• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• Archives of Craniofacial Surgery
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• v.21 no.2
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• pp.132-136
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• 2020

Oral mucosal melanoma is a very rare type of malignant melanoma, the characteristics of which differ from those of cutaneous melanoma. Primary amelanotic melanoma of the mandibular gingiva, which can invade the mandibular bone, is very rare worldwide. Here, we report a case in which we performed a reconstruction of the mandible and gingiva using the fibula osteocutaneous free flap procedure to treat a patient diagnosed with a primary amelanotic melanoma of the mandibular gingiva. The procedure was successful, and no recurrence was observed 10 months after surgery. Oral mucosal melanoma has a much poorer prognosis and a lower 5-year survival rate than cutaneous melanoma. However, recently, immunomodulatory therapies for mutations in melanocytic lesions have been used effectively to treat the increasing number of patients developing this type of melanoma, thus improving the prognosis of patients with oral mucosal melanoma.

• Archives of Plastic Surgery
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• v.34 no.5
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• pp.557-561
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• 2007

Purpose: Malignant melanoma is a fatal tumor arising in the melanocytic systems of the skin. The incidence of malignant melanoma, formerly considered a rare tumor in Korea, is observed to increase. The aim of this study is to analyze the clinical and histopathological pattern of malignant melanoma in one institute. Methods: Thirty patients with ages ranging from 33 to 80 years, diagnosed as malignant melanoma at our skin tumor department, were enrolled in a retrospective study over a 6 year period(2000. 9-2006. 7). The analyzed data included age, sex, location, duration before diagnosis, clinical type, level of invasion, and stage. Results: The cases were identified and analyzed by clinical and histopathologic study. The male to female ratio was 1:1.7. Lower extremities(especially, feet) were favored sites. The majority of cases were acral lentiginous melanoma(40%), followed by nodular melanoma (36.7%), superficial spreading melanoma(20%) in this study. Clark level IV was predominant in histopathologic study. There was merely narrow gap among each stage by AJCC. Conclusion: The clinicopathological characteristic of melanoma in our patients is quite different with that in the West. In this retrospective study, primary lesions of the foot were predominant with melanoma, and a high percentage of these were classified pathologically as acral lentiginous melanomas. Patients had a more advanced stage of disease at first presentation and a more deeply invasive primary lesion than Western patients. These suggest that malignant melanoma has a worse prognosis in our patients than in the West. So, further organized prospective studies are needed to approach the prudent and accurate diagnosis and management of melanoma in Korea.

• Molecules and Cells
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• v.41 no.2
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• pp.119-126
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• 2018

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.87-90
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• 2002

Malignant melanoma of the nasal cavity occurs rarely. Malignant melanoma, originated from the upper respiratory tract including nasal cavity, has clinical feature of local recurrence and easily metastasizes to regional or distant lymph nodes, lung, and liver. Malignant melanoma originated from nasal cavity frequently shows tumor cell invasion, ulceration, or infection. Owing to these characteristics, complete surgical excision of the malignant melanoma in nasal cavity is not easy. And also the prognosis of this tumor is not so good because of a high recurrence rate. Recently the authors have recently experienced a case of malignant melanoma originated from the inferior turbinate, which was treated with lateral rhinectomy, total maxillectomy. The defect developed after surgical extirpation was reconstructed with rotational forehead flap.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.25-32
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• 2022

Malignant melanoma has an aggressive nature and high metastatic potential that result in one of the highest cancer mortality rates. Over the past three decades, primary and metastatic melanoma incidence has rapidly increased. The recent advances in diagnostic technology have shown promise, but there is still an enormous need for specific detection methods to diagnose malignant melanoma. Positron emission tomography can visualize a particular biomarker of malignant melanoma and promise a noninvasive image of micrometastases. However, the development of PET radiopharmaceuticals remains necessary for diagnosing malignant melanoma by using positron emission tomography. In this review, the history and a general overview of PET radionuclide labeled benzamide derivatives, including their radiosynthesis, in vivo characterization, and evaluation, are provided as imaging agents for malignant melanoma.

• Archives of Plastic Surgery
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• v.43 no.1
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• pp.59-65
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• 2016

Background In East Asia, the foot is the most common site of cutaneous melanoma. The purpose of this study was to investigate the differences between cutaneous melanoma of the foot and melanomas of other sites. Methods We studied 52 patients who underwent surgical treatment for cutaneous melanoma of the foot from September 2000 to January 2015. Through a retrospective review of their medical records, we collected data relating to their sex, age, histopathological subtype, Clark level, tumor thickness, lymph node involvement, stage, and survival rate, and we compared these parameters to those of 61 patients treated for melanoma of other sites. Moreover, we analyzed the surgical procedures, complications, and mortality rates associated with cutaneous melanoma on various parts of the foot. Results Melanoma of the foot differed from other melanomas only in the histopathological subtype. Other clinical features, including survival rate, did not differ significantly between the two groups heel was the most common site of melanoma of the foot (22 cases, 42.3%). The method of reconstruction varied depending on the region involved. Conclusions A comparison of melanoma of the foot to other melanomas showed that melanoma of the foot was associated with a significantly different distribution of histological subtypes. Consistent with previous findings, we found that the acral lentiginous subtype was the most common among melanomas of the foot. Furthermore, in contrast with previous studies, we did not find a worse prognosis or lower survival rate for melanoma of the foot in comparison with other melanomas.

• Tuberculosis and Respiratory Diseases
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• v.72 no.2
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• pp.169-172
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• 2012

Melanoma can occur as a metastasis within subcutaneous tissue, lymph nodes, or viscera without a detectable primary tumor. Among patients with metastatic melanoma of unknown primary lesion, those with endobronchial metastasis are exceedingly rare. Herein we report a case of an endobronchial and pulmonary metastasis in a patient with melanoma originating from an unknown primary site. The patient without a previous history of melanoma presented with blood-tinged sputum. Fiberoptic bronchoscopy revealed a black polypoid tumor obstructing the posterior basal segmental bronchus of the right lower lobe. A final diagnosis of the malignant melanoma was made based on an immunohistochemical study of the bronchoscopic biopsy specimen. Skin, ophthalmic, oral, and nasal examinations failed to identify occult primary lesions. Subsequent evaluation including positron emission tomography/computed tomography scans did not uncover any abnormalities other than the metastatic pulmonary melanoma. We also describe the characteristic bronchoscopic features of melanoma.

• BMB Reports
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• v.36 no.2
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• pp.173-178
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• 2003

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanine biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination I evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.4
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• pp.1-18
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• 2009

Purpose: This study was performed to elucidate the inhibitory effect of Mibaeksan (MB) on melanin synthesis in B16F10 mouse melanoma cell. Methods: To demonstrate the inhibitory effects of MB on melanin synthesis, we measured the amount of released and produced melanin in B16F10 melanoma cell. Also, we evaluated tyrosinase-activity in vitro as well as in B16F10 melanoma cell. And to investigate the action mechanism, we assessed the gene expression of tyrosinase, TRP-1, TRP-2, MMP-2, PKA, $PKC{\beta}$, ERK-1 ERK-2, AKT-1 and MITF in B16F10 melanoma cells. Results: 1. MB decreased the release and production of melanin in B16F10 melanoma cells. 2. MB decreased tyrosinase activity in vitro and in B16F10 melanoma cells. 3. MB decreased the expression of tyrosinase, TRP-1, TRP-2, PKA, $PKC{\beta}$ and MMP-2 in B16F10 melanoma cells. 4. MB increased the expression of ERK-1, ERK-2 and AKT-1 in B16F10 melanoma cells. 5. MB decreased the expression of MITF in B16F10 melanoma cells. Conclusion: From these results, it may be concluded that MB has the antimelanogenetic effects.