• Korean Journal of Medicinal Crop Science
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• v.20 no.1
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• pp.16-19
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• 2012

The desmutagenic activity of the water extract of Areca catechu L. on the mutagenicity induced by aflatoxin $B_1$ ($AFB_1$), N-methyl-N-nitro-N'-nitrosoguani-dine (MNNG), mitomycin C (MMC) and 4-nitroquinoline 1-oxide (4-NQO) was studied by using the SOS Chromotest with Escherichia coli PQ37. The inhibition rates of water extract of Areca catechu L. at concentration of $100{\mu}g/assay$ were 41.0%, 47%, 46%, and 32% against $AFB_1$, MNNG, MMC and 4-NQO, respectively. The water extract of Areca catechu L. was separated into methanol soluble and methanol insoluble parts. The methanol insoluble part exhibited higher inhibition effect than the methanol soluble part against the mutagenic activities of MNNG. Step-wise fractionation of methanol insoluble part was done to obtain methanol, ethyl acetate and water fractions. Among these fractions, water fraction had the strongest inhibitory effect of 45.0% against mutagenicities of MNNG. The inhibition rates of aqueous fraction of methanol-insoluble from water extracted Areca catechu L. at concentrations of 1.61, 16.13, 161.29 and $322.58{\mu}g/mL$ were 12.0%, 24.0%, 47.5% and 62.0%, respectively. The water fraction showed the inhibitory effects with dose response against the mutagenic activity induced by MNNG.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.7-13
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• 1999

The stimulatory effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing was evaluated in healing-impaired animal models. Full-thickness wounds were made in prednisolone-treated mice, streptozotocin (STZ)-induced diabetic rats and mitomycin C (MMC)-treated rats. Saline or bFGF at a dose of 1, 5, or $25\mu\textrm{g}$ per wound was applied to the open wound once a day for three to five days. The degree of wound healing was assessed using wound size and histological parameters such as degree of epidermal and dermal regeneration. Local application of bFGF accelerated wound closure significantly in a dose-dependent manner in all healing-impaired wounds (p<0.05). The wound healing effect of bFGF was further confirmed by histological examination in MMC-treated rats. Epidermal and dermal regeneration were enhanced in bFGF-treated wounds with a dose-related response. Dermal regeneration parameters such as collagen matrix formation and angiogenesis were significantly increased in $5\mu\textrm{g}$, or $\25mu\textrm{g}$ of bFGF-treated wounds when compared to saline-treated wounds (p<0.05). pectin immunostaining on day 8 for vascular endothelium showed an increased number of neovessels in bFGF-treated wounds. These results suggest that topical application of bFGF has beneficial effects on wound healing by angiogenesis and granulation tissue formation in healing-impaired wounds.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.157-162
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• 1995

Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

• Journal of Gastric Cancer
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• v.4 no.4
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• pp.257-262
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• 2004

Purpose: We reported our preliminary result in 2001. At that time, the follow-up period was too short to evaluate the survival benefit of adjuvant chemotherapy in gastric cancer without serosal invasion. Therefore, we followed those patients for 66 months to determine the long-term effects of adjuvant chemotherapy. Materials and Methods: We analyzed the recurrence pattern, the survival rate, and the disease-specific survival of 135 patients by reviewing their medical records and calling the patients or their relatives. All enrolled patients were included in the intention-to-treat analysis of efficacy. Results: The follow-up rate was $89.6\%$ (121/135), and the median follow-up duration was 66 months. Among the 135 patients, 4 relapsed in group 1 (5-FU+cisplatin), 7 in group 2 (mitomycin C+oral 5-FU), and 6 in group 3 (oral 5-FU only). The overall survival rate was $89\%$ in group 1, $84\%$ in group 2, and $82\%$ in group 3. There were no differences in the overall survival rates and the disease-specific survival rates among the three groups. Conclusion: Oral chemotherapeutic agents have an acceptable effect for adjuvant chemotherapy compared with intravenous agent. However, a large-scale, prospective, randomized study, including a control group, is needed for an exact evaluation.

• Korean Journal of Food Science and Technology
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• v.26 no.2
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• pp.188-194
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• 1994

The inhibitory effects of rice extract on mutagenicity induced by 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole(Trp-P-1), 3-amino-1-methyl-5H-pyrido [4,3-b]indole(Trp-P-2), sodium azide(SA), 2-nitrofluorene(2NF), mitomycin C(MMC), aflatoxin $B_1(AFB_1)$ and 4-nitroquinoline oxide(4-NQO) were investigated using Salmonella typhimurium reversion assay, SOS chromotest and spore rec-assay. In Salmonella typhimurium reversion assay, methanol extract from brown rice (Illpumbyeo, Japonica variety) showed the highest inhibitory effect among other extracting solvent including hexane, chloroform and water. Methanol extract showed stronger inhibitory effect, above 85%, on indirect-acting mutagens(Trp-P-1, Trp-P-2 and $AFB_1$) than those on direct-acting mutagens(4-NQO, 2NF). In SOS chromotest, methanol extracts showed $77.6{\sim}88.9%$ effects on SOS function induced by Trp-P-1, Trp-P-2, $AFB_1$ and 4-NQO. In spore rec-assay, methanol extracts inhibited the mutagenicity induced by $AFB_1$ and MMC. As the concentration of methanol extract increased, inhibitory effect on mutagenicity increased but reached at steady state as inhibition rate of 90% when the concentration was above 5 mg/plate. In inhibitory effects of methanol extracts by various rice varieties, all of 11 varieties turned out to have inhibitory effect on mutagenicity. There was no significant difference (p>0.05) in inhibitory effect of methanol extracts between brown and white rice against Trp-P-1, but showed difference (p<0.05) against 4-NQO.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.82-88
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• 2001

Recently, there has been significant progress in understanding the control process of the cell division cycle. To investigate the influence of toxic substances on the cell cycle, the effect of benzo(a)pyrene (BAP) and mitomycine C (MMC) on synchronized HeLa cells was analyzed during the cell cycle. To synchronize the HeLa cells, 10$^{6}$ cells were grown for 1 day and then treated with 1 mM hydroxyurea for 14 h. The arrested cells were then allowed to proceed through their cell cycle by removing the hydroxyurea and resupplying a fresh medium. The arrested cells in the G1/S transition then proceeded to the S phase after 4 h, the G2/M phase after 8h, and the G1 phase after 12 h, subsequent to the resupply of a fresh medium. In the untreated HeLa cells, the p34$^{cdc2}$ kinase activity, measured using a p34$^{cdc2}$ specific peptide, peaked after 8h (G2/M) and then declined after 12 h (G1). However, treatment with 30 $\mu$M BAP delayed the peak of the p34$^{cdc2}$ kinase activity. The amount of p34$^{cdc2}$ remained unchanged in the untreated, BAP-, and MMC-treated cells throughout the cell cycle. The cyclin B level peaked after 8 h in the untreated cells, yet peaked after 10-12 h in the BAP-treated cells. There was no significant change in the cyclin B level in the MMC-treated cells.

• Biotechnology and Bioprocess Engineering:BBE
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• v.8 no.2
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• pp.151-157
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• 2003

Obtaining a sufficient amount of healthy keratinocytes from a small tissue is difficult. However, ORS cells can be a good source of epithelium since they are easily obtainable and patients do not have to suffer from scar formation at donor sites. Accordingly, the current study modified the conventional primary culture technique to overcome the low propagation and easy aging of epithelial cells during culturing. In a conventional primary culture, the average yield of human ORS tells is 2.↑ $\times$ 10$^3$cells/follicle based on direct incubation in a trypsin (0.1%)/EDTA(0.02%) solution for 15 min at 37$^{\circ}C$, however, our modified method was able to obtain about 6.9 $\times$ 10$^3$cel1s/follicle using a two-step enzyme digestion method involving dispase (1.2 U/mL) and a trypsin (0.1%)/EDTA (0.02%) solution. Thus, the yield of primary cultured ORS cells could be increasd three times higher. Furthermore, a total of 2.0 $\times$ 10$^{7}$ cells was obtained in a serum-free medium. while a modified E-medium with mitomycin C-treated feeder tells produced a total of 6.3 $\times$ 10$^{7}$ Cel1s over 17 days When Starting With 7.5 $\times$ 10$^4$cells. Finally, We Confirmed the effectiveness of our ORS tell isolation method by presenting their ability for reconstructing the bioartificial skin epithelium in vitro

• Clinical and Experimental Reproductive Medicine
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• v.31 no.4
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• pp.261-271
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• 2004

Objective: This study was performed to evaluate the possibility of prolonged culture of human embryonic stem cells (hESC; SNUhES2) on human amniotic fluid cells (hAFC), which had been storaged after karyotyping. Method: The hAFC was prepared for feeder layer in the presence of Chang's medium and STO medium (90% DMEM, 10% FBS) at $37^{circ}C$ in a 5% $CO_2$ in air atmosphere. Prior to use as a feeder layer, hAFC was mitotically inactivated by mitomycin C. The hESCs on hAFC were passaged mechanically every seven days with ES culture medium (80% DMEM/F12, 20% SR, bFGF). Results: The hAFC feeder layer support the growth of undifferentiated state of SNUhES2 for at least 59 passages thus far. SNUhES2 colonies on hAFC feeder appeared slightly angular and flatter shape as compared with circular and thicker colonies observed with STO feeder layer and showed higher level with complete undifferentiation in seven days. Like hESC cultured on STO feeders, SNUhES2 grown on hAFC expressed normal karyotype, positive for alkaline phosphatase activity, high telomerase activity, Oct-4, SSEA-3, SSEA-4, Tra-1-60 and Tra-1-81 and formed embryoid bodies (EBs). Conclusion: The hAFC supports undifferentiated growth of hESC. Therefore, these results may help to provide a clinically practicable method for expansion of hESC for cell therapies.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.25-31
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• 1996

Purpose : To evaluate the potential advantage for 'sandwich' technique radiotherapy compared to Postoperative radiotherapy in resectable rectal cancer. Materials and Methods : Between January 1989 and Mar 1994, 60 patients with resectable rectal cancer were treated at Inje University Seoul and Sanggye Paik Hospital. Fifty one patients were available for analysis: 20 patients were treated with sandwich technique radiotherapy and 31 patients were treated with Postoperative radiotherapy. In sandwich technique radiotherapy(RT), Patients were treated with preoperative RT 1500 cGy/5fx, followed by immediate curative resection. Patients staged as Astler-Coiler B2, C were considered for postoperative RT with 2500-4500 cGy. in postoperative RT total radiation dose of 4500-6120 cGy, 180 cGy daily at 4-Sweets was delivered. Patients were followed for median period of 25 months. Results : The overall 5-year survival rates for sandwich RT group and postoperative RT group were $60\%$ and $71\%$, respectively(p>0.05). The 5-rear disease free survival rates for each group were $63\%$. There was no difference in local failure rate between two groups($11\%$ versus $7\%$) Incidence of distant metastasis was $11\%$(2/20) in the sandwich technique RT group and $20\%$(6/31) in the postoperative RT group(p>0.05). The frequencies of acute and chronic complications were comparable in both groups. Conclusion : The sandwich technique radiotherapy group shows local recurrence and survival similar to those of Postoperative RT alone group but reduced distant metastasis compared to Postoperative RT group. But long term follow-up and large number of patients is needed to make an any firm conclusion regarding the value of this sandwich technique RT.