• Title/Summary/Keyword: 선택독성

Search Result 277, Processing Time 0.029 seconds

Effect of TNF-$\alpha$ Gene Transfer to Respiratory Cancer Cell Lines on Sensitivity to Anticancer drugs (호흡기계암세포주에서 TNF-$\alpha$ 유전자의 이입이 항암제 감수성에 미치는 효과)

  • Mo, Eun-Kyung;Lee, Jae-Ho;Lee, Kye-Young;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Choi, Hyung-Seok
    • Tuberculosis and Respiratory Diseases
    • /
    • v.42 no.3
    • /
    • pp.302-313
    • /
    • 1995
  • Background: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. Method: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MIT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-$\alpha$ gene-transfer and the two results were compared. Results: The cytotoxicity was not increased significantly in WEHI164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-$\alpha$ gene was transferred(p<0.05). Conclusion: These findings show that TNF-$\alpha$ gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

  • PDF

Modified FOLFOX-6 Chemotherapy for Recurrent or Inoperable Gastric Cancer Patients (진행성 위암 환자예시의 FOLFOX 6 항암치료)

  • Jee, Sung-Bae;Han, Jae-Hyun;Huh, Hoon;Song, Kyo-Young;Chin, Hyung-Min;Kim, Wook;Park, Cho-Hyun;Park, Seung-Man;Kim, Seung-Nam;Jeon, Hae-Myung
    • Journal of Gastric Cancer
    • /
    • v.8 no.1
    • /
    • pp.40-46
    • /
    • 2008
  • Purpose: We wanted to evaluate the efficacy and toxicity of modified FOLFOX-6 chemotherapy for treating recurrent or inoperable gastric cancer patients. Materials and Methods: From April 2006 to August 2007, 35 patients with recurrent gastric cancer after curative resection and 43 patients with inoperable gastric cancer underwent chemotherapy, and the results were retrospectively investigated. Results: 78 patients were assessable for response and toxicity, and they underwent an average of 7.1 cycles of chemotherapy. The response was evaluated according to the RECIST criteria. 11 partial responses (14.1%), 35 cases of stable disease (44.9%), and 32 cases of progressive disease (41%) were observed. The median time to progression was 6 months, and the average overall survival was 13 months. CTCAE grade 1 or 2 anemia (52.6%) was the most prevalent toxicity. Other common toxicities included thrombocytopenia (17.9%) and peripheral neuropathy (30.8%). There were 13 changes in the chemotherapy regimen to S1-cisplatin due to disease progression, but only an average of 1.76 cycles of S1-cisplatin were delivered due to severe toxicities and poor compliance. Conclusion: Acceptable efficacy and toxicity were seen as 59% of the patients showed non-progression, and no grade 3 or 4 toxicities were observed. In conclusion, the modified FOLFOX-6 chemotherapy is considered to be the proper 1st-line choice as a palliative treatment for recurrent or inoperable gastric cancer patients.

  • PDF

Comparison of Immune modulatary and Anticancer Activities according to the Parts of the Styrax japonica Sieb. et Zucc. (때죽나무의 부위별 면역 및 항암활성 비교)

  • Kwon, Oh-Woung;Kim, Cheol-Hee;Kim, Hyo-Sung;Kwon, Min-Chul;Ahn, Ju-Hee;Lee, Hak-Ju;Kang, Ha-Young;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.15 no.3
    • /
    • pp.170-176
    • /
    • 2007
  • This study was performed to anticancer activities and immune modulatary activities according to the parts of the S. japonica Sieb. et Zucc. The cytotoxicity on human kidney cell (HEK 293) was showed below 27.4% in adding the methanol extracts. The anticancer activity were increased in over 60% by barks extracts in AGS and MCF-7 cells. The immune cell growth using human immune B and T cells was improved by the barks extracts of S. japonica Sieb. et Zucc. in adding 1.0mg/ml concentration. The secretion of the IL-6 and TNF-${\alpha}$ from human immune B and T cells was showed secretion for the amount of cytokines by bark extracts of S. japonica Sieb. et Zucc. NK cell growth was increased against control all of the extracts of S. japonica Sieb. et Zucc. Densitometric analysis of Bcl-2 revealed that possible to decrease potentialities of taking cancer in adding of extracts from S. japonica Sieb. et Zucc. From the results, the roots and barks extracts of S. japonica Sieb. et Zucc. were showed useful biological activities.

Anticancer and Immune Activities of the Extracts from Amorpha fruticosa L. (족제비싸리 부위별 추출물의 항암 및 면역활성)

  • Kim, Jung-Hwa;Kim, Dae-Ho;You, Jin-Hyun;Kwon, Min-Chul;Lee, Hyun-Jung;Lee, Hak-Ju;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
    • /
    • v.13 no.1
    • /
    • pp.41-47
    • /
    • 2005
  • This study was performed to experiment about useful biological activities of the parts of the extracts from Amorpha fruticosa LINNE. Experimental studies were progressed through the anticancer activities and immune activities such as cell cytotoxicity, inhibition activities of cell growth, cell growth of human B and T cell, productivity of cytokines and natural killer cell activities. The cell cytotoxicity using human Lung normal cell (HEL299) was showed cytotoxicity of below 22% by extracts of Amorpha fruticosa L. in 1.0 g/l concentration. The anticancer activities were increased in over 70% by roots extracts of Amorpha fruticosa L. in A549 and AGS cells. The immune cell growth using human immune B and T cells was increased against control by barks extracts of Amorpha fruticosa L. The secretion of cytokines $(IL-6,\;TNF-{\alpha})$ from human immune B and T cells was showed secretion of the amount of cytokines by roots extracts of Amorpha fruticosa L. Also NK cell growth was increased against control all of the extracts of Amorpha fruticosa L. From the results, the roots and barks extracts of Amorpha fruticosa L. were showed useful biological activities.

Historical Change of Population Abundances of Panonychus ulmi and Tetranychus urticae (Acari: Tetranychidae) in Selected Apple Orchards in Suwon and Its Hypothetical Explanation (수원 지역 사과원에서 사과응애와 점박이응애 개체군의 역사적 변천과정 및 해석)

  • Kim Dong Soon;Lee Joon Ho
    • Korean journal of applied entomology
    • /
    • v.44 no.2
    • /
    • pp.115-123
    • /
    • 2005
  • Historical changes of population abundances of European red mite (ERM), Panonychus ulmi (Koch), and two-spotted spider mite (TSSM), Tetranychus urticae (Koch) (Acari: Tetranychidae), were described in selected apple orchards in the National Horticultural Research Institute (NHRI, Suwon, Korea), based on research reports of the NHRI from 1958 to 1998. ERM was an abundant species up to 1970, and TSSM became a dominant species after 1980. The change occurred around mid 1970. Three hypotheses were made to explain the change: TSSM competitively replaces ERM, ground cover weeds are a major influencing factor on movement of TSSM (TSSM movement into trees is accelerated by destroying weeds), and ERM and TSSM populations are regulated by natural enemy complexes when the orchard system is not disrupted. And long-term results of the interaction between two species were projected according to the combination of different orchard management strategies: pesticide sprays (non-selective toxic pesticide spray : heavy pesticide pressure (HPP), and selective soft pesticide spray = low pesticide pressure (LPP)) and weed control methods (grass planting, and clean culture system with herbicides). In the HPP and grass planting system, ERMs are abundant because ERM can avoid competition with TSSM as movement of TSSM to trees are restricted, and natural enemy complexes are destroyed by toxic pesticides. In the HPP and clean culture system, TSSMs are abundant because TSSM moves to trees from early season and competitively replaces ERM. In the LPP and grass planting system, ERMs are abundant because movement of TSSM to trees is reduced, but they do not build up a high population density since their densities are regulated by natural enemy complexes. In the LPP and clean culture system, TSSM moves to trees and competes with ERM, but the competition pressure is reduced because population densities of mites are regulated in a lower level by natural enemy complexes. So, ERM can occurs in late season. Thus, two species can coexist temporarily with more ERM in early season and more TSSM in late season. TSSM abundant phenomenon presented in this study can be partially explained as a result of long-term interaction between ERM and TSSM under the HPP and clean culture system.

Suppression of VCAM-1 Expression in Human Aortic Smooth Muscle Cells Treated with Ethanol Extracts of Cynanchum wilfordii Radix, Arctium lappa L., and Dioscorea opposita (백수오, 우엉, 마 추출물 혼합비율에 따른 혈관부착인자 VCAM-1의 발현억제 효과)

  • Cho, Young-Mi;Song, Hae-Seong;Jang, Seon-A;Park, Dae-Won;Shin, Yu Su;Jeong, Yong Joon;Kang, Se Chan
    • Korean Journal of Plant Resources
    • /
    • v.29 no.5
    • /
    • pp.525-531
    • /
    • 2016
  • Cynanchum wilfordii Radix (CWR), Arctium lappa L (ALL), and Dioscorea opposite (DO) have been known to improve blood lipid profile, blood pressure, and inflammation. To find the optimal combination ratio of CWR, ALL, and DO in terms of vascular health improvement, we compared the effects of various combinations on gene expression of Vascular cell adhesion protein 1 (VCAM-1) in human aortic smooth muscle cells (HASMC). VCAM-1 mediates endothelial leukocyte adhesion and is upregulated in atherosclerosis. Cells was stimulated by TNF-α (10 ng/㎖, 2h) and treated with various combinations for 24 h. A combination (CADM5, CWR:ALL:DO = 2:1:1) showed the strongest suppression of VCAM-1 so that CADM5 was chosen for further experiments. We performed cell viability test with CADM5 (0, 3.125, 12.5, 25, 50, and 100 ㎍/㎖) and no cytotoxicity was found. We also investigated the effect of CADM5 on protein expression of VCAM-1, ICAM-1, Nrf-2, and HO-1 using western blotting. We found that CADM5 diminished the expression of VCAM-1 and increased the expression of Nrf-2 and HO-1. Therefore, we concluded that CADM5 (CWR:ALL:DO = 2:1:1) effectively improves vascular health by regulating the expression of VCAM-1.

Anti-Toxoplasmosis Effect of the Herbal Extracts Plantago asiatica L. (차전초(Plantago asiatica L.)의 항톡소포자충증 효과)

  • Hong, Sunhwa;Kim, Okjin
    • Korean Journal of Plant Resources
    • /
    • v.29 no.1
    • /
    • pp.26-31
    • /
    • 2016
  • Toxoplasmosis is an important cause of foodborne, inflammatory illnesses, as well as congenital abnormalities. Currently available therapies are ineffective for persistent chronic disease and congenital toxoplasmosis or have severe side effects which may result in life-threatening complications. There is an urgent need for safe and effective therapies to eliminate or treat this cosmopolitan infectious disease. The aim of this study was to investigate the in vitro anti-Toxoplasma activities of Plantago asiatica L., one of the herbal extracts, using tachyzoit of T. gondii RH strain infected HeLa cells. As the results, the selectivity of Plantago asiatica L. extract was 4.5, which was higher than Sulfadiazine selectivity (0.4). Also, we perfomed the cell proliferation inhibition test and the morphological study to evaluate the anti-T. gondii activity of Plantago asiatica L. extract with HeLa cells. As the results, the inhibition rate of the Plantago asiatica L. extract was high inhibition rate. This indicates that the Plantago asiatica L. extract may be used for new anti-T. gondii agent.

Development of Classification Model for hERG Ion Channel Inhibitors Using SVM Method (SVM 방법을 이용한 hERG 이온 채널 저해제 예측모델 개발)

  • Gang, Sin-Moon;Kim, Han-Jo;Oh, Won-Seok;Kim, Sun-Young;No, Kyoung-Tai;Nam, Ky-Youb
    • Journal of the Korean Chemical Society
    • /
    • v.53 no.6
    • /
    • pp.653-662
    • /
    • 2009
  • Developing effective tools for predicting absorption, distribution, metabolism, excretion properties and toxicity (ADME/T) of new chemical entities in the early stage of drug design is one of the most important tasks in drug discovery and development today. As one of these attempts, support vector machines (SVM) has recently been exploited for the prediction of ADME/T related properties. However, two problems in SVM modeling, i.e. feature selection and parameters setting, are still far from solved. The two problems have been shown to be crucial to the efficiency and accuracy of SVM classification. In particular, the feature selection and optimal SVM parameters setting influence each other, which indicates that they should be dealt with simultaneously. In this account, we present an integrated practical solution, in which genetic-based algorithm (GA) is used for feature selection and grid search (GS) method for parameters optimization. hERG ion-channel inhibitor classification models of ADME/T related properties has been built for assessing and testing the proposed GA-GS-SVM. We generated 6 different models that are 3 different single models and 3 different ensemble models using training set - 1891 compounds and validated with external test set - 175 compounds. We compared single model with ensemble model to solve data imbalance problems. It was able to improve accuracy of prediction to use ensemble model.

Fabrication of a palladium alloy composite membrane by vacuum electrodeposition (Vacuum electrodeposition에 의한 팔라듐 합금 금속막 제조 및 수소 분리에 관한 연구)

  • 남승은;이규호
    • Proceedings of the Membrane Society of Korea Conference
    • /
    • 1998.10a
    • /
    • pp.96-98
    • /
    • 1998
  • 1. 서론 : 팔라듐이나 이의 합금막들은 높은 선택적 투과특성으로 인해 수소 정제나 분리막 반응기와 같은 산업응용 분야에서 매우 높은 관심을 갖고 있다. 상업적으로 이용되고 있는 이러한 막들은 통상적인 metallugical process에 의해 제조괸 self-supported type으로 수소 투과 속도가 낮을 뿐만 아니라 팔라듐 등은 고가의 귀금속이므로 비경제적이다. 따라서 현재 대부분의 연구자들은 기계적 강도를 유지하기 의한 다공성 지지체 위에 얇은 금속 박막을 코팅함으로서 투과성을 높이는 동시에 경제적인 복합막 형태의 막을 만드는데 연구의 촛점을 맞추고 있다. 이러한 형태의 막을 제조하기 위한 금속 박막 제조법은 무전해 도금법(electroless deposition), 화학증착법(CVD), 스퍼터링(sputtering), 전해도금법(electrodeposition) 등이 시도되었다. 그러나 수소에 대한 우수한 선택적 투과 특성을 갖기 의해서는 대부분 5$\mu$m 이상의 두꺼운 막을 제조하였으며 이보다 얇은 막의 제조에 한계가 있기 때문에 이들 막에 대한 기체 투과 특성에 대한 연구결과는 많지 않다. 본 연구에서는 기존의 전기도금법을 응용한 소위 'vacuum electrodeposition' 이란 새로운 기술을 도입함으로써 우수한 선택적 투과성을 갖는 2$\mu$m 이하의 팔라듐 합금 박막 제조를 가능하게 하였다. 지지체 표면의 거칠음 정도, 평균 기공 크기 등의 지지체 성질의 조절에 의한 금속 박막의 핀홀을 최소화함으로써 질소와 같은 inert gas의 투과도는 거의 없게 유지하는 동시에 금속 박막 두께, 결정 구조(e.g. grain size), 합금 조성 등을 조절함으로써 수소의 투과도를 높이고자 하였다. 있다. 후자의 경우, 미량의 과산화수소수 (1~10,000 ppm)를 이용해 처리 해주는 방법의 경우 경제적으로 큰 장점이 있고, 처리가 단순하다는 장점이 있으나 과산화수소수 자체에 포함하고 있는 높은 impurit level, 그리고 처리후 장시간의 flushing time을 가져야 한다는 단점등이 존재 하고 있다.요구된다. 몰입이 가능하여 임계치가 저하된 것으로 여겨진다. 또한 광학적 이득의 존재는 이 구조에 의한 극단파장 반도체 레이저다이오드의 실현 가능성을 나타내는 것이다.548 mL에 비해 통계학적으로 의의 있게 적었다(p<0.05). 결론: 관상동맥우회로 조성수술에서 전방온혈심정지액을 사용할 때 희석되지 많은 고농도 포타슘은 fliud overload와 수혈을 피하고 delivery kit를 사용하지 않음으로써 효과적이고 만족할 만한 심근보호 효과를 보였다.를 보였다.4주까지에서는 비교적 폐포는 정상적 구조를 유지하면서 부분적으로 소폐동맥 중막의 비후와 간질에 호산구 침윤의 소견이 특징적으로 관찰되었다. 결론: 분리 폐 관류는 정맥주입 방법에 비해 고농도의 cisplatin 투여로 인한 다른 장기에서의 농도 증가 없이 폐 조직에 약 50배 정도의 고농도 cisplatin을 투여할 수 있었으며, 또한 분리 폐 관류 시 cisplatin에 의한 직접적 폐 독성은 발견되지 않았다이 낮았으나 통계학적 의의는 없었다[10.0%(4/40) : 8.2%(20/244), p>0.05]. 결론: 비디오흉강경술에서 재발을 낮추기 위해 수술시 폐야 전체를 관찰하여 존재하는 폐기포를 놓치지 않는 것이 중요하며, 폐기포를 확인하지 못한 경우와 이차성 자연기흉에 대해서는 흉막유착술에 더 세심한 주의가 필요하다는 것을 확인하였다. 비디오흉강경수술

  • PDF

Melanogenesis Promotion by 3-Deazaneplanocin A, a Specific Inhibitor of S-Adenosylhomocysteine Hydrolase, in B16/F10 Melanoma Cells (B16/F10 흑색종 세포에서 S-Adenosylhomocysteine Hydrolase 의 선택적 저해제 3-Deazaneplanocin A 에 의한)

  • Hwang, Yun Jeong;Boo, Yong Chool
    • Journal of the Society of Cosmetic Scientists of Korea
    • /
    • v.47 no.2
    • /
    • pp.107-121
    • /
    • 2021
  • Skin hypopigmentation, which is observed in albinism or vitiligo, occurs when melanin synthesis is decreased by genetic, epigenetic, and other factors. To identify drug candidates that can promote melanin synthesis in cells, we screened an epigenetic modulator library consisting of 141 cell-permeable, small molecule drugs. B16/F10 murine melanoma cells were treated with each drug at 0.1 𝜇M and melanin synthesis and cell viability were subsequently monitored. As a result, (-)-neplanocin A, 3-deazaneplanocin A (DZNep), and DZNep hydrochloride were found to increase cellular melanin synthesis without causing cytotoxicity. Because these three structurally related drugs exhibited similar dose-dependent effects on melanin synthesis and cell viability, DZNep was selected as a representative drug for additional experiments. DZNep increased intracellular melanin content and tyrosinase (TYR) activity. DZNep also induced the expression of TYR, tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT) at the mRNA and protein levels. DZNep also induced the mRNA and protein expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanin synthesis. DZNep is a specific inhibitor of S-adenosylhomocysteine hydrolase and it caused the accumulation of S-adenosylhomocysteine that inhibits histone methyltransferases in cells. This study suggests that melanogenesis can be modulated by targeting S-adenosylhomocysteine hydrolase in certain cellular contexts.