Malignant melanoma is a highly malignant tumor derived from melanocyte. Malignant melanoma of the oral cavity occurs mainly in the palatine mucosa and the maxillary gingiva in men in their 50s. Malignant melanoma can be divided into pigmented and non-pigmented(amelanotic). Among them, non-pigmented malignant melanoma accounts for 2-8% of all malignant melanomas. Pigmented malignant melanoma is detected through changes in pigmentation, whereas non-pigmented malignant melanoma is characterized by no pattern of color change. In this study, at the initial visit, a malignant lesion was suspected and a biopsy was performed. According to the biopsy results, it was diagnosed as polymorphic sarcoma, but the histological examination performed during the operation revealed that it was amelanotic melanoma. As such, the differential diagnosis is important because there is no clinical change in non-pigmented malignant melanoma. Diseases to be differentially diagnosed when non-pigmented malignant melanoma occurs in the oral cavity include squamous cell carcinoma, lymphoma, sarcoma, inflammation, and osteomyelitis. In this study, we report a case that showed the histopathological characteristics of malignant melanoma without superficial pigmentation.

The objective of the present study was to investigate the molecular mechanisms involved in the activity of [10]-gingerol using A2058 human melanoma cells. [10]-Gingerol inhibited the proliferation of A2058 cells by 50% at a concentration of 52 μM. Such inhibition was dose-dependent accompanied by morphological change indicative of apoptosis. Furthermore, flow cytometric analysis by Annexin V and PI double staining showed that [10]-gingerol increased the extent of apoptosis. Analysis of the mechanism of these events indicated that [10]-gingerol increased the ratio of Bax to Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner.

Mucosal malignant melanoma is an uncommon tumor of the head and neck, and patient cannot easily recognize the lesion. Most patients are diagnosed with advanced lesions, and the 5-year survival rate is very low. Therefore, intraoral pigmented lesions require an incisional biopsy for differential diagnosis from malignant melanoma. As the size of the tumor increases, lesion showing vertical growth and lymph node metastasis increases, and the prognosis becomes poor. In this study, we report a case of mucosal malignant melanoma in the oral cavity that shows radial growth and no lymph node metastasis despite its relatively large size.

우르솔릭산은 항암, 항산화, 항염증 작용과 같은 다양한 효과를 지니고 있다. 본 연구에서는 우르솔릭산이 인간 흑색종 암세포인 A375SM과 A375P 세포에 항암효과가 있는지 확인하였다. 두 세포의 생존율은 MTT assay를 통하여 확인하였으며 증식률은 Wound healing assay로 확인하 였다. 두 세포의 apoptotic body와 apoptosis 비율의 확인을 위한 DAPI 염색과 유세포 분석을 진행하였다. 그리고 웨스턴 블로팅을 통하여 흑색종 세포의 우르솔릭산의 농도에 따른 apoptosis 단백질의 유도를 조사하였다. 우르솔 릭산의 처리 농도에 따라 흑색종 세포의 생존율 감소와 증식률 감소를 확인하였다. DAPI 염색을 통하여 우르솔 릭산의 농도가 증가함에 따라 흑색종 세포의 염색체 응축 이 농도 의존적으로 증가하였고, 유세포 분석을 통하여 우르솔릭산에 대하여 농도 의존적으로 흑색종 세포의 apoptosis 비율의 증가를 확인하였다. 그리고 웨스턴 블로팅을 통해 흑색종 세포 A375SM과 A375P의 우르솔릭산 12 μM 농도에서 cleaved-PARP와 Bax의 증가와 Bcl-2의 감소를 확 인하였다. 본 연구는 우르솔릭산의 농도를 0 에서 20 μM 수준의 저농도에서 진행하였으며, 물질 처리 후 24 시간 뒤 결과를 가지고 분석하였다. 본 연구의 결과로 보아 우르솔릭산은 흑색종 세포 A375SM과 A375P에서 apoptosis 관련 단백질들의 조절을 통해 항암효과를 일으키는 것으로 사료된다.

Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and –metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and –metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelialmesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.

Ganoderma lucidum, a species of the class Basidiomycetes, attracts international attention due to the wide variety of its biological activities and great potential as cosmetic ingredient, such as skin care cosmetics including ‘skin-whitening’. However, there is little information available regarding the tyrosinase inhibitory activity. Therefore, the objectives of this study were to investigate the chemical composition and tyrosinase inhibitory activity of the G. lucidum. To isolate active single compound from G. lucidum (GASC), we conducted ethanol extraction and chloroform fractionation. In addition, we assayed the inhibitoty effect of tyrosinase activity and melanin biosynthesis in B16F10 mouse melanoma cells. In the present study, we identified a GASC, which exhibited inhibitory effects of cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-1, 2. In additional, microphthalmia-associated transcription factor (MITF), as known as crucial regulator of melanogenesis-related genes, was down-regulated by treatment with GASC in a concentration-dependent manner. GASC exhibited significant inhibition of tyrosinase activity and melanin synthesis in B16F10. The finding that melanogenesis inhibitory effect of GASC will contribute to facilitate various approaches of this mushroom for use in skin whitening products.

We investigated the synergistic apoptotic effects of co- treatments with Chios gum mastic (CGM) and eugenol on G361 human melanoma cells. An MTT assay was cond-ucted to investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment. The induction and augmentation of apop-tosis were confirmed by DNA electrophoresis, Hoechst stai-ning, and analyses of DNA hypoploidy. Western blot ana-lysis and immunofluorescent staining were also performed to evaluate expression and translocation of apoptosis- related proteins following CGM and eugenol co-treatment. Proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed.The results indicated that the co-treatment of CGM and eugenol induces multiple pa-thways and processes associated with an apoptotic response in G361 cells. These include nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome acti-vity, an increase of Bax and decrease of Bcl-2, a decreased DNA content, cytochrome c release into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of 40 µg/ml CGM or 300 µM eugenol for 24 hours did not induce apoptosis. Our present data thus suggest that a combination therapy of CGM and eugenol is a potential treatment strategy for human melanoma.

Resistance to the induction of apoptosis is a possible me- chanism by which tumor cells can survive anti-neoplastic treatments. Melanoma is notoriously resistant to anti-neop- lastic therapy. Previous studies have demonstrated focal adhesion kinase (FAK) overexpression in melanoma cell lines. Given its probable role in mediating resistance to apo- ptosis, many researchers have sought to determine whether the downregulation of FAK in melanoma cells would confer a greater sensitivity to anti-neoplastic agents. Genistein is a known inhibitor of protein-tyrosine kinase (PTK), which may attenuate the growth of cancer cells by inhibiting the PTK- mediated signaling pathway. This present study was under- taken to investigate the effect of genistein on the expression of FAK and cell cycle related proteins in the G361 me- lanoma cell line. Genistein was found to have a preferential cyto- toxic effect on G361 melanoma cells over HaCaT normal ke- ratinocytes. Genistein decreased the expression of 125 kDa phosphotyrosine kinase and the FAK protein in particular. Genistein treatment did not affect the expression of p53 in G361 cells in which p21 is upregulated. The expression of cy- clin B and cdc2 was downregulated by genistein treatment. Taken together, our data indicate that genistein induces the decreased proliferation of G361 melanoma cells via the in-hibition of FAK expression and regulation of cell cycle genes. This suggests that the use of genistein may be a via- ble approach to future melanoma treatments.

Eugenol (4-allyl-2-methoxyphenol) is a naturally occurring phenolic compound that is widely used in dentistry as a component of zinc oxide eugenol cement that is commonly applied to the mouth environment. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatments with eugenol and cisplatin on human melanoma (G361) cells. To investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment, an MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis of DNA hypoploidy. Western blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed. The results indicated that a co-treatment with eugenol and cisplatin induced multiple pathways and processes associated with an apoptotic response in G361 cells including nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome activity, the increase and decrease of Bax and Bcl-2, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of 300 μM eugenol or 3 μM cisplatin for 24 h did not induce apoptosis. Our present data thus suggest that a combination therapy of eugenol and cisplatin is a potential treatment strategy for human melanoma.

Eugenol is an essential oil found in cloves and cinnamon that is used widely in perfumes. However, the significant anesthetic and sedative effects of this compound have led to its use also in dental procedures. Recently, it was reported that eugenol induces apoptosis in several cancer cell types but the mechanism underlying this effect has remained unknown. In our current study, we examined whether the cytotoxic effects of eugenol upon human melanoma G361 cells are associated with cell cycle arrest and apoptosis using a range of methods including an XTT assay, Hoechst staining, immunocytochemistry, western blotting and flow cytometry. Eugenol treatment was found to decrease the viability of the G361 cells in both a time- and dose-dependent manner. The induction of apoptosis in eugenol-treated G361 cells was confirmed by the appearance of nuclear condensation, the release of both cytochrome c and AIF into the cytosol, the cleavage of PARP and DFF45, and the downregulation of procaspase-3 and -9. With regard to cell cycle arrest, a time-dependent decrease in cyclin A, cyclin D3, cyclin E, cdk2, cdk4, and cdc2 expression was observed in the cells after eugenol treatment. Flow cytometry using a FACScan further demonstrated that eugenol induces a cell cycle arrest at S phase. Our results thus suggest that the inhibition of G361 cell proliferation by eugenol is the result of an apoptotic response and an S phase arrest that is linked to the decreased expression of key cell cycle-related molecules.

Melanoma is the most aggressive form of skin cancer and is the fastest growing type of cancer in the United States. We report here the synthesis of a novel series of quinazolinylmethoxybenzene derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line. Among them, urea compound 1a (IC50 = 4.8 μM) having 4-chloro-3-trifluoromethylphenyl moiety showed superior antiproliferative activity to Sorafenib (IC50 = 5.5 μM) as a reference compound. These results will helpful for designing structure of a therapeutic agent for the treatment of melanoma.

Melanoma is the most serious type of skin cancer as a malignant tumor of melanocytes. In this work, the syntheses of a novel series of benzaminoquinoline derivatives 1a-c and their antiproliferative activities against A375 human melanoma cell line were described. All the compounds (IC50=0.78-1.02μM) showed superior antiproliferative activities to Sorafenib (IC50=5.58μM) as a reference compound. These results suggested that benzaminoquinoline derivatives have potentials as a therapeutic agent for the treatment for melanoma.

In this work, a novel series of aminoisoquinolinylamide derivatives 1a-c and 2a-f were synthesized via several reaction steps, starting from 2-methyl-4-nitrobenzonitrile (3) and 1-chloro-5-nitroquinoline (8). And their antiproliferative activities were screened against A375 human melanoma cell line compared to Sorafenib as a reference compound. Among them, compound 1b and 1c exhibited meaningful inhibitory activities. These results demonstrated that aminoisoquinolinylamide scaffold possesses the possibility as the treatment for melanoma.

Oral malignant melanoma of the oral cavity is rare. Although the Asian population has a relatively high incidence of oral malignant melanoma in contrast to Caucasians, the clinical information in Korean has been rarely known. In addition, the clinical and histological classification of oral malignant melanoma has not been established up to now. So we investigated 26 cases of oral malignant melanomas on the basis of clinicopathological and immunohistochemical findings and reclassified the clinical and histological type. The results of this study are as followed. Oral malignant melanomas occurred at any age from 28 years to 73 years and their mean age was 58.6 years. Of 26 cases, 14 occurred in male and 12 in female. Oral malignant melanomas occurred almost in palate and/or maxillary gingiva (25 cases; 96.2%). Only one case occurred in mandibular gigiva. Oral malignant melanomas were clinically divided into macular(9 cases) and nodular type(17 cases), showing that the nodular type occurred more frequently. Oral malignant melanomas were histologically divided into in situ spreading(5 cases), invasive(13 cases), and combined type(8 cases), showing that the invasive type occurred most frequently. All cases showed positivity for S-100 and 15 cases(57.7%) for HMB-45 in immunohistochemical analysis. It was thought these results could provide basic data for the research on oral malignant melanoma in Korean and additional prospective and retrospective studies would be needed in order to find the relations with the prognosis of the patients

This r esearch was designed to find the specific and economic methods of diagnosis about malignant melanoma For this study, we selected a typical case that was ambiguous in diagnosis between malignant melanoma and simple mela notic pigmentation, Tissue sections was st ained by H&E method, and immunohistochemical analyses was performed about 8-100 protein and MART-1 molecule, This research showed that MART-l had a more specificity for melanocytes than 8-100 protein , Patterns of MART-1 molecule distribution was more helpful in estimation of malignancies than 8-100 protein distribution patterns, On the basis of diagnostic usefulness and economical aspects, 8-100 protein and MART-1 molecule showed synergis tic and complementary relationship in confirming of tumor origin and they would be much useful for accurate diagnosis of malignant melanoma

Wnt genes encode a large fami ly of secreted cysteine-rich signaling mol ecules involved in cell growth‘ differentiation and tumorigenesis, Wnt5a, a non-transforming member of the Wnt fa mily behaves as a putative onco 一 gene in many cancers including melanomas, The aim of our study was to determine Wnt5a ex pression pattern in pnmalγ oral mucosal melanomas(Ol\αÆ) and correlate it with tumor thlckness Archival ti ssues from 18 OMM cases were subjected to immunohistochemical detection of Wnt5a by the streptavidin-biotin method , These were categorized into tumors of (4 mm(thin and intermediate thickness lesions) and )4 mm(t hi ck lesions) t hickness, Most OMM cases(17/18; 94, 4%) stained positive for Wnt5a, though heterogeneously, Seven t hi ck(7/11: 64%) and one in termediate thickness(1/7‘ 14%) ol\α‘ demonstrated strongly positive Wnt5a staining(P(O, 05), The only Wnt5a-neg ative case was a thi ck OMM without local recurrence after treatment Strong Wnt5a express ion at tumor adva ncing sites suggests a role in local tumor spread, Identification of pleomorphi c epitheli oid and spindle cells as mel anoma cell populations with the most pronounced Wnt5a staining suggests that Wnt5a overexpression inJ] uences cellular phenotype, These results taken together suggest that Wnt5a is up- regulated in OMM a nd may play a role in tumor progression, Wnt5a activity is most frequently detected in advanced OMM suggesting its function in tumor progression, Expression level of Wnt5a in OMM correlated with tumor grade and t hickness