• Radiation Oncology Journal
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• v.19 no.3
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• pp.252-258
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• 2001

Purpose : The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after $\gamma-ray$ irradiation in human H&N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and method : Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. Results : Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index. Apoptotic fractions at 2 Gy were $46\%,\;48\%,\;46\%,\;24\%,\;and\;19\%$ and at 6 Gy were $20\%,\;33\%,\;35\%,\;17\%,\;and\;20\%$ for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy, but there was not such correlation at 6 Gy. Conclusion : All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important mode of cell death than apoptotic death in all cell lines used in this study. But there was correlation between apoptotic fraction and radiation sensitivity at 2 Gy.

• Radiation Oncology Journal
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• v.18 no.1
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• pp.51-58
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• 2000

Purpose :The effect of PTK inhibitors (herbimycin A and genistein) on the induction of radiation-induced apoptosis in Ph-positive KS62 leukemia cell line was investigated. Materials and Methods :K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For 6 MV X-ray irradiation and drug treatment, cultures were initiated at 2×106 cells/mL. The cells were irradiated with 10 Gy. Stock solutions of herbimycin A and genistein were prepared in dimethyl sulphoxide (DMSO). After incubation at 37$^{\circ}C$ for 0$\~$48 h, the extent of apoptosis was determined using agarose gel electrophoresis and TUNEL assay. The progression of cells through the cell cycle after irradiation and drug treatment was also determined with flow cytometry. Western blot analysis was used to monitor bel-2, bel-X$_{L}$ and bax protein levels. Results :Treatment with 10 Gy X-irradiation did not result in the induction of apoptosis. The HMA alone (500 nM) also failed to induce apoptosis. By contrast, incubation of K562 cells with HMA after irradiation resulted in a substantial induction of nuclear condensation and fragmentation by agarose gel electro-phoresis and TUNEL assay. Genistein failed to enhance the ability of X-irradiation to induce DNA fragmentation. Enhancement of apoptosis by HMA was not attributable to downregulation of the bel-2 or bel-X$_{L}$ anti-apoptotic proteins. When the cells were irradiated and maintained with HMA, the percentage of cells in G2/M phase decreased to 30$\~$40$\%$ at 48 h. On the other hand, cells exposed to 10 Gy X-irradiation alone or maintained with genistein did not show marked cell cycle redistribution. Conclusion : We have shown that nanomolar concentrations of the PTK inhibitor HMA synergize with X-irradiation in inducing the apoptosis in Ph (+) K562 leukemia cell line. While, genistein, a PTK inhibitor which is not selective for p210$^{bcr/abl}$ failed to enhance the radiation induced apoptosis in KS62 cells. It is unlikely that the ability of HMA to enhance apoptosis in K562 cells is attributable to bel-2 family. It is plausible that the relationship between cell cycle delays and cell death is essential for drug development based on molecular targeting designed to modify radiation-induced apoptosis.

• Childhood Kidney Diseases
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• v.13 no.2
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• pp.130-137
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• 2009

Purpose : Stem cell transplantation (SCT) has gained worldwide acceptance as a treatment for hematologic disorders. This study was performed to evaluate the clinical characteristics and outcomes of the acute kidney injury after SCT in children. Methods : The records of 53 patients who were treated with SCT at the pediatric department of Yeungnam University Hospital between January, 1996 and April, 2009 were used as subjects. Their were divided into two groups ; 'Early renal insufficiency' (ERI, n=18) and 'Non-early renal insufficiency' (NERI, n=35). ERI had greater than 25% of drop in GFR after SCT. Results: Total 53 patients were analyzed. In cord blood SCT (n=11), ERI was 4 (36.4%) and NERI was 7 (63.6%). In bone marrow SCT (n=16), ERI was 8 (50.0%) and NERI was 8 (50.5%). In autologous peripheral blood SCT (n=26), ERI was 6 (23.1%) and NERI was 20 (76.9%). There is no difference in both groups according to kinds of SCT. GVHD was developed in 22 patients, and there is no difference in each group. Twenty two of 53 patients died. ERI was 12 (66.7%) and NERI was 10 (28.6%). Acute renal failure is most important cause of the deaths. Conclusion : Out of 53 pediatric patients who were treated with SCT, 18 patients had greater than 25% of drop in GFR. There is no difference in both groups according to kinds of SCT. GVHD was found in 22 patients and there is no relation between GVHD development and acute kideney injury.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.281-286
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• 1999

Background: The purpose of this study is to analyze the types of complications, the incidences of complications, and preoperative and postoperative risk factors affecting the incidence of the complication. Material and Method: Between August 1990 and August 1997 in Asan Medical Center, 42 patients(24 men and 18 women) underwent surgical resection for pulmonary aspergilloma. The mean age was 46.6${\pm}$11.5 years(range 29 to 69 years). Hemoptysis(90%) was the most common presentation. Pulmonary tuberculosis was the most common predisposing cause(81%). The associated diseases were bronchiectasis(n=11), active puolmonary tuberculosis(n=9), diabetes mellitus(n=8), lung carcinoid(n=1), and acute myeloblastic leukemia(n=1). Lobectomy was done in 32 cases(76%), segmentectomy or wedge resection in 4, pneumonectomy in 2, and lobectomy combined with segmentectomy in 4. Result: Operative mortality was 2%. The most common postoperative complication was persistent air leakage(n=6). The variables such as age, sex, pulmonary function test, amount and duration of hemoptysis, associated diseases(diabetes mellitus, active pulmonary tuberculosis), mode of preoperative management(steroid, antifungal agent, bronchial arterial embolization), and modes of operative procedures were statistically insignificant. The radiologic extent of infiltration to normal lung parenchyme was statistically significant(p=0.04). Conclusion: We conclude that the extent of the infiltration to normal lung parenchyme in preoperative radiologic studies should be carefully evaluated to reduce the postoperative complications in surgery for pulmonary aspergilloma.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.181-186
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• 2006

Purpose : The hematologic change during the treatment of acute lymphoblastic leukemia(ALL) is critical as a prognostic determinant and a variable to determine the dose of chemotherapeutic agents. It is known that the dose of vincristine used in the maintenance phase of ALL is small enough to increase the count of platelet. To investigate the change of platelet count according to the vincristine administration in maintenance phase of ALL chemotherapy, we performed this study. Methods : Eleven patients eligible under the criteria of Children's Cancer Study Group(CCG)-1882 and who had completed chemotherapy were enrolled in this study. The count of platelets before vincristine administration was compared with those of vincristine administration 1, 2 and 3 weeks after the early and last periods of maintenance phases. The platelet count before vincristine administration was defined as 100 percent and that after vincristine were compared. In addition, we tentatively defined an enhancing effect of vincristine as positive when the relative count was more than 120 percent. Results : Platelet count did not differ according to the early and last periods of maintenance phase. Platelet count at first week after vincristine administration increased more significantly than that before vincristine in early and last periods. There was an enhancing effect in 10(90.9 percent) of 11 patients after 1 week vincristine administration both in the early and last periods of the maintenance phase. Conclusion : Vincristine, used in ALL maintenance phases as a low dose, increased platelet count 1 week after administration. The increased platelet count resumed to the previous level 2-3 weeks later. However, the thrombocytosis observed in the maintenance phase by vincristine was not high enough to induce thrombosis. In addition, vincristine is known to reduce the activity of platelets. Therefore, the risk of thrombosis in the maintenance phase of ALL chemotherapy would be low.

• Journal of Life Science
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• v.26 no.3
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• pp.376-386
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• 2016

Apoptosis induction has been proposed as an efficient mechanism by which malignant tumor cells can be removed following chemotherapy. The intrinsic mitochondria-dependent apoptotic pathway is frequently implicated in chemotherapy-induced tumor cell apoptosis. Since DNA-damaging agent (DDA)-induced apoptosis is mainly regulated by the tumor suppressor protein p53, and since more than half of clinical cancers possess inactive p53 mutants, microtubule-damaging agents (MDAs), of which apoptotic effect is mainly exerted via p53-independent routes, can be promising choice for cancer chemotherapy. Recently, we found that the apoptotic signaling pathway induced by MDAs (nocodazole, 17α-estradiol, or 2-methoxyestradiol) commonly proceeded through mitotic spindle defect-mediated prometaphase arrest, prolonged Cdk1 activation, and subsequent phosphorylation of Bcl-2, Mcl-1, and Bim in human acute leukemia Jurkat T cells. These microtubule damage-mediated alterations could render the cellular context susceptible to the onset of mitochondria-dependent apoptosis by triggering Bak activation, Δψm loss, and resultant caspase cascade activation. In contrast, when the MDA-induced Bak activation was inhibited by overexpression of anti-apoptotic Bcl-2 family proteins (Bcl-2 or Bcl-xL), the cells in prometaphase arrest failed to induce apoptosis, and instead underwent mitotic slippage and endoreduplication cycle, leading to formation of populations with 8N and 16N DNA content. These data indicate that cellular apoptogenic mechanism is critical for preventing polyploid formation following MDA treatment. Since the formation of polyploid cells, which are genetically unstable, may cause acquisition of therapy resistance and disease relapse, there is a growing interest in developing new combination chemotherapies to prevent polyploidization in tumors after MDA treatment.