonas putida ,Monooxygenase ,biology.organism_classification ,equipment and supplies ,Oxidative Stress ,030104 developmental biology ,Bioprocess engineering ,chemistry ,Mutation ,biology.protein ,Biocatalysis ,Mutagenesis, Site-Directed ,Medicine ,Energy source ,Ricinoleic Acids ,Oxidation-Reduction - Abstract
Baeyer–Villiger monooxygenases (BVMOs) can be used for the biosynthesis of lactones and esters from ketones. However, the BVMO-based biocatalysts are not so stable under process conditions. Thereby, this study focused on enhancing stability of the BVMO-based biocatalysts. The biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid by the recombinant Escherichia coli expressing the BVMO from Pseudomonas putida and an alcohol dehydrogenase from Micrococcus luteus was used as a model system. After thorough investigation of the key factors to influence stability of the BVMO, Cys302 was identified as an engineering target. The substitution of Cys302 to Leu enabled the engineered enzyme (i.e., E6BVMOC302L) to become more stable toward oxidative and thermal stresses. The catalytic activity of E6BVMOC302L-based E. coli biocatalysts was also greater than the E6BVMO-based biocatalysts. Another factor to influence biocatalytic performance of the BVMO-based whole-cell biocatalysts was availability of carbon and energy source during biotransformations. Glucose feeding into the reaction medium led to a marked increase of final product concentrations. Overall, the bioprocess engineering to improve metabolic stability of host cells in addition to the BVMO engineering allowed us to produce (Z)-11-(heptanoyloxy)undec-9-enoic acid to a concentration of 132 mM (41 g/L) from 150 mM ricinoleic acid within 8 h.
- Published
- 2018
21. High temperature stimulates acetic acid accumulation and enhances the growth inhibition and ethanol production by Saccharomyces cerevisiae under fermenting conditions
- Author
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Kyung Mi Yang, Sae Um Kim, Lars M. Blank, Jin Byung Park, and Ji Min Woo
- Subjects
chemistry.chemical_classification ,Ethanol ,Chemistry ,Glucose uptake ,Temperature ,Saccharomyces cerevisiae ,General Medicine ,Tricarboxylic acid ,Ethanol fermentation ,Applied Microbiology and Biotechnology ,Carbon ,Metabolic Flux Analysis ,chemistry.chemical_compound ,Acetic acid ,Adenosine Triphosphate ,Glucose ,Biochemistry ,Fermentation ,Ethanol fuel ,Ethanol metabolism ,Energy Metabolism ,Acetic Acid ,Biotechnology - Abstract
Cellular responses of Saccharomyces cerevisiae to high temperatures of up to 42 °C during ethanol fermentation at a high glucose concentration (i.e., 100 g/L) were investigated. Increased temperature correlated with stimulated glucose uptake to produce not only the thermal protectant glycerol but also ethanol and acetic acid. Carbon flux into the tricarboxylic acid (TCA) cycle correlated positively with cultivation temperature. These results indicate that the increased demand for energy (in the form of ATP), most likely caused by multiple stressors, including heat, acetic acid, and ethanol, was matched by both the fermentation and respiration pathways. Notably, acetic acid production was substantially stimulated compared to that of other metabolites during growth at increased temperature. The acetic acid produced in addition to ethanol seemed to subsequently result in adverse effects, leading to increased production of reactive oxygen species. This, in turn, appeared to cause the specific growth rate, and glucose uptake rate reduced leading to a decrease of the specific ethanol production rate far before glucose depletion. These results suggest that adverse effects from heat, acetic acid, ethanol, and oxidative stressors are synergistic, resulting in a decrease of the specific growth rate and ethanol production rate and, hence, are major determinants of cell stability and ethanol fermentation performance of S. cerevisiae at high temperatures. The results are discussed in the context of possible applications.
- Published
- 2014
22. Androgen Therapy for Lower-Risk Myelodysplastic Syndrome
- Author
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Miee Seol, Eun-Ji Choi, Young-Shin Lee, Jung-Hee Lee, Han-Seung Park, Ji Min Woo, Kyoo Hyung Lee, Je-Hwan Lee, Mijin Jeon, and Young-Ah Kang
- Subjects
Danazol ,medicine.medical_specialty ,Cytopenia ,Univariate analysis ,business.industry ,Immunology ,Hazard ratio ,Cell Biology ,Hematology ,Lower risk ,medicine.disease ,Biochemistry ,Gastroenterology ,International Prognostic Scoring System ,Androgen Therapy ,Internal medicine ,Oxymetholone ,medicine ,business ,medicine.drug - Abstract
Background Improvement of cytopenia is one of the primary treatment purposes for patients with the lower-risk myelodysplastic syndrome (MDS). Androgens have been used for the treatment of aplastic anemia, immune thrombocytopenia, and telomere diseases. In this retrospective study, we aimed to evaluate the efficacy of androgen therapy in lower-risk MDS. Methods We analyzed the data of 139 patients who received androgens (danazol or oxymetholone) for treatment of cytopenia between February 1997 and May 2018. All patients had the international prognostic scoring system low or intermediate-1 risk at the time of androgen therapy. The assessment of hematologic improvement (HI) was based on the international working group response criteria for MDS. Results Androgens (oxymetholone for 83 patients and danazol for 56) were given as first (n=108, 77.7%) or over second (n=31, 22.3%)-line treatment for MDS (Table 1). The time interval between diagnosis and androgen treatment was median 1.3 months (range, 0-240.6), and 75 patients (54.0%) were red blood cell (RBC) transfusion-dependent before treatment. The dose intensity of oxymetholone and danazol was 79 and 385 mg/day respectively, and the median treatment duration was 5.8 months (range, 0.9-92.2). Seventy-nine patients (56.8%) achieved HI at any lineage: 29.0% for erythroid (HI-E), 51.9% for platelet (HI-P), and 60.5% for neutrophil (HI-N). The median time to HI following androgen therapy was 4.1 months (range, 0.6-124.5) for HI-E, 1.7 (range, 0.4-40.4) for HI-P, and 1.8 (range, 0.2-8.4) for HI-N. In univariate analysis, presence of RBC transfusion-dependence (46.7% vs. 68.8%, P=.009), pre-treatment low hemoglobin (45.2% vs. 74.5%, P=.001), high platelet count (46.5% vs. 73.6%, P=.002), and high neutrophil count (4.94% vs. 67.2%, P=.036) were associated with lower HI rate (Table 2). In multivariate analysis, pre-treatment low hemoglobin, high platelet count, and high neutrophil count remained as significant factors for lower HI rate (Table 2). During the median follow-up duration of survivors of 40.8 months (95% confidence interval [CI], 38.0-67.5), the estimated 5-year overall survival (OS) and acute myeloid leukemia-free survival was 68.8% and 67.7%, respectively. Achievement of HI was associated with longer OS (hazard ratio, 0.346; 95% CI, 0.174-0.688). There were no significant differences in HI and OS rates between danazol and oxymetholone. Conclusion Our data suggest that androgen can be a reasonable treatment option for lower-risk MDS patients with significant cytopenia. Prospective studies are warranted to investigate the efficacy of androgen therapy in lower-risk MDS. Disclosures No relevant conflicts of interest to declare.
- Published
- 2018
23. 3 '-UTR engineering to improve soluble expression and fine-tuning ofactivity of cascade enzymes in Escherichia coli
- Author
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Ji-Won Song, Ji-Min Woo, Jin-Byung Park, Gyoo Yeol Jung, and Uwe T. Bornscheuer
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0301 basic medicine ,Untranslated region ,RNase P ,030106 microbiology ,Heterologous ,Pseudomonas fluorescens ,medicine.disease_cause ,Protein Engineering ,Article ,Mixed Function Oxygenases ,Substrate Specificity ,03 medical and health sciences ,Endoribonucleases ,medicine ,Escherichia coli ,3' Untranslated Regions ,chemistry.chemical_classification ,Multidisciplinary ,biology ,Protein engineering ,Monooxygenase ,biology.organism_classification ,Molecular biology ,Kinetics ,030104 developmental biology ,Enzyme ,chemistry ,Biochemistry ,Genes, Bacterial ,Biocatalysis - Abstract
3′-Untranslated region (3′UTR) engineering was investigated to improve solubility of heterologous proteins (e.g., Baeyer-Villiger monooxygenases (BVMOs)) in Escherichia coli. Insertion of gene fragments containing putative RNase E recognition sites into the 3′UTR of the BVMO genes led to the reduction of mRNA levels in E. coli. Importantly, the amounts of soluble BVMOs were remarkably enhanced resulting in a proportional increase of in vivo catalytic activities. Notably, this increase in biocatalytic activity correlated to the number of putative RNase E endonucleolytic cleavage sites in the 3′UTR. For instance, the biotransformation activity of the BVMO BmoF1 (from Pseudomonas fluorescens DSM50106) in E. coli was linear to the number of RNase E cleavage sites in the 3′UTR. In summary, 3′UTR engineering can be used to improve the soluble expression of heterologous enzymes, thereby fine-tuning the enzyme activity in microbial cells.
- Published
- 2016
24. Role of Daunorubicin Dose Intensification for Induction Therapy in Acute Myeloid Leukemia Patients with FLT3-ITD Mutants
- Author
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Jung-Hee Lee, Eun-Ji Choi, Han-Seung Park, Ji Min Woo, Kyoo-Hyung Lee, Sun-Hye Ko, Je-Hwan Lee, and Miee Seol
- Subjects
Acute promyelocytic leukemia ,Daunorubicin ,business.industry ,Immunology ,Mutant ,Myeloid leukemia ,Cell Biology ,Hematology ,Impedance threshold device ,medicine.disease ,Biochemistry ,Induction therapy ,medicine ,Cancer research ,Idarubicin ,Dose intensification ,business ,medicine.drug - Abstract
Background Patients with FLT3-ITD mutated acute myeloid leukemia (AML) have generally poor survival. Recent update of ECOG trial comparing standard- vs. high-dose daunorubicin showed that daunorubicin dose intensification improved survival in AML with FLT3-ITD mutants (Blood 2016;127:1551). In subgroup analysis of our previous randomized trial, high-dose daunorubicin seemed to be more effective than idarubicin in AML patients with FLT3-ITD mutants (ASH abstract No. 2535, 2015). In this retrospective investigation, we aimed to evaluate the role of daunorubicin dose intensification for induction therapy in AML patients with FLT3-ITD mutants who were treated at a single institute. Methods We analyzed data from 120 patients of newly diagnosed FLT3-ITD mutated AML patients who received induction chemotherapy between January 2002 and March 2016. The regimens consisted of high-dose daunorubicin (HD-DN, 90 mg/m2/d x 3d, n=39), standard-dose daunorubicin (SD-DN, 45 mg/m2/d x 3d, n=48), or idarubicin (IDA, 12 mg/m2/d x 3d, n=33) in combination with cytarabine (200 mg/m2/d x 7d). Patients with acute promyelocytic leukemia were not included. Results After the first round of induction chemotherapy, 53 patients had persistent leukemia; 50 received the second round of induction chemotherapy consisting of daunorubicin (45 mg/m2/d x 2d) or idarubicin (8 mg/ m2/d x 2d) in addition to cytarabine (200 mg/m2/d x 5d) and 3 received other regimens. A total of 81 patients achieved CR, and the CR rates were 76.9%, 58.3%, and 69.7% in HD-DN, SD-DN, and IDA, respectively (P=0.175). The 4-year cumulative incidence of relapse (CIR) of these 81 patients was 48.8%. With the median follow-up duration of survivors of 59.9 months (range, 4.6-170.7), 4-year overall survival (OS) and event-free survival (EFS) were 57.1%/27.7%/35.7% (P=0.025) and 45.2%/23.9%/36.0% (P=0.042) in HD-DN, SD-DN, and IDA, respectively. HD-DN showed statistically higher OS (hazard ration [HR], 0.424; P=0.005) and EFS (HR, 0.497; P=0.01), and lower CIR (P=0.036) than SD-DN, while OS and EFS differences between HD-DN and IDA were not statistically significant. Conclusion Daunorubicin dose intensification for induction therapy seemed to be effective in AML patients with FLT3-ITD mutants. Further studies are needed to investigate whether HD-DN is superior to IDA in this population. Considering high relapse rate, combination strategies of daunorubicin dose intensification and targeted agents such as FLT3 inhibitors should be developed. Disclosures No relevant conflicts of interest to declare.
- Published
- 2016
25. Ethanol reduces mitochondrial membrane integrity and thereby impacts carbon metabolism of Saccharomyces cerevisiae
- Author
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Wonja Choi, Na-Rae Lee, Kyung Mi Yang, Lars M. Blank, Martin Zimmermann, Jin Byung Park, and Ji Min Woo
- Subjects
Cell Membrane Permeability ,Saccharomyces cerevisiae ,Citric Acid Cycle ,Applied Microbiology and Biotechnology ,Microbiology ,chemistry.chemical_compound ,Adenosine Triphosphate ,Ethanol fuel ,Inner mitochondrial membrane ,Membrane potential ,Membrane Potential, Mitochondrial ,Ethanol ,biology ,Chemiosmosis ,General Medicine ,Metabolism ,biology.organism_classification ,Carbon ,Citric acid cycle ,Biochemistry ,chemistry ,Mitochondrial Membranes ,Biophysics ,Energy Metabolism - Abstract
Saccharomyces cerevisiae is an excellent ethanol producer, but is rather sensitive to high concentration of ethanol. Here, influences of ethanol on cellular membrane integrity and carbon metabolism of S. cerevisiae were investigated to rationalize mechanism involved in ethanol toxicity. Addition of 5% (v/v) ethanol did neither significantly change the permeability of the cytoplasmic membrane of the reference strain S. cerevisiae BY4741 nor of the ethanol-tolerant strain iETS3. However, the addition of ethanol resulted in a marked decrease in the mitochondrial membrane potential and in increased concentrations of intracellular reactive oxygen species (ROS). The carbon flux was redistributed under these conditions from mainly ethanol production to the TCA cycle. This redistribution was possibly a result of increased energy demand for cell maintenance that increased from about zero to 20-40 mmol ATP (g(CDW) h)(-1) . This increase in maintenance energy might be explained by the ethanol-induced reduction of the proton motive force and the required removal of ROS. Thus, the stability of the mitochondrial membrane and subsequently the capacity to keep ROS levels low could be important factors to improve tolerance of S. cerevisiae against ethanol.
- Published
- 2012
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