• Toxicological Research
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• v.8 no.2
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• pp.235-253
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• 1992

A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.955-959
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• 2007

This study was carried out to determine the antioxidative and antigenotoxic effects of buckwheat (Fagopyrum esculentum Moench) sprout using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical donating method and micronucleus test. Buckwheat sprout were extracted with 70% ethanol and then further fractionated to n-hexane, chloroform, ethyl acetate (EtOAc), butanol and water. Among the five fractions, the EtOAc fraction showed the highest electron donating activity ($RC_{50}$ 26.1 ${\mu}g/mL$). The effects of buckwheat sprout extracts on the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) induced by MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) were investigated in the bone marrow. 10, 20, 40 and 80 mg/kg of each extract were administered to animals immediately after injection of MNNG and the exposure time was 36 hrs. Inhibition effects of buckwheat sprout ethanol extract were 23.4%, 40.6%, 56.3% and 73.4%, respectively. When the fraction of hexane, chloroform, ethyl acetate, butanol and water from 70% ethanol extract were treated with concentration of 80 mg/kg, the suppression rates of the MNPCE were 64.1, 67.9, 75.8, 74.2 and 63.3%, respectively.

• Food Science and Preservation
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• v.24 no.8
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• pp.1122-1128
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• 2017

Pumpkin has long been used as traditional health materials in oriental medicine, pharmacy, medicine, and food industries in many countries. In this study, the water extract and two active components from tendril of young C. moschata Duch. were investigated on inflammation inhibitory activity. The water extract of young C. moschata Duch. showed high cell viability over 95% and it decreased the production of interlukin 6 (IL-6) and tumor necrosis factor (TNF-${\alpha}$) in the capacity of mouse bone marrow-derived macrophages (BMDM) upon lipopolysaccharide (LPS) stimulation. Also, isolated fraction (B4) suppressed the secretion of IL-6 and TNF-${\alpha}$. Among the domestically cultivated pumpkins, B4 fraction contained in the tendril part of them and it comprised of the order of tendril from Cucurbita pepo var. cylindrica, old of C. moschata Duch., and young of C. moschata Duch. These results suggest that water extracts of C. moschata Duch. and purified active compound, rutin, show anti-inflammation activity by suppression of the secretion of IL-6 and TNF-${\alpha}$. It can be applicable as pharmaceutical materials.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.53-59
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• 1996

Purpose : Radiation-induced alteration in the immune function is well known phenomenon in cancer patients. Our purpose is to evaluate the extent of immune suppression immediately after mediastinal or pelvic irradiation, which include significant volume of active bone marrow in adults. Materials and Methods'48 cancer patients with mediastinal(N=29) and pelvic irradiation(N=19) were the basis of this analysis. Age ranged from 36 to 76 and mean and median value was 57 years, respectively Sex ratio was 1.3(M: F=27/21). The immunological parameters were the complete blood cell(CBC) with differential cell(D/C) count, T cell subset(CD3, CD4, CD8 CDl9), NK cell test(CDl6, CD56), and serum immunoglobulin(IgG, IgA, IgM) level. Results : The mean value of white blood cell(WBC) was reduced from 7017 to 4470 after irradiation(p=0.0000). In the differential count, the number of lymphocyte, neutrophil, and basophil was markedly reduced with statistical significance(p<0.01) and the number of monocyte was not changed and, on the contrary, that of eosinophil was increased by irradiation. In the lymphocyte subpopulation analysis, the number of all subpopulations, CD3(T cell), CD4(helper T cell), CD8(suppressor T cell), CDl6(NK cell), CDl9(B, cell) was reduced with statistical significance. The mean ratio of CD4 to CD8 in all patients was 1.09 initially and reduced to 0.99 after radiotherapy(p=0.34) , but the proportional percentage of all subpopulations was not changed except CD19(B cell) after irradiation. In the immunoglobulin study, initial values of Ig G, Ig A, and Ig M were relatively above the normal range and the only Ig M was statistically significantly reduced after radiotherapy(p=0.02). Conclusion : Mediastinal and pelvic irradiation resulted in remarkable suppression of lymphocyte count in contrast to the relatively good preservation of other components of white blood cells. But the further study on the functional changes of lymphocyte after radiotherapy may be necessary to conclude the effects of the radiation on the immunity of the cancer Patients.

• KSBB Journal
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• v.22 no.1
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• pp.22-29
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• 2007

The water-soluble materials extracted from fruit bodies and mycelium of H. erinaceum were prepared. In-vitro anticancer activities on cancer cells and In-vivo proliferation effect on mouse peritoneal exudate cell and spleen cell of samples were investigated. Also, nitric oxide (NO) generation of peritoneal exudate cell, IL-2 production capacity of spleen cells and phagocytic activity of peritoneal macrophages were examined. The water extracts of H. erinaceum suppressed the proliferation of cancer cell (HeLa, Raw264.7, Jurkat, KATO3, EL4, LyD9) with concentration-dependent. The water extract from fruit body showed better suppression effect than that from mycelium in most of cancer cells used. The anticancer effect of water extract of fruits body in the range of 0.01 and 10 mg/ml for Raw 264.7 and EL4 cell lines were the same as the Taxol with one thousandth equivalent of fruit body concentration. Water extracts of fruit body and liquid-cultured products of H. erinaceum induced nitric oxide (NO) generation of peritoneal exudate cell and increased NO generation by stimulus of lipopolysaccharide. Water extracts alone did not induce the proliferation and IL-2 production capacity of spleen cells. However, spleen's proliferation and IL-2 production were induced significantly by the addition of lipopolysaccharide and Con A (concanavalin A) or Con A alone, and the effectiveness of mycelium extract with water were more active than those from fruit body.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.321-328
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• 1999

Purpose : Total body irradiation (TBI) or whole body irradiation is used to acquire immune suppression, to treat malignant lymphoma and leukemia, and as an conditioning regimen for bone marrow transplantation. For these purposes, many methods were developed to obtain homogenous dose distribution. The objective of this study was to analyze and confirm the accuracy and the homogeneity of the treatment setup, the parallel opposed lateral technique, currently used in Seoul National University Hospital. Materials and Metheods : Surface dose data, measured with a thermoluminescent dosimeter, of 8 patients among 10 patients, who were given total body irradiation with the parallel opposed lateral technique between September 1996 to August 1998, at Seoul National University Hospital were analyzed. Surface doses were measured at the head, neck, axilla, thigh, and ankle level. Surface and midline doses were measured with similar set-up and technique in the Humanoid phantom. Results : Measured surface doses relative to prescribed dose for the head, neck, axilla, thight, and ankle leve were $91.3{\pm}7.8,{\;}98.3{\pm}7.5,{\;}95.1{\pm}6.3,{\;}98.3{\pm}5.5$, and $95.3{\pm} 6.3\%$, respectively. The midline doses of the head, neck, axilla, thigh, and ankle level estimated from the surface-to-midline ratios in the Humanoid Phantom were $103.4{\pm}9.0,{\;}107.8{\pm}10.5,{\;}91.1{\pm}6.1,{\pm} 93.8{\pm}4.5,{\;}and{\;}104.5{\pm}9.3\%$, respectively. Measured surface doses and estimated midline doses ranged from $-8.9\%$ to $+7.8\%$. Midline doses at the neck and the axilia level deviated more than $5\%$ from the prescribed doses. The difference of the estimated midline doses at the neck and the axilla level and the actual doses were attributed to the thickness differences between the Humanoid phantom and the patients. Conclusion Distribution of the midline doses as well as the suface doses were measured to be within $-8.7\~{\pm}7.8\%$ range. Actual dose distribution in the patient is expected to be better than the measured dose range mainly attributed to thickness difference between the patient and the Humanoid phantom.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.255-262
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• 1997

Purpose : This is retrospective study to compare the results of radiation therapy alone and neoadjuvant chemotherapy and radiation in advanced stage of uterine cervical cancer. Materials and Methods : Seventy-six Patients who were treated with definitive radiation therapy for locally advanced cervical cacinoma between June 1988 and December 1993 at the department of radiation oncology, Keimyung University Dong-san Hospital. Thirty six patients were treated with radiation therapy alone and forty patients were treated with cisplatin based neoadjuvant chemotherapy and radiation therapy. According to FIGO staging system. there were 48 patients in stage IIb, 3 patients in stage IIIa, 23 patients in stage lIIb and two patients in stage IVa with median age of 53 years old. Follow-up periods ranged from 7 to 95 months with median 58 months. Results : Complete response (CR) rate were $86.1\%$ in radiation alone group and $80\%$ in chemoradiation group. There was no statistical difference in CR rate between the two groups. Overall five-year survival rate was $67.3\%$. According to stage, overall five-rear survival rates were $74\%$ in stage IIb, $66.7\%$ in stage IIIa, $49.8\%$ in stage IIb, $50\%$ in stage IVa. According to treatment modality overall five year survival rates were $74.1\%$ in radiation alone and $61.4\%$ in chemoradiation group (P=0.4) Five rear local failure free survival rates were $71.5\%$ in radiation alone group and $60\%$ in chemoradiation group (P=0.17). Five year distant metastasis free survival rates were $80.7\%$ in radiation aione group and $89.9\%$ in chemoradiation group (P=0.42). Bone marrow suppression (more than noted in 3 cases of radiaion alone group and 1 case of chemoradiation group. Grade II retal complication was noted in 5 patients of radiation group and 4 patients In chemoradiation group. Bowel obstruction treated with conservative treatment (1 patient) and bowel perforation treated with surgery (1 patient) were noted in radiation alone group. There was no statistical difference in complication between two groups. Conclusion : There was no statistical difference in survival, failure and complication between neoadjuvant chemotherapy and radiation versus radiation alone in locally advanced uterine cervical carcinoma.

• The Korean Journal of Nuclear Medicine
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• v.28 no.1
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• pp.124-132
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• 1994

Radioactive iodine has been widely used in patients with thyroid cancer combined with surgical treatment. However, due to individual variations in absorption and excretion and uptake by tumor tissue of radioactive iodine, there are differences in therapeutic effect and adverse effects even if the same doses are administrated. So this study compared the therapeutic effect and radiation hazard by measuring internal radiation dose. Of total 27 patients with well differentiated thyroid cancer who had been thyroidectomized, we administered radioactive iodine 100 mCi, 150 mCi, 200 mCi. According to BEL DOSIMETRY PROTO-COL, beta and gamma ray dose were estimated from a pelt of the logarithm of the percent of dose per liter of whole blood versus day, and percent dose retained versus day using somilogarithmic paper, respectively. 1) Physical dose to whole blood averaged $56.54{\pm}13.02$ rad in 100 mCi administered group, $76.83{\pm}19.97$ rad in 150 mCi administered group, $95.08{\pm}25.51$ rad in 200 mCi administered group and there has been a significant correlation among the groups. 2) Mean percent dose retained 48 hours later was 26.34%. 3) There was no significant correlation of physical dose between absence and presence of metastasis. 4) 17 of 19 patients who has been followed up with TSH and serum throglobulin, Thallium scan were successfully ablated by radioactive iodine. 5) Leukocyte, lymphocyte, neutrophil, platelet counts all deelined in 4.6 weeks and most of all were restored 3 months later. 6) There was no significant correlation between physical dosimetry and biologic dosimetry. Generally administered doses of radioactive iodine (100-200 mCi) to patients with thyroid cancer postoperatively had developed transient bone marrow suppression and minimal chromosomal aberration, but they were within safety dose to blood (200 rad). And there has been no significant differences in residual dose 48 hours later between Korean and western people.

• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.343-349
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• 1995

Background : For biological dosimetry of radiation exposure, both observing hematologic change and calculating Ydr by chromosomal analysis as biological indicators are widely used. However, due to the lack of studies on biological dosimetry of radiation dose absorbed in the body such as in the cases of radioactive iodine therapy, the maximal and safe dose is not well known, nor is the extent to which the body can safely endure radiation exposure. Purpose : To investegate the practical applicability of hematologic changes and Ydr as an indicator for estimating radiation exposure, to patients with thyroid diseases after doses of radioactive iodine. Material and Methods : 5 patients with hyperthyroidism and 35 patients who have had thyroid cancer operation were under treatment with radioactive iodine, changes in number of lymphocytes were tracked and Ydr was calculated for more than 2 months by chromosomal analysis in peripheral lymphocytes. Results ; 1) The number of lymphocytes began to decrease 2 weeks after doses of radioactive iodine, and reached the nadir after 6 and 8 weeks, then gradually recovered. 2) The nadir count of lymphocytes was reversely correlated with the administered dosage of radioactive iodine. 3) Ydr was generally stable between 2 and 8 weeks. 4) The maximal value of Ydr was correlated with the administered dosage of radioactive iodine. 5) Ydr value at the 2nd week increased with augmented dosage of radioactive iodine. 6) Ydr value at the 2nd week was correlated with fall of lymphocyte count. Conclusion : Patients must be closely observed, because temporary bone marrow suppression and slight chromosomal aberration can be produced by even generally used dosages of radioactive iodine for diagnosis and therapy. Maximal percent fall of lymphocyte count, Ydr at the 2 week interval and maximal Ydr can be used as the biological predictor of administered dosage of radioactive iodine.