• BMB Reports
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• 제51권11호
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10451-10456
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• 2015

Background: We defined melanoma distribution in a large series of Turkish patients and evaluated the prognostic parameters of melanomas. Materials and Methods: A total of 1574 patients' data was retrospectively collected at 18 centers in Turkey. Demographic characteristics were questioned and noted. Prognostic parametres were evaluated based on sentinel lymph node involvement. Results: Mean age was 56.7 (4-99) years. While 844 (53.6%) cases were male, 730 (46.4%) cases were female. One thousand four hundred forty-seven (92%) cases were invasive melanoma and 127 (8%) cases were in-situ melanoma. The most common histopathological form was the superficial spreading melanoma (SSM) which was found in 549 patients (37.9%). It was followed by nodular melanoma in 379 (26.2%), acral lentiginous melanoma (ALM) in 191 (13.2%) and lentigo maligna melanoma in 132 (9.1%), respectively. On univariate analysis, lymphovascular invasion (p<0.001), tumor thickness (p<0.001), histopathological subtype (p<0.001), Clark level (p=0.001), ulceration (p<0.001), ${\geq}6/mm^2$ mitosis (p=0.005), satellite formation (p=0.001) and gender (p=0.03) were found to be associated with sentinel lymph node positivity. Regression was associated with sentinel lymph node negativity (p=0.017). According to multivariate analysis, lymphovascular invasion and tumor thickness were significant independent predictive factors of SLN positivity. Patient age, tumor localization, precursor lesions, lymphocytic infiltration and neurotropism were not related with sentinel lymph node involvement. Conclusions: In this retrospective analysis, it was found that the prevalence of SSM is at a lower rate while the prevalence of ALM is at a higher rate when compared to western countries. According to Breslow index; most of the melanoma lesions' thickness were greater than 2 mm, corresponding Clark IV. Vascular invasion and tumor thickness are the most important factors for sentinel lymph node involvement.

• Archives of Plastic Surgery
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• 제36권4호
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• pp.411-416
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• 2009

Purpose: Malignant melanoma is recognized as the most serious skin cancer. We examined anatomical distribution and 5 - year survival rate of each stage of malignant melanoma on lower leg. Methods: We retrospectively analyzed the medical records of 91 patients(46 males and 45 females) with malignant melanoma on lower leg from 1985 to 2008. Age, sex, anatomical distribution and 5 - year survival rates of each stage of malignant melanoma on lower leg were investigated. Also, 5 - year survival rates of each stage and invasion depth of malignant melanoma on heel pad were investigated. Results: On lower leg, most frequently 32 cases(35.1%) occurred on heel pad, 27 cases(29.7%) occurred on dorsum of foot, 18 cases(19.8%) in toe and 14 cases(15.4%) on others in lower leg. We used the excision margin as 3 ~ 5 cm. After wide excision, in stage III, IV, the patients underwent the immunologic / chemo - therapy. The incidences of each stage were 22 cases(24.2%) in stage I, 47(51.6%) in II, 17(18.7%) in III and 5(5.5%) in IV. The 5 - year survival rates of each stage were 85%, 53.2%, 47.1% and 40%. On heel pad, the incidences of each stage were 5 cases(15.6%) in stage I, 19 cases(59.4%) in II, 7 cases(21.9%) in III and 1 case(3.1%) in IV. The 5 - year survival rates of each stage were 80%, 63.2%, 42.9% and 100%. On heel pad, incidence of local recurrence was 2 and 5 - year survival rate of this case was 100%. And systemic recurrence was 9 and 5 - year survival rate of this case was 55.6%. Conclusion: The 5 - year survival rate of malignant melanoma on heel pad was higher than previous study. To maintain the weight - bearing function of foot, we recommend the active reconstructive surgery for heel pad reconstruction after wide excision of heel pad malignant melanoma.

• 생명과학회지
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• 제23권12호
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• pp.1516-1524
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• 2013

본 연구는 Monascus purpureus (Mp), Aspergillus oryzae (Ao), Aspergillus kawachii (Ak) 및 Rhizopus oryzae (Ro) 균주로 Cordycepin-고함유 동충하초(Cordyceps militaris)(CM${\alpha}$)를 발효시켜 수용성 추출물을 얻어 페놀화합물 및 플라보노이드 농도와 항산화 및 티로시나제 저해 활성을 측정한 결과 Ak로 발효시킨 CM${\alpha}$ (AkF-CM${\alpha}$)에서 각각 46 mg/g 및 093 mg/g과 6274% 및 7997%로 가장 우수한 효과를 나타내었다. 이러한 결과로부터 AkF-CM${\alpha}$를 선택하여 멜라닌 세포(B16F0 mouse melanoma cell)에서 미백효과를 검토하였다. 양성 대조구 arbutin 처리 B16F10 melanoma 세포는 92% 이상의 세포 생육과 43%의 멜라닌 생성 억제 효능을 보였고, AkF-CM${\alpha}$ 1, 3 및 5 mg/ml 처리 시 멜라닌 생성은 각각 35, 45 및 53% 억제되었다. 또한 AkF-CM${\alpha}$은 멜라닌 세포 내 tyrosinase 활성과 mushroom tyrosinase 활성 모두를 저해시켰고, 멜라닌 생성 관련 tyrosinase 단백질 발현량도 무첨가군에 비해 처리 농도 의존적으로 억제되었다. 이상의 결과에 따라 Aspergillus kawachii 균주로 발효시킨 Cordycepin-고함유 동충하초(Cordyceps militaris)의 수용성 추출물은 미백 화장품 소재로 개발 가능성이 높은 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.57-62
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• 2012

Neural precursor cell-expressed developmentally down-regulated 8 (NEDD8), a ubiquitin-like protein, mainly functions through covalent ligation to cullin proteins. Conjugation of NEDD8 with cullins can promote ubiquitination, which plays a critical role in the degradation of many proteins. UBA3 is the subunit of NEDD8-activating enzyme which is one of the keys for NEDD8 linkage to cullin proteins. Previous research showed NEDD8 conjugation to be up-regulated in highly proliferative cell lines. In the present study, up-regulated NEDD8 conjugation was observed in melanoma cell lines by Western blot analysis. After down-regulation with a RNAi to UBA3, proliferation of M14 was suppressed in vitro and in vivo. In conclusion, up-regulated NEDD8 conjugation may be involved in the development of melanoma. Interference in this pathway might offera promising method for melanoma therapy.

• BMB Reports
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• 제42권12호
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• pp.806-811
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• 2009

Recently, various phenolic acid phenethyl ureas (PAPUs) have been synthesized from phenolic acids by Curtius rearrangement for the development of more effective anti-oxidants. In this study, we examined the anti-tumor activity and cellular mechanism of the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1) using melanoma B16/F10 and M-3 cells. Results showed that PAPU1 inhibited the cell proliferation and viability, but did not induce cytotoxic effects on primary cultured fibroblasts. PAPU1 induced apoptotic cell death rather than necrosis in melanoma cells, a result clearly proven by the shift of cells into sub-$G_1$ phase of the cell cycle and by the substantial increase in cells positively stained with TUNEL or Annexin V. Collectively, this study revealed that PAPU1 induced apoptosis in a caspase-dependent manner, suggesting a potential role as a cancer chemopreventive agent for melanoma cells.

• 대한두경부종양학회지
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• 제11권2호
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• pp.178-184
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• 1995

Melanoma of the scalp is rare condition and seems to be to have a poor prognosis than melanoma of other portion of the body. We had 2 patients suffering from malignant melanoma of scalp. Their charts were reviewed for epidemiologic data, location, Breslow thickness, lymph node involvement and outcome. The therapeutic treatment was wide excision and skin grafting or free flap reconstruction. The early recognition of all the nevi at scalp and proper follow-up of the lesion are key stones to eradicating the changing mole and to preventing this thread to life.

• 대한의생명과학회지
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• 제14권1호
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• pp.33-38
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• 2008

In order to examine oxidative stress of reactive oxygen species and the antioxidant effect of Citri Reticulatae Pericarpium (CRP) extract, human skin melanoma cells were treated with various concentrations of hydrogen peroxide ($H_2O_2$). Antioxidant effect of CRP extract on $H_2O_2$-induced cytotoxicity, cell viability, DPPH-radical scavenging activity and superoxide dismutase (SOD)-like activity. In this study, $H_2O_2$ decreased cell viability of cultured human skin melanoma cells in dose- and time-dependent manners, and then, midcytotoxicity value (MCV) was determined at $60\;{\mu}M$ after human skin melanoma cells were cultured for 5 hours in the media containing $20{\sim}60\;{\mu}M$ of $H_2O_2$, respectively. The $H_2O_2$ was on cultured human skin melanoma cells because MCV of $H_2O_2$ was lower than $100\;{\mu}M$. In the antioxidant effect of CRP extract, CRP extract increased cell viability DPPH-radical scavenging activity and SOD-like activity. From these results, it is suggested that $H_2O_2$ was very toxic on cultured human skin melanoma cells. And also, CRP extract has the antioxidant effect on $H_2O_2$-induced cytotoxicity.

• 대한한방내과학회지
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• 제21권3호
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• pp.453-460
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• 2000

Experimental studies were performed to investigate the effect of Houttuyniae herba Aqua-acupuncture on the growth of Melanoma 816 tissue and Mononuclear cell subsets in mice. The results are as follows : 1. In the study of lymphocytes numbers in mice circulating blood, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, but without stastistical significance. 2. In the study of $CD4^+$ T cell percentage in mice circulating blood, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, but without stastistical significance. 3. In the study of $CD8^+$ T cell percentage in mice circulating blood, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, with stastistical significance. 4. in the study of lymphocytes numbers in mice spleen tissue, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, but without stastistical significance. 5. In the study of $CD4^+$ T cell percentage in mice spleen tissue, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, but without stastistical significance. 6. In the study of $CD8^+$ T cell percentage in mice spleen tissue, Houttuyniae herba Aqua-acupuncture showed inhibitory effect, but without stastistical significance. 7. In the measurement of melanoma tissue weight, Houttuyniae herba Aqua-acupuncture showed increasing effect, but without stastistical significance. According to above results, it is concluded that Houttuyniae herba Aqua-acupuncture is effective upon immune responses in Melanoma 816 inoculated mice.

• 대한방사선치료학회지
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• 제9권1호
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• pp.50-55
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• 1997

The optimal management of uveal melanoma is still a matter of controversy. To determine the effect of Gamma Knife surgery for patients with uveal malanoma. the authors reviewed the results of 5 patients underwent Gamma Knife sugery between Sep. 1993 and Dec. 1996. The mean age was 60.7 years ranging from 42.5 to 76.5 years. Median follow-up was 13.29 months and the patient with follow up period more than 6 months was 4. The mean tumor volume was $3442 mm^3$(mean diameter 15.3 mm) and all patients were irradiated with a mean maximum dose of 74Gy(range $60\~80\;Gy$), using the $50\%$ isodose. After Gamma Knife surgery. one pateint showed complete disapperance in tumor size with follow-up 32 months, one enucleation due to progression, and 2 no interval change. In regard to vision, one patient blind. one enucleation, and 2 patients had no interval change. According to our experiences, Gamma Knife surgery for uveal melanoma be able to achieve local tumor control, spare the eyeball, and have possibility of save vision.