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Dong-Wook Kim

Publications and source records attributed to Dong-Wook Kim.

At least 37 records · Page 2Linked to original sources
PubMed2005

Risk-adapted preemptive therapy for cytomegalovirus disease after allogeneic stem cell transplantation: a single-center experience in Korea.

Cytomegalovirus (CMV) remains a major cause of infection in recipients of hematopoietic stem cell transplants (HSCT) and results in significant mortality and morbidity. We present the results of CMV pp65 antigenemia-guided, risk-adapted preemptive therapy aimed at preventing CMV disease in allogeneic HSCT. Preemptive ganciclovir treatment was started when more than 5 CMV antigen-positive cells were detected in the low-risk group (with grade 0-I acute GVHD and matched related HSCT) and when any antigen-positive cells were seen in the high-risk group (with grade II-IV acute GVHD or matched unrelated HSCT). At least 1 episode of antigenemia was observed in 53 (59.6%) of 89 patients before day 100, and preemptive therapy was performed in 33 patients. CMV disease occurred in 6 patients (5 in the high-risk group and 1 in the low-risk group), and late CMV disease developed in 4 patients. Only 1 patient died of CMV pneumonitis before day 100. Neutropenia was observed in 51.5% of ganciclovir-treated patients, and coinfection/superinfection was observed in 42.4%. A strategy of ganciclovir treatment focusing on patients at higher risk could reduce the toxicity from the antiviral drug and be cost-effective. Extended surveillance for CMV disease using more sensitive diagnostic methods is necessary in high-risk patients.

Adolescent↗
PubMed2005

Comparison of 2 preparative regimens for stem cell transplantation from HLA-matched sibling donors in patients with advanced myelodysplastic syndrome.

The objective of this study was to compare how cyclophosphamide (CY) and oral busulfan (BU) therapies, each in combination with total body irradiation (TBI), affect the outcome of stem cell transplantation in patients with advanced myelodysplastic syndrome. This study was conducted with 31 patients who received bone marrow from an HLA-matched sibling and underwent treatment with BU-TBI (n = 18) or CY-TBI (n = 13). The incidence of acute graft-versus-host disease (GVHD) grades II to IV was higher, but not significantly, in the BU-TBI group (58.8%) than in the CY-TBI group (30.8%). However, the incidences of chronic extensive GVHD were significantly different (41.7% [CY-TBI] versus 80.0% [BU-TBI], P = .04). Trends after BU-TBI conditioning indicated a lower 3-year probability of disease-free survival (DFS) (38.1% versus 53.9%, P = .4), lower relapse rates (28.5% versus 36.4%, P = .8), and higher nonrelapse mortality rates (46.7% versus 15.4%, P = .2). After adjusting for the International Prognostic Scoring System risk group and the cytogenetic risk group, DFS in the CY-TBI group (relative risk, 9.0; 95% confidence interval, 1.5-52.5; P = .015) was found to be significantly increased compared with the BU-TBI group. Approaches to minimize transplantation-related toxicity should be pursued, and efforts other than the potentiation of the conditioning regimen should be made to reduce the likelihood of posttransplantation relapse.

Administration, Oral↗
PubMed2005

Derivation and characterization of new human embryonic stem cell lines: SNUhES1, SNUhES2, and SNUhES3.

Here we report the derivation and characterization of new human embryonic stem cell (hESC) lines, SNUhES1, SNUhES2, and SNUhES3. These cells, established from the inner cell mass using an STO feeder layer, satisfy the criteria that characterize pluripotent hESCs: The cell lines express high levels of alkaline phosphatase, cell surface markers (such as SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81), transcription factor Oct-4, and telomerase. When grafted into severe combined immunodeficient mice after prolonged proliferation, these cells maintained the developmental potentials to form derivatives of all three embryonic germ layers. The cell lines have normal karyotypes and distinct identities, revealed from DNA fingerprinting. Interestingly, analysis by electron microscopy clearly shows the morphological difference between undifferentiated and differentiated hESCs. Undifferentiated hESCs have a high ratio of nucleus to cytoplasm, prominent nucleoli, indistinct cell membranes, free ribosomes, and small mitochondria with a few crista, whereas differentiated cells retain irregular nuclear morphology, desmosomes, extensive cytoplasmic membranes, tonofilaments, and highly developed cellular organelles such as Golgi complex with secretory vesicles, endoplasmic reticulum studded with ribosomes, and large mitochondria. Existence of desmosomes and tonofilaments indicates that these cells differentiated into epithelial cells. When in vitro differentiation potentials of these cell lines into cardiomyocytes were examined, SNUhES3 was found to differentiate into cardiomyocytes most effectively.

Cell Differentiation↗
PubMed2005

Methods for expansion of human embryonic stem cells.

The manipulation of human embryonic stem cells (hESCs) requires refined skills. Here we introduce both mechanical and enzymatic transfer methods for hESCs depending on experimental purpose. We use the mechanical transfer method for maintenance of hESC lines. Although the method is laborious and time-consuming, the technique permits efficient transfer of undifferentiated hESCs and results in similar clump sizes. We implement the enzymatic transfer method when we need the bulk production of cells for various experiments. The enzyme-treated expansion rapidly produces greater amounts of hESCs within a limited time frame. However, the cell clumps vary in size, and there is a probability that both the differentiated and undifferentiated cells will be transferred. In cases in which there are differentiated colonies, the combination of two methods allows mass production of hESCs by excluding differentiated colonies from passage by manual selection before enzyme treatment.

Cell Culture Techniques↗
PubMed2004

Large-scale and effective screening of Korean medicinal plants for inhibitory activity on matrix metalloproteinase-9.

Matrix metalloproteinase-9 (MMP-9) degrades type IV collagen constituting the major structural component of the basement membrane and extra cellular membrane. The enzymatic activity is found to be elevated in tumor tissues. With the aim of finding novel MMP-9 inhibitors from natural products, 87 extracts of oriental medicinal herbs, which are used as prescriptions for cancer treatment in traditional Korean medicine, were screened for their inhibitory activities towards MMP-9. It was found that most of the hexane and chloroform fractions as well as water extracts showed a weak inhibitory effect on MMP-9 activity at a concentration of 100mug/ml. However, a strong inhibition was found in the butanol fractions of Cinnamomum cassia PRESL, Magnolia obovata THUEB., Magnolia officinalis REHD. et WILS., Magnolia officinalis REHD. et WILS. var. biloba REHD. et WILS., and Euonymus alatus (THUNB.) SIEB. with inhibitory activity (>90%) at a concentration of 100 microg/ml.

Cell Line, Tumor↗
PubMed2004

Protective effect of Lycium chinense fruit on carbon tetrachloride-induced hepatotoxicity.

In the present study, we investigated the protective effect of Lycium chinense Miller (Solanaceae) fruit (LFE) against CCl(4)-induced hepatotoxicity and the mechanism underlying these protective effects in rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum aspartate and alanine aminotransferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation. In addition, pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CCl(4)-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC(50) = 83.6 microg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. The expression level of cytochrome P450 2E1 (CYP2E1) mRNA and protein, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis, was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE might be related to antioxidative activity and expressional regulation of CYP2E1.

Alanine Transaminase↗
PubMed2004

Efficient induction of dopaminergic neurons from embryonic stem cells for application to Parkinson's disease.

For cell replacement therapy of neurodegenerative diseases such as Parkinson's disease (PD), methods for efficiently generating midbrain dopaminergic (DA) neurons from embryonic stem (ES) cells have been investigated. Two aspects of DA neuron generation are considered: genetic modification and manipulation of culture conditions. A transcription factor known as critical for development of DA neurons, Nurr1, was introduced into ES cells to see how they facilitate the generation of DA neurons from ES cells. Also, two culture procedures, the 5-stage method and stromal cell-derived inducing activity (SDIA) method, were used for ES cell differentiation. Using the 5-stage method, we and others previously demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+ neurons). Furthermore, using the SDIA method with treatment of signaling molecules, we found that Nurr1-overexpressing ES cells can differentiate to DA neurons with the highest efficiency ever reported (approximately 90% of TH+/Tuj1+ neurons). Importantly, our semi-quantitative and real-time PCR analyses demonstrate that all known DA marker genes (e.g., TH, AADC and DAT) were up-regulated in Nurr1- overexpressing ES cells when compared to the na ve ES cells. These cells produced increased dopamine compared to na ve D3 cells after differentiation. In the in vivo context after transplantation, the genetically modified ES cells also showed the highly increased dopaminergic neuronal phenotypes. Thus, the combination of genetic engineering and appropriate culture conditions provides a useful tool to generate a good cell source from ES cells for cell replacement therapy of degenerative diseases such as PD.

Cell Differentiation↗
PubMed2004

Efficient transduction with recombinant adenovirus in EBV-transformed B lymphoblastoid cell lines.

The Epstein-Barr-transformed B lymphoblastoid cell lines, LCL, which express antigens, are potential antigen-presenting cells (APCs) for the induction of cytotoxic T lymphocytes in vitro. However, transfecting LCL with subsequent selection by antibiotics is notoriously difficult because the plating efficiencies of LCL are reported to be 1% or less. Therefore, this study investigated the optimal conditions for increasing the transduction efficiency of a recombinant adenovirus to LCL for use as a source of APCs. The transduction efficiencies were < 13% (SD +/- 2.13) at a multiplicity of infection (MOI) of 100, while it was increased to 28% (SD +/- 9.43) at an MOI of 1000. Moreover, its efficiencies to LCL that expressed the coxsackie adenovirus receptor were increased to 60% (SD +/- 6.35) at an MOI of 1000, and were further increased to 70% (SD +/- 4.56) when combined with the centrifugal method. The cationic liposome or anionic polymer had no effect on the transduction efficiency when compared to that of the centrifugal method. These results may be used as a convenient source of target cells for a CTL assay and/or autologous APCs for the induction of the in vitro CTL responses that are specific to viral and tumor antigens.

Adenoviridae↗
PubMed2004

Paroxetine in the treatment of depressed patients with haematological malignancy: an open-label study.

OBJECTIVE: The efficacy and tolerability of paroxetine in the treatment of depressive disorders is well known, however, its efficacy and safety for the treatment of depression in patients with cancer has been poorly studied. Therefore this study was aimed at evaluating the efficacy and tolerability of paroxetine in the treatment of depressed patients with haematological malignancy (HM). METHOD: Fifty-two patients with major depressive disorder (MDD) based on DSM-IV criteria along with comorbid HM were allotted to an 8 week trial with a flexible-dose regime of paroxetine in combination with their chemotherapy or supportive pharmacotherapy. The treatment response was assessed at baseline, week 2, week 4 and week 8 with the 17-item Hamilton rating scale for depression (HAM-D17), the Montgomery Asberg depression rating scale (MADRS) and the clinical global impression-severity (CGI-S). Side effects were collected with reported adverse events and laboratory tests throughout the study period. RESULTS: 44.2% of 52 patients completed the 8 week trial. Scores on the HAM-D17, MADRS and CGI-s (last observation carried forward, LOCF) at baseline were significantly reduced with a mean reduction of 30.5%, 32.8% and 39.1%, respectively, after 8 weeks treatment with paroxetine. CONCLUSION: In this preliminary study, paroxetine was found to be effective and moderately tolerated in the treatment of depressed patients with HM, and the present study calls for a controlled study in this field to extend and form a framework on the psychopharmacological data in this field.

Adult↗
PubMed2004

Early prediction of molecular remission by monitoring BCR-ABL transcript levels in patients achieving a complete cytogenetic response after imatinib therapy for posttransplantation chronic myelogenous leukemia relapse.

Imatinib induces a high complete cytogenetic response (CCR) rate in relapsed chronic myelogenous leukemia. By analyzing minimal residual disease (MRD) under the levels of CCR, we tried to assess the molecular response after imatinib therapy. By using real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR), MRD was evaluated in 23 patients (3 in cytogenetic relapse, 6 in chronic phase, 9 in accelerated phase, and 5 in blast crisis) who were treated with standard-dose imatinib for relapsed chronic myelogenous leukemia after allogeneic stem cell transplantation. With a median therapy time of 399 days (range, 35-817 days), 19 (83%) patients achieved a CCR. Meanwhile, 11 (58%) of them achieved a molecular remission (MR), which was associated with improved survival. The Q-RT-PCR data were compared according to the best response (MR, n = 11; CCR, n = 8) in the patients achieving a CCR. The BCR-ABL/ABL ratios were similar in 2 groups at 3 months but were significantly different at 6 months (median, 0.0000012 for MR and 0.00022 for CCR; P =.003). The probability of a subsequent MR was significantly higher in patients with a lower BCR-ABL/ABL ratio at 6 months (100% for <0.0001 versus 33% for >/=0.0001; P =.006) or a greater reduction in the level between 3 and 6 months (log-reduction >/=1.0;, 100%; <1.0, 17%; P =.003). Q-RT-PCR is a reliable method for monitoring MRD: the early trends in the BCR-ABL/ABL ratio may be clinically useful in discriminating patients who will achieve an MR from those who will remain in CCR.

Adult↗
PubMed2004

Inhibitory effect of Sihoga-Yonggol-Moryo-Tang on matrix metalloproteinase-2 and -9 activities and invasiveness potential of hepatocellular carcinoma.

A Korean traditional herbal formulation, Sihoga-Yonggol-Moryo-Tang (SGYMT), is being used for the treatment of many diseases such as tumor, neuropsychiatric, and vascular disorders. The extracts prepared from SGYMT and its herbal ingredients were assayed for the inhibitory effects on tumor-specific matrix metalloproteinases-2 and -9 (MMP-2/9) activities using gelatin zymography. The results showed that SGYMT decreased the gelatinolytic activities of MMP-2 and -9, which were secreted from SK-Hep1 cells. The IC(50) values of SGYMT against these enzymes were 85 and 145 micrograms ml(-1), respectively. The cytotoxocities of SGYMT and its ingredients on human hepatocellular carcinoma (HCC) cell, SK-Hep1 cells, were very low (IC(50)>150 micrograms ml(-1)) as measured by the XTT assay method. The extract were then investigated the inhibitory effect on the invasion of SK-Hep1 cells using matrigel precoated transwell chambers. The results showed that SGYMT effectively inhibited the invasion of SK-Hep1 cells as compared with the control groups. In addition, among herbal ingredients of SGYMT, the bark of Cinnamomum cassia BLUME (Cinnamomi Cortex) and roots of Scutellaria baicalensis GEORGI (Scutelleria Radix) have shown significant inhibition against MMP-2 and -9 activity and invasion of SK-Hep1 cells. From these results, it was suggested that SGYMT could be used as potential anti-tumor agent.

Carcinoma, Hepatocellular↗
PubMed2004

PKC-theta knockout mice are protected from fat-induced insulin resistance.

Insulin resistance plays a primary role in the development of type 2 diabetes and may be related to alterations in fat metabolism. Recent studies have suggested that local accumulation of fat metabolites inside skeletal muscle may activate a serine kinase cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and glucose transport in skeletal muscle. To test this hypothesis, we examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resistance in skeletal muscle. Skeletal muscle and hepatic insulin action as assessed during hyperinsulinemic-euglycemic clamps did not differ between WT and PKC-theta KO mice following saline infusion. A 5-hour lipid infusion decreased insulin-stimulated skeletal muscle glucose uptake in the WT mice that was associated with 40-50% decreases in insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated PI3K activity. In contrast, PKC-theta inactivation prevented fat-induced defects in insulin signaling and glucose transport in skeletal muscle. In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced insulin resistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the treatment of type 2 diabetes.

Adipose Tissue↗
PubMed2004

Spontaneous pneumothorax developed in patients with bronchiolitis obliterans after unrelated hematopoietic stem cell transplantation: case report and review of the literature.

Spontaneous pneumothorax following unrelated hematopoietic stem cell transplantation developed in our 2 patients with bronchiolitis obliterans. Bronchiolitis obliterans is a form of obstructive airway disease and is considered a manifestation of chronic graft-versus-host disease (GVHD). Both of the patients were the recipients of marrow from HLA-matched unrelated donors after a preparative regimen with total body irradiation. Chronic GVHD after transplantation is a common feature in these cases. In contrast to other patients with pneumothorax described in the literature, our patients did not develop bullae. We describe a pneumothorax secondary to bronchiolitis obliterans that complicated the posttransplantation course.

Adult↗
PubMed2004

Megadose CD34+ hemopoietic stem cell transplantation for patients with high risk acute myeloid leukemia who have no HLA matched donor--a pilot study of a full haplotype mismatch transplantation.

BACKGROUND: Haploidentical transplantation has become a popular modality of treatment for acute myeloid leukemia (AML) patients lacking donors with matching HLA. We attempted to assess the success rate and ramifications of full haplotype mismatch transplantation. METHODS: Four patients received stem cell transplantation from their full haplotype mismatched family donors. The conditioning regimen included total-body irradiation, intravenous busulfan, antithymocyte globulin, and fludarabine. Megadose CD34+ stem cell transplants were performed, in a dosage range between 10.9 x 10(6)/kg and 20.6 x10(6)/kg. Neither GvHD prophylaxis nor post-transplant G-CSF were administered. We monitored patients' bone marrow cellularity and peripheral blood chimerism using real-time PCR. RESULTS: All patients evidenced stable engraftment. The most frequent side effect was severe mucositis, but all patients recovered successfully, without early death. No patients exhibited acute GvHD. Two refractory patients relapsed soon after transplantation. The other 2 patients have remained in good clinical condition, with a follow-up duration of 1-4 months. CONCLUSION: Using a newly-developed conditioning regimen, we were able to circumvent GvHD and graft failure, which are the main limitations associated with full haplotype mismatch transplantation. According to our analysis of the relevant literature, it appears that this is the first report of such a conditioning regimen.

Adolescent↗
PubMed2003

Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation.

Although the infusion of umbilical cord blood (UCB) from multiple donors can be a strategy to overcome the cell dose limitation frequently encountered in UCB transplantation, clinical trials have revealed that cells from one donor dominate engraftment. To investigate the origin of and the factors influencing this inequality, we performed mixed transplantation of 2 UCB units with varying degrees of HLA disparities into NOD/SCID mice and determined donor origins by polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) or real-time quantitative (RQ)-PCR for human short tandem repeats (STRs). When total mononuclear cells from 2 units were transplanted as a mixture, cells from one donor predominated (ratio, 81:19), despite comparable overall engraftment when infused as single units, and no augmentation in overall engraftment was observed when compared with the single-unit controls. However, lineage depletion or cotransplantation of mesenchymal stromal cells (MSCs) expanded from third-party bone marrow resulted in more balanced coengraftment. Direct comparison of double UCB transplantation in the presence or absence of MSCs showed that the reduced deviation in the donor ratio (1.8:1 vs. 2.8:1) correlated with a higher overall level of engraftment with MSC cotransplantation. These results indicate that third-party MSCs can be used to alleviate donor deviation and to facilitate engraftment of multidonor UCB.

Animals↗
PubMed2003

Minimal residual disease-based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Fourteen adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. After the first imatinib cycle, 11 patients remained in sustained CHR with a decrease in the BCR-ABL/ABL ratios (0.89 logs), and one refractory patient achieved CHR. Meanwhile, 2 patients were resistant to imatinib. Ten patients receiving a second imatinib cycle following consolidation showed sustained CHR, including 2 molecular CR, with a further decrease in the BCR-ABL/ABL ratios (0.19 logs). Twelve patients underwent SCT in a favorable status, and of these, 11 are still alive in a leukemia-free status at 9 to 28+ months after SCT. First-line imatinib interim therapy appears to be a useful strategy to bridge the time to SCT for patients with Ph+ ALL.

Adult↗