Cancer Research and Treatment

Original Articles

Outcomes of Stereotactic Body Radiation Therapy for Large Uveal Melanoma: A Retrospective Analysis of Asian Population: Jong Won Park, Seowoong Jun, Ki Chang Keum, Christopher Seungkyu Lee, Kyung Hwan Kim; Received June 20, 2024 Accepted December 28, 2024 Published online December 31, 2024; DOI: https://doi.org/10.4143/crt.2024.580 [Accepted]

Abstract PDF: Purpose
To investigate the clinical outcomes of stereotactic body radiation therapy (SBRT) in patients with large uveal melanoma (UM).
Materials and Methods
We conducted a retrospective review of 64 consecutive patients with UM treated with Cyberknife at Yonsei Cancer Center from September 2015 to October 2021. The median radiation dose was 60 Gy (range 48-64 Gy) administered in four fractions every alternate day. The local failure-free rate (LFFR), distant metastasis-free rate (DMFR), progression-free survival (PFS), and overall survival (OS) were assessed using the Kaplan–Meier method and log-rank test. Cox regression analysis was performed to analyze the predictive factors affecting survival outcomes and the factors associated with vision loss.
Results
The median tumor diameter and height were 11.5 mm and 8.4 mm, respectively. After a median follow-up of 32.1 months (range 4.9–89.9), the 3-year LFFR, DMFR, PFS, and OS were 89.5%, 70.5%, 65.5%, and 89.4%, respectively. Enucleation was performed in 13 (20.3%) patients, with three cases attributed to disease progression. A larger tumor diameter was associated with significantly worse DMFR (HR=1.35, p=0.015) and OS (HR=1.49, p=0.026) in the multivariate analysis. Regarding visual prognosis, 41 (64.1%) patients had baseline visual acuity ≥20/200, but only 4 (6.3%) patients maintained visual acuity ≥20/200 by the final follow-up. Initial visual acuity ≥20/40 (HR 0.45, p=0.030) was the single favorable significant factor predicting visual retention ≥20/200 in multivariate analysis.
Conclusion
SBRT using CyberKnife demonstrated a comparable local control rate to that observed in historical studies for patients with large UM. Distant metastasis and treatment-related ocular toxicity remain the limitations of this treatment.

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Skin cancer

Incidence and Survival Rates of Cutaneous Melanoma in South Korea Using Nationwide Health Insurance Claims Data: TaeHo Kim, Siyeong Yoon, Dong-Eun Shin, Sang Cheol Lee, Jisu Oh, So-Young Lee, Do Kyung Kim, Segi Kim, Bosung Jung, Minsup Kim, Soonchul Lee; Cancer Res Treat. 2022;54(3):937-949. Published online September 30, 2021; DOI: https://doi.org/10.4143/crt.2021.871

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Purpose
Melanoma incidence is rising worldwide along with the associated personal and socioeconomic health expenditures. We investigated the incidence and survival-rate patterns of melanoma in South Korea using nationwide data.
Materials and Methods
This retrospective cohort study included patients with melanoma between 2004 and 2017, based on National Health Insurance (NHI) claims data in South Korea. The incidence, prevalence, and survival rate were analyzed along with baseline demographic characteristics. We collected solar irradiation dose (SID) and healthcare ranking score (HRS) according to the administrative district from the Korea Meteorological Administration and Korea Health Promotion Institute. The incidence and survival rates were assessed using Pearson's correlation, the Kaplan-Meier estimation, multiple linear regression, and multiple logistic regression methods.
Results
Twenty-five thousand, five hundred ninety-one patients with melanoma were diagnosed during the study period. The age-standardized incidence of melanoma steadily increased from 2004 to 2017 from 2.6 to 3.0/100,000/yr. The incidence of melanoma increased with significantly higher income (p < 0.05). The prevalence followed a similar pattern as the incidence. According to multivariate analysis, HRS significantly influenced the incidence of melanoma in high sun-exposed sites (p < 0.001). There was no significant change in annual mortality. Women had a higher 5-year survival rate than men (78.4% vs. 72.8%). Mortality by the administrative district was highly correlated with HRS.
Conclusion
The incidence of melanoma is increasing in South Korea. A low HRS is associated with both higher incidence and mortality. The findings of this study could be utilized as a guideline for treating melanoma patients.

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Risk of second primary malignancies among survivors of cutaneous melanoma: A nationwide population-based study in the Republic of Korea
Joon Min Jung, Do Hyung Kim, Ye-Jee Kim, Ik Jun Moon, Woo Jin Lee, Sung Eun Chang, Mi Woo Lee, Chong Hyun Won
Scientific Reports.2025;[Epub] CrossRef
Incidence and survival rates of primary cutaneous malignancies in Korea, 1999–2019: A nationwide population‐based study
Soon‐Hyo Kwon, Sangmin Choi, Joung Soo Kim, Sang Seok Kim, Mihn‐Sook Jue, Soo Hong Seo, Jihye Park, Mi Ryung Roh, Je‐Ho Mun, Jun Young Kim, Jee Woong Choi, Ji Won Byun, Sanghyun Park, Min Sung Kim, Seok‐Jong Lee
The Journal of Dermatology.2024; 51(4): 532. CrossRef
The Effect of Interval Training and Urtica Dioica Hydroalcoholic Extract on some Growth and Immune Factors in C57 Rats with Melanoma Cancer
Maryam Firoozi, Alireza Barari, Asieh Abbassi Daloii, Hossein Abednatanzi
Complementary Medicine Journal.2024; 13(4): 44. CrossRef
Hellebrigenin induces apoptosis by triggering cellular inhibitor of apoptosis 1 and Jun N-terminal kinase pathway in melanoma cells
Mu-Kuei Shieu, Yi-Ching Chuang, Hsin-Yu Ho, Chia-Chieh Lin, Yu-Sheng Lo, Ming-Ju Hsieh
Dermatologica Sinica.2024; 42(1): 19. CrossRef
Analyses of Osteogenesis Imperfecta in South Korea Using the Nationwide Health Insurance Service Claim Data: A Propensity Score-Matched Study
Sin Hyung Park, Ho Yoon, Siyeong Yoon, Jaiwoo Chung, Jae-hyun Kim, Soonchul Lee
Calcified Tissue International.2024; 115(6): 915. CrossRef
Pediatric melanoma incidence and survival: a fifteen-year nationwide retrospective cohort study in Korea
Isaac Kim, Jisu Oh, Siyeoung Yoon, Man-Yong Han, Jaiwoo Chung, Younghoon Jung, Hyun-Il Lee, Soonchul Lee
Melanoma Research.2024; 34(6): 528. CrossRef
FOXN3 Regulates Autophagic Activity to Suppress Drug Resistance in Melanoma Cells
Yaqi Wang, Hui Su, Xiaopeng Wang, Chen Tu, Tong Xiao, Bincheng Ren, Shuang Wang
Clinical, Cosmetic and Investigational Dermatology.2024; Volume 17: 2505. CrossRef
The effects of exposure to solar radiation on human health
R. E. Neale, R. M. Lucas, S. N. Byrne, L. Hollestein, L. E. Rhodes, S. Yazar, A. R. Young, M. Berwick, R. A. Ireland, C. M. Olsen
Photochemical & Photobiological Sciences.2023; 22(5): 1011. CrossRef
Survival rates for invasive cutaneous malignant melanoma in South Korea in accordance with the Eighth edition AJCC Cancer Staging Manual: A retrospective single center study
Seon Hwa Lee, Gi Ung Ha, Hyun Ji Lee, Ho Yun Chung, Seung Huh, Dae-Lyong Ha, Kyung Duck Park, Yong Hyun Jang, Weon Ju Lee, Seok-Jong Lee, Jun Young Kim
Indian Journal of Dermatology, Venereology and Leprology.2023; 90: 163. CrossRef
Clinicopathological characteristics and prognosis of Merkel cell carcinoma: a single-center retrospective study in Korea
Ik Jun Moon, Hyungmin Na, Hye Soo Cho, Chong Hyun Won, Sung Eun Chang, Mi Woo Lee, Woo Jin Lee
Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10065. CrossRef

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Clinical Outcomes of Immune Checkpoint Blocker Therapy for Malignant Melanoma in Korean Patients: Potential Clinical Implications for a Combination Strategy Involving Radiotherapy: Jeongshim Lee, Jee Suk Chang, Mi Ryung Roh, Minkyu Jung, Choong-Kun Lee, Byung Ho Oh, Kee Yang Chung, Woong Sub Koom, Sang Joon Shin; Cancer Res Treat. 2020;52(3):730-738. Published online February 13, 2020; DOI: https://doi.org/10.4143/crt.2019.598

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Purpose
We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT).
Materials and Methods
We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR).
Results
The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders.
Conclusion
ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).

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Hydrogels as a Potential Biomaterial for Multimodal Therapeutic Applications
Harpreet Kaur, Bishmita Gogoi, Ira Sharma, Deepak Kumar Das, Mohd Ashif Azad, Devlina Das Pramanik, Arindam Pramanik
Molecular Pharmaceutics.2024; 21(10): 4827. CrossRef
Injectable hydrogels for personalized cancer immunotherapies
Neda Mohaghegh, Amir Ahari, Fatemeh Zehtabi, Claire Buttles, Saya Davani, Hanna Hoang, Kaylee Tseng, Benjamin Zamanian, Safoora Khosravi, Ariella Daniali, Negar Hosseinzadeh Kouchehbaghi, Isabel Thomas, Hamed Serati Nouri, Danial Khorsandi, Reza Abbasghol
Acta Biomaterialia.2023; 172: 67. CrossRef
Efficacy of radiotherapy combined with immune checkpoint inhibitors in patients with melanoma: a systemic review and meta-analysis
Gaofei Yin, Wei Guo, Zhigang Huang, Xiaohong Chen
Melanoma Research.2022; 32(2): 71. CrossRef
The pharmacotherapeutic management of nail unit and acral melanomas
Julianne M. Falotico, Shari R. Lipner
Expert Opinion on Pharmacotherapy.2022; 23(11): 1273. CrossRef
A Comparison of 2 Disease Burden Assessment Methods (3D Volume Versus the Number of Lesions) for Prognostication of Survival in Metastatic Melanoma: Implications for the Characterization of Oligometastatic Disease
Jina Kim, Jee Suk Chang, Wonmo Sung, Jin Sung Kim, Tae Hyung Kim, Seo Hee Choi, Kyung Hwan Kim, Heejoo Ko, Hye Sun Lee, Soyoung Jeon, Sang Joon Shin, Mitchell Liu, Robert Olson
International Journal of Radiation Oncology*Biology*Physics.2022; 114(5): 883. CrossRef
Prediction of Immune-Checkpoint Blockade Monotherapy Response in Patients With Melanoma Based on Easily Accessible Clinical Indicators
Hwa Kyung Byun, Jee Suk Chang, Minkyu Jung, Woong Sub Koom, Kee Yang Chung, Byung Ho Oh, Mi Ryung Roh, Kyung Hwan Kim, Choong-Kun Lee, Sang Joon Shin
Frontiers in Oncology.2021;[Epub] CrossRef
Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review
Jennifer Ben Shimol, Yuli Guzman-Prado, Maria Karlinskaya, Tima Davidson
Critical Reviews in Oncology/Hematology.2021; 167: 103499. CrossRef

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A Potential Therapy Using Engineered Stem Cells Prevented Malignant Melanoma in Cellular and Xenograft Mouse Models: Jae-Rim Heo, Kyung-A Hwang, Seung U. Kim, Kyung-Chul Choi; Cancer Res Treat. 2019;51(2):797-811. Published online September 14, 2018; DOI: https://doi.org/10.4143/crt.2018.364

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Purpose
In the present study, human neural stem cells (hNSCs) with tumor-tropic behavior were used as drug delivery vehicle to selectively target melanoma. A hNSC line (HB1.F3) was transduced into two types: one expressed only the cytosine deaminase (CD) gene (HB1.F3. CD) and the other expressed both CD and human interferon-β (IFN-β) genes (HB1.F3.CD. IFN-β).
Materials and Methods
This study verified the tumor-tropic migratory competence of engineered hNSCs on melanoma (A375SM) using a modified Boyden chamber assay in vitro and CM-DiI staining in vivo. The antitumor effect of HB1.F3.CD and HB1.F3.CD.IFN-β on melanoma was also confirmed using an MTT assay in vitro and xenograft mouse models.
Results
A secreted form of IFN-β from the HB1.F3.CD.IFN-β cells modified the epithelial-mesenchymal transition (EMT) process and metastasis of melanoma. 5-Fluorouracil treatment also accelerated the expression of the pro-apoptotic protein BAX and decelerated the expression of the anti-apoptotic protein Bcl-xL on melanoma cell line.
Conclusion
Our results illustrate that engineered hNSCs prevented malignant melanoma cells from proliferating in the presence of the prodrug, and the form that secreted IFN-β intervened in the EMT process and melanoma metastasis. Hence, neural stem cell-directed enzyme/prodrug therapy is a plausible treatment for malignant melanoma.

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Engineering colloidal systems for cell manipulation, delivery, and tracking
Olga A. Sindeeva, Zhanna V. Kozyreva, Arkady S. Abdurashitov, Gleb B. Sukhorukov
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Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma
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Vahid Alimardani, Zahra Rahiminezhad, Mahvash DehghanKhold, Ghazal Farahavar, Mahboobeh Jafari, Mehdi Abedi, Leila Moradi, Uranous Niroumand, Mohammad Ashfaq, Samira Sadat Abolmaali, Gholamhossein Yousefi
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Genetically engineered neural stem cells expressing cytosine deaminase and interferon-beta enhanced T cell-mediated antitumor immunity against gastric cancer in a humanized mouse model
Youngdong Choi, Hong Kyu Lee, Dohee Ahn, Min-Woo Nam, Ryeo-Eun Go, Kyung-Chul Choi
Life Sciences.2023; 328: 121866. CrossRef
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Ryota Tamura, Hiroyuki Miyoshi, Kazunari Yoshida, Hideyuki Okano, Masahiro Toda
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Jiayi Zhang, Zhaohu Yuan, Weijie Zhong, Yaming Wei
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Nadia Sadanandan, Alex Shear, Beverly Brooks, Madeline Saft, Dorothy Anne Galang Cabantan, Chase Kingsbury, Henry Zhang, Stefan Anthony, Zhen-Jie Wang, Felipe Esparza Salazar, Alma R. Lezama Toledo, Germán Rivera Monroy, Joaquin Vega Gonzales-Portillo, Al
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Ali Hassanzadeh, Somayeh Shamlou , Niloufar Yousefi, Marzieh Nikoo, Javad Verdi
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Erin A. Kimbrel, Robert Lanza
Nature Reviews Drug Discovery.2020; 19(7): 463. CrossRef
A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth
Geraldine Xue En Tu, Yoon Khei Ho, Zhi Xu Ng, Ke Jia Teo, Tseng Tsai Yeo, Heng-Phon Too
Stem Cell Research & Therapy.2020;[Epub] CrossRef

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Founder Mutations for Early Onset Melanoma as Revealed by Whole Exome Sequencing Suggests That This is Not Associated with the Increasing Incidence of Melanoma in Poland: Tadeusz Dębniak, Rodney J Scott, Rodney A Lea, Bohdan Górski, Bartłomiej Masojć, Cezary Cybulski, Andrzej Kram, Romuald Maleszka, Tomasz Gromowski, Katarzyna Paszkowska-Szczur, Aniruddh Kashyap, Marcin R. Lener, Karolina Malińska, Emilia Rogoża, Dawid Murawa, Helena Rudnicka, Jakub Deptuła, Jan Lubiński; Cancer Res Treat. 2019;51(1):337-344. Published online May 14, 2018; DOI: https://doi.org/10.4143/crt.2018.157

Abstract PDF PubReader ePub

Purpose
Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing (WES).
Materials and Methods
Herein we performed WES on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2Avariants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken.
Results
We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls.
Conclusion
Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.

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Haifeng Jiang, Liping Li, Tao Ma, Ruixiao Wang, Xiaozhen Chen, Ke Xu, Chen Chen, Zijin Liu, Hongmei Wang, Lingyan Huang
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Yingming Liu, Gang Wu, Xingru Tao, Jiayu Dong, Tiefeng Shi, Chenlei Shi
International Journal of Biological Macromolecules.2024; 280: 136176. CrossRef
Identification and Validation of a m5C RNA Modification-Related Gene Signature for Predicting Prognosis and Immunotherapeutic Efficiency of Gastric Cancer
Li Song, Shouguo Wang, Qiankun Li, Yao Lu, Rungong Yang, Xianqi Feng, İbrahim Hakkı Cigerci
Journal of Oncology.2023; 2023: 1. CrossRef
MYCT1 in cancer development: Gene structure, regulation, and biological implications for diagnosis and treatment
Jianan Xu, Yuanyuan Sun, Weineng Fu, Shuang Fu
Biomedicine & Pharmacotherapy.2023; 165: 115208. CrossRef
Family-based whole-exome sequencing identifies rare variants potentially related to cutaneous melanoma predisposition in Brazilian melanoma-prone families
Felipe Fidalgo, Giovana Tardin Torrezan, Bianca Costa Soares de Sá, Bruna Durães de Figueiredo Barros, Luciana Facure Moredo, Renan Valieris, Sandro J. de Souza, João Pereira Duprat, Ana Cristina Victorino Krepischi, Dirce Maria Carraro, Danillo G. August
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Unfolded protein response is involved in the metabolic and apoptotic regulation of oral squamous cell carcinoma
B. Seo, D.E. Coates, J. Lewis, G.J. Seymour, A.M. Rich
Pathology.2022; 54(7): 874. CrossRef
Constitutional variants in POT1, TERF2IP, and ACD genes in patients with melanoma in the Polish population
Karolina Malińska, Jakub Deptuła, Emilia Rogoża-Janiszewska, Bohdan Górski, Rodney Scott, Helena Rudnicka, Aniruddh Kashyap, Paweł Domagała, Jolanta Hybiak, Bartłomiej Masojć, Cezary Cybulski, Andrzej Kram, Magdalena Boer, Magdalena Kiedrowicz, Jan Lubińs
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A Systematic Literature Review of Whole Exome and Genome Sequencing Population Studies of Genetic Susceptibility to Cancer
Melissa Rotunno, Rolando Barajas, Mindy Clyne, Elise Hoover, Naoko I. Simonds, Tram Kim Lam, Leah E. Mechanic, Alisa M. Goldstein, Elizabeth M. Gillanders
Cancer Epidemiology, Biomarkers & Prevention.2020; 29(8): 1519. CrossRef

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Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions: Si-Hyung Lee, Jee Eun Kim, Hong Sun Jang, Kyu Hyun Park, Byung Ho Oh, Sang Joon Shin, Kee Yang Chung, Mi Ryung Roh, Sun Young Rha; Cancer Res Treat. 2018;50(4):1378-1387. Published online January 22, 2018; DOI: https://doi.org/10.4143/crt.2017.535

Abstract PDF Supplementary Material PubReader ePub

Purpose
Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected.
Materials and Methods
In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions.
Results
Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. Conclusion
Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

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Danar Wicaksono, Nurpudji Astuti Taslim, Vincent Lau, Rony Abdi Syahputra, Aiman Idrus Alatas, Purnawan Pontana Putra, Trina Ekawati Tallei, Raymond Rubianto Tjandrawinata, Apollinaire Tsopmo, Bonglee Kim, Fahrul Nurkolis
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PTEN Promoter Hypermethylation Is Associated with Breslow Thickness in Acral Melanoma on the Heel, Forefoot, and Hallux
Hae Seok Park, Jong Hoon Kim, Mi Yeon Cho, Kee Yang Chung, Mi Ryung Roh
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Heterogeneity of GNAQ/11 mutation inversely correlates with the metastatic rate in uveal melanoma
Chen Liang, Lan ya Peng, Ming Zou, Xuemei Chen, Yingying Chen, Hou Chen, Lirong Xiao, Naihong Yan, Junjun Zhang, Qing Zhao, Xi Huang
British Journal of Ophthalmology.2021; 105(4): 587. CrossRef
Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition
Jian-Ching Wu, Han-En Tsai, Yi-Hsiang Hsiao, Ji-Syuan Wu, Chieh-Shan Wu, Ming-Hong Tai
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Male sex and Breslow thickness are important risk factors for recurrence of localized melanoma in Korean populations
Yeongjoo Oh, Sooyie Choi, Mi Yeon Cho, Kyoung Ae Nam, Sang Joon Shin, Jee Suk Chang, Byung Ho Oh, Mi Ryung Roh, Kee Yang Chung
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Tumor Heterogeneity on FDG PET/CT and Immunotherapy: An Imaging Biomarker for Predicting Treatment Response in Patients With Metastatic Melanoma
Y. Sanli, J. Leake, A. Odu, Y. Xi, R. M. Subramaniam
American Journal of Roentgenology.2019; 212(6): 1318. CrossRef
BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis
Kyueng-Whan Min, Ji-Young Choe, Mi Jung Kwon, Hye Kyung Lee, Ho Suk Kang, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Yun Joong Kim, Nan Young Kim, Ho Young Kim
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Molecular and genetic diversity in melanoma of eye
N. N. Mazurenko, I. V. Tsyganova, V. V. Nazarova, I. A. Utyashev, K. V. Orlova, D. A. Ponkratova, D. V. Martinkov, L. V. Demidov
Advances in molecular oncology.2018; 5(3): 51. CrossRef

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Prognoses and Clinical Outcomes of Primary and Recurrent Uveal Melanoma: Jee Hung Kim, Su-Jin Shin, Soo Jin Heo, Eun-Ah Choe, Chang Gon Kim, Minkyu Jung, Ki Chang Keum, Jin Sook Yoon, Sung Chul Lee, Sang Joon Shin; Cancer Res Treat. 2018;50(4):1238-1251. Published online December 28, 2017; DOI: https://doi.org/10.4143/crt.2017.534

Abstract PDF Supplementary Material PubReader ePub

Purpose
Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood ofrecurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters.
Materials and Methods
Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival, and overall survival from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy.
Results
Forty-nine patients (21.7%) had distant recurrences, which occurred most frequently in the liver (87.7%). In a multivariate analysis, local radiotherapy improved RFS among patients with multiple recurrence risk factors relative to excision (not reached vs. 19.0 months, p=0.004). Patients with BRCA1-associated protein-1 (BAP1)‒negative primary tumors showed a longer RFS duration after primary treatments, while those with BAP1-negative metastatic tissues had a shorter OS2 compared to those with BAP1-positive tumors, both not statistically insignificance (RFS: not reached vs. 82.0 months, p=0.258; OS2: 15.7 vs. 24.4 months, p=0.216). Male sex (hazard ratio [HR], 3.79; p=0.012), a short RFS (HR, 4.89; p=0.014), and a largest metastatic tumor linear diameter ≥ 45 mm (HR, 5.48; p=0.017) were found to correlate with worse post-recurrence survival.
Conclusion
Risk factors could be used to classify uveal melanoma cases and subsequently direct individual treatment strategies. Furthermore, metastasectomy appears to contribute to improved survival outcomes.

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Favorable Outcomes of Patients With High-Risk Uveal Melanoma Treated With a Novel Linear Accelerator-Based Frameless Fractionated Stereotactic Radiosurgery
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Prognostic Factors and Decision Tree for Long-Term Survival in Metastatic Uveal Melanoma: Daniel Lorenzo, María Ochoa, Josep Maria Piulats, Cristina Gutiérrez, Luis Arias, Jaume Català, María Grau, Judith Peñafiel, Estefanía Cobos, Pere Garcia-Bru, Marcos Javier Rubio, Noel Padrón-Pérez, Bruno Dias, Joan Pera, Josep Maria Caminal; Cancer Res Treat. 2018;50(4):1130-1139. Published online December 4, 2017; DOI: https://doi.org/10.4143/crt.2017.171

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree.
Materials and Methods
The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristicswere assessed in both groups.
Results
Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making.
Conclusion
The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

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Ahao Wu, Lianghua Luo, Qingwen Zeng, Changlei Wu, Xufeng Shu, Pang Huang, Zhonghao Wang, Tengcheng Hu, Zongfeng Feng, Yi Tu, Yanyan Zhu, Yi Cao, Zhengrong Li
Scientific Reports.2024;[Epub] CrossRef
Impact of Metastatic Pattern on Survival in Patients with Posterior Uveal Melanoma: A Retrospective Cohort Study
Tine G. Hindso, Peter S. Jensen, Mette B. Sjøl, Kristoffer Nissen, Camilla W. Bjerrum, Eric von Benzon, Carsten Faber, Steen F. Urbak, Marco Donia, Inge M. Svane, Eva Ellebaek, Steffen Heegaard, Karine Madsen, Jens F. Kiilgaard
Cancers.2024; 16(19): 3346. CrossRef
Orthotopic murine xenograft model of uveal melanoma with spontaneous liver metastasis
Raquel Ramos, Eduard Cabré, Antònia Vinyals, Daniel Lorenzo, Josep R. Ferreres, Mar Varela, Montse Gomá, Maria José Paules, Cristina Gutierrez, Josep M. Piulats, Àngels Fabra, José M. Caminal
Melanoma Research.2023; 33(1): 1. CrossRef
Determinants of Long-Term Survival in Metastatic Choroidal and Ciliary Body Melanoma
Elina S. Rantala, Raffaele Parrozzani, Micaela M. Hernberg, Vanna Chiarion-Sileni, Tero T. Kivelä, Edoardo Midena
American Journal of Ophthalmology.2023; 246: 258. CrossRef
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Development of a Prognostic Nomogram for Liver Metastasis of Uveal Melanoma Patients Selected by Liver MRI
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Nationwide Trends in the Incidence of Melanoma and Non-melanoma Skin Cancers from 1999 to 2014 in South Korea: Chang-Mo Oh, Hyunsoon Cho, Young-Joo Won, Hyun-Joo Kong, Yun Ho Roh, Ki-Heon Jeong, Kyu-Won Jung; Cancer Res Treat. 2018;50(3):729-737. Published online July 14, 2017; DOI: https://doi.org/10.4143/crt.2017.166

Abstract PDF Supplementary Material PubReader ePub

Purpose
This descriptive study was aimed to examine trends in the incidence of melanoma and nonmelanoma in South Korea.
Materials and Methods
The nationwide incidence data for melanoma and non-melanoma skin cancer was obtained from the Korea Central Cancer Registry. Age-standardized rates were calculated and analyzed, using a Joinpoint regression model.
Results
The incidence of basal cell carcinoma has increased dramatically both in men (average annual percentage change [AAPC], 8.0 [95% confidence interval (CI), 6.0 to 10.1]) and women (AAPC, 9.0 [95% CI, 7.5 to 10.4]). Squamous cell carcinoma has also steadily increased both in men (AAPC, 3.3 [95% CI, 2.6 to 4.0]) and women (AAPC, 6.8 [95% CI, 5.3 to 8.4]). Cutaneous melanoma increased continuously from 1999 to 2014 inwomen (AAPC, 3.5 [95% CI, 2.4 to 4.6]), whilst rapidly increasing in men until 2005 (APC, 7.9 [95% CI, 2.4 to 13.7]) after which no increase has been observed (APC, ‒0.2 [95% CI, ‒2.3 to 2.0]).
Conclusion
The incidence rates of melanoma and non-melanoma skin cancer have increased over the past years, with the exception of melanoma in men. Further studies are required to investigate the reasons for the increased incidence of these skin cancers in South Korea.

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Applied Sciences.2019; 9(20): 4227. CrossRef
Sex‑biased differences in the correlation between epithelial‑to‑mesenchymal transition‑associated genes in cancer cell lines
Sun Kim, Seungeun Lee, Eunhye Lee, Hyesol Lim, Ji Shin, Joohee Jung, Sang Kim, Aree Moon
Oncology Letters.2019;[Epub] CrossRef
Melanoma signature in Brazil: epidemiology, incidence, mortality, and trend lessons from a continental mixed population country in the past 15 years
Andréia C. de Melo, Alberto J.A. Wainstein, Antonio C. Buzaid, Luiz C.S. Thuler
Melanoma Research.2018; 28(6): 629. CrossRef

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Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study: Shu-Hui Wang, Ching-Chi Chi, Zi-Hao Zhao, Tao-Hsin Tung; Cancer Res Treat. 2018;50(2):428-435. Published online May 10, 2017; DOI: https://doi.org/10.4143/crt.2017.110

Abstract PDF PubReader ePub

Purpose
Previous western studies have found Caucasians with skin cancer, either melanoma or nonmelanoma skin cancer (NMSC), have an elevated risk of second primary cancer. Our objective was to assess the risk of second primary cancer in Taiwanese with NMSC.
Materials and Methods
By using data from Taiwan’s National Health Insurance Research Database, we conducted a population-based cohort study to assess the risk of incident second primary cancer in Taiwanese affected by NMSC.
Results
We identified 505 subjects with NMSC and 2,020 matched controls. After adjustment for potential confounders including age, sex, urbanization, and Charlson Comorbidity Index, people who had NMSC had a 1.43-fold (95% confidence interval [CI], 1.05 to 1.96) risk for the development of second primary cancer as comparedwith control group. Menwith NMSC had a 2.99-fold (95% CI, 1.00 to 9.10) risk for second primary cancer involving the lip, oral cavity, and pharynx and a 3.51-fold (95% CI, 1.21 to 10.17) risk for second primary cancer involving the genitourinary organs when compared to the control group. By contrast, women with NMSC did not have an increased risk of second primary cancer.
Conclusion
This study revealed Asians with NMSC have an increased risk of second primary cancer. Our findings can be a useful reference for health care for people diagnosed with NMSC.

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Epidemiological and genetic insights into the co-occurrence of cutaneous melanoma and hematologic malignancies: A meta-analytic review
Ashmitha Kumar, Arunan Jeyakumar, Alfred K. Lam, Vinod Gopalan
Leukemia Research.2024; 147: 107610. CrossRef
Non‐melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population‐based cohort study
S.J. Yun, J.M. Bae, H. Kim, B.C. Park, J.S. Kim, S.H. Seo, H.H. Ahn, D.Y. Lee, Y.C. Kim, H.J. Park, K.Y. Chung
Journal of the European Academy of Dermatology and Venereology.2020; 34(4): 746. CrossRef

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2 Crossref

Clinical Outcomes of Proton Beam Therapy for Choroidal Melanoma at a Single Institute in Korea: Tae Wan Kim, Euncheol Choi, Jeonghoon Park, Dong-ho Shin, Su Kyung Jung, Susie Seok, Kwan Ho Cho, Joo-Young Kim, Dae Yong Kim, Tae Hyun Kim, Yang Kwon Suh, Yeon Joo Kim, Sung Ho Moon; Cancer Res Treat. 2018;50(2):335-344. Published online April 19, 2017; DOI: https://doi.org/10.4143/crt.2017.070

Abstract PDF PubReader ePub

Purpose
This study retrospectively evaluated the clinical outcomes and complications of proton beam therapy (PBT) in a single institution in Korea and quantitatively analyzed the change in tumor volume after PBT using magnetic resonance imaging (MRI).
Materials and Methods
Twenty-four treatment-naïve patients who underwent PBT for choroidal melanoma between 2009 and 2015 were reviewed. Dose fractionation was 60-70 cobalt gray equivalents over 5 fractions. Orbital MRIs were taken at baseline and 3, 6, and 12 months after PBT and annually thereafter. The tumor volume was reconstructed and evaluated by stacking the tumor boundary in each thin-sliced axial T1-weighted image using MIM software.
Results
The median follow-up duration was 36.5 months (range, 9 to 82 months). One patient had suspicious local progression and two patients had distant metastasis. The 3-year local progression-free survival, distant metastasis-free survival, and overall survival rates were 95.8%, 95.8%, and 100%,respectively. Five Common Terminology Criteria for Adverse Event ver. 4.03 grade 3-4 toxicities were observed in four patients (16.7%), including one with neovascular glaucoma. The mean tumor volume at the baseline MRI was 0.565±0.084 mL (range, 0.074 to 1.610 mL), and the ratios of the mean volume at 3, 6, and 12 months to that at baseline were 81.8%, 67.3%, and 60.4%, respectively.
Conclusion
The local controlrate and complication profile after PBT in patientswith choroidal melanoma in Korea were comparable with those reported in a previous PBT series. The change in tumor volume after PBT exhibited a gradual regression pattern on MRI.

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Efficacy and safety of proton radiotherapy in treating choroidal melanoma: a systematic review and meta-analysis
Yuxin Miao, Tingwei Zheng, Qiuning Zhang, Meixuan Li, Qihang Lei, Qin Liu, Hongtao Luo, Huiling Bai
Radiation Oncology.2025;[Epub] CrossRef
Monte Carlo simulation of polymer phantoms in proton therapy for eye tumor treatment
Engin Aşlar, Fatih Ekinci
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Opportunities and challenges of upright patient positioning in radiotherapy
Lennart Volz, James Korte, Maria Chiara Martire, Ye Zhang, Nicholas Hardcastle, Marco Durante, Tomas Kron, Christian Graeff
Physics in Medicine & Biology.2024; 69(18): 18TR02. CrossRef
Magnetic Resonance Imaging in the Clinical Care for Uveal Melanoma Patients—A Systematic Review from an Ophthalmic Perspective
Myriam G. Jaarsma-Coes, Lisa Klaassen, Marina Marinkovic, Gregorius P. M. Luyten, T. H. Khanh Vu, Teresa A. Ferreira, Jan-Willem M. Beenakker
Cancers.2023; 15(11): 2995. CrossRef
When Is the Optimum Radiological Response to Proton Beam Therapy in Uveal Melanoma?
Matthew Gillam, Glenn Ace Fenech, Oliver Chadwick, Jonathan Nairn, Vikas Chadha, Julie Connolly, Oliver Cram, Wilma Kincaid, Paul Cauchi
Ocular Oncology and Pathology.2023; 9(5-6): 130. CrossRef
Optimization of proton therapy eye-treatment systems toward improved clinical performances
Eustache Gnacadja, Cédric Hernalsteens, Stewart Boogert, Quentin Flandroy, Carolina Fuentes, Laurence J. Nevay, Nicolas Pauly, Eliott Ramoisiaux, William Shields, Robin Tesse, Raphael Van Roermund, Marion Vanwelde
Physical Review Research.2022;[Epub] CrossRef
Who Will Benefit from Charged-Particle Therapy?
Kyung Su Kim, Hong-Gyun Wu
Cancer Research and Treatment.2021; 53(3): 621. CrossRef
Uveal Melanoma: A Review of the Literature and Personal Experiences
Yong Joon Kim, Christopher Seungkyu Lee, Sung Chul Lee
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Carbon Fiducial Markers for Tumor Localization in Stereotactic Irradiation of Uveal Melanoma
Timothy T. Xu, Jose S. Pulido, Ian F. Parney, Cristiane M. Ida, Lauren A. Dalvin, Timothy W. Olsen
Ocular Oncology and Pathology.2021; 7(5): 368. CrossRef
Uveal Melanoma in Asians: A Review
Pradeep Manchegowda, Arun D. Singh, Carol Shields, Swathi Kaliki, Parag Shah, Lingam Gopal, Pukhraj Rishi
Ocular Oncology and Pathology.2021; 7(3): 159. CrossRef
Preliminary Dosimetric Study of Proton Minibeam Radiation Therapy for the Treatment of Choroidal Melanoma
Myeongsoo Kim, Sang Soo Kim, Haksoo Kim, Sung Ho Moon, Young Kyung Lim, Ui-Jung Hwang, Sang Hyoun Choi
Journal of the Korean Physical Society.2020; 77(5): 447. CrossRef
Visual outcomes of proton beam therapy for choroidal melanoma at a single institute in the Republic of Korea
Su-Kyung Jung, Young-Hoon Park, Dong-ho Shin, Hak-Soo Kim, Jong-Hwi Jung, Tae-Hyun Kim, Sung Ho Moon, Vikas Khetan
PLOS ONE.2020; 15(12): e0242966. CrossRef

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Ruthenium-106 Brachytherapy with or without Additional Local Therapy Shows Favorable Outcome for Variable-Sized Choroidal Melanomas in Korean Patients: Yeona Cho, Jee Suk Chang, Jin Sook Yoon, Sung Chul Lee, Yong Bae Kim, Joo Ho Kim, Ki Chang Keum; Cancer Res Treat. 2018;50(1):138-147. Published online March 24, 2017; DOI: https://doi.org/10.4143/crt.2016.391

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to report clinical outcomes of ruthenium-106 (¹⁰⁶Ru) brachytherapy with or without additional local therapy for choroidal melanomas in Korean patients.
Materials and Methods
A total of 88 patients diagnosed with choroidal melanomas were treated with ¹⁰⁶Ru brachytherapy between 2006 and 2012. Patients were divided into two groups according to their tumor height: a large group (≥ 6 mm, n=50) and a small group (< 6 mm, n=38). Most patients in the large group received combined therapy with local excision and/or transpupillary thermotherapy. In general, 85-95 Gy was administered to the apex of the tumor, while 100 Gy was administered to the point 2-6 mm from the outer surface of the sclera for patients undergoing combined therapy.
Results
The median follow-up duration was 30 months. The 3-year local control rate was significantly higher in the small group than in the large group (94% vs. 70%, p=0.047). The free from distant metastasis (FFDM) rate and the overall survival (OS) rate were also higher in patients in the small group (3-year FFDM, 97% vs. 76%; p=0.031 and 3-year OS, 97% vs. 72%; p=0.036). A total of 13 patients underwent enucleation. The eye-preservation rate was also higher in the small group (3-year eye-preservation rate, 94% vs. 70%; p=0.050), and tumor height was a significant prognostic factor for eye-preservation.
Conclusion
¹⁰⁶Ru brachytherapy showed favorable outcomes in small choroidal melanomas in Korean patients. Although additional local treatment could improve eye-preservation rate for large tumors, other strategies should be considered for disease control.

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Incidence, risk factors and outcomes of cataract surgery after plaque brachytherapy for posterior uveal melanoma
Viktor T. Gill, Gustav Stålhammar
Heliyon.2024; 10(1): e23447. CrossRef
Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma
Gustav Stålhammar
International Journal of Radiation Oncology*Biology*Physics.2023; 117(5): 1125. CrossRef
The Role of Ruthenium Compounds in Neurologic Diseases: A Minireview
Fátima Virgínia Gama Justi, Gabriella Araújo Matos, Juan de Sá Roriz Caminha, Cássia Rodrigues Roque, Edinilton Muniz Carvalho, Márcio Wilker Soares Campelo, Ludmila Belayev, Luiz Gonzaga de França Lopes, Reinaldo Barreto Oriá
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Long-Term Outcomes in Uveal Melanoma After Ruthenium-106 Brachytherapy
Gilda Cennamo, Daniela Montorio, Luca D’ Andrea, Antonio Farella, Elide Matano, Mario Giuliano, Raffaele Liuzzi, Maria Angelica Breve, Sabino De Placido, Giovanni Cennamo
Frontiers in Oncology.2022;[Epub] CrossRef
Uveal Melanoma: A Review of the Literature and Personal Experiences
Yong Joon Kim, Christopher Seungkyu Lee, Sung Chul Lee
Journal of Retina.2021; 6(2): 65. CrossRef
Prognostic Factors and Decision Tree for Long-Term Survival in Metastatic Uveal Melanoma
Daniel Lorenzo, María Ochoa, Josep Maria Piulats, Cristina Gutiérrez, Luis Arias, Jaume Català, María Grau, Judith Peñafiel, Estefanía Cobos, Pere Garcia-Bru, Marcos Javier Rubio, Noel Padrón-Pérez, Bruno Dias, Joan Pera, Josep Maria Caminal
Cancer Research and Treatment.2018; 50(4): 1130. CrossRef

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Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF: Jae-Hyeon Kim, Jun-Ho Ahn, Michael Lee; Cancer Res Treat. 2017;49(4):947-959. Published online January 3, 2017; DOI: https://doi.org/10.4143/crt.2016.280

Abstract PDF Supplementary Material PubReader ePub

Purpose
Intrinsic and acquired resistance limit the therapeutic benefits of inhibitors of oncogenic BRAF in melanoma. To identify microRNAs (miRNAs) associated with resistance to a BRAF inhibitor, we compared miRNA expression levels in three cell lines with different BRAF inhibitor sensitivity.
Materials and Methods
miRNA microarray analysis was conducted to compare miRNA expression levels. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to confirm the expression of differentially expressed miRNAs. The cellular effects of miR-1246 were further examined by MTT assay, immunoblotting analysis, cell cycle analysis, flow cytometric assay of apoptosis, and autophagy assay.
Results
The miRNA microarray analysis and qRT-PCR identified five miRNAs (miR-3617, miR-92a-1, miR-1246, miR-193b-3p, and miR-17-3p) with expression that was consistently altered in two BRAF inhibitor-resistant cell lines. Among the five miRNAs, a miR-1246 mimic significantly reduced the antiproliferative effects of the BRAF inhibitor PLX4720 in BRAF inhibitor–resistant A375P (A375P/Mdr) cells, suggesting that miR-1246 upregulation confers acquired resistance to BRAF inhibition. In particular, apoptosis was identified as a major type of cell death in miR-1246–transfected cells; however, necrosis predominated in mimic-control-transfected cells, indicating that the resistance to PLX4720 in miR-1246 mimic-transfected cells is predominantly due to a reduction in necrosis. Furthermore, we found that miR-1246 promoted G2/M arrest through autophagy as a way to escape cell death by necrosis and apoptosis in response to PLX4720. The promotion of BRAF inhibitor resistance by miR-1246 was associated with lowered levels of p-ERK.
Conclusion
These results suggest that miR-1246 may be a potential therapeutic target in melanoma with acquired resistance to BRAF inhibitors.

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Ipilimumab Real-World Efficacy and Safety in Korean Melanoma Patients from the Korean Named-Patient Program Cohort: Minkyu Jung, Jeeyun Lee, Tae Min Kim, Dae Ho Lee, Jin Hyung Kang, Sung Young Oh, Soo Jung Lee, Sang Joon Shin; Cancer Res Treat. 2017;49(1):44-53. Published online April 27, 2016; DOI: https://doi.org/10.4143/crt.2016.024

Abstract PDF PubReader ePub

Purpose
Ipilimumab improves survival in advanced melanoma patients. However, the efficacy and safety of ipilimumab has not been evaluated in Asian melanoma patients with a high frequency of mucosal and acral melanoma subtypes.
Materials and Methods
Advanced melanoma patients treated with 3 mg/kg ipilimumab in a Korean multicenter named-patient program (NPP) were evaluated between September 2014 and July 2015. Baseline characteristics and blood parameters including neutrophil to lymphocyte ratio (NLR) were assessed, and outcome and adverse events were evaluated according to subtypes.
Results
A total of 104 advanced melanoma patients were treated. The primary sites were acral (31.7%), mucosal (26%), cutaneous (26%), uveal (9.6%), and unknown (6.7%). Sixty-eight patients (65.4%) experienced adverse events, and the most common toxicity was skin rash (22.1%), 10 patients (9.6%) experienced adverse events of grade 3 or higher. The median progression-free survival (PFS) was 2.73 months (95% confidence interval, 2.67 to 2.85), and there was no difference in PFS according to subtypes. Poor performance status, liver metastasis, and NLR (≥5) were independent poor prognostic factors by multivariate analysis.
Conclusion
In the Korean NPP cohort, ipilimumab showed similar efficacy and tolerability compared to Western patients, regardless of subtypes. All subtypes should benefit from ipilimumab with consideration of performance status, liver metastasis, and NLR.

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Jialin Su, Yuning Li, Shuhua Tan, Tianli Cheng, Yongzhong Luo, Lemeng Zhang
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Baseline neutrophil-to- ratio combined with the change during treatment provides risk stratification for metastatic malignant melanoma patients treated with PD-1 inhibitors in a Chinese population
Chen Wang, Shengyan Liu, Xin Li, Kang Cui, Weijie Zhang, Yabing Du
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Náthali Felícia Mineiro dos Santos Garrett, Ana Cristina Carvalho da Costa, Elaine Barros Ferreira, Giovanni Damiani, Paula Elaine Diniz dos Reis, Christiane Inocêncio Vasques, Gayle E. Woloschak
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Perspectives: Neutrophil-to-lymphocyte Ratio as a Potential Biomarker in Immune Checkpoint Inhibitor for Non–Small-Cell Lung Cancer
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Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Outcome of Immune Checkpoint Inhibitors
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Ernesto Rossi, Giovanni Schinzari, Ilaria Grazia Zizzari, Brigida Anna Maiorano, Monica Maria Pagliara, Maria Grazia Sammarco, Vincenzo Fiorentino, Gianluigi Petrone, Alessandra Cassano, Guido Rindi, Emilio Bria, Maria Antonietta Blasi, Marianna Nuti, Gia
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Uveal Melanoma Metastatic to the Liver: Treatment Trends and Outcomes
Lucy T. Xu, Pauline F. Funchain, James F. Bena, Manshi Li, Ahmad Tarhini, Eren Berber, Arun D. Singh
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Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: a meta-analysis
Tao Jiang, Meng Qiao, Chao Zhao, Xuefei Li, Guanghui Gao, Chunxia Su, Shengxiang Ren, Caicun Zhou
Cancer Immunology, Immunotherapy.2018; 67(5): 713. CrossRef
Prognostic value of neutrophil-to-lymphocyte ratio in melanoma
Yingguo Ding, Shan Zhang, Jianjun Qiao
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Older melanoma patients aged 75 and above retain responsiveness to anti-PD1 therapy: results of a retrospective single-institution cohort study
Tony Ibrahim, Christine Mateus, Maria Baz, Caroline Robert
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Pretreatment hematological markers predict clinical outcome in cancer patients receiving immune checkpoint inhibitors: A meta‐analysis
Qiaoyun Tan, Shuxia Liu, Caixia Liang, Xiaohong Han, Yuankai Shi
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Cost Estimate of Immune-Related Adverse Reactions Associated with Innovative Treatments of Metastatic Melanoma
Francesco S. Mennini, Chiara Bini, Andrea Marcellusi, Michele Del Vecchio
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A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a predictor of poor progression-free survival in patients with metastatic melanoma
Antoine Finon, Julia Zaragoza, Hervé Maillard, Nathalie Beneton, Guido Bens, Mahtab Samimi, Agnès Caille, Laurent Machet
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Markus V. Heppt, Theresa Steeb, Justin Gabriel Schlager, Stefanie Rosumeck, Corinna Dressler, Thomas Ruzicka, Alexander Nast, Carola Berking
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Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A Systematic Review
Charissa A. C. Jessurun, Julien A. M. Vos, Jacqueline Limpens, Rosalie M. Luiten
Frontiers in Oncology.2017;[Epub] CrossRef

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Preliminary Suggestion about Staging of Anorectal Malignant Melanoma May Be Used to Predict Prognosis: Won Young Chae, Jong Lyul Lee, Dong-Hyung Cho, Chang Sik Yu, Jin Roh, Jin Cheon Kim; Cancer Res Treat. 2016;48(1):240-249. Published online March 6, 2015; DOI: https://doi.org/10.4143/crt.2014.305

Abstract PDF PubReader ePub

Purpose
Anorectal malignant melanomas (AMM) are rare and have poor survival. The study aims to evaluate the clinicopathologic characteristics and outcomes of patients with AMM, and to devise a staging system predictive of survival outcome.
Materials and Methods
This was a retrospective study of 28 patients diagnosed with, and treated for AMM. Patients classified by clinical staging of mucosal melanoma (MM) were reclassified via rectal and anal TNM staging. Survival outcomes were compared among patients grouped by the three different staging systems.
Results
The three staging systems were equated with similar figures for 5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients diagnosed with stage I disease. Patients (n=19) diagnosed with MM stage II disease were reclassified by rectal TNM staging into three subgroups: IIIA, IIIB, and IIIC. For these patients, both 5-year OS and 5-year DFS differed significantly between the subgroups IIIA and IIIC (OS: IIIA vs. IIIC, 66.7% vs. 0%, p=0.002; DFS: IIIA vs. IIIC, 51.4% vs. 0%, p < 0.001).
Conclusion
The accuracy of prognosis in patients diagnosed with AMM and lymph node metastasis has improved by using rectal TNM staging, which includes information regarding the number of lymph node metastases.

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Survival and Prognosis for Patients with Rectal Melanomas in the United States: A SEER-Based Study
Fan Zhang, Boqi Xu, Yao Peng, Runda Wu, Shan Tong, Zhongqi Mao
Journal of Investigative Surgery.2024;[Epub] CrossRef
Incidence and survival of patients with primary gastrointestinal melanoma: a population-based study
Yu Du, Xiaona Chang, Xiangxiang Li, Shugang Xing
International Journal of Colorectal Disease.2023;[Epub] CrossRef
Melanoma anorrectal primario: reporte de un caso y revisión de una neoplasia infrecuente
Hernando Marulanda Fernández, Felipe Vera-Polanía, Juan Antonio Trejos Naranjo, Julian Ernesto Parga Bermudez, William Otero Regino
Revista colombiana de Gastroenterología.2023; 38(4): 504. CrossRef
A New Anorectal Melanoma Cell Line Derived from a Primary Human Rectal Tumor
Seiichi Shinji, Yuuki Shichi, Takeshi Yamada, Goro Takahashi, Ryo Ohta, Hiromichi Sonoda, Akihisa Matsuda, Kazuhide Yonaga, Takuma Iwai, Kohki Takeda, Koji Ueda, Sho Kuriyama, Toshimitsu Miyasaka, Yoshibumi Ueda, Norihiko Sasaki, Kimimasa Takahashi, Ryuji
Journal of Nippon Medical School.2022; 89(4): 368. CrossRef
Difficulties in diagnosing anorectal melanoma: A case report and review of the literature
Raluca Cristina Apostu, Elena Stefanescu, Radu Razvan Scurtu, Gabriel Kacso, Radu Drasovean
World Journal of Clinical Cases.2021; 9(36): 11369. CrossRef
Outcomes of Surgical Treatment for Patients with Anorectal Malignant Melanoma; Results of Nine Cases in a Single Institution
Tomoyuki Nagaoka, Toshiya Nagasaki, Takashi Akiyoshi, Toshiki Mukai, Tomohiro Yamaguchi, Eiji Shinozaki, Yosuke Fukunaga
Journal of the Anus, Rectum and Colon.2021; 5(2): 192. CrossRef
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Hari Menon, Roshal R Patel, Taylor R Cushman, Arya Amini, Steven N Seyedin, Anngela C Adams, Chi Lin, Vivek Verma
Future Oncology.2020; 16(8): 329. CrossRef
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Mireia Merichal Resina, Carlos Cerdan Santacruz, Enrique Sierra Grañón, Jordi Antoni Tarragona Foradada, Jorge Juan Olsina Kissler
Cirugía Española.2020; 98(8): 491. CrossRef
Anal Melanoma, a Radically Different Pathology to the Cutaneous Melanoma, With an Infaustic Forecast
Mireia Merichal Resina, Carlos Cerdan Santacruz, Enrique Sierra Grañón, Jordi Antoni Tarragona Foradada, Jorge Juan Olsina Kissler
Cirugía Española (English Edition).2020; 98(8): 491. CrossRef
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Min Ren, Yawen Lu, Jiaojie Lv, Xuxia Shen, Jincheng Kong, Bo Dai, Yunyi Kong
Human Pathology.2018; 79: 77. CrossRef

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Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine: Choong-kun Lee, Minkyu Jung, Hye Jin Choi, Hye Ryun Kim, Hyo Song Kim, Mi Ryung Roh, Joong Bae Ahn, Hyun Cheol Chung, Su Jin Heo, Sun Young Rha, Sang Joon Shin; Cancer Res Treat. 2015;47(4):781-789. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.261

Abstract PDF PubReader ePub

Purpose
There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. Materials and Methods We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR).
Results
Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Conclusion Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

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Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals
Courtney R. Croley, Joshua Pumarol, Blake E. Delgadillo, Andrew C. Cook, Faith Day, Tea Kaceli, Caroline C. Ward, Imran Husain, Ali Husain, Sabyasachi Banerjee, Anupam Bishayee
Pharmacology & Therapeutics.2023; 248: 108479. CrossRef
A Phase 1 study of ADI‐PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1‐negative metastatic uveal melanoma
Pui Ying Chan, Melissa M. Phillips, Stephen Ellis, Amanda Johnston, Xiaoxing Feng, Amit Arora, Gordon Hay, Victoria M. L. Cohen, Mandeep S. Sagoo, John S. Bomalaski, Michael T. Sheaff, Peter W. Szlosarek
Pigment Cell & Melanoma Research.2022; 35(4): 461. CrossRef
iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma
Yueping Ren, Congcong Yan, Lili Wu, Jingting Zhao, Mingwei Chen, Meng Zhou, Xiaoyan Wang, Tonghua Liu, Quanyong Yi, Jie Sun
npj Systems Biology and Applications.2022;[Epub] CrossRef
Systemic and Liver-Directed Therapies in Metastatic Uveal Melanoma: State-of-the-Art and Novel Perspectives
Francesca Comito, Paola Valeria Marchese, Angela Dalia Ricci, Nastassja Tober, Chiara Peterle, Francesca Sperandi, Barbara Melotti
Future Oncology.2021; 17(33): 4583. CrossRef
New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review
Mario Damiano Toro, Lucia Gozzo, Luciano Tracia, Marco Cicciù, Filippo Drago, Claudio Bucolo, Teresio Avitabile, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Yacoub A. Yousef, Rashed Nazzal, Giovanni Luca Romano
Biomedicines.2021; 9(10): 1311. CrossRef
Interferon-α versus interleukin-2 in Chinese patients with malignant melanoma
Shenglong Li, Xixi Wu, Peng Chen, Yi Pei, Ke Zheng, Wei Wang, Enduo Qiu, Xiaojing Zhang
Anti-Cancer Drugs.2019; 30(4): 402. CrossRef
Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways
Bo Shen, Wenjing Mao, Jin‑Chul Ahn, Phil‑Sang Chung, Peijie He
Molecular Medicine Reports.2018;[Epub] CrossRef
Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment
Mohamed Hassan
World Journal of Experimental Medicine.2015; 5(4): 206. CrossRef

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8 Crossref

Construction of MAGE - 3 Expressing Plasmid for Development of DNA Vaccine Encoding MAGE - 3 Cancer Antigen: Jong Wook Park, Mi Hyun Lee, Soo Jung Yoon, Won Ki Baek, Seong Il Suh, Min Ho Suh, Kang Dae Lee, Tae Hyun Yu; J Korean Cancer Assoc. 2000;32(1):191-199.

Abstract PDF: PURPOSE
The spectrum of melanoma antigen gene (MAGE)-expressing tumor is very wide and the gene of MAGE express antigens that are targets for specific recognition by cytotoxic T lymphocytes derived from tumor-bearing patients. All of these characteristics represent MAGE as tumor vaccine can be useful for cancer prevention or treatment. Here, we detected MAGE-3 gene expression in cancer cell lines and evaluated recombinant MAGE-3 protein producibility of MAGE plasmid to develope MAGE DNA vaccine.
MATERIALS AND METHODS
MAGE-3 gene expression of cancer cell lines was evaluated by reverse transcription-polymerase chanin reaction (RT-PCR). Two kinds of MAGE-3 expressing plasmids were constructed and their MAGE-3 protein producibility was evaluated by immunohistochemistry and immunoblotting using monoclonal anti-MAGE-3 antibody.
RESULTS
Among 13 cell lines, SNU484, AMC-HN-3, AMC-HN-4, AMC-HN-7, HeLa, NCI H1703 and HT29 expressed MAGE-3 mRNA. In order to make MAGE plasmid, cDNA that showed 100% DNA homology with MAGE-3 gene was cloned into pcDNA 3 plasmid and pSecTag plasmid. Intracytoplasmic and secretory recombinant MAGE-3 was produced by MAGE-3 containing pcDNA 3 plasmid and pSecTag plasmid, respectively.
CONCLUSION
In this study, we showed high expression frequency of MAGE-3 in cancer cell line, and established two kinds of plasmid that produce recombinant MAGE-3 in cell lines. We expect these plasmids will be used in cancer treatment or MAGE-3 function study in future.

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Effects of Lipid Soluble Components of Korean Red Ginseng on Proliferation and Cell Cycle Regulation Factors in Human Melanoma Cell Lines: Hye Jeong Kim, Joo Young Roh, Jong Ouck Choi, Sul Hee Park, In Sun Kim, Jeongwon Sohn, Chong Kun Ryu; J Korean Cancer Assoc. 1997;29(6):965-976.

Abstract PDF: PURPOSE
Growth inhibitory effects of lipid soluble components of the Korean red ginseng and the antineoplastic mechanism against human melanoma cell lines were investigated. To examine molecular mechanism of growth inhibitory effects of GX-PE, we analyzed the effect of GX-PE on cell cycle progression and expression of cell cycle regulatory factors such as retinoblastoma gene product (Rb), p27 (Kip1), p21 (WAF1), cdk2, cdk4 and cyclin D1 which are known to regulate cell cycle progression.
MATERIALS AND METHODS
Petroleum ether extract of the Korean red ginseng (GX-PE) was added to cultures of three human melanoma cell lines, SK-MEL-1, SK-MEL-2, and SK-MEL-5. Proliferation was measured by 3H-thymidine incorporation assay. Cell cycle and expression of cell cycle regulatory factors were analyzed by flow cytometry and Western blotting, respectively.
RESULTS
Growth of melanoma cells was inhibited by GX-PE in proportion to the concentration. GX-PE significantly inhibited cell cycle progression at G1 phase. GX-PE increased expression of negative cell cycle regulators, i.e., p27 (Kip1) in SK-MEL-2 and p21 (WAF1) and Rb in SK-MEL-1.
CONCLUSION
These results suggest that GX-PE inhibits proliferation of melanoma cells at a G1-S transition point of the cell cycle. The effect of GX-PE is most likely due to induction of negative cell cycle regulatory factors.

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A Case of the Pancreatic Pseudocyst due to Metastatic Malignant Melanoma: Bong Soo Chung, Jin Cheon Kim, Chang Sik Yu, Han Il Lee, Chang Nam Kim, Duck Jong Han, Gyeong Hoon Kang; J Korean Cancer Assoc. 1997;29(3):528-533.

Abstract PDF: Malignant melanoma constitutes approximately 1% of all cancer (1,2). As the biologic behavior seems to be unpredictable, variation in the metastatic spread are not infrequently met. The common sites of metastasis are lymph nodes, lung, liver, brain, bone, heart, adrenal glands, and gastrointestinal tract in descending order (2). However multiple organ involvement is a common feature at the advanced stage. A 38-year-old male had developed pancreatic pseudocyst during the course of malignant melanoma at right sole. It was proven to be from matastatic malignant melanoma.

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Malignant Melanoma of the Cecum , Unknown Origin: Jin n Yeo, Nam Il Kim, Jung Soo Kim, Hae Myung Jeon, Seung Jin Yoo, Jae Sung Kim, Eun Jung Lee; J Korean Cancer Assoc. 1995;27(6):1077-1083.

Abstract PDF: Malignant melanoma is a relatively rare disease in Korea. But its incidence is increasing. The potentiality of malignant melanoma to metastasize to all parts of the body is well known. An often-unsuspected complication is metastasis to the gastrointestinal tract, which leads to bowel obstruction or intussusception. The most common symptoms in patients with gastrointestinal metastasis are vomiting, abdominal pain and abdominal distension. We experienced a case of malignant cecal melanoma presenting as adult intussusception. The primary origin was not found. We managed by right hemicolectomy with DTIC chemotherapy.

2,513 View
14 Download

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