• 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.

• Journal of Microbiology and Biotechnology
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• v.25 no.12
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• pp.1997-2006
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• 2015

Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.

• 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.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.273-278
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• 1995

The effect of methamphetamine on the pulmonary metastasis was investigated in C57BL/6 mice injected with Bl6 melanoma cells. Bl6 melanoma cells (2$\times$10$^{5}$ cells) were injected intravenously into 5~7 weeks old C57BL/6 mice. Mice were then treated intraperitoneally with methamphetamine either acutely (two times with one week interval) or subchronically (daily for 14 days). Degree of pulmonary metastasis was investigated and specific immunologic parameters such as natural killer cell cytotoxicity(NKCC), antibody-dependent cellular cytotoxicity(ADCC) and blastogenic responses of splenocytes were examined. Mice which had been subchronically treated with methamphetamine showed significant decreases in the number of pulmonary metastasis of Bl6 melanoma cells, NKCC and ADCC without a significant change in blastogenic responses. In the acutely-treated group, slight trends of decrease in the numbers of pulmonary metastasis, NKCC and ADCC were observed without statistical significances whereas there was a significant increase in blastogenic responses. The mechanism underlying the decrease in the degree of metastasis despite diminished NKCC and ADCC after methamphetamine treatment and the relationship between the degree of pulmonary metastasis and duration of methamphetamine treatment remain to be investigated.

• YAKHAK HOEJI
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• v.44 no.6
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• pp.601-606
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• 2000

Recently, studies on missile antitumor drugs, which selectively act on tumor cell and display drug effects, have been performed. These missile antitumor drugs which can increase drug effects and decrease side effects, are ideal medication method. Lectin has been reported as tumor cell specific binding protein and tannin as antitumor substance. In this study, we studied inhibition of melanoma metastasis by lectin-conjugated ellagitannin and used praecoxin A as ellagitannin source. Mouse melanoma cell, B16-F10, was injected into the sole of forefoot of C57BL/6 mouse, and after administration with drug, the number of pulmonary tumor colony was counted. The administration of praecoxin A, lectin-praecoxin A mixiture, and lectin-conjugated praecoxin A was started after amputation of established tumor foci at right forefoot of mice and continued for 3 weeks with i.p. injection of one of those drugs A every 24 hours. Lectin-praecoxin A mixture, and lectin-conjugated praecoxin A significantly reduced the number of spontaneous pulmonary metastasis. Exposure to 5 mg/kg of lectin-praecoxin A mixiture and lectin-conjugated praecoxin A produced a statistically significant 38.3%, 41.8% reduction in the number of remaining pulmonary metastasis. These results suggest that metastasis inhibition by lectin-praecoxin A mixiture and lectin-conjugated praecoxin A are better than that of praecoxin A.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1833-1840
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• 2013

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), ${\gamma}$-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

• Archives of Plastic Surgery
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• v.36 no.4
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• pp.485-488
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• 2009

Purpose: Malignant melanoma of the lower extremity is well known to metastasize to the lymph nodes of the groin. However, in rare cases, the initial site of the nodal disease can be the popliteal fossa. As of yet, there has not been any report on cases with popliteal lymph node metastasis in Koreans. In the following report, authors would like to present two cases of popliteal node metastasis. Methods: A 60 - year - old male patient presented with nodular mass at his left sole. He had popliteal node metastasis detected on preoperative positron emission tomography(PET). Another 67 - year - old man presented with pigmented lesion at his right heel. He also had popliteal node metastasis detected on the MRI. They underwent wide excision of the primary lesion with popliteal node dissection. Results: In the first case, $2.5{\times}2.5cm$ sized metastatic melanoma in popliteal node was pathologically confirmed. There were no postoperative complications, and to date(18 months after the surgery), the patient is alive with no evidence of disease. In the second case, multiple(4) metastatic melanoma in popliteal nodes was confirmed. The patient is alive, but has had interferon therapy for liver metastasis. Conclusion: By increasing the use of lymphoscintigraphy or PET as a preoperative diagnostic work - up for metastasis, even popliteal node metastasis undetectable in a physical exam becomes detectable. When metastatic lymph node is found, node dissection is the standard of care. Therefore, it is essential that we know the anatomy and surgical technique for popliteal lymph node dissection.

• Toxicological Research
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• v.22 no.4
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• pp.349-356
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• 2006

Diallyl disulfide (DADS), an oil-soluble organosulfur compound in garlic has been reported to suppress tumor growth and to induce apoptosis in cancer. In the present study, we investigated the effects of DADS on pulmonary metastasis of B16-F10 murine melanoma cells. DADS (i.p. 40 mg/kg) significantly (p<0.05) reduced the number of pulmonary metastatic nodules (48%) in experimental pulmonary metastasis assay. We also found that DADS inhibited adhesion, invasion and migration of B16-F10 melanoma cells in a dose-dependent manner. To study the antimetastatic potential of DADS, we performed the effects of DADS on matrix metalloproteinase activity. DADS significantly inhibited the expression of matrix metalloproteinase-2 activity in B16-F10 cells by gelatin zymography. These results suggest that DADS prevent metastasis in part through suppression of migration of B16-F10 melanoma cells by Inhibiting matrix metalloproteirase-2 responsible for degradation of extracellar matrix.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1122-1126
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• 2002

We have examined whether Soamsan 1 (SA 1) augment the inhibitory effect of oral administration of Soamsan (SA) on lung metastasis of mouse 816 melanoma cells. The inhibitory effect was slightly enhanced by increase in administration dosage of SA 1. SA 1 as well as SA inhibited effectively the lung metastasis regardless of the pretreatment with anti-mouseNK monoclonal antibody. However, in the case of 2-chloroadenosine-pretreated mice, the inhibitory effects of SA and SA 1 were decreased by 18 and 23%, respectively. In vitro stimulation of the mouse splenocytes with mitogens showed that SA or SA 1 significantly augmented the proliferation of mouse splenocytes. Especially, the activity was more prominent in the presence of a B cell mitogen. LPS than a T cell mitogen, Con A. These results suggest that oral administration of SA 1 or SA inhibited lung metastasis of B16 melanoma cells, possibly through a mechanism mediated by the activation of macrophages and B lymphocytes in the host immune system. However, SA 1 did not showed more significant augment of the activation of immune system than SA.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.25-30
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• 1998

An in vivo model for human melanoma was established with the growth and metastasis of SK-MEL-2 cells. The tumor was introduced into C.B-17 SCID(severe combined immunodeficiency) mice intraperiotneally subcutaeously and intravenous inoculations. Tumors developed in 100% of mice inoculated subcutaneously and intraeritoneally both at site of inoculation and as metastatic tumor in the liver lungs and diaphragm. With intravenous inoculation 50% of mice showed metastasis in the spleen. Additionally metastatic foci that were not detected either by gross and/or standard histopathologic examination were demonstrated in the spleen and lungs by immunohistochemistry with HMB-45 monoclonal antibody. We conclude that the SCID mouse supports growth and metastasis of human malignant melanoma SK-MEL-2 cells.