• Biomolecules & Therapeutics
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• v.3 no.2
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• pp.154-158
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• 1995

We isolated Streptomyces spry. from Korean soil, which showed high cytotoxicity against tumor cell lines, L1210 and P388Dl. Among 30 strains, three strains (DKM 104, DKM 128, DKM 409) were appeared to possess plasmid. Strain DKM 104 and DKM 128 had two CCC(Covalently Closed Circular) form plasmid, about 20 Kb in size and about 1 Kb compared with λ Hind III DNA size marker. And strain DKM 409 had three plasmids, among which two plasmic were CCC form about 20 Kb and about 20 Kb compared with same size marker. To find out whether plasmid involved in production of antitumor agent or not, we performed to curing experiment. Comparing cytotoxicity between culture filtrate of plasmid-containing strains and cured strains, we knew that only the cytotoxic activity of the strain DKM 128 was involved in plasmid.

• Microbiology and Biotechnology Letters
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• v.22 no.2
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• pp.182-189
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• 1994

The highest antitumor activity was observed in water soluble AS fraction of the Ganoderma lucidum IY 009. AS fraction did not show any cytotoxicity on sarcoma 180 cell but stimulated antibody production, opsonization of macrophage in ICR mouse and superoxide ion production from isolated macrophage. AS fraction activated complement C3 in human serum, and their antitumor activity was inhibited by EDTA, a chelator of cation related complementary activation. AS fraction exerted om prolong of life span and ingibition of tumor growth in the leukemia P388 or L1210 transplanted inbreed mouse,k BDF1 but krestin did not. AS fraction did not show any serious and lethal effects through oral administration on ICR mouse, and LD$_{50}$ of those was above 2,230 mg/kg.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.155-158
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• 2000

Bioassay-guided fractionation of Crataegus pinnatifida (Rosaceae) gave two cytotoxic ursane-type triterpenes which were identified as uvaol (1) and ursolic acid (2) by physicochemical and spectroscopic methods. 3-Oxo-ursolic acid (3) was synthesized from ursolic acid (2) by Jones method. The cytotoxic activities of these compounds were tested against murine L1210 and human cancer cell lines (A549, SK-OV-3, SK-MEL-2, XF498, and HCT15) in vitro. Compounds 1 and 2 showed moderate cytotoxicities against L1210, whereas they showed weak activities against human cancer cell lines. However compound 3 exhibited potent cytotoxic activities both in murine and in human cancer cell lines.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.1097-1100
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• 2003

This study was performed to evaluate the immunoregulatory effects of Gungchihwadam-Jeon(궁치화담전, GCHDJ) and Cheongsinhwadam-Jeon(청신화담전, CSHDJ) was administered(p.o.) once a day for 14 days to mice. By the treatment of GCHDJ or CSHDJ was increased the cell viability of cultured mice splenocytes, thymocytes and mesenteric lymph node cells. Administration of GCHDJ or CSHDJ was increased the splenic T lymphocyte, especially the Tc cell subpopulation was increased by the GCHDJ, on the while the TH cell was increased by the CSHDJ. The administration of GCHDJ or CSHDJ was significantly increased the apoptosis of transplanted-L1210 leukemia cells to mice peritoneal cavity. These results suggest that GCHDJ and CSHDJ have an immunoregulatory action

• Korean Journal of Pharmacognosy
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• v.28 no.4
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• pp.209-214
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• 1997

This study was carried out to find new antitumor agents from plant resource. Three cytotoxic agents were isolated from the root of Dictamnus albus by hexane extraction, silica gel column chromatography and HPLC. They were identified to be dictamnine $(C_{12}H_9NO_2)$, preskimmianine $(C_{17}H_{21}NO_4)$ and fraxinellone $(C_{14}H_{16}O_3)$ on the basis of spectroscopic evidences. In this study, it was newly found that these compounds possess a cytotoxic activity against lung lymphoma L1210 cell line. Among them. Preskimmianine was the most potent against the lymphoma L1210 with a $IC_{50}$ of $3.125\;{\mu}g/ml\;(10.3\;{\mu}M)$. Toxicity of preskimmianine against normal Iymphocyte was observed at the concentration of $50\;{\mu}g/ml\;(165\;{mu}M)$. These results support the pharmacological role of D. albus, a herb known as Paeksun in Korea and used as an anticancer agent in folk medicine.

• YAKHAK HOEJI
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• v.44 no.2
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• pp.149-154
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• 2000

Flavin mononucleotide (1,4-butanediamine) Pt(II) complex (7FMN) was synthesized and screened anticancer activity [J. Pharm. Soc. Korea 43(6),762-770 (1999)]. 7FMN have good water solubility and moderate anticancer activiy In this paper cell-cycle specificity and nephrotoxicity were studied. Interaction of DNA with cisplatin and synthesized 7FMN was analyzed by flow cytometry and showed G2 arrest in L1210 cell line. It means that cell-cycle on L1210 was inhibit in S phase by cisplatin and 7FMN. In order to biochemically analyze nephrotoxicity of cisplatin and 7FMN, after injecting each agent intraperitoneally, blood was exsanguinated after 6 hours, 1 day, 3 days and 7 days, respectively. Then, serum was separated from the blood. The serum level of BUN, creatinine and uric acid in cisplatin and 7FMN administated mice (25~35 g, ICR strain, a dose each 8,12 and 16 times of the $IC_{50}$/ value, cisplatin; 7 times) were determined by autochemistry analyzer. In cisplatinadministered mice group, BUN level was elevated than normal control group at 3rd day and repaired at 7th day. In 7FMN administrated group was not elevated. Creatinine and uric acid level were no difference with the normal control group. Therefore synthesized 7FMN is less toxic than cisplatin in nephrotoxiciaty.

• Radiation Oncology Journal
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• v.12 no.2
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• pp.129-141
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• 1994

Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cellls but not CCL-120 normal cells to radiation. Ouabain inhibits the $Na^+-K^+$-pump rapidly thus it increases intracellular Na concentration, Vanadate which is distributed extensively in almost all living organisms is known to be a $Na^+-K^+$-ATPase inhibitors, This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of $Na^+-K^+$ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMC cells and frypan blue dye exclusion test for L120, and spleen cells. Measurements of $Na^+-K^+$-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined $10^{-6}M$ vanadate and radiation treated cells were done. The results were summerized as fellows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Mininum or no cytotoxicity was seen with vanadate below concentration of $10^{-6}M$. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. e. 2- Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. $Na^+-K^+$-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiaiton itself inhibited $Na^+-K^+$-ATPase activity of tumor cell with high $Na^+-K^+$-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with orginal $Na^+-K^+$-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized tumor cells to radiation. Inhibitory effect of vanadate on $Na^+-K^+$-ATPase activity might be one of the contributing factors for radiosensitization to tumor cells which has greater enzyme activity than that of normal cell. It was suggested vanadate could be used as a potential radiosensitizer for tumor cells.

• The Korean Journal of Nuclear Medicine
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• v.33 no.2
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• pp.152-162
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• 1999

Purpose: To determine whether $^{99m}Tc$-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively $^{99m}Tc$-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular $^{99m}Tc$-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. Materials and Methods: We measured percentage uptake of $^{99m}Tc$-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of $^{99m}Tc$-MIBI were also evaluated with or without overex-pression of mdr1 gene in cultured murine leukemia Ll210 cells. Results: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of $^{99m}Tc$-MIBI was higher in mdr1 negative Ll210 cells than those of mdr1 positive cells, and higher when incubated in $37^{\circ}C$ than $4^{\circ}C$. In the presence of verapamil, cyclosporin or dipyridamole, $^{99m}Tc$-MIBI uptake was increased upto 604% in mdr1 positive cells. Conclusion: Cellular uptake of $^{99m}Tc$-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MBR-reversing agents increase cellular uptake. These results suggest that $^{99m}Tc$-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.199-199
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• 1994

Thioglycerol과 glycerol로부터 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL -PTBA-P)와 rac-1-O-octadecyl-2-O-palmitoyl-g1ycerol-3-phosphate (DL-PBA-P)등을 합성하였고, 이들에 ara-C 유도체인 ara-CMP morpholidate를 반응시켜 최종 산물인 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 최종산믈의 항암효과는 L1210 lymphoid leukemia, colon 26 carcioma, M5076 sarcoma, C-1300 neuroblastoma, 3-Lewis lung carcinoma, WEHI-3B leukemia, human colon cancer, hum an pancreatic cancer 등의 암세포주를 사용하여 실험하였다. L1210를 DB/2J의 뇌막 또는 복강, DBA/1J의 복강내에 이식하여 ara-C, Ehss thioether lipid의 ara-C 유도체 (ara-CDP-L-DP, ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara -CDP-DL-PTCA, ara-CDP-D-PTBA, ara-CDP-L-PTBA, ara-CDP-DL-PTBA)를 단일 투여 또는 중복 투여하였고, 3-Lewis는 C57BL/6 의 발바닥 피하, colon26은 BALB/C의 견갑상부 히아조직, M5076은 C57BL/6의 피하, WEHI-3B는 BALB/C의 복강, C-1300는 A/strong Ros에 각각 이식한 후 ara-C 또는 ara-CDP-DL-PTBA를 단일 또는 중복 투여하였다.