• 대한수의학회지
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• 제43권2호
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• pp.211-218
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• 2003

Human ovarian cancerous cells survive in a way that they trigger the nucleotide excision repair (NER) or double-strand DNA repair (dsDNA) repair mechanism to show resistance to anticancer drugs and activate many kinds of repair protein, thus removing damaged DNAs. Two experiments on the PA-1 human ovarian teratocareinoma cell line that hardly has any expression of epidermal growth factor receptor (EGFR) were conducted in the study; first, EGF-R was transfected and its receptor was obtained. The receptor was investigated in terms of its mutual relations with many kinds of protein concerning NER or dsDNA repair. Second, it was examined what kind impact cisplatin and adriamycin had on the effects of EGF-R over the PA-1 cell line lacking EGF-R. When being administered with cisplatin and adriamycin, Hey and Hey C2 cell lines showed a high level of resistance while PA-1 cell line a high level of sensitivity. Hey and Hey C2 cell lines that are resistant against anticancer drugs exhibited a high level of EGF-R expression while PA-1 cell line that is sensitive to them did a much lower level of the expression. When PA-1 cell line was transfected for the expression of DNA adduct and EGF-R, it showed a higher level of resistance compared to the control group. There was no difference in the expression of DNA repair proteins (DNA- dependent protein kinase, Ku70, and Ku80) between Hey and the PA-1 cell lines. The results indicate that the Hey cell line that is resistant against cisplatin and adriamycin works along the signaling system responding to the changes of EGF-R while the PA-1 cell line that is sensitive to both of them does to the lack of EGF-R.

• Applied Biological Chemistry
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• 제51권2호
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• pp.124-128
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• 2008

개비자나무의 유효성분으로 알려진 homoharringtonine의 암세포주 K562에 대한 세포증식 저해 활성을 분석하였고, 마우스를 이용한 만성독성시험을 수행하였다. 총 약물처리 시간에 따른 최적 투여조건 결정 실험에서는 HHT를 9일, 6일, 3일 동안 매일 처리할 경우 각각 0.27, 0.37, 1.10mM의 농도에서 K562세포의 성장을 50% 감소시킴을 확인하였다. 기존 백혈병 치료제로 사용되고 있는 adriamycin과의 비교실험 결과 HHT는 K562 세포주에 대하여 adriamycin보다 낮은 저해율을 나타냈으나 비교적 근사한 값을 가졌다. HHT의 만성독성 실험 결과 혈액학적 지표 측정 실험에서 적혈구수(RBC)는 대조군과 HHT 투여군 사이에 유의적인 차이가 없었고, 간 기능 관련 효소의 혈액을 분석한 결과, 간 손상과 관련된 효소glutamate-oxalate-transferase, glutamate-pyruvate- transferase, cholesterol 및 alkaline phosphatase 모두 정상 범위에 있었다. 그러나 간 조직학적 검사에서는 HHT를 투여한 마우스의 간 조직에서 밴드형의 호중구를 침착시키는 것이 확인되었다.

• 한국산학기술학회논문지
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• 제20권3호
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• pp.188-193
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• 2019

경동맥 화학색전술은 널리 이용되며 빠르게 발전하고 있는 간세포암의 비수술적 치료법이다. 만족할만한 치료결과를 얻기 위해서는 환자의 해부학적 특성을 이해하고 종양 공급 동맥을 찾아내서 올바른 치료 계획을 세워야 한다. 본 연구에서는 간세포암의 경동맥 화학색전술 중에 방해요인으로 작용한 후천성 동정맥 기형의 증례를 보고하고자 한다. 72세 남자가 2일전부터 지속된 복통으로 내원하였다. 만성 B형 간염환자로 10년 전 간세포암에 대한 고식적 경동맥 화학색전술을 시행 받고 완치된 과거력이 있었다. 전산화 단층 촬영상 간우엽의 8분절에 결절성 간세포암이 발견되었으며 우간동맥은 상장간막동맥에서 기시하는 기형을 가지고 있었으며 종양 주변에 과혈관성 종양 구조가 관찰되었다. 1차 경동맥 화학색전술을 실시하였을 때 좌간동맥에서 기시하는 종양 공급동맥을 찾아 이를 약물방출미세구와 Adriamycin 50mg을 이용하여 화학색전하였다. 우간동맥조영술을 시행하였을 때 동정맥 기형이 관찰되었으며 간세포암은 관찰되지 않았다. 1개월 후 시행한 전산화 단층 촬영상 괴사된 종양과 남은 병변이 관찰되어 2차 경동맥 화학색전술을 시행하였다. 우간동맥을 통하여 미세유도철사와 카테터를 이용하여 동정맥 기형을 지나쳐 초선택하였고 시행한 조영술에서 남은 간세포암의 병변이 조영됨을 확인할 수 있었다. 이를 약물방출미세구와 Adriamycin을 이용하여 화학색전하였다. 시술 후 혈관 조영술에서 간세포암이 조영되지 않는 것을 확인하였고, 그 후 환자는 특별한 합병증 없이 퇴원하였다. 저자들은 매우 드물게 발생하는 간세포암 주변의 후천성 동정맥 기형을 발견하였고, 방해요인으로 작용한 동정맥 기형을 넘어 초선택적 경동맥화학색전술을 시행하여 간세포암을 치료하였다.

• 약학회지
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• 제34권4호
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• pp.219-223
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• 1990

7,8-Dihydro-6,11-dihydroxy-9(10H)benzo(b)phenazinone was prepared from 1,2,3,4-tetra-hydrophenazine as a potential isostere of anthracyclinone. The attempts to functionalize at $C_9$ were not successful due to the unstability of the above ketone.

• 한국미생물·생명공학회지
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• 제24권2호
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• pp.242-246
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• 1996

Hatomarubigins inhibited the growth of various cancer cell lines including multidrug-resistance cells. Hatomarubigins were found to potentiate the colchicine- and vinblastine-induced cytotoxicity against KB-C2 cell, but not the adriamycin-induced cytotoxicity against KB-C2 cells. Hatomarubigins didn't affect the sensitive KB cells. These results suggest that hatomarubigins are specific potentiators of colchicine. Among four hatomarubigins, hatomarubigin A sho- wed the highest synergestic effect on colchine-induced cytotoxicity. Similar effect of hatomarubigin A was found against V79/ADM cells.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.59-65
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• 2000

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemica. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined bycell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic dose of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

• 대한약리학회지
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• 제30권2호
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• pp.227-242
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• 1994

The general pharmacological effects of a new anthracycline anticancer agent, DA-125 $[7-0-(2,\;6-dideoxy-2-fluoro-{\alpha}-L-talopyranosyl)-adriamycinone-14-{\beta}-alaninate{\cdot}HCI]$ were investigated in mice, rats, guinea pigs, rabbits and dogs. Intravenous administration of DA-125 presented no significant effects on the central and peripheral nervous systems of ICR mice except a decrease in the numbers of acetic acid-induced writhing response at a dose of 10 mg/kg. In anesthetized rats and dogs, DA-125 produced a transient depression of blood pressure and an increase in heart rate, but did not affect the peripheral blood flow in the isolated ear vessels of rabbits and the mechanical functions of the isolated hearts of guinea pigs. No significant effects were observed on the gastrointestinal functions and the contractilities of smooth muscle preparations obtained from guinea pig trachea, rabbit ileum, pregnant and non-pregnant uterus and vas deferens of rats. DA-125 Increased the contractility of the isolated ileum of guinea pigs in a dose range of $10^{-6}{\sim}10^{-9}g/ml$, and also increased, but weaker than adriamycin, the vascular permeability in rat skin. DA-125 had no effect on the kallikrein-induced increase in permeability and the permeability of the visceral organs. DA-125 did not adversely affect the liver function and the blood coagulation system, and did not induce hemolysis in vitro. It is concluded from the results that the general pharmachological effects of DA-125 are similar to or weaker than those of adriamycin, and that little adverse effects are anticipated with a therapeutic dose range.

• 대한골관절종양학회지
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• 제2권1호
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• pp.38-46
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• 1996

The traditional methodology in Ewing's sarcoma was chemotherapy and radiotherapy. Recently surgery is reemerging as an important therapeutic tool and some paper report increased survival with it. The purpose of this nonrandomized study is to evaluate our result of Ewing's sarcoma with surgery, retrospectively. We experienced 30 cases for seven years and among them 6 were extraskeletal. In location, axial was 10 cases and peripheral was 20. By Enneking's classification, state IIB was 26 cases and IIIB was 4. Eighteen patients took operation, chemotherapy and/or radiotherapy, and remaining twelve took chemotherapy and/or radiotherapy only. Type of operation was limb salvage in 16 cases and amputation 2. Average dosage of radiation was 45.1Gy. Six kinds of chemotherapeutic regimen were used, but among them main protocols were Ifosfamide-Adriamycin(17 cases) and IESS(Cytoxan, Adriamycin, Methotrexate, Vincristine:8 cases). Complications were as follows. In operation group, there were 3 local recurrence and one case of nonunion. In nonoperated group, one local recurrence and one pancytopenia resulting in death. Average follow up was 29.7 months. Kaplan-Meier's ten year actuarial survival rate for the whole 30 cases was 26.8%. Significant difference in survival exists between central and peripheral lesions(p=0.05, by log rank test). Types of chemotherapy and surgery itself showed no significance. But surgery is important in function and local control. More intensive chemotherapeutic regimen to prevent distant metastasis and combined surgery and radiotherapy may be needed in Ewing's sarcoma.

• Archives of Pharmacal Research
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• 제27권9호
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• pp.893-900
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• 2004

2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (％) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

• BMB Reports
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• 제40권6호
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• pp.853-860
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• 2007

Resistance to anticancer drugs is a major obstacle in the effective treatment of tumors. To understand the mechanisms responsible for multidrug resistance (MDR), a proteomic approach was used to identify proteins that were expressed in different levels by the adriamycinresistant human gastric cancer cell line, SGC7901/ADR, and its parental cell line, SGC7901. Two-dimensional gel electrophoresis (2-DE) and image analysis was used to determine which protein spots were expressed in different levels by the two cell lines. These spots were then partially identified using ESI-Q-TOF mass spectrometry, and the differential expressional levels of the partially identified proteins were then determined by western blot analysis and real-time RT-PCR. Additionally, the association of Nucleophosmin (NPM1), a protein that was highly expressed by SGC7901/ADR, with MDR was analyzed using siRNA. As a result of this study, well-resolved, reproducible 2-DE patterns of SGC7901/ADR and SGC7901 were established, and 16 proteins that may playa role in the development of thermo resistance were identified. Additionally, suppression of NPMl expression was found to enhance adriamycin chemosensitivity in SGC7901/ADR. These results provide a fundamental basis for the elucidation of the molecular mechanism of MDR, which may assist in the treatment of gastric cancer.