• Bulletin of the Korean Chemical Society
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• 제32권10호
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• pp.3666-3674
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• 2011

Overexpression of P-glycoprotein (Pgp) is associated with multidrug resistance (MDR) of tumor cells to a number of chemotherapeutic drugs. Pgp inhibitors have been shown to effectively reverse Pgp-mediated MDR. We prepared a series of phenoxy-N-phenylacetamide derivatives and tested for their ability to inhibit Pgp as potential MDR reversing agents, using a Pgp over-expressing MCF-7/ADR cell line. Some of the synthesized compounds exhibited moderate to potent reversal activity. Of note, compound 4o showed a 3.0-fold increased inhibition compared with verapamil, a well-known Pgp inhibitor. In addition, co-treatment of the representative compound 4o and a substrate anticancer agent doxorubicin resulted in a remarkable increase in doxorubicin's antitumor effect and inhibition of DNA synthesis in the MCF-7/ADR cell line. Taken together, these findings suggest that compound 4o could be a useful lead for development of a novel Pgp inhibitor for treatment of MDR.

• Journal of Chest Surgery
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• 제16권3호
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• pp.356-361
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• 1983

Pulmonary tuberculosis is still one of unsolved problems in Korea due to increased number of far-advanced and drug-resistant patients, who have poor pulmonary function. We have analyzed 1332 operated Gases during the period of 1958-1981. Annual incidence of the disease decreased from 110 [1960] to 21 [1980]. The ratio between male and female was 7:3 and the age of peak incidence was in the 3rd and 4th decades. Recently, patients below the age of 20 years were slightly decreased, but above 50 years were slightly increased. The patients consisted of far-advanced case in 60% and moderately-advanced in 39% in 1980, as compared with 40% and 59% correspondingly in 1965. Preoperative sputum positively decreased from 91% [1958-1963] to 43.8% [ 1974-1981 ]. Medically treated patients for more than 3 years increased from 16% [1958-1963] to 51% [1974-1981]. From the view of surgical indication, totally destroyed hung increased from 27% [1958-1963] to 4396 [1974-1981 ]. Therefore, pneumonectomy occupied 53.8% of total surgical management recently. Mode of surgical treatment showed that thoracoplasty [33%], resection [57%] in 1958-1963 and thoracoplasty [2%], resection [98%] in 1974-1981. As Semb`s thoracoplasty was the first choice of treatment until 1960, thereafter resection became the choice. Postoperative mortality increased from 1.6-2.096 to 396 recently as well as morbidity. It was mainly due to increased number of poor pulmonary function and postoperative spread of disease. On the basis of our experience, far-advanced and drug-resistant patients increased in number recently, whose pulmonary function was poor. So postoperative mortality and morbidity increased. Proper surgical intervention should be considered before the appearance of resistance for all chemotherapeutic drugs.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.22-28
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• 1999

Induction of apoptosis is considered to be the underlying mechanism that accounts for the efficiency of chemotherapeutic drugs. It has recently been proposed that doxorubicin (DOX) can induce apoptosis in human leukemic cells via the Fas/Fas Ligand (FasL) system. Comparison of Fas and FasL mRNA expression between drug- and anti-Fas antibody(Fas-Ab)- induced apoptosis was analyzed for examining the role of Fas/FasL system in the mediation of drug-induced apoptosis. After HL-60 cells were routinely cultured, MTT assay was performed for cytotoxicity test. Giemsa staining was carried out to monitor the apoptosis morphologically. By semiquantitative RT-PCR analysis, the expression of Fas and FasL at 4, 10, 24 hours was determined after DOX and Fas-Ab treatment. Dose-dependent cytotoxicity was induced by DOX-treatment, while Fas-Ab treatment showed the similar dose-dependent pattern but the cytotoxicity is not reached at LD$_{50}$ at 100 ng/ml concentration of Fas-Ab. In the 10ng/m1 DOX and 10ng/m1 Fas-Ab treated group, typical apoptotic cell morphology was shown such as fragmented nuclei and cell membrane budding in the Giemsa-stained slide. Fas mRNA expression was not changed significantly in the both groups. But, FasL mRNA expression was induced significantly at initial period of apoptosis. In this study, Fas/FasL interaction assumed to be involved in drug-induced apoptosis.s.

• Nuclear Medicine and Molecular Imaging
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• 제40권2호
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• pp.90-95
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• 2006

Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are able to uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. $^{131}I$-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. $^{111}In,\;^{90}Y\;and\;^{177}Lu$ radiolabeled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. for all radionuclides used for therapy, long-term and survival statistics are not yet available and only partial tumour responses have been obtained using $^{131}I$-MIBG and $^{111}In$-octreotide. Experimental results using $^{90}Y$-DOTA-lanreotide as well as $^{90}Y-DOTA-D-Phe1-Tyr^3-octreotide$ and/or $^{177}Lu-DOTA-Tyr^3-octreotate$ have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy it may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation.

• Korean Journal of Radiology
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• 제20권1호
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• pp.34-49
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• 2019

Conventional transcatheter arterial chemoembolization (c-TACE) is a widely used first-line palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). Despite the effectiveness of c-TACE, to date, technique and procedure scheduling has not yet been standardized. Drug-eluting microspheres (DEMs) were therefore introduced to ensure more sustained and tumor-selective drug delivery for permanent embolization. These DEMs can load various drugs and release them in a sustained manner over a prolonged period. This approach ensures the delivery of high concentrations of chemotherapeutic agents to tumors, without increasing systemic concentrations, and promote tumor ischemia and necrosis. This review summarizes the recent advances in the use of DEM-TACE to treat HCC.

• 한국엔터테인먼트산업학회논문지
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• 제13권2호
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• pp.253-259
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• 2019

본 연구는 식물성 모링가와 칡이 호르몬-민감성 전립선암에 어떤 효능을 나타내는지를 확인하고자 전립선 특이항원 및 항산화 활성과 항암활성을 분석하였다. 각각 에탄올로 추출하여 control, 0.1, 1.0, 10.0, 50.0mg/ml의 농도에서 DPPH 분석한 결과 칡은 50mg/ml에서 42.1%, 과라나는 73.9%의 소거율을 보여 유의적인 항산화 활성이 있음을 확인하였다(p<0.05). 호르몬에 민감한 인체 전립선암 세포주인 LNCaP에서 항암효과를 분석한 결과, 10mg/ml의 농도에서 모링가는 22±4.24%, 칡은 39.9±3.53%의 성장률을 나타냄으로써 분석한 두 가지 추출물 모두에서 뚜렷한 항암 효과가 있었고, 모링가 추출물이 칡 추출물보다 다소 높은 항산화 활성과 항암효과를 나타내었다. 이와 같은 결과는 천연 식물성 성분인 칡과 모링가가 호르몬에 민감한 전립선암의 예방과 치료에 새로운 항암제로서의 기초자료를 제공하는 것이며, 향후 이들 추출물 중에 어떤 특정성분이 이러한 역할을 하는지와 이에 대한 작용기작 및 안전성연구가 뒷받침되어야 할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.131-134
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• 2016

Breast cancer is the most common malignancy and also the second leading cause of cancer death among women and also in women that have a high mortality. Previous studies showed that magnesium (Mg) has cytotoxic effects on malignant cell lines. However, the anti-cancer effects of Mg on MCF-7 breast cancer cells are uncertain. This study was aimed at the comparison of the cytotoxic effect of Mg salt (MgCl2) and cisplatin on MCF-7 cells and fibroblasts (as normal cells). After treatment with various concentrations of MgCl2, and cisplatin as a positive control for 24 and 48 hours (h), cytotoxicity activity was measured by MTT assay. In addition, apoptosis was determined by annexin V/propidium iide assay. Both cisplatin and the MgCl2 exhibited dose-dependent cytotoxic effects in the MCF-7 cell line, although the LD50 of the Mg was significantly higher when compared to cispaltin ($40{\mu}g/ml$ vs. $20{\mu}g/ml$). Regarding annexin V/propidium results, treatment of MCF-7 cells with LD50 concentrations of cisplatin and Mg showed 59% and 44% apoptosis at 24h, respectively. Finally, the results indicated that Mg has cytotoxic effects on MCF-7 cells, but less than cisplatin as a conventional chemotherapeutic agent. However, regarding the side effects of chemotherapy drugs, it seems that Mg can be considered as a supplement for the treatment of breast cancer.

• 대한약리학회지
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• 제32권1호
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• pp.93-102
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• 1996

일부 malignant tumor에 Pt-complex의 임상 응용 과정에서 신장독성등의 심한 부작용이 문제점으로 지적되고 있다. 이 연구에서는 기존의 cisplatin보다 항암효과는 우수하면서, 부작용을 감소시킨 새로운 Pt complex의 개발에 역점을 두었다. 본 연구에서 합성한 Pt(II) complex는 carrier ligand로서 1,2-diaminocyclohexane(dach)을 사용하였고, leaving group으로는 diphosphine류인 1,3-bis (diphenylphosphine의 propane(DPPP) 을 도입하였으며, 물에 대한 용해도를 높이기 위해 dinitrate로 만들었다. 새로이 합성한 [Pt(II)(cia-dach)(DPPP)].$(NO_3)_2$ 은 원소 분석, IR 및 $^{13}C-NMR$ 분석 data에 의하여 위의 물질임이 확인되었다. PC-1은 MTT assay method에 의한 항암활성 연구를 통하여 SKOV-3, OVCAR-3 human ovarian adenocarcinoma cells에서 항암효과가 인정되었으며, 이 항암효과는 대조 약물로 사용된 cisplatin과 유사하였다. PC-1은 토끼의 신세뇨관 세포와 인체의 신피질 세포를 이용한 cytotoxity 및 thymidine 섭취율과 인체 신피질 조직 배양을 이용한 glucose consumption 실험을 통하여 모두 cisplatin보다 신장독성이 현저히 감소되었다. 이상의 결과로 보아 Pt(II) complex는 carrier ligand와 leaving group의 선택에 따라 항암활성의 증가와 신독성의 감소를 일으키는 요인으로 보여지며, 이 연구에서 만들어진 새로운 Pt(II) complex는 앞으로 다각적인 검토를 거쳐 새로운 anticancer chemotherapeutic agent로 개발될 가능성이 있을 것으로 생각된다.

• 한국수산과학회지
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• 제6권3_4호
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• pp.112-122
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• 1973

붕어와 금붕어에 기생하는 사상충, Philometroides carassii (Ishii, 1931)를 구제할 목적으로 1971년 4월부터 1972년 12월까지 당년어 붕어 200마리와 금붕어 150마리에 이 충의 유충을 여러가지 방법으로 감염시켜, 생활사를 규명하고 약물치료 실험을 하여 다음과 같은 결과를 얻었다. 1. 이 충은 Cyclops sp.가 중간숙주이며 이것의 복강에 침입한 유충은 3시간 이후에 감염력을 가졌다. 2. Cyclops sp.를 경유하지 않고 직접 먹힌 유충은 어체내에서 24시간내 장에서 소화되거나 배설되었다. 3. 중간숙주를 경유하여 어체의 장에 기생한 유충은 $1\~10$일후 복강속으로 침입하고, 여기서 성장하여 미성숙성충이 되었다. 붕어 복강속에서 기생하는 미성숙 성충은 $18\~20$개월 후 꼬리지느러미로 나와 성충이 되었다. 금붕어 복강속에 기생하는 미성숙 성충은 $7\~8$개월 후 꼬리지느러미로 나와 성충이 되었다. 4. 어체 복강속에 기생하는 미성숙 성중에서 본 종의 수컷을 최초로 발견했으며 암컷보다 대형이었다. 5. 성충에 대한 약물 치료효과는 기대할 수 없었고 성충에서 방출되는 유충에 대해 약욕 치료실험한 결과 dipterex가 가장 효과가 있었으며 4ppm으로 5일만에 대부분 폐사되었다.

• 한국식품영양과학회지
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• 제38권4호
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• pp.442-450
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• 2009

후추의 주요 성분인 piperine은 다양한 생리활성을 나타내고 있으며, 특히 암예방 효과가 있는 것으로 생각되고 있다. 본 연구에서는 piperine의 항암 효과를 밝히기 위해 piperine이 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향과 작용 기전을 연구하였다. Piperine을 HT-29 세포 배양액에 여러 농도($0{\sim}40{\mu}M$)로 첨가하여 세포를 배양한 경우 piperine 처리 농도가 증가할수록 세포의 증식이 감소하였고, 세포사멸이 증가하였다. 이는 piperine이 HT-29 세포의 세포사멸을 유도하여 세포 증식을 억제함을 제시한다. Piperine의 세포사멸 기전을 조사하기 위해 세포사멸 조절인자의 변화를 조사하였다. Piperine에 의해 anti-apoptotic Bcl-2 family 단백질인 Bcl-2와 Mcl-1 단백질 수준은 감소하였고, BH3-only 단백질인 Bid 단백질 수준은 감소하였으나, Bik 단백질 수준은 증가하였다. 또한 piperine에 의해 미토콘드리아 막의 투과성이 증가하였고, cytochrome c의 세포질로의 방출이 증가하였다. 또한 piperine 처리에 의해 caspase의 활성형인 cleaved caspase-8, -9, -7, -3 단백질 수준이 증가하였고, PARP의 불활성형인 cleaved PARP 수준이 증가하였다. Caspase의 활성을 저해하는 세포사멸억제단백질 중의 하나인 survivin 단백질 발현이 piperine에 의해 감소하였다. 이 결과로부터 대장암세포인 HT-29 세포에서 piperine이 Bcl-2 family 단백질 발현 변화를 초래하여 미토콘드리아 막 투과성 증가시키고 cytochrome c 방출을 증가시키고, caspase 활성을 증가시키고 survivin 단백질 발현을 억제하여 세포사멸을 유도하여 항암 효과를 나타냄을 알 수 있다. 본 연구는 piperine이 대장암에 강한 항암 효과가 있음을 밝혔으나 향후 암예방 및 암치료제로서 piperine을 활용하기 위해서는 동물실험 및 임상실험 등 다양한 추가 실험이 필요할 것으로 보인다.