• 한국음향학회지
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• 제41권5호
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• pp.501-506
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• 2022

공학적으로 제작된 미소기포 중 가스층과 유체층을 함께 내포하는 echogenic liposome은 수용성 약물 탑재에 용이하다. 또한 특정 위치에서 약물을 방출할 수 있다는 점에서 초음파 조영제의 기능을 넘어서 초음파 기반 약물전달(sonoporation)에 활용될 수 있다. 이에 따라, 본 논문에서는 이전 연구에서 제안된 echogenic liposome의 구조를 EF-TEM으로 재확인하였으며 sonoporation에서 약물전달 매개체로의 효과를 세포실험을 통하여 입증하였다. 세포실험은 유방암 조직인 MDA-MB-231 세포 대상으로 대표적 암치료제인 Doxorubicin을 지표 약물로 활용하였다. 비교군(1 그룹), Doxorubicin 그룹(2 그룹), Doxorubicin 과 일반 기포를 추가하여 sonoporation을 한 그룹(3 그룹), Doxorubicin을 echogenic liposome에 탑재하여 sonoporation을 적용한 그룹(4 그룹)으로 구분하여 진행한 실험결과, 4 그룹에서 약물 전달 효과가 초기부터 급격히 증가하였으며, 최종적으로 2 그룹과 3그룹에 비하여 최소 1.4 배 이상 효과적으로 종양 세포 괴사를 유도하였다. 따라서 sonoporation에서 echogenic liposome은 기존 일반적 미소기포보다 더 효율적인 약물 매개체라고 결론 내릴 수 있다.

• BMB Reports
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• 제44권1호
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• pp.46-51
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• 2011

Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.342-347
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• 1996

Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of its parental cells, and it also revealed cross-resistance to actinomycin D, etoposide and vinblastine but not to displatin and tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin against both HCT15 and GCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the tosicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex mechanisms for MDR.

• BMB Reports
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• 제52권5호
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• pp.330-335
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• 2019

Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.

• 한국약용작물학회지
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• 제25권5호
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• pp.322-327
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• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

• 대한한방내과학회지
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• 제24권2호
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• pp.190-202
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• 2003

Object : The effect of Banhabakchulchunma-tang extracts on the hepatic, splenic and cardiac toxicity induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Methods : The changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. Results : 1. Decrease of body weight and The degrees of anorexia, ataxia and dehydration after Doxorubicin treatment were dose-dependently inhibited by Banhabakchulchunma-tang extracts. 2. Increase of absolute and relative liver and heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of liver congestion necrotic spot and the degrees of heart congestion enlargement were dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in doxorubicin treatment group were significantly decreased in Banhabakchulchunma-tang extracts dosing groups. 3. Decrease of absolute and relative spleen weight observed in doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. Conclusion : the toxicity of doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhabakchulchunma-tang extracts. According to these results, it is considered that Banhabakchulchunma-tang has some preventive effect against to doxorubicin induced toxicity.

• Journal of Acupuncture Research
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• 제23권1호
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• pp.105-120
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• 2006

To investigate anti-cancer effects of wild ginseng herbal acupuncture and mitigation of anti-cancer drug when taken concurrently, cancer cells from B16/F10 melanoma were injected intraperitoneally in C57BL/6. After inducing cancer, anti-cancer effects and mitigation of reproductive toxicity of Doxorubicin were evaluated. 1. For changes in weight, Doxorubicin treated group showed significant decrease, and administration of wild ginseng herbal acupuncture didn't cause any weight change. 2. Volume of tumor was significantly reduced in Doxorubicin teated group. Wild ginseng herbal acupuncture groups showed slight decrease but insignificant compared to the control group. 3. For hematological evaluation, Doxorubicin only group's reticulocytes were significantly decreased compared to the control group, and Platelet Count was significantly increased. Wild ginseng herbal acupuncture group showed significant increase of Neutrophils and significant decrease of Lymphocytes compared to the control group. 4. For histological evaluation of the tumor, necrosis occurred in a wide range in the Doxorubicin treated group. Wild ginseng herbal acupuncture didn't cause much histological changes. 5. For histological evaluation of the testis, seminiferous tubules of the control group suffered severe damage on epithelial cells. When wild ginseng herbal acupuncture was administered concurrently, damage on the seminiferous tubules was significantly inhibited compared to the Doxorubicin only group. 6. Diameter of seminiferous tubules and spermatogonia count were insignificant between the experiment groups. 7. For BrdU positive reaction of testicle tissue, Doxorubicin only group failed to show any reaction of spermatogonia, but spermatocytes and spermatids showed slight positive reaction. When wild ginseng herbal acupuncture was treated concurrently, much greater positive reaction was made but similar to that of the control and normal groups. 8. For observation of changes in BrdU spermatogonia count of the testicle tissue, Doxorubicin only group didn't show any positive reaction, and relative increase was shown in the group with concurrent administration of wild ginseng herbal acupuncture. 9. For observation of TUNEL positive reaction cells of the testicle tissue, no significant changes were witnessed in all the experiment groups.

• Journal of Yeungnam Medical Science
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• 제22권2호
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• pp.221-240
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• 2005

사람의 악성 골종양 세포주 Saos-2 를 이용하여 doxorubicin에 의해 발현이 증가 또는 감소하는 유전자들의 변화를 cDNA microarray를 이용하여 확인하였다. 그 결과 대조군에 비하여 2배 이상 증가 또는 감소하는 유전자 264개, 3배 이상 증가 또는 감소하는 유전자 35개를 선별할 수 있었다. Doxorubicin 처리 후 시간대 별로 발현변화가 비슷한 유전자들을 k-mean clustering으로 분석하여 5가지의 군으로 분류할 수 있었다. A군은 24시간 까지 계속 발현이 증가하는 67개 유전자, B군은 6시간까지는 변화가 없다가 24시간에는 감소하는 108개 유전자, C군은 6시간에 발현의 감소하고 24시간까지 지속되는 33개 유전자, D군은 6시간에 발현의 감소하였으나 24시간에는 다시 발현이 회복되는 5개 유전자, 그리고 E군은 6시간까지는 발현의 변화가 없다가 24시간에 발현이 증가하는 경향을 보이는 51개 유전자로 구분하였다. cDNA microarry 결과 발현차이가 현저한 22개의 유전자들을 대상으로 RT-PCR을 시행하여 발현정도를 비교하였다. cDNA microarry에서 발현증가를 보이는 13개 유전자 중에서, RT-PCR 결과 11개가 그 발현이 증가하였으며, cDNA microarry의 결과에서 발현감소를 보이는 9개 유전자 중에서 RT-PCR 결과에서 2개 유전자만 감소하였다. 이상의 결과 Saos-2 세포에서 doxorubicin에 의해 세포사멸과 세포성장, 세포신호전달, 세포골격, 세포주기, 운반, 대사 등에 관여하는 많은 유전자들의 발현이 변함을 확인할 수 있었다.

• 대한한방내과학회지
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• 제40권6호
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• pp.1278-1287
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• 2019

Objective: The aim of this study was to report the effects of herbal medicine Jayeumganghwa-tang on reducing the major side effects of doxorubicin and carboplatin in the treatment of ovarian cancer. Methods: The clinical outcomes for a 61-year-old patient treated with Jayeumganghwa-tang for the side effects of doxorubicin and carboplatin combination were recorded by self-evaluation. Results: In the treatment of adverse events caused by chemotherapy, the administration of Jayeumganghwa-tang showed a tendency to reduce their incidence and severity. Conclusions: This study suggests that Jayeumganghwa-tang may be a promising treatment for reducing the side effects of chemotherapy in patients with ovarian cancer.

• Advances in Traditional Medicine
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• 제5권1호
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• pp.62-68
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• 2005

Doxorubicin is a powerful anticancer antibiotic extensively used in the treatment of several types of cancers. Long-term administration of this drug results in cumulative dose related cardiotoxicity due to enhanced production of free radicals leading to oxidative stress. Our earlier investigations have demonstrated significant antioxidant, anti-inflammatory and antitumour properties of Ganoderma lucidum extracts. We extended our investigations to evaluate the protective effect of Ganoderma lucidum extract against doxorubicin-induced cardiotoxicity. Administration of 3 doses of doxorubicin, 6 mg/kg body weights, i.p. per each dose, alternative days, showed dear signs of cardiotoxicity in rats. The drug enhanced serum creatine kinase (CK) activity and lipid peroxidation in tissue drastically. The drug also induced significant decrease in GSH level and activities of CAT, SOD and GPx. Administration of methanolic extract of G.lucidum (500 and 1,000 mg/kg body weight) significantly increased the level of GSH and activities of CAT, SOD and GPx. Activity of CK was significantly lowered in a dose dependent manner. The treatment also caused significant decrease in lipid peroxidation (MDA). The results thus indicated that methanolic extract of G.lucidum prevented oxidative stress caused by doxorubicin administration and the increase in serum CK activity and lipid peroxidation in the tissue. The experimental findings suggest the therapeutic potential of G.lucidum as adjuvant in cancer chemotherapy.