• Journal of Life Science
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• v.17 no.5 s.85
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• pp.678-686
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• 2007

Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.

• Journal of the korean academy of Pediatric Dentistry
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• v.36 no.1
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• pp.157-167
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• 2009

The incidence of childhood cancer is greatest in the first year of life. Early diagnosis and advances in medicine have significantly improved outcomes of treatment resulting in higher survival rate; however, this progress comes at the expense of a higher incidence of adverse side effects because of more aggressive antineoplastic treatment strategies. The oral cavity, a trauma-prone environment, is extremely sensitive to toxicities from antineoplastic agents. Oral health care specialists, including pediatric and hospital dentists can support the oncology team by providing basic oral care, implementing oral care protocols, delivering emergency dental treatment, and assisting and/or managing oral complications from cancer therapy. This article covers the considerations in the dental management of pediatric patients undergoing cancer treatment, specifically chemotherapy, radiotherapy, and hematopoietic stem cell transplantation.

• Korean Journal of Head & Neck Oncology
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• v.16 no.2
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• pp.228-234
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• 2000

Objectives: Esthesioneuroblastoma is a rare malignant neoplasm that originates from the olfactory sensory cells. This tumor grows from the upper nasal cavity and ethmoid sinus and invades surrounding structures through the cribriform plate into intracranium or orbit in advanced stage. Even though there has been some controversies in determining standard treatment due to rarity of this tumor, the combination treatment of surgery and adjuvant radiation has been recommended for the locally advanced esthesioneuroblastomas. However, the recent clinical experiences of advanced cases showed that combination chemotherapy is highly effective to reduce tumor mass and improve clinical outcomes. Materials and Methods: The authors conducted a retrospective analysis of 6 esthesioneuroblastoma patients who were treated in our hospital from 1986. Results: The age of these patients was between 19 and 86 year-old. Among the 6 cases, 2 were diagnosed at stage B and 4 at stage C, according to Kadish classification. Anti-tumor treatments were performed in 5 patients. One patient refused active treatment and was lost to follow-up. Better survival outcome were observed in 3 patients who were treated with combination chemotherapy alone or combined modality treatment including chemotherapy. Conclusion: Based on our retrospective study, the combined treatment consisting of surgery, radiotherapy, and combination chemotherapy should be used to improve treatment results. And furthermore, innovative clinical approaches such as neoadjuvant chemotherapy, high-dose chemotherapy and autologous peripheral stem cell transplantation, which have been reported to have good therapeutic results, should be considered and applied actively.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.273-279
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• 2012

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

• Clinical and Experimental Pediatrics
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• v.56 no.11
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• pp.490-495
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• 2013

Purpose: The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graftversus- host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods: The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 $mg/m^2$ each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group]. Results: Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0- 3) group (median, 25 days; P =0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P =0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P =0.002), followed by female donor to male recipient transplant (P =0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion: Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.

• Journal of Chest Surgery
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• v.36 no.4
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• pp.219-228
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• 2003

Background:Liquid nitrogen freezing techniques have already met with widespread success in biology and medicine as a means of long-term storage for cells and tissues. The use of cryoprotectants such as glycerol and dimethylsulphoxide to prevent ice crystal formation, with carefully controlled rates of freezing and thawing, allows both structure and viability to be retained almost indefinitely. Cryopreservation of various tissues has various con-trolled rates of freezing. Material and Method: To find the optimal freezing curve and the chamber temperature, we approached the thermodynamic calculation of tissues in two ways. One is the direct calculation method. We should know the thermophysical characteristics of all components, latent heat of fusion, area, density and volume, etc. This kind of calculation is so sophisticated and some variables may not be determined. The other is the indirect calculation method. We performed the tissue freezing with already used freezing curve and we observed the actual freezing curve of that tissue. And we modified the freezing curve with several steps of calculation, polynomial regression analysis, time constant calculation, thermal response calculation and inverse calculation of chamber temperature. Result: We applied that freezing program on mesenchymal stem cell, chondrocyte, and osteoblast. The tissue temperature decreased according to the ideal freezing curve without temperature rising. We did not find any differences in survival. The reason is postulated to be that freezing material is too small and contains cellular components. We expect the significant difference in cellular viability if the freezing curve is applied on a large scale of tissues. Conclusion: This program would be helpful in finding the chamber temperature for the ideal freezing curie easily.

• The Journal of Korea Assosiation for Disability and Oral Health
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• v.12 no.2
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• pp.96-100
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• 2016

Metachromatic leukodystrophy (MLD) is a progressive and degenerative neurological disease caused by a deficiency of the catabolic enzyme arylsulfatase A. Deficiency of arylsulfatase A results in accumulation of sulfatide in the white matter of the peripheral and central nervous system and it occurs demyelination as a result. The patient gradually goes through mental and motor failure. General symptoms of MLD include gait disturbance, mental deterioration, muscle rigidity and impaired swallowing. Inheritance of the disease is autosomal recessive. We report a dental caries treatment of a 3-year old boy with MLD. The patient underwent hematopoietic stem cell transplantation (HSCT) to slow the progression of the disease. He was suffered from difficulties of mastication and swallowing from the degenerative neurological symptom. He was ingesting food by both oral feeding and tubal feeding after he took percutaneous endoscopic gastrostomy (PEG). The cause of multiple caries was mainly presumed as patient's prolonged time of meal. The treatment was performed under general anesthesia considering patient's incompliance. Severely affected lower primary molars were treated with pulp treatment and restored with stainless steel crown. Others were restored with composite resin. There were no postoperative complications. MLD is life threatening progressive disease and also has an impact on unfavorable condition for oral health. Routine home oral care and periodic professional dental care should be emphasized to the caregiver of patient considering the susceptibility of dental caries. Not only the medical care, but periodic dental office visit would benefit the quality of life of the patient.

• Neonatal Medicine
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• v.15 no.1
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• pp.22-31
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• 2008

Purpose : Bronchopulmonary dysplasia (BPD) is characterized by arrested vascular and alveolar growth in the premature lung. Considering the consequences of arrested lung growth, the idea of administering bone marrow cells to enhance the inborn repair mechanism is promising as this may reduce the morbidity and mortality of BPD. We followed enhanced green fluorescent protein (EGFP)-labeled bone marrow cells (BMC) injected intraperitoneally into non-EGFP mice in order to determine their fate after transplantation. Methods : An angiogenesis inhibitor, SU1498, was injected subcutaneously on day 3 in non-EGFP C57BL/6 newborn mice to create a model of arrested alveolar development. On the following day, $1{\times}10^6$ BMCs isolated from major histocompatibility complex (MHC)- matched syngenic EGFP mice were injected intraperitoneally to non-EGFP BPD mice. Morphometric analysis, immunostaining, and confocal microscopy were performed to determine the fate of EGFP-positive stem cells in the injured lung. Results : SU1498 injection reduced alveolar surface area and mean alveolar volume in newborn mice. BMC injection resulted in recovery of lung structure comparable to controls. EGFP-positive BMCs were identified in the lungs of the recipient mice after intraperitoneal injection. The injected EGFP cells were co-stained with endothelial and epithelial cells of the developing lung as determined by confocal microscopy. Conclusion : Our results illustrated that EGFP-positive BMCs engrafted and trans-differentiated into epithelial and endothelial cells after intraperitoneal injection in a mouse model of arrested alveolar development.

• Journal of the Korean Society of Radiology
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• v.7 no.4
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• pp.259-264
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• 2013

Total body irradiation in the treatment of childhood leukemia, which is one of the pre-treatment with stem cell transplantation is being used, the current organization using compensators are treated. However, under the terms of the compensator organization long-term impact on the human body, it is difficult to assess directly. In this study, we use the mathematical simulation of radiation exposures body energy and the distance to the crew and the patient (source surface distance, SSD), and patients with tissue compensators change of the distance along the body of the organ doses were evaluated. As a result, the surface dose of energy 4 MV, SSD 280 cm, tissue compensators and the patient when the distance 30 cm 5.84 G / min showed the highest levels. In addition, patients with tissue compensators and the distance apart when 30 cm TBI represents the ideal dose distribution was found.

• Pediatric Infection and Vaccine
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• v.18 no.2
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• pp.201-206
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• 2011

Purpose : Bacteremia is one of the most common causes of morbidity and mortality in children with cancer. The aim of this study was to evaluate the clinical features of bacteremia in pediatric cancer patients. Methods : We retrospectively analyzed bacteremia episodes occurred in pediatric cancer patients at Samsung Medical Center from January 2008 to December 2010. We excluded bacteremia episodes after hematopoietic stem cell transplantation. Results : A total of 141 blood cultures were positive in 121 patients. Thirteen cultures due to contamination were excluded. For analysis, 128 bacteremia episodes in 108 children were included. Gram-positive organisms accounted for 46.9% (60/ 128) and gram-negative organisms for 53.1% (68/128). The source of bacteremia was identified in 21.1% of episodes. Bacteremia due to catheter related infection was observed in 9.4% of episodes (12/128 episodes) and gram-positive organisms were isolated in 75% of episodes (9/12). There were 10 cases (7.8%) of bacteremia associated with septic shock and gramnegative organisms were isolated in 80% of episodes (8/10). Relapses were documented within 30 days in 2 patients who cleared bacteremia which was confirmed after negative blood cultures. Mortality associated with bacteremia was not observed. Conclusion : Continuous monitoring is needed to maintain the tailored strategies to manage pediatric cancer patients with neutropenic fever who are at high risk of developing bacteremia in each institution.