• Clinical and Experimental Pediatrics
• /
• v.56 no.8
• /
• pp.343-350
• /
• 2013

Purpose: Despite the established role of imatinib (IM) in chronic myelogenous leukemia (CML) in adults, there are few reports on its efficacy in children. In this study, we compared the outcomes of children with CML before and after the advent of IM-based treatment. Methods: The study cohort consisted of 52 patients treated for CML at the Department of Pediatrics, The Catholic University of Korea from January 1995 to October 2010. Patients were divided and analyzed according to the preImatinib group (pre-IMG) and imatinib group (IMG). Results: Median age at diagnosis for the overall cohort (pre-IMG, n=27; IMG, n=25) was 9 years, with a median follow-up duration of survivors of 84 months. Except for 5 patients in the IMG, all were diagnosed in chronic phase (CP). The overall survival (OS) of patients diagnosed in CP was 45.7% and 89.7% for pre-IMG and IMG, respectively (P=0.025). The OS of hematopoietic stem cell transplantation (HSCT) recipients in the 2 groups was similar, but the OS of patients diagnosed in CP who did not receive HSCT was superior in IMG (91.7% vs. 16.7%, P=0.014). Of the 12 patients in IMG who remained on IM without HSCT, 2 showed disease progression, compared to 11 of 12 in pre-IMG. No difference was observed in the progression free survival (PFS) of matched donor HSCT recipients and IM-based treatment recipients. Conclusion: Similar PFS of patients treated with IM and those who received matched donor HSCT underscore the potential of IM as effective first-line treatment in childhood CML.

• Environmental Analysis Health and Toxicology
• /
• v.22 no.2 s.57
• /
• pp.147-156
• /
• 2007

Six week-old ICR mice were divided into four groups including NC, RC, RR and RS, then they were injected with sun ginseng (RS), red ginseng (RR) and saline (RC) intraperitoneally as an amount of 60mg/kg body weight at 1 hour, 12 hours and 36 hours before the whole body irradiation with 6.5Gy of X-ray. And the mice were sacrificed at nine days after the irradiation. The RS group were significant increase in the weight of spleen (p<0.05) and the numbers of endogenous spleen colony (p<0.001) and WBC (p<0.05) especially neutrophils, lymphocytes and monocytes in comparison with the RC group. The RR group were significant increase in the numbers of endogenous spleen colony (p<0.01) and WBC (p<0.05) especially neutrophils, lymphocytes and eosinophils in comparison with the RC group. The RS group exhibited a more increase in the weight of spleen and the number of endogenous spleen colony than the RR group. The values of ALT (alanine transaminase) and AST (aspartate transaminase) were significantly elevated (p<0.05) by radiation and they were significantly decreased (p<0.05) in the RS group to the values of the NC group. The value of TBARS(thiobarbituric acid reactive substance) was significantly elevated (p<0.01) by radiation and it was significantly decreased (p<0.05) in the RS group. And the values of SOD (superoxide dismutase) and CAT (catalase) were significantly increased (p<0.05) in the RS group in comparison with the RC group. Taken together the above results, sun ginseng demonstrated the protective effects on hepatocytes and immune and hematopoietic cells in mice exposed to medium dose of irradiation, and those radioprotective effects were a little higher or similar to the red ginseng.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.355-362
• /
• 2014

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7501-7508
• /
• 2013

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of hematopoietic stem cell scarrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL1 fusion gene. The tyrosine kinase inhibitor (TKI) of BCR-ABL1 kinase is a treatment of choice for control of CML. Objective: Recent studies have demonstrated that miRNAs within exosomes from cancer cells play crucial roles in initiation and progression. This study was performed to assess miRNAs within exosomes of K562 cells. Methods: miRNA microarray analysis of K562 cells and K562 cell-derived exosomes was conducted with the 6th generation miRCURYTM LNA Array (v.16.0). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also carried out. GO terms and signaling pathways were categorized into 66 classes (including homophilic cell adhesion, negative regulation of apoptotic process, cell adhesion) and 26 signaling pathways (such as Wnt). Results: In exosomes, 49 miRNAs were up regulated as compared to K562 cells, and two of them were further confirmed by quantitative real-time PCR. There are differentially expressed miRNAs between K562 cell derived-exosomes and K562 cells. Conclusion: Selectively expressed miRNAs in exosomes may promote the development of CML via effects on interactions (e.g. adhesion) of CML cells with their microenvironment.

• Journal of Pharmaceutical Investigation
• /
• v.39 no.6
• /
• pp.411-416
• /
• 2009

The aim of this study was to investigate the frequency of the SNPs on PEPT1 exon 5 and 16 and to analyze haplotype frequency on PEPT1 exon 5 and 16 in Korean population. A total of 519 healthy subjects was genotyped for PEPT1, using pyrosequencing analysis and polymerase chain reaction-based diagnostic tests. Haplotype was statistically inferred using an algorithm based on the expectation-maximization (EM). PEPT1 exon 5 G381A genotyping revealed that the frequency for homozygous wild-type (G/G), heterozygous (G/A) and homozygous mutant-type (A/A) was 30.4, 53.4 and 16.2%, respectively. PEPT1 exon 16 G1287C genotyping revealed that the frequency for homozygous G/G, heterozygous G/C and homozygous C/C type was 88.8, 10.0 and 1.2%, respectively. Based on these genotype data, haplotype analysis between PEPT1 exon 5 G381A and exon 16 G1287C using HapAnalyzer and PL-EM has proceeded. The result has revealed that linkage disequilibrium between alleles is not obvious (|D'|=0.3667).

• Journal of Microbiology and Biotechnology
• /
• v.10 no.2
• /
• pp.215-220
• /
• 2000

Abstract White spot disease (WSD), resulting in more than 90% mortality of aquacultured penaeid shrimp, has been reported off the southern and western coasts of Korea since 1993. The pafuogen of WSD has been identified as being a virion wifu an envelope around a central nucleocapsid, and with an average size of 167 nm in diameter and 375 nm in length. In the present study, an in situ hybridization technique was developed as a rapid. sensitive, and specific diagnostic assay for the WSD viros infection in shrimp. Furthermore. the pathological changes ofWSD, in shrimp experimentally infected with WSD viroses. were investigated. Using a biotinylated 643 bp probe obtained from a peR using primers specific to the rod-shaped virus of Penaeus japonicus (RV-PJ), positive signals were detected in both naturally and experimentally infected shrimps. The in situ hybridization revealed positive reactions in the nuclei of the stromal matrix cells in the lymphoid organ, epithelia of the gills, foregut. epidermis, and hematopoietic cells of the interstitial tissues, suggesting the presence of WSD virus. Tills result indicates that the in situ hybridization method can be useful for a rapid and sensitive detection of WSD viruses in shrimp.shrimp.

• Journal of Veterinary Clinics
• /
• v.20 no.2
• /
• pp.159-165
• /
• 2003

This study was performed to determine the effect of green tea on the late biological effect (survival, hematological change, carcinogenesis) of mice irradiated with 3 Gy of gamma-radiation. There was little difference in body weights between normal and irradiated mice. Survival rate were decreased in irradiated mice and the survival rate and mean survival time of the groups treated with green tea were far better than the irradiation control group. An elevation of mean number of total leukocyte or lymphocyte counts was seen at week 12 of the group treated with green tea. Stimulated recovery by the extract from green tea was also observed in thrombocyte. Main gross findings of irradiated mice were appeared as enlargement of spleen, thymus and liver, tumorous nodules in lung and cyst or mass in ovary. Microscopically, there were various findings including hematopoietic and lymphoid tumor, lung cancer, ovarian cancer and cancer of other lesions. Green tea reduced the incidence of tumor development. Further studies are needed to characterize better the protective nature of active compounds.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.35 no.5
• /
• pp.304-309
• /
• 2009

Purpose: Fibrous dysplasia (FD) is a fibro-osseous disease associated with activating missense mutations of the gene encoding the $\alpha$-subunit of stimulatory G protein. FD may affect a single bone (called monostotic form) or multiple bones (called polyostotic form). The extent of lesions reflects the onset time of mutation. In this study, cells from monostotic FD in maxilla of a patient were isolated and cultured in vitro for characterization. Materials and Methods: The single cells were released from FD lesion which was surgical specimen from 15 years-old boy. These isolated cells were cultured in vitro and tested their proliferation activity with MTT assay. In osteogenic media, these cells underwent differentiation process comparing with its normal counterpart i.e. bone marrow stromal cells. The proliferated FD cells were detached and transplanted into the dordsal pocket of nude mouse and harvested in 6 weeks and 12 weeks. Results and Summary: FD cells have an increased proliferation rate and poor differentiation. As a result, cells isolated from FD lesion decreased differentiation into osteoblast and increased proliferation capacity. MTT assay presented that proliferation rate of FD cells were higher than control. However, the mineral induction capacity of FD was lesser than that of control. Monostotic FD cells make fewer amounts of bone ossicles and most of them are woven bone rather than lamellar bone in vivo transplantation. In transplanted FD cells, hematopoietic marrow were not seen in the marrow space and filled with the organized fibrous tissue. Therefore, they were recapitulated to the original histological features of FD lesion. Collectively, these results indicated that the FD cells were shown that the increased proliferation and decreased differentiation potential. These in vitro and in vivo system can be useful to test FD cell's fate and possible.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8149-8153
• /
• 2016

An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin's disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it's appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin's disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8629-8631
• /
• 2016

Background: Primary idiopathic myelofibrosis (PMF) is a clonal Philadelphia chromosome-negative myeloproliferative neoplasm characterized by extramedullary hematopoiesis and marrow fibrosis. It is an uncommon hematopoietic malignancy which primarily affects elderly individuals. The rational of this study was to determine its clinico-epidemiological profile along with risk stratification in Pakistani patients. Materials and Methods: In this retrospective cross sectional study, 20 patients with idiopathic myelofibrosis were enrolled from January 2011 to December 2014. Data were analyzed with SPSS version 22. Results: The mean age was $57.9{\pm}16.5years$ with 70% of patients aged above 50. The male to female ratio was 3:1. Overall only 10% of patients were asymptomatic and the remainder presented with constitutional symptoms. In symptomatic patients, major complaints were weakness (80%), weight loss (75%), abdominal discomfort (60%), night sweats (13%), pruritus (5%) and cardiovascular accidents (5%). Physical examination revealed splenomegaly as a predominant finding detected in 17 patients (85%) with the mean splenic span of $22.2{\pm}2.04cm$. The mean hemoglobin was $9.16{\pm}2.52g/dl$ with the mean MCV of $88.2{\pm}19.7fl$. The total leukocyte count of $17.6{\pm}19.2{\times}10^9/l$ and platelets count were $346.5{\pm}321.9{\times}10^9/l$. Serum lactate dehydrogenase, serum creatinine and uric acid were $731.0{\pm}154.1$, $0.82{\pm}0.22$ and $4.76{\pm}1.33$ respectively. According to risk stratification, 35% were in high risk, 40% in intermediate risk and 25% in low risk groups. Conclusions: The majority of PMF patients were male and presented with constitutional symptoms in our setting. Risk stratification revealed predominance of advanced disease in our series.