• Archives of Pharmacal Research
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• 제29권3호
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• pp.224-234
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• 2006

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

• Korean Journal of Acupuncture
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• 제20권3호
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• pp.101-114
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• 2003

To study the effects of anti-cancer, anti-metastasis and immune response improvement of herbal-acupuncture with Aucklandiae Radix diffusae herba infusion solution(AKL-HAS), we injected AKL-HAS into Zusanli(St36) of C57BL/6 mice implanted intravenously with B16-F10 melanoma. The results were obtained as follows : 1. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the spleen cell proliferation in Balb/c mouse was significantly increased compared with that of the control group. 2. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the percentage of $CD25^{+}/CD4^{+},\;CD8^{+}/CD3e^{+},\;CD69^{+}/B220^{+},\;NK1.1^{+}/CD3e^{+}$ cells in C57BL/6 mouse PBMCs was increased compared with that of the control group. 3. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, the pulmonary colony number of C57BL/6 mice implanted intravenously with B16-F10 melanoma was decreased significantly compared with that of the control group. 4. In the experiment groups treated with Aucklandiae Radix(AKL) Herbal-Acupuncture, MST(Median Survial Time) and ILS(Increase of Life Span) of C57BL/6 mice implanted intravenously with B16-F10 melanoma were increased significantly compared with those of the control group.

• 한국임상수의학회지
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• 제20권4호
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• pp.489-492
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• 2003

구강내에 출혈을 동반한 크기 $5{\times}6$ 센티미터의 종괴가 있는 종양을 가진 12년령의 거세되지 않은 수컷 래브라도 리트리버가 건국대학교 부속동물병원에 의뢰되었다. 임상증상은 2년전부터 시작되었고, 점진적인 진행양상을 보여왔다. 총백혈구검사에서 백혈구증가증과 경도의 빈혈증상이 관찰되었다. 구강 종양의 폐장으로의 전이는 흉부 방사선 검사에서 발견되었으며 왼쪽 하악 주위의 흑색 괴저성의 종괴는 흡인도말검사 및 조직병리학적 검사에 의해 악성 흑색종으로 진단되었다. 치료는 외과적으로는 반하악절제술과 항암제인 carboplatin을 이용한 화학요법이 시행되었다. Carboplatin투여후 심한 신장의 괴사는 관찰되지 않았지만 이차감염으로 투여 3개월 후 폐사하였다.

• 대한골관절종양학회지
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• 제11권2호
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• pp.141-147
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• 2005

목적: 악성 흑색종의 치료 중 가장 중요한 것은 외과적 전절제술이며, 수술시 광범위 절제술을 시행한다. 저자 등은 광범위절제와 면역화학요법을 시행한 후 각 병기별 5년 생존율을 알아보고 예후에 영향을 주는 요인을 주는 요인들을 분석하고자 한다. 대상 및 방법: 1995년 3월부터 2003년 8월까지 악성 흑색종으로 진단 받았던 35명(남자 17명, 여자 18명)을 대상으로 광범위절제술과 면역화학요법을 시행한 후 추시 관찰하였다. 절제술은 종양의 크기나 피부층의 침범정도와 상관없이 종양의 변연으로부터 2 cm으로 하였고, 절제술 후 덮이지 않는 피부 결손부는 피판 이식술이나 전층 피부 이식술을 이용하였다, 면역화학요법으로는 dacarbazine (DTIC) 400 mg과 인터페론-${\alpha}$ 300만 IU를 병용 투여 하는 방법을 사용하였다. 면역화학요법은 III기 이상의 환자에게 시행하였고, 병기는 2002년 개정된 AJCC 병기를 이용하여 판정하였다. 또 이들 환자들에 대해 국소재발과 국소전이, 그리고 원격전이여부를 조사하였고, 각 병기별 5년 생존율을 조사하였다. 결과: 발생부위는 족부가 15명(42.8%)으로 가장 많았고, 족관절부 5명(14.2%), 하퇴부 2명(5.7%), 대퇴부 2명(5.7%), 수부에 5명(14.2%)이었다. 병기별 발생빈도는 IA 8명(22.8%), IB 9명(25.7%), IIA 4명(11.4%), IIB 2명(5.7%), IIIA 1명(2.8%), IIIB 2명(5.7%), IIIC 2명(5.7%) 그리고 IV기는 7명(20.0%) 이었다. 각 병기별 5년 생존율은 I기에서 94.1%, II기에서 66.8%, III기에서 40%, IV기에서 14.3%로 나타났다. 결론: 악성 흑색종은 III기 이상에서는 5년 생존율이 낮았다. 악성 흑색종의 치료는 초기에 진단하여 병기에 따라 치료의 방법을 달리하므로 수술전 병기의 확인이 매우 중요하다. 광범위 절제연에 대해서는 종양 두께에 따라 1~3 cm의 절제연으로 광범위 절제를 권유한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3519-3528
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• 2012

Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and $30{\mu}g/ml$) as well as macluraxanthone and gerontoxanthone-I (3 and $10{\mu}M$) significantly inhibited B16F10 cell invasion, to a greater extent than $10{\mu}m$ doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform ($30{\mu}g/ml$) and geratoxanthone-I ($20{\mu}M$) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy.

• Archives of Plastic Surgery
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• 제42권4호
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• pp.478-483
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• 2015

Due to the fact that it reliably results in positive outcomes, lymph node flap transfer is becoming an increasingly popular surgical procedure for the prevention and treatment of lymphedema. This technique has been shown to stimulate lymphoangiogenesis and restore lymphatic function, as well as decreasing infection rates, minimizing pain, and preventing the recurrence of lymphedema. In this article, we investigate possible additional benefits of lymph node flap transfer, primarily the possibility that sentinel lymph nodes may be used to detect micrometastasis or in-transit metastasis and may function as an additional lymphatic station after the excision of advanced skin cancer.

• 약학회지
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• 제43권2호
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• pp.173-179
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• 1999

In the present study, we have evaluated cytotoxic effects, antitumor activities and metastasis inhibitory effects of Palsun brewing water in NIH 3T3 cells, human epitheloid carcinoma cells, and human skin melanoma cells. The light microscopic study showed morphological changes, AG-NOR (argyrophylic nucleolar organizer region) by silver chloride stain, and glycoprotein by PAS (periodic acid stain) reaction of the treated cells. Disruptions in cell organelles were determined by colorimetric methods; MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide) and SRB (sulforhodamine B protein) assays. These results suggest that Palsun Brewing Water retains no cytotoxic effects in NIH 3T3 cells and a growth-inhibitory activity in cancer cell lines.

• Journal of Microbiology and Biotechnology
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• 제12권2호
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• pp.286-291
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• 2002

Histone deacetylase I (HDAC1) works as one of the components in a nucleosome remodeling (NuRD) complex that consists of several proteins, including metastasis-associated protein 1 (MTA1). Since the protein-protein interaction of HDAC1 and MTA1 would appear to be important for both the integrity and functionality of the HDAC1 complex, the interruption of the HDAC1 and MTA1 interaction may be an efficient way to regulate the biological function of the HDAC1 complex. Based on this idea, a yeast two-hybrid system was constructed with HDAC1 and MTA1 expressing vectors in the DNA binding and activation domains, respectively. To verify the efficiency of the assay system, 3,500 microbial metabolite libraries were tested using the paper disc method, and KB0699 was found to inhibit the HDAC1 and MTA1 interaction without any toxicity to the wild-type yeast. Furthermore, KB0699 blocked the interaction of HDAC1 and MTA1 in an in vitro GST pull down assay and induced morphological changes in B16/BL6 melanoma cells, indicating the interruption of the HDAC1 complex function. Accordingly, these results demonstrated that the yeast assay strain developed in this study could be a valuable tool for the isolation of a HDAC1 complex disruptor.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5887-5895
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• 2012

Background: To determine the effect of essential oil obtained from a traditionally used medicinal plant Tridax procumbens L, on lung metastasis developed by B16F-10 melanoma cells in C57BL/6 mice. Materials and Methods: Parameters studied were toxicity, lung tumor nodule count, histopathological features, tumor directed capillary vessel formation, apoptosis and expression levels of $P^{53}$ and caspase-3 proteins. Results: In vitro the MTT assay showed cytotoxicity was found to be high as 70.2% of cancer cell death within 24hrs for $50{\mu}g$. In vivo oil treatment significantly inhibited tumor nodule formation by 71.7% when compared with untreated mice. Formation of tumor directed new blood vessels was also found to be inhibited to about 39.5%. TUNEL assays also demonstrated a significant increase in the number of apoptotic positive cells after the treatment. $P^{53}$ and caspase-3 expression was also found to be greater in the essential oil treated group than the normal and cancer group. Conclusions: The present investigation showed significant effects of the essential oil of Tridax procumbens L in preventing lung metastasis by B16F-10 cell line in C57BL/6 mice. Its specific preventive effect on tumor directed angiogenesis and inducing effect on apoptosis warrant further studies at the molecular level to validate the significance of Tridax procumbens L for anticancer therapy.

• 대한골관절종양학회지
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• 제18권2호
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• pp.78-82
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• 2012

목적: 고용량 인터페론-${\alpha}2b$를 이용한 악성흑색종의 면역요법은 외과적 절제술 후 현미경적 적이나 남아있는 종양의 재발을 막고 무병생존율과 전체 생존율을 높이는 것으로 알려져 있다. 저자 등은 악성 흑색종 환자군에서 외과적 절제술 후 고용량 인터페론-${\alpha}$ 면역요법을 시행한 그룹의 무병생존기간 및 전체 생존율 등을 비교 분석하여 면역요법의 치료결과를 예비 보고하고자 한다. 대상 및 방법: 2010년 2월부터 2012년 10월까지 본원에서 악성 흑색종으로 진단받고 외과적 수술 후 면역치료를 시행한 5명을 대상으로 분석 하였다. 병기는 AJCC 병기를 이용하여 판정하였으며 IIA 3예, IIB 1예, IV 1예로 나타났다. 추시기간은 최소 7개월에서 최대 32개월이었다. 면역 요법을 시행한 군에서는 먼저 유도요법으로 ${\alpha}2b$를 체표면적 당 20만 IU를 총 4주간 1주일에 5회 정주하였으며 이후 유지요법으로 체표면적당 10만 IU를 총 48주간 1주일에 3회 피하주사하였다. 이들 환자들에 대해 국소재발과 국소전이, 그리고 원격전이여부를 조사하였고 무병생존기간을 조사하였다. 결과: 인터페론-${\alpha}2b$ 면역요법을 시행한 환자군에서 추시 흉부 전산화 단층촬영 및 양전자 컴퓨터 단층촬영을 통한 평가 결과 현재까지 모두 국소 재발 및 국소전이 원격전이의 증거가 없는 것으로 나타났다. 결론: 고용량 인터페론-${\alpha}$ 면역요법 시행군에서 현재까지 종양의 국소 재발 및 전이를 막는 것으로 나타났으나 향후 궁극적인 생존율 및 무병생존율 향상이 달성되는가에 대해서는 추가적인 연구대상과 추적관찰이 필요하겠다.