Science.gov

Sample records for ajcc melanoma staging

  1. Comparative study between two different staging systems (AJCC TNM VS BALLANTYNE’S) for mucosal melanomas of the Head & Neck

    PubMed Central

    Aguilar-Romero, Madeleine; Villavicencio-Valencia, Verónica; Zepeda-Castilla, Ernesto; Vidrio-Morgado, Horacio; Peteuil, Nathalie; Mosqueda-Taylor, Adalberto

    2016-01-01

    Background Mucosal melanoma (MM) of head and neck (H &N) is a rare entity with a quite poor prognosis. Ballantyne’s staging system has been commonly used since 1970. In the 7th edition of the AJCC Staging Manual a new chapter for the staging of TNM Classification system for mucosal melanoma (MM) of the head and neck (H &N) has been introduced to reflect the particularly aggressive biological behavior of this neoplasm. The aim of this study was to analyze and compare among Ballantyne’s staging system vs TNM H &N in terms of overall survival (OS) and disease-free survival (DFS) in a consecutive population of patients with MM in a cancer centre. Material and Methods Descriptive analysis of demographic, clinical and pathological variables of MM of the Head & Neck were performed. We compared the survival curves for both systems according to the Kaplan-Meier method using the Log-rank test. Results An up-staging migration effect from Ballantyne’s localized disease to moderately and very advanced disease according to AJCC staging system. The 5-year DFS and OS for Ballantyne’s Localized Disease and AJCC Stage III were 31% and 36% vs. 47% and 50%, respectively. For locoregional disease the 5-year DFS / OS were 5% / 10% for Bal-lantyne’s system vs. 13.8% / 17.8% and 0 / 0% for AJCC Stages IVA and IVB, respectively. Conclusions In this series, the TNM staging system for MM of the H &N predicted better the prognosis of the disease when comparing with Ballantyne’s system. Key words:Head and neck, mucosal melanoma, AJCC TNM, Ballantynes´s staging system. PMID:27031071

  2. Vitronectin and dermcidin serum levels predict the metastatic progression of AJCC I-II early-stage melanoma.

    PubMed

    Ortega-Martínez, Idoia; Gardeazabal, Jesús; Erramuzpe, Asier; Sanchez-Diez, Ana; Cortés, Jesús; García-Vázquez, María D; Pérez-Yarza, Gorka; Izu, Rosa; Luís Díaz-Ramón, Jose; de la Fuente, Ildefonso M; Asumendi, Aintzane; Boyano, María D

    2016-10-01

    Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I-II patients may still develop metastasis during follow-up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow-up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease-free for more than 10 years after surgery. Five proteins were selected for validation as prognostic factors in 348 melanoma patients and 100 controls by ELISA: serum amyloid A and clusterin; immune system proteins; the cell adhesion molecules plakoglobin and vitronectin and the antimicrobial protein dermcidin. Compared to healthy controls, melanoma patients have high serum levels of these proteins at the moment of melanoma diagnosis, although the specific values were not related to the histopathological stage of the tumors. However, an analysis based on classification together with multivariate statistics showed that tumor stage, vitronectin and dermcidin levels were associated with the metastatic progression of patients with early-stage melanoma. Although melanoma patients have increased serum dermcidin levels, the REPTree classifier showed that levels of dermcidin <2.98 μg/ml predict metastasis in AJCC stage II patients. These data suggest that vitronectin and dermcidin are potent biomarkers of prognosis, which may help to improve the personalized medical care of melanoma patients and their survival. PMID:27216146

  3. Epacadostat and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-10-31

    Mucosal Melanoma; Recurrent Melanoma; Recurrent Uveal Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  4. TNM staging of pancreatic neuroendocrine tumors: an observational analysis and comparison by both AJCC and ENETS systems from 1 single institution.

    PubMed

    Yang, Min; Zeng, Lin; Zhang, Yi; Wang, Wei-guo; Wang, Li; Ke, Neng-wen; Liu, Xu-bao; Tian, Bo-le

    2015-03-01

    We aimed to analyze the clinical characteristics and compare the surgical outcome of pancreatic neuroendocrine tumors (p-NETs) using the 2 tumor-node-metastasis (TNM) systems by both the American Joint Committee on Cancer (AJCC) Staging Manual (seventh edition) and the European Neuroendocrine Tumor Society (ENETS). Moreover, we sought to validate the prognostic value of the new AJCC criterion. Data of 145 consecutive patients who were all surgically treated and histologically diagnosed as p-NETs from January 2002 to June 2013 in our single institution were retrospectively collected and analyzed. The 5-year overall survival (OS) rates for AJCC classifications of stages I, II, III, and IV were 79.5%, 63.1%, 15.0%, and NA, respectively, (P < 0.005). As for the ENETS system, the OS rates at 5 years for stages I, II, III, and IV were 75.5%, 72.7%, 29.0%, and NA, respectively, (P < 0.005). Both criteria present no statistically notable difference between stage I and stage II (P > 0.05) but between stage I and stages III and IV (P < 0.05), as well as those between stage II and stages III and IV (P < 0.05). Difference between stage III and IV by ENETS was significant (P = 0.031), whereas that by the AJCC was not (P = 0.144). What's more, the AJCC Staging Manual (seventh edition) was statistically significant in both uni- and multivariate analyses by Cox regression (P < 0.005 and P = 0.025, respectively). Our study indicated that the ENETS TNM staging system might be superior to the AJCC Staging Manual (seventh edition) for the clinical practice of p-NETs. Together with tumor grade and radical resection, the new AJCC system was also validated to be an independent predictor for p-NETs. PMID:25816036

  5. Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

    ClinicalTrials.gov

    2014-05-20

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  6. VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2015-02-02

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage III Melanoma; Stage IV Melanoma

  7. Comparison of the 7th and proposed 8th editions of the AJCC/UICC TNM staging system for non-small cell lung cancer undergoing radical surgery

    PubMed Central

    Jin, Ying; Chen, Ming; Yu, Xinmin

    2016-01-01

    The present study aims to compare the 7th and the proposed 8th edition of the AJCC/UICC TNM staging system for NSCLC in a cohort of patients from a single institution. A total of 408 patients with NSCLC who underwent radical surgery were analyzed retrospectively. Survivals were analyzed using the Kaplan –Meier method and were compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazard model. The Akaike information criterion (AIC) and C-index were applied to compare the two prognostic systems with different numbers of stages. The 7th AJCC T categories, the proposed 8th AJCC T categories, N categories, visceral pleural invasion, and vessel invasion were found to have statistically significant associations with disease-free survival (DFS) on univariate analysis. In the 7th edition staging system as well as in the proposed 8th edition, T categories, N categories, and pleural invasion were independent factors for DFS on multivariate analysis. The AIC value was smaller for the 8th edition compared to the 7th edition staging system. The C-index value was larger for the 8th edition compared to the 7th edition staging system. Based on the data from our single center, the proposed 8th AJCC T classification seems to be superior to the 7th AJCC T classification in terms of DFS for patients with NSCLC underwent radical surgery. PMID:27641932

  8. Comparison of the 7(th) and proposed 8(th) editions of the AJCC/UICC TNM staging system for non-small cell lung cancer undergoing radical surgery.

    PubMed

    Jin, Ying; Chen, Ming; Yu, Xinmin

    2016-01-01

    The present study aims to compare the 7(th) and the proposed 8(th) edition of the AJCC/UICC TNM staging system for NSCLC in a cohort of patients from a single institution. A total of 408 patients with NSCLC who underwent radical surgery were analyzed retrospectively. Survivals were analyzed using the Kaplan -Meier method and were compared using the log-rank test. Multivariate analysis was performed by the Cox proportional hazard model. The Akaike information criterion (AIC) and C-index were applied to compare the two prognostic systems with different numbers of stages. The 7(th) AJCC T categories, the proposed 8(th) AJCC T categories, N categories, visceral pleural invasion, and vessel invasion were found to have statistically significant associations with disease-free survival (DFS) on univariate analysis. In the 7(th) edition staging system as well as in the proposed 8(th) edition, T categories, N categories, and pleural invasion were independent factors for DFS on multivariate analysis. The AIC value was smaller for the 8(th) edition compared to the 7(th) edition staging system. The C-index value was larger for the 8(th) edition compared to the 7(th) edition staging system. Based on the data from our single center, the proposed 8(th) AJCC T classification seems to be superior to the 7(th) AJCC T classification in terms of DFS for patients with NSCLC underwent radical surgery. PMID:27641932

  9. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    ClinicalTrials.gov

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  10. Morphogenesis of early stage melanoma

    NASA Astrophysics Data System (ADS)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

    Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

  11. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

    ClinicalTrials.gov

    2016-05-06

    Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  12. Proper hepatic pedicle clamping during hepatectomy is associated with improved postoperative long-term prognosis in patients with AJCC stage IIIB hepatocellular carcinoma

    PubMed Central

    Guo, Lei; Zhang, Bo; Lin, Zhenhai; Zhang, Jubo; Ye, Qinghai

    2016-01-01

    Intermittent hepatic pedicle clamping (HPC) is often performed during hepatectomy. Whether it affects the long-term prognosis of hepatocellular carcinoma (HCC) patients is still controversial. This study evaluated the impact of HPC in patients with different stages of HCC. The study included 1401 patients who underwent hepatectomy in the primary cohort with 129 AJCC stage IIIB HCC patients; there were 80 AJCC stage IIIB HCC patients in the validation cohort. In each cohort, patients were placed in the long-term HPC (LTHPC) group or the short-term HPC (STHPC) group based on the cut-off time of HPC estimated by the receiver-operating characteristic (ROC) curve. Although HPC did not show significant effects on the prognosis of stage I–IIIA HCC patients in the primary cohort, 1−, 3−, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates of stage IIIB HCC patients who received LTHPC (HPC time > 12 minutes) were significantly higher than those with STHPC (HPC time ≤ 12 minutes or received no HPC), similar in the validation cohort. Multivariate analysis demonstrated HPC time was an independent protective factor for RFS and OS in stage IIIB HCC patients. Herein, we report that proper HPC improved the postoperative prognosis of stage IIIB HCC patients and served as an independent protective factor. PMID:27027437

  13. Melanoma staging: facts and controversies.

    PubMed

    Forschner, Andrea; Eigentler, Thomas Kurt; Pflugfelder, Annette; Leiter, Ulrike; Weide, Benjamin; Held, Laura; Meier, Friedegund; Garbe, Claus

    2010-01-01

    The value of staging examinations remains controversial for the initial staging in melanoma patients at the time of the primary diagnosis and for surveillance. Issues concerning tumor recurrences and progression must be discussed separately for different risk groups. For low-risk patients (stage IA; tumor thickness less than 1 mm), staging examinations like sentinel lymph node biopsy (SLNB), blood tests, or imaging can generally be abandoned. Baseline staging with simple techniques is at the discretion of the physician. In intermediate-risk patients (stages IB and IIA), an initial staging examination involving SLNB and computed tomography (CT) scans is recommended. Further follow-up may be restricted to physical examinations, blood tests of tumor marker protein S100beta, and to lymph node ultrasonography. If findings are suspicious, further imaging procedures may be involved. In high-risk patients (stages IIB to III), an initial staging examination with CT is recommended, and regular follow-up every 6 months with whole body imaging by CT or magnetic resonance imaging seems useful. Physical examinations, blood tests of tumor marker protein S100beta, and lymph node ultrasound imaging should be routine. This intense follow-up may enable surgical treatments with complete removal of all recognizable metastases in about 15% to 25% of patients and improve their prognosis. The risk of recurrence or tumor progression is very high in stage IV patients, and their management is individualized. PMID:20541679

  14. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    ClinicalTrials.gov

    2016-10-26

    Metastatic Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  15. How Does Magnetic Resonance Imaging Influence Staging According to AJCC Staging System for Nasopharyngeal Carcinoma Compared With Computed Tomography?

    SciTech Connect

    Liao Xinbiao; Mao Yanping; Liu Lizhi; Tang Linglong; Sun Ying; Wang Yan; Lin Aihua; Cui Chunyan; Li Li; Ma Jun

    2008-12-01

    Purpose: To analyze the degree and pattern of influence of magnetic resonance imaging (MRI) on staging according to the 6th edition of the American Joint Committee on Cancer staging system compared with computed tomography (CT). Methods and Materials: The MRI and CT scans and medical records of 420 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were analyzed retrospectively. The tumors of all patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system. Results: A significant difference (p <0.05) was found between CT and MRI in demonstrating involvement in the oropharynx (CT, 25.0% vs. MRI, 14.5%), prevertebral muscle (CT, 18.4% vs. MRI, 36.0%), parapharyngeal space (CT, 82.6% vs. MRI, 68.8%), skull base (CT, 31.0% vs. MRI, 52.6%), sphenoid sinus (CT, 13.6% vs. MRI, 16.7%), ethmoid sinus (CT, 7.1% vs. MRI, 3.3%), intracranial area (CT, 4.8% vs. MRI, 16.0%), and retropharyngeal lymph nodes (CT, 52.1% vs. MRI, 69.0%). The incidence of cervical lymph node metastasis and lymph node metastasis at each level was similar according to CT and MRI. MRI resulted in changes in 49.8% of T stage cases, 10.7% of N stage cases, and 38.6% of clinical stage cases. Conclusion: MRI demonstrated early primary tumor involvement more precisely and deep primary tumor infiltration more easily. The use of MRI caused dramatic changes in the results of the T stage and clinical staging and should be preferred to CT in staging NPC. Patients would benefit from changes in treatment strategies resulting from the use of MRI.

  16. Proposal for the 8th Edition of the AJCC/UICC Staging System for Nasopharyngeal Cancer in the Era of Intensity-Modulated Radiotherapy

    PubMed Central

    Pan, Jian Ji; Ng, Wai Tong; Zong, Jing Feng; Chan, Lucy L. K.; O’Sullivan, Brian; Lin, Shao Jun; Sze, Henry C. K.; Chen, Yun Bin; Choi, Horace C.W.; Guo, Qiao Juan; Kan, Wai Kuen; Xiao, You Ping; Wei, Xu; Le, Quynh Thu; Glastonbury, Christine M.; Colevas, A. Dimitrios; Weber, Randal S.; Shah, Jatin P.; Lee, Anne W. M.

    2016-01-01

    BACKGROUND An accurate staging system is crucial for cancer management. Evaluations for continual suitability and improvement are needed as staging and treatment methods evolve. METHODS This was a retrospective study of 1609 patients with nasopharyngeal carcinoma investigated by magnetic resonance imaging, staged with the 7th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system, and irradiated by intensity-modulated radiotherapy at 2 centers in Hong Kong and mainland China. RESULTS Among the patients without other T3/T4 involvement, there were no significant differences in overall survival (OS) between medial pterygoid muscle (MP)±lateral pterygoid muscle (LP), prevertebral muscle, and parapharyngeal space involvement. Patients with extensive soft tissue involvement beyond the aforementioned structures had poor OS similar to that of patients with intracranial extension and/or cranial nerve palsy. Only 2% of the patients had lymph nodes>6cm above the supraclavicular fossa (SCF), and their outcomes resembled the outcomes of those with low extension. Replacing SCF with the lower neck (extension below the caudal border of the cricoid cartilage) did not affect the hazard distinction between different N categories. With the proposed T and N categories, there were no significant differences in outcome between T4N0-2 and T1-4N3 disease. CONCLUSIONS After a review by AJCC/UICC preparatory committees, the changes recommended for the 8th edition include changing MP/LP involvement from T4 to T2, adding prevertebral muscle involvement as T2, replacing SCF with the lower neck and merging this with a maximum nodal diameter>6 cm as N3, and merging T4 and N3 as stage IVA criteria. These changes will lead not only to a better distinction of hazards between adjacent stages/categories but also to optimal balance in clinical practicability and global applicability. PMID:26588425

  17. AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

    ClinicalTrials.gov

    2015-06-01

    Acral Lentiginous Malignant Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Intraocular Melanoma; Iris Melanoma; Lentigo Maligna Malignant Melanoma; Recurrent Melanoma; Stage, Intraocular Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

  18. CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301in Treating Patients With Stage IIB-IV Melanoma

    ClinicalTrials.gov

    2016-06-21

    Carcinoma of Unknown Primary Origin; Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Small Size Posterior Uveal Melanoma; Stage IIB Skin Melanoma; Stage IIB Uveal Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  19. Suggestions for Lymph Node Classification of UICC/AJCC Staging System: A Retrospective Study Based on 1197 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiation Therapy

    PubMed Central

    Guo, Qiaojuan; Pan, Jianji; Zong, Jingfeng; Zheng, Wei; Zhang, Chun; Tang, Linbo; Chen, Bijuan; Cui, Xiaofei; Xiao, Youping; Chen, Yunbin; Lin, Shaojun

    2015-01-01

    Abstract This article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era. A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified. Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%). Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N

  20. High-Dose Recombinant Interferon Alfa-2B, Ipilimumab, or Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery

    ClinicalTrials.gov

    2016-11-03

    Metastatic Non-Cutaneous Melanoma; Non-Cutaneous Melanoma; Recurrent Melanoma of the Skin; Recurrent Non-Cutaneous Melanoma; Stage III Mucosal Melanoma of the Head and Neck; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Stage IVA Mucosal Melanoma of the Head and Neck; Stage IVB Mucosal Melanoma of the Head and Neck; Stage IVC Mucosal Melanoma of the Head and Neck

  1. Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

    PubMed Central

    Thomas, Nancy E.; Busam, Klaus J.; From, Lynn; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Groben, Pamela A.; Hao, Honglin; Orlow, Irene; Reiner, Anne S.; Luo, Li; Paine, Susan; Ollila, David W.; Wilcox, Homer; Begg, Colin B.; Berwick, Marianne

    2013-01-01

    Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions. PMID:24127443

  2. Isolated Limb Perfusion With Melphalan in Treating Patients With Stage IIIB-IV Melanoma or Sarcoma

    ClinicalTrials.gov

    2015-07-22

    Basal Cell Carcinoma of the Skin; Eccrine Carcinoma of the Skin; Recurrent Adult Soft Tissue Sarcoma; Recurrent Melanoma; Recurrent Skin Cancer; Squamous Cell Carcinoma of the Skin; Stage III Adult Soft Tissue Sarcoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Melanoma

  3. Axitinib in Treating Patients With Melanoma That is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-05-31

    Extraocular Extension Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  4. Gene Network Rewiring to Study Melanoma Stage Progression and Elements Essential for Driving Melanoma

    PubMed Central

    Kaushik, Abhinav; Bhatia, Yashuma; Ali, Shakir; Gupta, Dinesh

    2015-01-01

    Metastatic melanoma patients have a poor prognosis, mainly attributable to the underlying heterogeneity in melanoma driver genes and altered gene expression profiles. These characteristics of melanoma also make the development of drugs and identification of novel drug targets for metastatic melanoma a daunting task. Systems biology offers an alternative approach to re-explore the genes or gene sets that display dysregulated behaviour without being differentially expressed. In this study, we have performed systems biology studies to enhance our knowledge about the conserved property of disease genes or gene sets among mutually exclusive datasets representing melanoma progression. We meta-analysed 642 microarray samples to generate melanoma reconstructed networks representing four different stages of melanoma progression to extract genes with altered molecular circuitry wiring as compared to a normal cellular state. Intriguingly, a majority of the melanoma network-rewired genes are not differentially expressed and the disease genes involved in melanoma progression consistently modulate its activity by rewiring network connections. We found that the shortlisted disease genes in the study show strong and abnormal network connectivity, which enhances with the disease progression. Moreover, the deviated network properties of the disease gene sets allow ranking/prioritization of different enriched, dysregulated and conserved pathway terms in metastatic melanoma, in agreement with previous findings. Our analysis also reveals presence of distinct network hubs in different stages of metastasizing tumor for the same set of pathways in the statistically conserved gene sets. The study results are also presented as a freely available database at http://bioinfo.icgeb.res.in/m3db/. The web-based database resource consists of results from the analysis presented here, integrated with cytoscape web and user-friendly tools for visualization, retrieval and further analysis. PMID

  5. Melanoma: diagnosis, staging, and treatment. Consensus group recommendations.

    PubMed

    Berrocal, Alfonso; Cabañas, Luis; Espinosa, Enrique; Fernández-de-Misa, Ricardo; Martín-Algarra, Salvador; Martínez-Cedres, José Carlos; Ríos-Buceta, Luis; Rodríguez-Peralto, José Luis

    2014-09-01

    The incidence of malignant melanoma is increasing worldwide. In Spain, its incidence is increasing faster than any other cancer type, with a 5-year survival rate of about 85%. The impact and characteristics of malignant melanoma in the Spanish population can be ascertained from the national melanoma registry of the Academia Española de Dermatología y Venereología. This review presents consensus group recommendations for the diagnosis, staging and treatment of malignant melanoma in Spain. Incidence and mortality are discussed, as well as evaluation of various prevention and treatment strategies. Prognostic factors, such as BRAF and C-KIT mutations, which are expected to become routine staging procedures over the next few years, are outlined, especially in relation to treatment options. The use of recently approved targeted agents such as ipilimumab, a cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitor, and vemurafenib, a BRAF inhibitor, in metastatic disease are also discussed.

  6. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  7. Association Between NRAS and BRAF Mutational Status and Melanoma-Specific Survival Among Patients With Higher Risk Primary Melanoma

    PubMed Central

    Thomas, Nancy E.; Edmiston, Sharon N.; Alexander, Audrey; Groben, Pamela A.; Parrish, Eloise; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; From, Lynn; Busam, Klaus J.; Hao, Honglin; Orlow, Irene; Kanetsky, Peter A.; Luo, Li; Reiner, Anne S.; Paine, Susan; Frank, Jill S.; Bramson, Jennifer I.; Marrett, Lorraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Cust, Anne E.; Ollila, David W.; Begg, Colin B.; Berwick, Marianne; Conway, Kathleen

    2015-01-01

    Importance NRAS and BRAF mutations in melanoma inform current treatment paradigms but their role in survival from primary melanoma has not been established. Identification of patients at high risk of melanoma-related death based on their primary melanoma characteristics before evidence of recurrence could inform recommendations for patient follow-up and eligibility for adjuvant trials. Objective To determine tumor characteristics and survival from primary melanoma by somatic NRAS and BRAF status. Design, Setting, and Participants A population-based study with median follow-up of 7.6 years for 912 patients with first primary cutaneous melanoma analyzed for NRAS and BRAF mutations diagnosed in the year 2000 from the United States and Australia in the Genes, Environment and Melanoma Study and followed through 2007. Main Outcomes and Measures Tumor characteristics and melanoma-specific survival of primary melanoma by NRAS and BRAF mutational status. Results The melanomas were 13% NRAS+, 30% BRAF+, and 57% with neither NRAS nor BRAF mutation (wildtype). In a multivariable model including clinicopathologic characteristics, NRAS+ melanoma was associated (P<.05) with mitoses, lower tumor infiltrating lymphocyte (TIL) grade, and anatomic site other than scalp/neck and BRAF+ melanoma was associated with younger age, superficial spreading subtype, and mitoses, relative to wildtype melanoma. There was no significant difference in melanoma-specific survival for melanoma harboring mutations in NRAS (HR 1.7, 95% CI, 0.8–3.4) or BRAF (HR, 1.5, 95% CI, 0.8–2.9) compared to wildtype melanoma adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center. However, melanoma-specific survival was significantly poorer for higher risk (T2b or higher stage) tumors with NRAS (HR 2.9; 95% CI 1.1–7.7) or BRAF (HR 3.1; 95% CI 1.2–8.5) mutations but not for lower risk (T2a or lower) tumors (P=.65) adjusted for age, sex, site, AJCC tumor stage, TIL grade, and study center

  8. Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma

    PubMed Central

    Wilson, Joshua B.; Walling, Hobart W.; Scupham, Richard K.; Bean, Andrew K.; Ceilley, Roger I.

    2016-01-01

    Introduction: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. Materials and methods: Charts from the authors’ private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. Results: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4±10.2 years, range 48-87 years) with 68 tumors were treated in the authors’ office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0±0.55mm with a recurrence rate of 5.9 percent. Limitations: The limitations of this study include the retrospective nature of the authors’ review, and data collected from a single, private practice setting. Conclusion: The authors’ findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue. PMID:27386048

  9. Booster Vaccination in Preventing Disease Recurrence in Previously Vaccinated Patients With Melanoma That Has Been Removed By Surgery

    ClinicalTrials.gov

    2015-01-23

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  10. Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

    ClinicalTrials.gov

    2013-03-29

    Recurrent Melanoma; Stage IIB Melanoma (Locally Advanced); Stage IIC Melanoma (Locally Advanced); Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma (Limited, Resectable)

  11. Vaccine Therapy With or Without Sargramostim in Treating Patients Who Have Undergone Surgery for Melanoma

    ClinicalTrials.gov

    2015-04-14

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Extraocular Extension Melanoma; Iris Melanoma; Stage IIB Melanoma; Stage IIC Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma

  12. Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.

    PubMed

    Thomas, Nancy E; Kricker, Anne; Waxweiler, Weston T; Dillon, Patrick M; Busman, Klaus J; From, Lynn; Groben, Pamela A; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Orlow, Irene; Paine, Susan; Ollila, David W; Reiner, Anne S; Luo, Li; Hao, Honglin; Frank, Jill S; Begg, Colin B; Berwick, Marianne

    2014-12-01

    IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex

  13. Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas: A Population-Based Study

    PubMed Central

    Thomas, Nancy E.; Kricker, Anne; Waxweiler, Weston T.; Dillon, Patrick M.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Orlow, Drs. Irene; Paine, Susan; Ollila, David W.; Reiner, Anne S.; Luo, Li; Hao, Honglin; Frank, Jill S.; Begg, Colin B.; Berwick, Marianne

    2014-01-01

    Importance Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathology review, or no adjustment for stage limit interpretation or generalization of results from prior studies. Objective To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study. Design Survival analysis with median follow-up of 7.6 years. Setting The Genes, Environment, and Melanoma study enrolled incident cases of melanoma diagnosed in 1998-2003 from international population-based cancer registries. Participants A total of 2,995 patients with 3,486 invasive primary melanomas centrally scored for histologic pigmentation. Main Outcomes and Measurements Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively. Results Eight percent of melanomas (275 of 3,467) were histopathologically amelanotic. Female sex, nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a co-existing nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally of a higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (P for trend <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than pigmented melanoma [hazard ratio (HR), 2.0; 95% confidence interval (CI), 1.4-3.0; P< .001], adjusted for age, sex anatomic site, and study design variables; but survival did not differ once AJCC tumor stage was also taken into account, (HR, 0.8; 95% CI, 0.5-1.2; P = .36). Conclusions and Relevance At the population level

  14. Update and Review on the Surgical Management of Primary Cutaneous Melanoma.

    PubMed

    Leilabadi, Solmaz Niknam; Chen, Amie; Tsai, Stacy; Soundararajan, Vinaya; Silberman, Howard; Wong, Alex K

    2014-06-10

    The surgical management of malignant melanoma historically called for wide excision of skin and subcutaneous tissue for any given lesion, but has evolved to be rationally-based on pathological staging. Breslow and Clark independently described level and thickness as determinant in prognosis and margin of excision. The American Joint Committee of Cancer (AJCC) in 1988 combined features from each of these histologic classifications, generating a new system, which is continuously updated and improved. The National Comprehensive Cancer Network (NCCN) has also combined several large randomized prospective trials to generate current guidelines for melanoma excision as well. In this article, we reviewed: (1) Breslow and Clark classifications, AJCC and NCCN guidelines, the World Health Organization's 1988 study, and the Intergroup Melanoma Surgical Trial; (2) Experimental use of Mohs surgery for in situ melanoma; and (3) Surgical margins and utility and indications for sentinel lymph node biopsy (SLNB) and lymphadenectomy. Current guidelines for the surgical management of a primary melanoma of the skin is based on Breslow microstaging and call for cutaneous margins of resection of 0.5 cm for MIS, 1.0 cm for melanomas ≤1.0 mm thick, 1-2 cm for melanoma thickness of 1.01-2 mm, 2 cm margins for melanoma thickness of 2.01-4 mm, and 2 cm margins for melanomas >4 mm thick. Although the role of SLNB, CLND, and TLND continue to be studied, current recommendations include SLNB for Stage IB (includes T1b lesions ≤1.0 with the adverse features of ulceration or ≥1 mitoses/mm²) and Stage II melanomas. CLND is recommended when sentinel nodes contain metastatic deposits.

  15. Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye

    ClinicalTrials.gov

    2015-06-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  16. Adjuvant therapy of melanoma.

    PubMed

    Agarwala, S S; Kirkwood, J M

    1998-06-01

    Patients with AJCC Stage IIB and III melanoma have a poor 5-year survival rate which has been the driving force behind attempts to find an effective adjuvant therapy for this stage of disease that would effectively reduce relapse and improve survival. Immunotherapy with bacillus Calmette-Guerin (BCG), Corynebacterium parvum, and levamisole have not been successful in achieving this goal, nor have trials with chemotherapy in the adjuvant setting, including high-dose chemotherapy with autologous bone marrow transplantation. The recent Eastern Cooperative Oncology Group (ECOG) 1684 study showed significant improvement in relapse-free and overall survival with high doses of alpha interferon (IFNalpha) given for 1 year. Lower dosages of IFNalpha have to date been unsuccessful in impacting upon long-term survival. Recent data with vaccines have been encouraging, and the GM2-KLH vaccine is the focus of ongoing intergroup study comparing this treatment with IFNalpha in resected Stage IIB and III melanoma. The various regimens are reviewed in this article. PMID:9588723

  17. The new seventh edition American Joint Committee on Cancer staging of cutaneous non-melanoma skin cancer: a critical review.

    PubMed

    Warner, Christina L; Cockerell, Clay J

    2011-06-01

    The seventh edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual includes a major revision of the staging protocol for cutaneous carcinomas. There are several significant improvements to the Tumor, Nodes, and Metastases (TNM) staging system, including consideration of high-risk factors within the primary T grade, a decrease in the tumor size threshold from 5 cm to 2 cm, improved stratification of patient lymph node status, as well as exclusion of Merkel cell carcinomas from the staging system for squamous cell carcinoma (SCC) and other cutaneous carcinomas. However, some important variables in cutaneous SCC were excluded from consideration. In addition, the AJCC Cancer Staging Manual makes some recommendations that will likely prove difficult to apply in clinical practice, particularly that Clark level, depth of invasion, and presence or absence of perineural invasion should be recorded for each peripheral SCC. In this review, we examine the new recommendations with an emphasis on their utility and practicality. PMID:21469759

  18. Identifying predictive factors in melanoma progression.

    PubMed

    Dabrowska, D M; Elashoff, R M; Ho, W; Morton, D L

    1998-01-01

    Identification of risk factors is a fundamental goal of melanoma studies. The current understanding of melanoma progression is based primarily on two-stage modeling. A multistate Markov chain process combined with Cox proportional hazard regression is used to model the melanoma progression. The model is applied to 3,434 patients initially diagnosed as AJCC stage I or stage II. Parameter estimates are obtained using Cox regression and supplemented by plots of survival probabilities. Age is associated with increased risk of progression from stage I, II to stage III and from stage III to stage IV. Males experienced an increased risk of stage I, II to stage III progression. Primary tumor located on extremities decreased the risk of all transitions. Clark's level of invasion >III and Breslow's depth >1 mm increased the risk of progression from stage I, II to stage III and stage IV. The following interactions among the prognostic factors were identified for the first time in this research: interaction of age and gender in progression from stage I, II to stage III; interactions of level and depth and site by gender were found in the progression from stage I, II to stage III; interaction of site and gender in progression from stage III to stage IV and stage IV to death. Also we identified primary site as a new prognostic factor for the progression from stage IV to death. The study employed a multistate model in order to identify prognostic factors relevant for disease progression. The unique feature is the modeling of interactions among the prognostic factors and their identification. PMID:9538154

  19. Metastasectomy for Stage IV Melanoma in the Era of Effective Systemic Agents.

    PubMed

    Ollila, David W; Lopez, Nicole E; Hsueh, Eddy C

    2016-01-01

    There is an increasing body of literature that strongly suggests that complete metastasectomy for stage IV melanoma can improve overall survival. Before 2011, the efficacy of systemic therapy for melanoma was poor, making surgical resection the mainstay for treatment and the only realistic chance for cure. Now, in just a short time span (2011-2014), we have six Food & Drug Administration (FDA)-approved drugs for patients with stage IV metastatic melanoma. In the absence of prospective clinical trials evaluating the most advantageous sequence and timing for systemic therapy and surgical resection in the setting of stage IV melanoma, the treating surgical and medical oncologists must jointly devise individual treatment plans that take into account the advantages and disadvantages of each modality. This multidisciplinary approach gives the patient the best chance for prolonged survival. This article briefly reviews the FDA-approved systemic therapy options, discusses the data for site-specific metastasectomy, critiques the previous stage IV metastasectomy trials, and presents a view for moving forward with a multidisciplinary approach in mind. PMID:27481001

  20. Melanoma

    MedlinePlus

    ... have melanoma that has spread. Help the patient’s immune system fight the cancer Ipilimumab (Yervoy®), which was FDA ... How ipilimumab works : This drug helps the patient’s immune system to recognize, target, and attack cancer cells. Healthy ...

  1. Hemostatic alterations are unrelated to the stage of tumor in untreated malignant melanoma and breast carcinoma.

    PubMed

    Mannucci, P M; Vaglini, M; Maniezzo, M; Magni, E; Mari, D; Cascinelli, N

    1985-06-01

    A study of hemostatic variables was carried out in 80 untreated patients with breast adenocarcinoma or malignant melanoma, chosen as examples of tumors that can be accurately staged for localization or spread. The most marked abnormalities were high levels of clotting factors V and VIII, plasminogen, von Willebrand factor and fibrogen-fibrin degradation products. These abnormalities occurred in both types of tumors, albeit slightly more markedly in melanomas, and were also present in localized tumors. Our data indicate that in tumors, abnormalities of the hemostatic system are an early phenomenon unrelated to the presence of widespread malignancy.

  2. Analysis of the Clinical and Histopathological Patterns of 100 Consecutive Cases of Primary Cutaneous Melanoma and Correlation with Staging

    PubMed Central

    Nam, Kyung Wook; Bae, Seong Hwan; Song, Kyung Ho; Kim, Hoon Soo; Choi, Young Jin

    2015-01-01

    Background This study analyzed 100 consecutive patients with primary cutaneous melanoma over the course of 13 years to determine whether epidemiological differences correspond to different stages of the disease. We also investigated whether epidemiological characteristics affected the survival rate. Our results were compared with those of selected descriptive studies of melanoma in other East Asian populations, in order to determine whether cutaneous melanoma patterns are similar in East Asian populations. Methods The patients' medical records were reviewed retrospectively, and we analyzed the relationship of epidemiological characteristics to staging and survival rate. Additionally, papers from Hong Kong and Japan describing these phenomena in East Asian populations were subjected to a statistical comparison. Results The ratio of males to females was 1:1.8, and the foot was the most frequent tumor site (49%). Acral lentiginous melanoma occurred most frequently (55%). Nodular melanoma was associated with a higher stage. Stage III-IV tumors with Clark levels of IV-V were significantly associated with a low survival rate. A statistical analysis of comparable papers reported in Hong Kong and Japan showed similar results with regard to age, tumor location, and histopathological subtypes. Conclusions This study provides the first full epidemiological description of 100 consecutive cases of primary cutaneous melanoma in Korea, with results similar to those observed in other East Asian populations. Corresponding to previous findings, nodular melanoma tended to occur at a higher stage than other types, and tumors with high Clark levels and high stages showed a lower survival rate. PMID:26618123

  3. Metastatic lymph node ratio, 6th or 7th AJCC edition: witch is the best lymph node classification for esophageal cancer? Prognosis factor analysis in 487 patients

    PubMed Central

    CORAL, Roberto V.; BIGOLIN, André V.; CORAL, Roberto P.; HARTMANN, Antonio; DRANKA, Carolina; ROEHE, Adriana V.

    2015-01-01

    Background The esophageal cancer is one of the most common and aggressive worldwide. Recently, the AJCC changed the staging system, considering, among others, the important role of the lymph node metastasis on the prognosis. Aim To discuss the applicability of different forms of lymph node staging in a western surgical center. Methods Four hundred eighty seven patients with esophageal cancer were enrolled. Three staging systems were evaluated, the 6th and the 7th AJCC editions and the Lymph Node Metastatic Ratio. Results The majority of the cases were squamous cell carcinoma. The mean lymph node sample was eight. Considering the survival, there was no significant difference between the patients when they were classified by the 7th AJCC edition. Analysis of the Lymph Node Metastatic Ratio, just on the group of patients with 0 to 25%, has shown significant difference (p=0,01). The 6th AJCC edition shows the major significant difference between among the classifications evaluated. Conclusion In this specific population, the 7th AJCC edition for esophageal cancer was not able to find differences in survival when just the lymph node analysis was considered. PMID:26176242

  4. The CASC15 long intergenic non-coding RNA locus is involved in melanoma progression and phenotype-switching

    PubMed Central

    Lessard, Laurent; Liu, Michelle; Marzese, Diego M.; Wang, Hongwei; Chong, Kelly; Kawas, Neal; Donovan, Nicholas C; Kiyohara, Eiji; Hsu, Sandy; Nelson, Nellie; Izraely, Sivan; Sagi-Assif, Orit; Witz, Isaac P; Ma, Xiao-Jun; Luo, Yuling; Hoon, Dave SB

    2015-01-01

    In recent years, considerable advances have been made in the characterization of protein-coding alterations involved in the pathogenesis of melanoma. However, despite their growing implication in cancer, little is known about the role of long non-coding RNAs in melanoma progression. We hypothesized that copy number alterations of intergenic non-protein coding domains could help identify long intergenic non-coding RNAs (lincRNAs) associated with metastatic cutaneous melanoma. Among several candidates, our approach uncovered the chromosome 6p22.3 CASC15 lincRNA locus as a frequently gained genomic segment in metastatic melanoma tumors and cell lines. The locus was actively transcribed in metastatic melanoma cells, and up-regulation of CASC15 expression was associated with metastatic progression to brain metastasis in a mouse xenograft model. In clinical specimens, CASC15 levels increased during melanoma progression and were independent predictors of disease recurrence in a cohort of 141 patients with AJCC stage III lymph node metastasis. Moreover, siRNA knockdown experiments revealed that CASC15 regulates melanoma cell phenotype switching between proliferative and invasive states. Accordingly, CASC15 levels correlated with known gene signatures corresponding to melanoma proliferative and invasive phenotypes. These findings support a key role for CASC15 in metastatic melanoma. PMID:26016895

  5. Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.

    PubMed

    Huang, Sharon K; Hoon, Dave S B

    2016-03-01

    Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post-treatment drug resistance often developed in melanoma patients. Non-invasive blood biomarker assays allow for regular dynamic monitoring of disease. "Liquid Biopsy" of blood, which exploits circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and cell-free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. With advancements of improving molecular assays, liquid biopsy analysis as a powerful, routine clinical assay for melanoma patients, is highly promising prospective. PMID:26778792

  6. Expression of the RNase III enzyme DROSHA is reduced during progression of human cutaneous melanoma

    PubMed Central

    Jafarnejad, Seyed Mehdi; Sjoestroem, Cecilia; Martinka, Magdalena; Li, Gang

    2016-01-01

    Aberrant expression of miRNAs and their biogenesis factors has been frequently observed in different types of cancer. We recently reported that expression of DICER1 is reduced in metastatic melanoma. Nevertheless, so far very little is known about the expression pattern of other miRNA biogenesis factors in this type of malignancy. Here, we investigated the expression pattern of DROSHA in a large set of melanocytic lesions by tissue microarray and immunohistochemistry (n = 409). We found that nuclear expression of DROSHA is markedly reduced in the early stages of melanoma progression (P = 0.0001) and is inversely correlated with melanoma thickness (P = 0.0001), AJCC stages (P = 0.0001), and ulceration status (P = 0.002). We also confirmed the reduced expression of nuclear DROSHA by a second specific antibody raised against a different region of the DROSHA protein. In addition, we observed that the reduced nuclear expression of DROSHA during melanoma progression is accompanied by an increased cytoplasmic expression of this protein (P = 0.0001). Finally, we found that expression pattern of DROSHA varies from that of DICER1 and concomitant loss of expression of both DICER1 and DROSHA confers the worse outcome for melanoma patients. Our results demonstrate a reduced nuclear expression of DROSHA which further highlights a perturbed miRNA biogenesis pathway in melanoma. In addition, the aberrant subcellular localization of DROSHA indicates possible deregulation in the mechanisms responsible for its proper localization in the nucleus. PMID:23370771

  7. Adjuvant Sunitinib or Valproic Acid in High-Risk Patients With Uveal Melanoma

    ClinicalTrials.gov

    2016-07-25

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Iris Melanoma; Stage I Intraocular Melanoma; Stage IIA Intraocular Melanoma; Stage IIB Intraocular Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIC Intraocular Melanoma

  8. [Incidence of melanoma and changes in stage-specific incidence after implementation of skin cancer screening in Schleswig-Holstein].

    PubMed

    Eisemann, N; Waldmann, A; Katalinic, A

    2014-01-01

    A pilot project in skin cancer screening (SCREEN) was conducted in Schleswig-Holstein from July 2003 to June 2004. Although the impact of this screening on the stage-specific incidence of melanoma is of great importance for screening evaluation, it remains unknown. In theory, an effective skin cancer screening program should result in a medium-term incidence decrease of melanomas with a prognostically unfavorable stage. This is studied on a population-based level by using cancer registry data. Based on data from the Cancer Registry of Schleswig-Holstein for 1999-2009, stage-specific (T-category of the TNM-classification system) age-standardized incidence rates were calculated. After implementation of the SCREEN project, the incidence of prognostically favorable melanomas (in situ and T1) was higher than before, while the incidence of advanced melanomas (T2, T3, and for women also T4) decreased considerably. The classification of tumor stages changed during the project period, which may have contributed to an artificial decrease of the stages with a poor prognosis. Nevertheless, the results are in agreement with the observed decrease of melanoma mortality in the screening region.

  9. Radioembolization and Ipilimumab in Treating Patients With Uveal Melanoma With Liver Metastases

    ClinicalTrials.gov

    2016-03-09

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Liver Metastases; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage IV Intraocular Melanoma

  10. A Novel Role for Microphthalmia-Associated Transcription Factor–Regulated Pigment Epithelium-Derived Factor during Melanoma Progression

    PubMed Central

    Dadras, Soheil S.; Lin, Richard J.; Razavi, Gita; Kawakami, Akinori; Du, Jinyan; Feige, Erez; Milner, Daniel A.; Loda, Massimo F.; Granter, Scott R.; Detmar, Michael; Widlund, Hans R.; Horstmann, Martin A.; Fisher, David E.

    2016-01-01

    Microphthalmia-associated transcription factor (MITF) acts via pigment epithelium-derived factor (PEDF), an antiangiogenic protein, to regulate retinal pigment epithelium migration. PEDF expression and/or regulation during melanoma development have not been investigated previously. Using immunohistochemistry, we determined expression of PEDF in common and dysplastic melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma (n = 102). PEDF expression was consistently decreased in invasive and metastatic melanoma, compared with nevi and melanoma in situ (P < 0.0001). PEDF was lost in thicker melanomas (P = 0.003), and correlated with depth of invasion (P = 0.003) and distant metastasis (P = 0.0331), but only marginally with mitotic index, AJCC stage, nodal metastasis, or blood vascular density (0.05 < P < 0.10). Quantitative real-time PCR and microarray analyses confirmed PEDF down-regulation at the mRNA level in several melanoma lines, compared with melanocytes. MITF positively correlated with PEDF expression in invasive melanomas (P = 0.0003). Searching for PEDF regulatory mechanisms revealed two occupied conserved E-boxes (DNA recognition elements) in the first intron of the human and mouse PEDF promoter regions, confirmed by binding assays. Dominant-negative and siRNA approaches in vivo demonstrated direct transcriptional influence of MITF on PEDF, establishing the PEDF gene (SERPINF1) as a MITF target in melanocytes and melanoma cells. These findings suggest that loss of PEDF expression promotes early invasive melanoma growth. PMID:25447045

  11. [Sentinel lymph node procedure in melanoma patients: a staging procedure, not a therapy].

    PubMed

    van Akkooi, Alexander C J; Kukutsch, Nicole A; Soetekouw, Patricia M M B

    2014-01-01

    The definitive results of the MSLT-1 study in melanoma patients were published recently. The sentinel lymph node (SLN) procedure shows no survival benefit compared with observation. The authors reported, however, that there was a survival benefit with "biopsy management" of patients. This statement is based on subgroup analyses that we find to be incorrect for three reasons: (a) patients with a false negative SLN were incorrectly left out of consideration; (b) accelerated failure time latent subgroup analysis is an unproven statistical hypothesis, which was developed on interim data from the MSLT-1 study, and therefore cannot be used as validation; (c) there is a significant difference in terms of the percentage of patients with affected lymph nodes between the SLN group and the observation group. This excess of "prognostic false positive" patients would have incorrectly falsely improved the survival of the SLN group. We concluded that the SLN procedure does not give a survival benefit and that its role in melanoma patients should be for staging purposes and not for therapeutic purposes.

  12. Long-term effects of laser-imiquimod combination in the treatment of late-stage melanoma patients

    NASA Astrophysics Data System (ADS)

    Naylor, Mark F.; Le, Henry; Li, Xiaosong; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2012-03-01

    Topical application of a potent immunological modulator, imiquimod, followed by laser irradiation has been used for the treatment of late-stage melanoma patients. This novel approach, laser-assisted laser immunotherapy (LIT), targets the root course of melanoma, a highly metastatic cancer. We started a phase I clinical trial in 2006 with promising initial outcomes. The laser-imiquimod combination showed significant palliative effects for these patients with multiple treatment cycles. For the returning patients, we found that the recurrent tumors were less aggressive than usually seen in untreated patients. The current protocol uses a light-absorbing dye for selective laser photothermal interaction with a non-invasive treatment mode. It has limitations for patient treatment, particularly for large, deeper tumors, and for patients with dark pigmented skins. This study provides some information on the treated patients (both stage IV and stage IV) during the past several years. We also discuss the future directions of LIT, particularly in the area of photothermal treatment mode with a new approach of interstitial irradiation. The current results in melanoma treatment using LIT indicate that the combination of photothermal therapy and immunological stimulation may hold the key for the treatment of late-stage, metastatic cancers, not only for cutaneous cancers such as melanoma and breast cancer, but also for deep and internal tumors using different operations modes such as interstitial laser irradiation.

  13. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response. PMID:27622047

  14. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response.

  15. Amelanotic Melanoma in the Vicinity of Acquired Melanocytic Nevi and not Arising from Agminated Melanocytic Nevi: Masquerading as Pyogenic Granuloma

    PubMed Central

    Rao, Angoori Gnaneshwar; Babu, V Ashok; Koppada, Divya; Haritha, M; Chandana, P; Swapna; Anoosha

    2016-01-01

    Amelanotic melanoma (AMM) presenting as pyogenic granuloma and occurring in the vicinity of acquired melanocytic nevi is rare. Herein, we report such a manifestation in a 68-year-old male who presented with the painful red nodule and multiple pigmented patches involving the left great toe. Histopathological examination of skin biopsy taken from the nodule with an immunohistochemical study using HMB45 and S-100 confirmed the diagnosis of AMM. Biopsy from the pigmented patch near the nodule showed features of melanocytic nevus. Investigative work up revealed metastatic deposits in the left inguinal lymph node with no evidence of systemic involvement, placing him in malignant melanoma Stage IIIC of American Joint Committee on Cancer (AJCC) tumor node metastasis system. The development of AMM in the vicinity of acquired melanocytic nevi and manifesting as granuloma pyogenicum is unique in this case. PMID:26955141

  16. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  17. Lock-in thermal imaging for the early-stage detection of cutaneous melanoma: a feasibility study.

    PubMed

    Bonmarin, Mathias; Le Gal, Frédérique-Anne

    2014-04-01

    This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed.

  18. Melanoma susceptibility as a complex trait: genetic variation controls all stages of tumor progression.

    PubMed

    Ferguson, B; Ram, R; Handoko, H Y; Mukhopadhyay, P; Muller, H K; Soyer, H P; Morahan, G; Walker, G J

    2015-05-28

    Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4(R24C) and NRAS(Q61K). In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations.

  19. Melanoma susceptibility as a complex trait: genetic variation controls all stages of tumor progression.

    PubMed

    Ferguson, B; Ram, R; Handoko, H Y; Mukhopadhyay, P; Muller, H K; Soyer, H P; Morahan, G; Walker, G J

    2015-05-28

    Susceptibility to most common cancers is likely to involve interaction between multiple low risk genetic variants. Although there has been great progress in identifying such variants, their effect on phenotype and the mechanisms by which they contribute to disease remain largely unknown. We have developed a mouse melanoma model harboring two mutant oncogenes implicated in human melanoma, CDK4(R24C) and NRAS(Q61K). In these mice, tumors arise from benign precursor lesions that are a recognized strong risk factor for this neoplasm in humans. To define molecular events involved in the pathway to melanoma, we have for the first time applied the Collaborative Cross (CC) to cancer research. The CC is a powerful resource designed to expedite discovery of genes for complex traits. We characterized melanoma genesis in more than 50 CC strains and observed tremendous variation in all traits, including nevus and melanoma age of onset and multiplicity, anatomical site predilection, time for conversion of nevi to melanoma and metastases. Intriguingly, neonatal ultraviolet radiation exposure exacerbated nevus and melanoma formation in most, but not all CC strain backgrounds, suggesting that genetic variation within the CC will help explain individual sensitivity to sun exposure, the major environmental skin carcinogen. As genetic variation brings about dramatic phenotypic diversity in a single mouse model, melanoma-related endophenotype comparisons provide us with information about mechanisms of carcinogenesis, such as whether melanoma incidence is dependent upon the density of pre-existing nevus cells. Mouse models have been used to examine the functional role of gene mutations in tumorigenesis. This work represents their next phase of development to study how biological variation greatly influences lesion onset and aggressiveness even in the setting of known somatic driver mutations. PMID:25088201

  20. Utility of adjuvant systemic therapy in melanoma

    PubMed Central

    Eggermont, A. M. M.; Testori, A.; Marsden, J.; Hersey, P.; Quirt, I.; Petrella, T.; Gogas, H.; MacKie, R. M.; Hauschild, A.

    2009-01-01

    The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. PMID:19617295

  1. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma.

    PubMed

    Stanojevic, Ivan; Miller, Karolina; Kandolf-Sekulovic, Lidija; Mijuskovic, Zeljko; Zolotarevski, Lidija; Jovic, Milena; Gacevic, Milomir; Djukic, Mirjana; Arsenijevic, Nebojsa; Vojvodic, Danilo

    2016-02-01

    Seventy-eight melanoma patients and 10 healthy individuals were examined. Follow-up examinations of all melanoma patients were performed regularly every three months. Myeloid-derived suppressor cells (MDSC) were defined as lineage negative (CD3(-), CD19(-), CD56(-)), HLA-DR(-/low), CD11b(+) and CD33(+). Classification of granulocytic (GrMDSC) and monocytic (MoMDSC) subsets was based on the CD15 and CD14 expression, respectively. Unlike the MoMDSC, that were present in 60% of healthy controls and 15% of melanoma patients, the GrMDSC were present in all examined participants, and the melanoma patients were found to have statistically higher frequencies compared with healthy controls. Accordingly, we kept focused on GrMDSC frequencies in relation to the melanoma stages and course of the disease. The GrMDSC values are highest in stage IV melanoma patients, with statistical significance compared with stages IA, IB, IIA and IIB. Patients with progression had statistically higher GrMDSC counts comparing with those with stable disease (P = 0.0079). Patients who had progression-free interval (PFI) < 12 months showed significantly higher GrMDSC values compared with those with PFI > 12 months (P = 0.0333). GrMDSC showed significant negative correlation with PFI intervals (P = 0.0095). The GrMDSC subset was predominant in all our patients. We confirmed that GrMDSC do accumulate early in the peripheral blood of melanoma patients and their frequencies correlate narrowly with the clinical stage and the spread of the disease. The increase in GrMDSC frequencies correlates well with a progressive disease and could be considered a potential predictive biomarker of high-risk melanoma cases that are more likely to have a shorter PFI. PMID:26391013

  2. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease. PMID:23244383

  3. Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.

    PubMed

    Fox, Matthew C; Lao, Christopher D; Schwartz, Jennifer L; Frohm, Marcus L; Bichakjian, Christopher K; Johnson, Timothy M

    2013-01-01

    The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease.

  4. Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

    PubMed Central

    Bol, Kalijn F; Aarntzen, Erik H J G; Hout, Florentien E M in 't; Schreibelt, Gerty; Creemers, Jeroen H A; Lesterhuis, W Joost; Gerritsen, Winald R; Grunhagen, Dirk J; Verhoef, Cornelis; Punt, Cornelis J A; Bonenkamp, Johannes J; de Wilt, Johannes H W; Figdor, Carl G; de Vries, I Jolanda M

    2016-01-01

    Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional metastatic disease who underwent RLND with curative intent. In this retrospective study, 78 melanoma patients with regional lymph node metastasis who underwent RLND received autologous DCs loaded with gp100 and tyrosinase and were analyzed for functional tumor-specific T cell responses in skin-test infiltrating lymphocytes. The study shows that adjuvant DC vaccination in melanoma patients with regional lymph node metastasis is safe and induced functional tumor-specific T cell responses in 71% of the patients. The presence of functional tumor-specific T cells was correlated with a better 2-year overall survival (OS) rate. OS was significantly higher after adjuvant DC vaccination compared to 209 matched controls who underwent RLND without adjuvant DC vaccination, 63.6 mo vs. 31.0 mo (p = 0.018; hazard ratio 0.59; 95%CI 0.42–0.84). Five-year survival rate increased from 38% to 53% (p < 0.01). In summary, in melanoma patients with regional metastatic disease, who are at high risk for recurrence and metastatic disease after RLND, adjuvant DC vaccination is well tolerated. It induced functional tumor-specific immune responses in the majority of patients and these were related to clinical outcome. OS was significantly higher compared to matched controls. A randomized clinical trial is needed to prospectively validate the efficacy of DC vaccination in the adjuvant setting. PMID:26942068

  5. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    NASA Astrophysics Data System (ADS)

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Edward; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-02-01

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1-250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5-371.5 CMCs ml-1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma.

  6. Expression of Molecular Markers of Angiogenesis, Lymphangiogenesis, and Proliferation Depending on the Stage of Skin Melanoma.

    PubMed

    Bgatova, N P; Lomakin, A I; Fursov, S A; Kachesov, I V; Chepko, S A; Isakova, N B; Borodin, Yu I; Voytsitsky, V E; Konenkov, V I

    2016-08-01

    The expression of molecular markers characterizing activity of the tumor process and metastases (proliferation marker Ki-67, angiogenesis marker CD34, and lymphangiogenesis markers podoplanin and LYVE-1) was assessed by immunohictochemical method in the primary tumor specimens collected during surgery for cutaneous melanoma (40 patients). Proliferative activity of the tumor tissue and volume density of peritumoral blood and lymph vessels increased with increasing tumor malignancy, which could indicate the risk of metastases. PMID:27590758

  7. Limited Genomic Heterogeneity of Circulating Melanoma Cells in Advanced Stage Patients

    PubMed Central

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Ed; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-01-01

    Purpose Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design Blood samples from 40 metastatic melanoma patients and 10 normal blood donors (NBD) were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAb) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification (WGA) and copy number variation (CNV) analysis. Results Based on CSPG4 expression and nuclear size, 1 to 250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5 to 371.5 CMCs/ml). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this population may contribute to develop effective therapeutic strategies. PMID:25574741

  8. Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

    PubMed Central

    2010-01-01

    Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects. PMID:20540720

  9. Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline--Update 2012.

    PubMed

    Garbe, Claus; Peris, Ketty; Hauschild, Axel; Saiag, Philippe; Middleton, Mark; Spatz, Alan; Grob, Jean-Jacques; Malvehy, Josep; Newton-Bishop, Julia; Stratigos, Alexander; Pehamberger, Hubert; Eggermont, Alexander M

    2012-10-01

    Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically and staging is based upon the AJCC system. CMs are excised with one to two centimetre safety margins. Sentinel lymph node dissection (SLND) is routinely offered as a staging procedure in patients with tumours more than 1mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival (DFS) and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. BRAF inhibitors like vemurafenib for BRAF mutated patients as well as the CTLA-4 antibody ipilimumab offer new therapeutic opportunities apart from conventional chemotherapy. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team ('tumour board'). PMID:22981501

  10. Cutaneous melanoma.

    PubMed

    Eggermont, Alexander M M; Spatz, Alan; Robert, Caroline

    2014-03-01

    In the past decade, major advances have been made in the understanding of melanoma. New predisposition genes have been reported and key somatic events, such as BRAF mutation, directly translated into therapeutic management. Surgery for localised melanoma and regional lymph node metastases is the standard of care. Sentinel-node biopsy provides precise staging, but has not been reported to affect survival. The effect of lymph-node dissection on survival is a topic of investigation. Two distinct approaches have emerged to try to extend survival in patients with metastatic melanoma: immunomodulation with anti-CTLA4 monoclonal antibodies, and targeted therapy with BRAF inhibitors or MEK inhibitors for BRAF-mutated melanoma. The combination of BRAF inhibitors and MEK inhibitors might improve progression-free survival further and, possibly, increase overall survival. Response patterns differ substantially-anti-CTLA4 immunotherapy can induce long-term responses, but only in a few patients, whereas targeted drugs induce responses in most patients, but nearly all of them relapse because of pre-existing or acquired resistance. Thus, the long-term prognosis of metastatic melanoma remains poor. Anti-PD1 and anti-PDL1 antibodies have emerged as breakthrough drugs for melanoma that have high response rates and long durability. Biomarkers that have predictive value remain elusive in melanoma, although emerging data for adjuvant therapy indicate that interferon sensitivity is associated with ulceration of the primary melanoma. Intense investigation continues for clinical and biological markers that predict clinical benefit of immunotherapeutic drugs, such as interferon alfa or anti-CTLA4 antibodies, and the mechanisms that lead to resistance of targeted drugs.

  11. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients.

    PubMed

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H T; Aarntzen, Erik H J G; Schreibelt, Gerty; Creemers, Jeroen H A; Punt, Cornelis J A; Figdor, Carl G; de Vries, I Jolanda M; Gerritsen, Winald R; Bol, Kalijn F

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8 T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  12. Immune-related Adverse Events of Dendritic Cell Vaccination Correlate With Immunologic and Clinical Outcome in Stage III and IV Melanoma Patients

    PubMed Central

    Boudewijns, Steve; Westdorp, Harm; Koornstra, Rutger H.T.; Aarntzen, Erik H.J.G.; Schreibelt, Gerty; Creemers, Jeroen H.A.; Punt, Cornelis J.A.; Figdor, Carl G.; Gerritsen, Winald R.; Bol, Kalijn F.

    2016-01-01

    The purpose of this study was to determine the toxicity profile of dendritic cell (DC) vaccination in stage III and IV melanoma patients, and to evaluate whether there is a correlation between side effects and immunologic and clinical outcome. This is a retrospective analysis of 82 stage III and 137 stage IV melanoma patients, vaccinated with monocyte-derived or naturally circulating autologous DCs loaded with tumor-associated antigens gp100 and tyrosinase. Median follow-up time was 54.3 months in stage III patients and 12.9 months in stage IV patients. Treatment-related adverse events occurred in 84% of patients; grade 3 toxicity was present in 3% of patients. Most common adverse events were flu-like symptoms (67%) and injection site reactions (50%), and both correlated with the presence of tetramer-positive CD8+ T cells (both P<0.001). In stage III melanoma patients experiencing flu-like symptoms, median overall survival (OS) was not reached versus 32.3 months in patients without flu-like symptoms (P=0.009); median OS in patients with an injection site reaction was not reached versus 53.7 months in patients without an injection site reaction (P<0.05). In stage IV melanoma patients (primary uveal and mucosal melanomas excluded), median OS in patients with or without flu-like symptoms was 13.1 versus 8.9 months, respectively (P=0.03); median OS in patients with an injection site reaction was 15.7 months versus 9.8 months in patients without an injection site reaction (P=0.003). In conclusion, DC vaccination is safe and tolerable and the occurrence of the immune-related side effects, such as flu-like symptoms and injection site reactions, correlates with immunologic and clinical outcome. PMID:27227325

  13. A phase 2, multicenter, open-label study of sepantronium bromide (YM155) plus docetaxel in patients with stage III (unresectable) or stage IV melanoma

    PubMed Central

    Kudchadkar, Ragini; Ernst, Scott; Chmielowski, Bartosz; Redman, Bruce G; Steinberg, Joyce; Keating, Anne; Jie, Fei; Chen, Caroline; Gonzalez, Rene; Weber, Jeffrey

    2015-01-01

    Survivin is a microtubule-associated protein believed to be involved in preserving cell viability and regulating tumor cell mitosis, and it is overexpressed in many primary tumor types, including melanoma. YM155 is a first-in-class survivin suppressant. The purpose of this Phase 2 study was to evaluate the 6-month progression-free survival (PFS) rate in patients with unresectable Stage III or IV melanoma receiving a combination of YM155 plus docetaxel. The study had two parts: Part 1 established the dose of docetaxel that was tolerable in combination with YM155, and Part 2 evaluated the tolerable docetaxel dose (75 mg/m2) in combination with YM155 (5 mg/m2 per day continuous infusion over 168 h every 3 weeks). The primary endpoint was 6-month PFS rate. Secondary endpoints were objective response rate (ORR), 1-year overall survival (OS) rate, time from first response to progression, clinical benefit rate (CBR), and safety. Sixty-four patients with metastatic melanoma were treated with docetaxel and YM155. Eight patients received an initial docetaxel dose of 100 mg/m2 and 56 patients received 75 mg/m2 of docetaxel. Six-month PFS rate per Independent Review Committee (IRC) was 34.8% (n = 64; 95% CI, 21.3–48.6%), and per Investigator was 31.3% (n = 64; 95% CI, 19.5–43.9%). The best ORR (complete response [CR] + partial response [PR]) per IRC was 12.5% (8/64). The stable disease (SD) rate was 51.6% (33/64), leading to a CBR (CR + PR + SD) of 64.1% (41/64). Estimated probability of 1-year survival was 56.3%. YM155 is a novel agent showing modest activity when combined with docetaxel for treating patients with melanoma. YM155 was generally well tolerated, but the predetermined primary efficacy endpoint (i.e., 6-month PFS rate ≥20%) was not achieved. PMID:25533314

  14. Stage III Melanoma in the Axilla: Patterns of Regional Recurrence After Surgery With and Without Adjuvant Radiation Therapy

    SciTech Connect

    Pinkham, Mark B.; Foote, Matthew C.; Burmeister, Elizabeth; Thomas, Janine; Meakin, Janelle; Smithers, B. Mark; Burmeister, Bryan H.

    2013-07-15

    Purpose: To describe the anatomic distribution of regionally recurrent disease in patients with stage III melanoma in the axilla after curative-intent surgery with and without adjuvant radiation therapy. Methods and Materials: A single-institution, retrospective analysis of a prospective database of 277 patients undergoing curative-intent treatment for stage III melanoma in the axilla between 1992 and 2012 was completed. For patients who received radiation therapy and those who did not, patterns of regional recurrence were analyzed, and univariate analyses were performed to assess for potential factors associated with location of recurrence. Results: There were 121 patients who received adjuvant radiation therapy because their clinicopathologic features conferred a greater risk of regional recurrence. There were 156 patients who received no radiation therapy. The overall axillary control rate was 87%. There were 37 patients with regional recurrence; 17 patients had received adjuvant radiation therapy (14%), and 20 patients (13%) had not. The likelihood of in-field nodal recurrence was significantly less in the adjuvant radiation therapy group (P=.01) and significantly greater in sites adjacent to the axilla (P=.02). Patients with high-risk clinicopathologic features who did not receive adjuvant radiation therapy also tended to experience in-field failure rather than adjacent-field failure. Conclusions: Patients who received adjuvant radiation therapy were more likely to experience recurrence in the adjacent-field regions rather than in the in-field regions. This may not simply reflect higher-risk pathology. Using this data, it may be possible to improve outcomes by reducing the number of adjacent-field recurrences after adjuvant radiation therapy.

  15. Melanoma Diagnosis

    NASA Astrophysics Data System (ADS)

    Horsch, Alexander

    The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

  16. Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.

    PubMed

    Nsengimana, Jérémie; Laye, Jon; Filia, Anastasia; Walker, Christy; Jewell, Rosalyn; Van den Oord, Joost J; Wolter, Pascal; Patel, Poulam; Sucker, Antje; Schadendorf, Dirk; Jönsson, Göran B; Bishop, D Timothy; Newton-Bishop, Julia

    2015-05-10

    Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3 x 10(-4)), Breslow thickness (P=5 x 10(-10)), ulceration (P=9.x10-8) and mitotic rate (P=3 x 10(-7)), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.

  17. Evaluation of the 7th edition of the UICC-AJCC tumor, node, metastasis classification for esophageal cancer in a Chinese cohort

    PubMed Central

    Huang, Yan; Guo, Weigang; Shi, Shiming

    2016-01-01

    Background To assess and evaluate the prognostic value of the 7th edition of the Union for International Cancer Control–American Joint Committee on Cancer (UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients with esophageal cancer in comparison with the 6th edition. Methods A retrospective review was performed on 766 consecutive esophageal cancer patients treated with esophagectomy between 2008 and 2012. Patients were staged according to the 6th and 7th editions for esophageal cancer respectively. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed using Cox regression model. Results Overall 3-year survival rate was 59.5%. There were significant differences in 3-year survival rates among T stages both according to the 6th edition and the 7th edition (P<0.001). According to the 7th edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%) and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier curve revealed a good discriminatory ability from stage I to IV, except for stage IB, IIA and IIB in the 7th edition staging system. Based on the 7th edition, the degree of differentiation, tumor length and tumor location were not independent prognostic factors on multivariate analysis. The multivariate analyses suggested that pT-, pN-, pTNM-category were all the independent prognostic factors based on the 6th and 7th edition staging system. Conclusions The 7th edition of AJCC TNM staging system of esophageal cancer should discriminate pT2–3N0M0 (stage IB, IIA and IIB) better when considering the esophageal squamous cell cancer patients. Therefore, to improve and optimize the AJCC TNM classification for Chinese patients with esophageal cancer, more considerations about the value of tumor grade and tumor location in pT2–3N0M0 esophageal squamous cell cancer should be taken in the next new TNM staging system. PMID:27499956

  18. TNM Staging of Pancreatic Neuroendocrine Tumors

    PubMed Central

    Yang, Min; Zeng, Lin; Zhang, Yi; Wang, Wei-guo; Wang, Li; Ke, Neng-wen; Liu, Xu-bao; Tian, Bo-le

    2015-01-01

    Abstract We aimed to analyze the clinical characteristics and compare the surgical outcome of pancreatic neuroendocrine tumors (p-NETs) using the 2 tumor-node-metastasis (TNM) systems by both the American Joint Committee on Cancer (AJCC) Staging Manual (seventh edition) and the European Neuroendocrine Tumor Society (ENETS). Moreover, we sought to validate the prognostic value of the new AJCC criterion. Data of 145 consecutive patients who were all surgically treated and histologically diagnosed as p-NETs from January 2002 to June 2013 in our single institution were retrospectively collected and analyzed. The 5-year overall survival (OS) rates for AJCC classifications of stages I, II, III, and IV were 79.5%, 63.1%, 15.0%, and NA, respectively, (P < 0.005). As for the ENETS system, the OS rates at 5 years for stages I, II, III, and IV were 75.5%, 72.7%, 29.0%, and NA, respectively, (P < 0.005). Both criteria present no statistically notable difference between stage I and stage II (P > 0.05) but between stage I and stages III and IV (P < 0.05), as well as those between stage II and stages III and IV (P < 0.05). Difference between stage III and IV by ENETS was significant (P = 0.031), whereas that by the AJCC was not (P = 0.144). What's more, the AJCC Staging Manual (seventh edition) was statistically significant in both uni- and multivariate analyses by Cox regression (P < 0.005 and P = 0.025, respectively). Our study indicated that the ENETS TNM staging system might be superior to the AJCC Staging Manual (seventh edition) for the clinical practice of p-NETs. Together with tumor grade and radical resection, the new AJCC system was also validated to be an independent predictor for p-NETs. PMID:25816036

  19. Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer

    ClinicalTrials.gov

    2016-06-01

    Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Male Breast Carcinoma; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIC Breast Cancer AJCC v6; Stage IV Breast Cancer

  20. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    ClinicalTrials.gov

    2016-02-05

    Adult Solid Neoplasm; Hormone-Resistant Prostate Cancer; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  1. Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

    PubMed

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G; Harcharik, Sara T; Hall, Lawrence D; Bernardo, Sebastian G; Moskalenko, Marina M; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C; Tismenetsky, Mikhail; Tsui, Cindy L; Friedlander, Philip A; Parides, Michael K; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G; Wolchok, Jedd D; Bhardwaj, Nina; Burakoff, Steven J; Oh, William K; Palucka, Karolina; Merad, Miriam; Schadt, Eric E; Saenger, Yvonne M

    2014-08-01

    Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.

  2. Dissection of Immune Gene Networks in Primary Melanoma Tumors Critical for Antitumor Surveillance of Patients with Stage II–III Resectable Disease

    PubMed Central

    Sivendran, Shanthi; Chang, Rui; Pham, Lisa; Phelps, Robert G.; Harcharik, Sara T.; Hall, Lawrence D.; Bernardo, Sebastian G.; Moskalenko, Marina M.; Sivendran, Meera; Fu, Yichun; de Moll, Ellen H.; Pan, Michael; Moon, Jee Young; Arora, Sonali; Cohain, Ariella; DiFeo, Analisa; Ferringer, Tammie C.; Tismenetsky, Mikhail; Tsui, Cindy L.; Friedlander, Philip A.; Parides, Michael K.; Banchereau, Jacques; Chaussabel, Damien; Lebwohl, Mark G.; Wolchok, Jedd D.; Bhardwaj, Nina; Burakoff, Steven J.; Oh, William K.; Palucka, Karolina; Merad, Miriam; Schadt, Eric E.; Saenger, Yvonne M.

    2014-01-01

    Patients with resected stage II–III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II–III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data. PMID:24522433

  3. Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

    ClinicalTrials.gov

    2016-10-20

    Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

  4. Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients.

    PubMed

    Bins, Adriaan; Mallo, Henk; Sein, Johan; van den Bogaard, Colette; Nooijen, Willem; Vyth-Dreese, Florry; Nuijen, Bastiaan; de Gast, Gijsbert C; Haanen, John B A G

    2007-01-01

    Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.

  5. Stages of Melanoma

    MedlinePlus

    ... and treatments will also be taken. Lymph node mapping and sentinel lymph node biopsy : Procedures in which ... has spread to the lymph nodes . Lymph node mapping and sentinel lymph node biopsy are done to ...

  6. The outcomes of Polish patients with advanced BRAF-positive melanoma treated with vemurafenib in a safety clinical trial

    PubMed Central

    Rutkowski, Piotr; Mackiewicz, Jacek; Krzemieniecki, Krzysztof; Nawrocki, Sergiusz; Wasilewska-Teśluk, Ewa; Kwinta, Łukasz; Wysocki, Piotr; Koseła-Paterczyk, Hanna; Świtaj, Tomasz

    2015-01-01

    Aim of the study The BRAF inhibitor vemurafenib has improved progression-free survival and overall survival in patients with BRAFV600-mutation-positive metastatic melanoma. Here we present the results of an open-label safety study with vemurafenib in patients with metastatic melanoma enrolled in Polish oncological centres. Material and methods Patients with untreated or previously treated Stage IIIC/IV BRAFV600 mutation-positive melanoma were treated with oral vemurafenib in an initial dose of 960 mg twice daily. Assessments for safety and efficacy were made every 28 days. For the survival analysis the Kaplan-Meier estimator was used with the log-rank tests for bivariate comparisons. Results In total, 75 Polish patients were enrolled in the safety study across four centres. At data cut-off, 28 patients died (37%), mainly (26) due to disease progression; 33 (44%) patients continued vemurafenib after disease progression. The objective response rate was 46%, including two patients with a complete response and 29 with a partial response. Median progression-free survival was 7.4 months. The one-year overall survival rate was 61.9% (median overall survival was not reached). Seventy-three (97.3%) patients reported adverse events (AEs), and grade 3–5 toxicity was reported in 49.4% (37) patients. The most common AEs were: skin lesions (including rash and photosensitivity), arthralgia, and fatigue. Conclusions The overall safety profile and response rate of vemurafenib were comparable to those reported in previous studies of this drug. Our study confirmed the value of well-established prognostic features for overall survival, such as initial LDH (lactate dehydrogenase) level and AJCC staging. PMID:26557775

  7. Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

    PubMed Central

    Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

    2016-01-01

    There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

  8. Comparative analysis of BRAF, NRAS and c-KIT mutation status between tumor tissues and autologous tumor cell-lines of stage III/IV melanoma.

    PubMed

    Knol, Anne-Chantal; Pandolfino, Marie-Christine; Vallée, Audrey; Nguyen, Frédérique; Lella, Virginie; Khammari, Amir; Denis, Marc; Puaux, Anne-Laure; Dréno, Brigitte

    2015-01-01

    In the last decade, advances in molecular biology have provided evidence of the genotypic heterogeneity of melanoma. We analysed BRAF, NRAS and c-KIT alterations in tissue samples from 63 stage III/IV melanoma patients and autologous cell-lines, using either allele-specific or quantitative PCR. The expression of BRAF V600E protein was also investigated using an anti-BRAF antibody in the same tissue samples. 81% of FFPE samples and tumor cell-lines harboured a genetic alteration in either BRAF (54%) or NRAS (27%) oncogenes. There was a strong concordance (100%) between tissue samples and tumor cell-lines. The BRAF V600E mutant-specific antibody showed high sensitivity (96%) and specificity (100%) for detecting the presence of a BRAF V600E mutation. The correlation was of 98% between PCR and immunohistochemistry results for BRAF mutation. These results suggest that BRAF and NRAS mutation status of tumor cells is not affected by culture conditions.

  9. Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe – a systematic review of the literature

    PubMed Central

    Svedman, Fernanda Costa; Pillas, Demetris; Taylor, Aliki; Kaur, Moninder; Linder, Ragnar; Hansson, Johan

    2016-01-01

    Background Given the increasing incidence in cutaneous malignant melanoma (CMM) and the recent changes in the treatment landscape, it is important to understand stage-specific overall and recurrence-free survival patterns in Europe. Despite publications such as EUROCARE-5, there is limited information on stage-specific survival for CMM in Europe. Method We carried out a systematic literature review to provide an up-to-date summary of stage-specific survival and recurrence-free survival patterns in patients with CMM in Europe. Studies were included if they were published in Medline during the past 12 years and included information on stage-specific survival and/or recurrence in CMM. Results Of the 8,749 studies identified, 26 studies were included, representing nine countries. Collectively, the studies covered a population of 152,422 patients and included data from 1978 to 2011. Randomized clinical trials and single-center observational studies comprised the most common study designs, including five large registry-based studies. Stage-specific information for survival and recurrence varied: 5-year overall survival: 95%–100% (stage I), 65%–92.8% (stage II), 41%–71% (stage III), and 9%–28% (stage IV); 5-year relapse-free survival was reported less frequently: 56% (stage II), and 28%–44% (stage III). Studies reporting survival by sentinel node (SN) status reported 5-year overall survival as 80%–95% for negative SN (stage I/II) and 35%–75% for positive SN (stage III) status; recurrence-free survival at 5 years: 76%–90% for negative and 35%–58% for positive SN status. Some studies included comparisons of survival by key patient sociodemographic characteristics, suggesting that these have a substantial influence on survival and recurrence estimates. Conclusion The studies identified in this review show large variations in stage-specific overall and recurrence-free survival by study type and by country. Owing to differing study designs and populations, it

  10. Zebrafish Melanoma.

    PubMed

    Kaufman, Charles K

    2016-01-01

    Melanoma skin cancer is a potentially deadly disease in humans and has remained extremely difficult to treat once it has metastasized. In just the last 10 years, a number of models of melanoma have been developed in the zebrafish that are biologically faithful to the human disease and have already yielded important insights into the fundamental biology of melanoma and offered new potential avenues for treatment. With the diversity and breadth of the molecular genetic tools available in the zebrafish, these melanoma models will continue to be refined and expanded upon to keep pace with the rapidly evolving field of melanoma biology. PMID:27165365

  11. Oncogenes in melanoma: an update.

    PubMed

    Kunz, Manfred

    2014-01-01

    Melanoma is a highly aggressive tumour with poor prognosis in the metastatic stage. BRAF, NRAS, and KIT are three well-known oncogenes involved in melanoma pathogenesis. Targeting of mutated BRAF kinase has recently been shown to significantly improve overall survival of metastatic melanoma patients, underscoring the particular role of this oncogene in melanoma biology. However, recurrences regularly occur within several months, which supposedly involve further oncogenes. Moreover, oncogenic driver mutations have not been described for up to 30% of all melanomas. In order to obtain a more complete picture of the mutational landscape of melanoma, more recent studies used high-throughput DNA sequencing technologies. A number of new oncogene candidates such as MAPK1/2, ERBB4, GRIN2A, GRM3, RAC1, and PREX2 were identified. Their particular role in melanoma biology is currently under investigation. Evidence for the functional relevance of some of these new oncogene candidates has been provided in in vitro and in vivo experiments. However, these findings await further validation in clinical studies. This review provides an overview on well-known melanoma oncogenes and new oncogene candidates, based on recent high-throughput sequencing studies. The list of genes discussed herein is of course not complete but highlights some of the most significant of recent findings in this area. The new candidates may support more individualized treatment approaches for metastatic melanoma patients in the future. PMID:24468268

  12. Uveal melanoma: Estimating prognosis

    PubMed Central

    Kaliki, Swathi; Shields, Carol L; Shields, Jerry A

    2015-01-01

    Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately. PMID:25827538

  13. Inherited Variation at MC1R and Histological Characteristics of Primary Melanoma

    PubMed Central

    Taylor, Nicholas J.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Anton-Culver, Hoda; Cust, Anne E.; Begg, Colin B.; Dwyer, Terence; Gallagher, Richard P.; Gruber, Stephen B.; Orlow, Irene; Rosso, Stefano; Thomas, Nancy E.; Zanetti, Roberto; Rebbeck, Timothy R.; Berwick, Marianne; Kanetsky, Peter A.

    2015-01-01

    Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype. PMID:25790105

  14. Chemotherapy for Melanoma.

    PubMed

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  15. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

    Berman, C.G.; Norman, J.; Cruse, C.W.; Reintgen, D.S.; Clark, R.A. )

    1992-01-01

    The development and rationale for the use of lymphoscintigraphy in the preoperative evaluation of patients with malignant melanoma being considered for elective lymph node dissection is reviewed. This overview is updated by an analysis of 135 patients with early stage malignant melanoma involving the head, neck, shoulders, and trunk at Moffitt Cancer Center and Research Institute at the University of South Florida (Tampa, FL). High discordancy rates (overall, 41%) were seen between drainage patterns predicted from historical anatomical guidelines and those revealed by the lymphoscintigraphic examination. The high discordancy rate was most pronounced in the head (64%) and the neck (73%). Surgical management was changed in 33% of the patients, overall. A preoperative lymphoscintigram is recommended for all patients with melanoma with head, neck, and truncal lesions evaluated for elective lymph node dissection as the lymphatic drainage patterns are often unpredictable and variable.

  16. Prospective Multicenter Phase II Trial of Systemic ADH-1 in Combination With Melphalan via Isolated Limb Infusion in Patients With Advanced Extremity Melanoma

    PubMed Central

    Beasley, Georgia M.; Riboh, Jonathan C.; Augustine, Christina K.; Zager, Jonathan S.; Hochwald, Steven N.; Grobmyer, Stephen R.; Peterson, Bercedis; Royal, Richard; Ross, Merrick I.; Tyler, Douglas S.

    2011-01-01

    Purpose Isolated limb infusion (ILI) with melphalan (M-ILI) dosing corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit melanoma with a 29% complete response rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes. In a preclinical animal model, systemic ADH-1 given with regional melphalan demonstrated synergistic antitumor activity, and in a phase I trial with M-ILI it had minimal toxicity. Patients and Methods Patients with American Joint Committee on Cancer (AJCC) stage IIIB or IIIC extremity melanoma were treated with 4,000 mg of ADH-1, administered systemically on days 1 and 8, and with M-ILI corrected for IBW on day 1. Drug pharmacokinetics and N-cadherin immunohistochemical staining were performed on pretreatment tumor. The primary end point was response at 12 weeks determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results In all, 45 patients were enrolled over 15 months at four institutions. In-field responses included 17 patients with complete responses (CRs; 38%), 10 with partial responses (22%), six with stable disease (13%), eight with progressive disease (18%), and four (9%) who were not evaluable. Median duration of in-field response among the 17 CRs was 5 months, and median time to in-field progression among 41 evaluable patients was 4.6 months (95% CI, 4.0 to 7.1 months). N-cadherin was detected in 20 (69%) of 29 tumor samples. Grade 4 toxicities included creatinine phosphokinase increase (four patients), arterial injury (one), neutropenia (one), and pneumonitis (one). Conclusion To the best of our knowledge, this phase II trial is the first prospective multicenter ILI trial and the first to incorporate a targeted agent in an attempt to augment antitumor responses to regional chemotherapy. Although targeting N-cadherin may improve melanoma sensitivity to chemotherapy, no difference in response to treatment was seen in this study. PMID:21343562

  17. Diagnostic Challenge of Desmoplastic Melanoma

    PubMed Central

    Andreevscaia, Olga; Theate, Ivan; Goossens, Cathy; Vanhooteghem, Olivier

    2016-01-01

    Desmoplastic melanoma (DM) is a rare variant of spindle-cell malignant melanoma. DM is easily misdiagnosed at an early stage because it can be confused with benign entities. Histological analysis, including careful attention to the presence of atypical spindle cells, as well as to lymphocytic aggregates in an abundant fibrotic stroma in the dermis, provides clues for diagnosis. The adjunction of an immunohistochemical panel, and particularly testing for S-100 protein, is needed for the final diagnosis. PMID:27134705

  18. [Choroidal melanoma].

    PubMed

    Desjardins, Laurence

    2016-03-01

    Choroidal melanoma is the most common form of eye cancer in adults. Treatments enabling the tumour to be destroyed or removed while preserving the eye socket are mainly based on surgery, proton therapy and brachytherapy. PMID:26944641

  19. Fas-mediated apoptosis of melanoma cells and infiltrating lymphocytes in human malignant melanomas.

    PubMed

    Shukuwa, Tetsuo; Katayama, Ichiro; Koji, Takehiko

    2002-04-01

    In a rodent system, melanoma cells expressing Fas ligand (FasL) could kill Fas-positive lymphocytes, suggesting that FasL expression was an essential factor for melanoma cell survival in vivo. These findings led us to investigate apoptosis, and to histochemically analyze involvement of Fas and FasL in the induction of apoptosis, in human malignant melanoma tissues. The percentages of terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL)-positive melanoma cells and of proliferating cell nuclear antigen (PCNA)-positive melanoma cells in melanoma tissues (n = 22) were greater than those in melanocytes in uninvolved skin (n = 6) and nevus cells in nevi tissues (n = 9). The infiltrating lymphocytes around melanomas were also TUNEL positive. Immunohistochemistry revealed expression of Fas and FasL in melanoma cells and lymphocytes, whereas no Fas or FasL expression was detected in normal skin melanocytes and nevus cells. There was significant correlation between Fas-positive indices and TUNEL indices in melanoma tissues. Moreover, TUNEL-, Fas-, and FasL-positive indices of melanoma cells from patients with Stage 3 melanomas were significantly lower than those with Stage 2 melanomas. The PCNA index of Stage 1 melanoma was significantly lower than that of the other stages, although the difference of PCNA index was insignificant among Stages 2 to 4. Among Stages 1 to 4, there was no difference in the PCNA, TUNEL-, and Fas-positive indices of lymphocytes, although the FasL-positive index of lymphocytes from Stage 3 melanomas was significantly lower than in that from Stage 2. These data reveal that melanoma cells and infiltrating lymphocytes have the potential to induce their own apoptosis regulated by Fas and FasL in an autocrine and/or paracrine fashion and that the decline of Fas-mediated apoptosis of melanoma cells, rather than the apoptosis of infiltrating lymphocytes, may affect the prognosis of melanoma patients, possibly through the

  20. Choroidal melanoma

    PubMed Central

    Singh, Parul; Singh, Abhishek

    2012-01-01

    Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma. PMID:22557869

  1. Targeted Radionuclide Therapy of Melanoma.

    PubMed

    Norain, Abdullah; Dadachova, Ekaterina

    2016-05-01

    An estimated 60,000 individuals in the United States and 132,000 worldwide are yearly diagnosed with melanoma. Until recently, treatment options for patients with stages III-IV metastatic disease were limited and offered marginal, if any, improvement in overall survival. The situation changed with the introduction of B-RAF inhibitors and anti-cytotoxic T-lymphocyte antigen 4 and anti-programmed cell death protein 1 immunotherapies into the clinical practice. With only some patients responding well to the immune therapies and with very serious side effects and high costs of immunotherapy, there is still room for other approaches for the treatment of metastatic melanoma. Targeted radionuclide therapy of melanoma could be divided into the domains of radioimmunotherapy (RIT), radiolabeled peptides, and radiolabeled small molecules. RIT of melanoma is currently experiencing a renaissance with the clinical trials of alpha-emitter (213)Bi-labeled and beta-emitter (188)Rhenium-labeled monoclonal antibodies in patients with metastatic melanoma producing encouraging results. The investigation of the mechanism of efficacy of melanoma RIT points at killing of melanoma stem cells by RIT and involvement of immune system such as complement-dependent cytotoxicity. The domain of radiolabeled peptides for targeted melanoma therapy has been preclinical so far, with work concentrated on radiolabeled peptide analogues of melanocyte-stimulating hormone receptor and on melanin-binding peptides. The field of radiolabeled small molecule produced radioiodinated benzamides that cross the cellular membrane and bind to the intracellular melanin. The recent clinical trial demonstrated measurable antitumor effects and no acute or midterm toxicities. We are hopeful that the targeted radionuclide therapy of metastatic melanoma would become a clinical reality as a stand-alone therapy or in combination with the immunotherapies such as anti-PD1 programmed cell death protein 1 monoclonal antibodies

  2. Immunohistochemical diagnostic and prognostic markers for melanoma.

    PubMed

    Nosrati, Mehdi; Kashani-Sabet, Mohammed

    2014-01-01

    Recent studies in our laboratory have identified novel molecular diagnostic and prognostic markers based on analyses in large cohorts of melanoma patients. These markers were initially derived from gene expression profiling analyses of distinct stages of melanoma progression. Immunohistochemical analyses confirmed the differential expression of these markers, and immunohistochemistry-based multimarker assays were developed to assess melanoma diagnosis and prognosis at the molecular level. In this chapter we review the development of these assays and the methodologies used to assess marker expression in both nevi and primary melanomas. PMID:24258983

  3. Uveal Melanoma

    PubMed Central

    Papastefanou, Vasilios P.; Cohen, Victoria M. L.

    2011-01-01

    Uveal melanoma is the most common primary intraocular malignancy and the leading primary intraocular disease which can be fatal in adults. In this paper epidemiologic, pathogenetic, and clinical aspects of uveal melanoma are discussed. Despite the advance in local ocular treatments, there has been no change in patient survival for three decades. Development of metastases affects prognosis significantly. Current survival rates, factors predictive of metastatic potential and metastatic screening algorithms are discussed. Proposed and emerging treatments for uveal melanoma metastases are also overviewed. Current advances in genetics and cytogenetics have provided a significant insight in tumours with high metastatic potential and the molecular mechanisms that underlie their development. Biopsy of those lesions may prove to be important for prognostication and to allow further research into genetic mutations and potential new therapeutic targets in the future. PMID:21773036

  4. Primary mucosal melanomas: a comprehensive review

    PubMed Central

    Mihajlovic, Marija; Vlajkovic, Slobodan; Jovanovic, Predrag; Stefanovic, Vladisav

    2012-01-01

    Primary mucosal melanomas arise from melanocytes located in mucosal membranes lining respiratory, gastrointestinal and urogenital tract. Although a majority of mucosal melanomas originate from the mucosa of the nasal cavity and accessory sinuses, oral cavity, anorectum, vulva and vagina, they can arise in almost any part of mucosal membranes. Most of mucosal melanomas occur in occult sites, which together with the lack of early and specific signs contribute to late diagnosis, and poor prognosis. Because of their rareness the knowledge about their pathogenesis and risk factors is insufficient, and also there are not well established protocols for staging and treatment of mucosal melanomas. Surgery is the mainstay of treatment, with trends toward more conservative treatment since radical surgery did not show an advantage for survival. Radiotherapy can provide better local control in some locations, but did not show improvement in survival. There is no effective systemic therapy for these aggressive tumors. Compared with cutaneous and ocular melanoma, mucosal melanomas have lowest percent of five-year survival. Recently revealed molecular changes underlying mucosal melanomas offer new hope for development of more effective systemic therapy for mucosal melanomas. Herein we presented a comprehensive review of various locations of primary melanoma along mucosal membranes, their epidemiological and clinical features, and treatment options. We also gave a short comparison of some characteristics of cutaneous and mucosal melanomas. PMID:23071856

  5. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    ClinicalTrials.gov

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

  6. Melanoma immunotherapy.

    PubMed

    Sivendran, Shanthi; Glodny, Bradley; Pan, Michael; Merad, Miriam; Saenger, Yvonne

    2010-01-01

    Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.

  7. Malignant melanoma at a scientific laboratory

    SciTech Connect

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-11-15

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs.

  8. Malignant Melanoma of the Foot

    MedlinePlus

    ... Javascript in your browser. Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  9. Regression of advanced melanoma upon withdrawal of immunosuppression: case series and literature review

    PubMed Central

    Thomas, N.; Sharpless, N.; Collichio, F.

    2013-01-01

    We report two cases of stage IV malignant melanoma arising in patients treated with azathioprine for myasthenia gravis. In both cases, the melanoma metastases regressed upon withdrawal of immunosuppression. One patient remains melanoma free at 10 years, and the second patient experienced an 18-month disease free period. There is one prior case report in the medical literature to support full immune reconstitution for treatment in advanced immunosuppression-related melanoma, and one case series suggesting that transplant patients developing melanoma may benefit from a switch to sirolimus. Virtually, no data exist for the medical management of early stage melanoma in the immunosuppressed patients. We review the limited preclinical data in support of immune reconstitution and the data on immunosuppression as a risk factor for melanoma. We conclude that reduction or withdrawal of immunosuppression may be beneficial in patients with advanced stage melanoma and warrants further consideration in patients with early stage melanoma. PMID:19890737

  10. Delay in cutaneous melanoma diagnosis

    PubMed Central

    Xavier, Marcus H.S.B.; Drummond-Lage, Ana P.; Baeta, Cyntia; Rocha, Lorena; Almeida, Alessandra M.; Wainstein, Alberto J.A.

    2016-01-01

    Abstract Advanced melanoma is an incurable disease with complex and expensive treatments. The best approach to prevent melanoma at advanced stages is an early diagnosis. A knowledge of factors associated with the process of detecting cutaneous melanomas and the reasons for delays in diagnosis is essential for the improvement of the secondary prevention of the disease. Identify sociodemographic, individual, and medical aspects related to cutaneous melanoma diagnosis delay. Interviews evaluated the knowledge of melanoma, signals, symptoms, persons who were suspected, delays in seeking medical attention, physician's deferrals, and related factors of 211 patients. Melanomas were self-discovered in 41.7% of the patients; healthcare providers detected 29.9% of patients and others detected 27%. The main component in delay was patient-related. Only 31.3% of the patients knew that melanoma was a serious skin cancer, and most thought that the pigmented lesion was not important, causing a delay in seeking medical assistance. Patients (36.4%) reported a wait interval of more than 6 months from the onset of an observed change in a pigmented lesion to the first visit to a physician. The delay interval from the first physician visit to a histopathological diagnosis was shorter (<1 month) in 55.5% of patients. Improper treatments without a histopathological confirmation occurred in 14.7% of patients. A professional delay was related to both inappropriate treatments performed without histopathological confirmation (P = 0.003) and long requirements for medical referrals (P < 0.001). A deficient knowledge in the population regarding melanoma and physicians’ misdiagnoses regarding suspicious lesions contributed to delays in diagnosis. PMID:27495055

  11. Treatment Options by Stage (Melanoma)

    MedlinePlus

    ... and treatments will also be taken. Lymph node mapping and sentinel lymph node biopsy : Procedures in which ... has spread to the lymph nodes . Lymph node mapping and sentinel lymph node biopsy are done to ...

  12. Stages of Intraocular (Uveal) Melanoma

    MedlinePlus

    ... eye : A procedure in which high-energy sound waves (ultrasound) are bounced off the internal tissues of ... a small probe that sends and receives sound waves is placed gently on the surface of the ...

  13. Clinical and Prognostic Factors for Renal Parenchymal, Pelvis, and Ureter Cancers in SEER Registries: Collaborative Stage Data Collection System, Version 2

    PubMed Central

    Altekruse, Sean F.; Dickie, Lois; Wu, Xiao-Cheng; Hsieh, Mei-Chin; Wu, Manxia; Lee, Richard; Delacroix, Scott

    2015-01-01

    BACKGROUND The American Joint Committee on Cancer’s (AJCC) 7th edition cancer staging manual reflects recent changes in cancer care practices. This report assesses changes from the AJCC 6th to the AJCC 7th edition stage distributions and the quality of site-specific factors (SSFs). METHODS Incidence data for renal parenchyma and pelvis and ureter cancers from 18 Surveillance, Epidemiology, and End Results (SEER) registries were examined, including staging trends during 2004–2010, stage distribution changes between the AJCC 6th and 7th editions, and SSF completeness for cases diagnosed in 2010. RESULTS From 2004 to 2010, the percentage of stage I renal parenchyma cancers increased from 50% to 58%, whereas stage IV and unknown stage cases decreased (18% to 15%, and 10% to 6%, respectively). During this period, the percentage of stage 0a renal pelvis and ureter cancers increased from 21% to 25%, and stage IV and unknown stage tumors decreased (20% to 18%, and 7% to 5%, respectively). Stage distributions under the AJCC 6th and 7th editions were about the same. For renal parenchymal cancers, 71%–90% of cases had known values for 6 required SSFs. For renal pelvis and ureter cancers, 74% of cases were coded as known for SSF1 (WHO/ISUP grade) and 47% as known for SSF2 (depth of renal parenchymal invasion). SSF values were known for larger proportions of cases with reported resections. CONCLUSIONS Stage distributions between the AJCC 6th and 7th editions were similar. SSFs were known for more than two-thirds of cases, providing more detail in the SEER database relevant to prognosis. PMID:25412394

  14. Biomarkers in melanoma.

    PubMed

    Griewank, Klaus G

    2016-01-01

    Malignant melanoma remains the skin cancer with the highest number of mortalities worldwide. While early diagnosis and complete surgical excision remain the best possibility for curing disease, prognosis at the stage of metastasis is still poor. Recent years have brought about considerable advances in terms of understanding the pathogenesis of melanoma and treating advanced disease. The discovery of activating BRAF mutations in around 50% of tumors has led to the introduction of targeted therapies downregulating BRAF signaling output. These have been further refined as combination therapies, which by targeting multiple targets have further improved the clinical outcome. A comparable, potentially even superior therapeutic alternative has been the introduction of immunotherapeutic approaches, including PD-1 and CTLA-4 checkpoint blockade therapies. Despite all genetic knowledge acquired in recent years, a clearly applicable prognostic signature of clinical value has not been established. General prognostic assessment of cutaneous melanoma remains based on clinical and pathological criteria (most importantly tumor thickness). The main challenges lying ahead are to establish a reliable prognostic test effectively determining which tumors will metastasize. Additionally establishing biomarkers which will allow patients to be stratified according to the most promising systemic therapy (immunotherapies and/or BRAF inhibitor therapies) is of utmost importance for patients with metastasized disease. Identifying serum biomarkers enabling disease to be monitored as well as determining tumor properties (i.e. resistance) would also be of great value. While initial results have proven promising, there remains much work to be done. PMID:27467728

  15. Staged Radiosurgical Ablation for Choroid Melanoma: A Case Report with Emphasis on the Role of Patient Preparation, Treatment Planning, and Precision of Delivery.

    PubMed

    Adamczyk, Marta; Janiga, Piotr

    2016-01-01

    The aim of reporting this case of choroid melanoma of the left eye is to introduce the in-house-designed treatment planning protocol for fractionated radiosurgical ablation of an intraocular lesion. This is a clinical case with emphasis on treatment preparation and delivery using the Accuray CyberKnife Robotic Radiosurgery System (Accuray, Sunnyvale, CA, USA) for a patient immobilized with a head mask and our in-house-made eye fixation system.

  16. Iridociliary melanoma – Clinical case

    PubMed Central

    Schmitzer, S; Butea-Simionescu, C; Gheorghe, A; Zemba, M; Cioboata, M

    2016-01-01

    Abstract Iris and ciliary body melanoma is an aggressive tumor, which, unfortunately, presents symptoms only in advanced stages and is often discovered accidentally during a routine eye examination. There are several treatment options, ranging from in time monitorization in order to observe the tumor’s evolution to more aggressive methods such as radiotherapy and enucleation. We present a case of iridociliary melanoma, who underwent conservative surgery, iridocyclectomy under scleral flap, with good results, and maintenance of the function and integrity of the eyeball. PMID:27713771

  17. Hyperspectral imaging for melanoma screening

    NASA Astrophysics Data System (ADS)

    Martin, Justin; Krueger, James; Gareau, Daniel

    2014-03-01

    The 5-year survival rate for patients diagnosed with Melanoma, a deadly form of skin cancer, in its latest stages is about 15%, compared to over 90% for early detection and treatment. We present an imaging system and algorithm that can be used to automatically generate a melanoma risk score to aid clinicians in the early identification of this form of skin cancer. Our system images the patient's skin at a series of different wavelengths and then analyzes several key dermoscopic features to generate this risk score. We have found that shorter wavelengths of light are sensitive to information in the superficial areas of the skin while longer wavelengths can be used to gather information at greater depths. This accompanying diagnostic computer algorithm has demonstrated much higher sensitivity and specificity than the currently commercialized system in preliminary trials and has the potential to improve the early detection of melanoma.

  18. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis.

  19. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  20. Endothelin-1 in the tumor microenvironment correlates with melanoma invasion.

    PubMed

    Chiriboga, Luis; Meehan, Shane; Osman, Iman; Glick, Michael; de la Cruz, Gelo; Howell, Brittny S; Friedman-Jiménez, George; Schneider, Robert J; Jamal, Sumayah

    2016-06-01

    Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype.

  1. Cutaneous Melanoma in Asians

    PubMed Central

    Kim, Sang Yub

    2016-01-01

    Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians. PMID:27689028

  2. Nutrition and melanoma prevention.

    PubMed

    Jensen, J Daniel; Wing, Gregory J; Dellavalle, Robert P

    2010-01-01

    Melanoma has continued to rise in incidence despite public efforts to promote sun protection behaviors. Because sunscreen use does not completely prevent skin cancer induced by ultraviolet radiation, additional chemopreventive methods for protecting against and reversing the effects of ultraviolet photodamage need evaluation. Recent years have brought increased interest in dietary factors, such as natural botanicals and vitamins, for the prevention of melanoma. This contribution provides a narrative review of the relevant, nutrition-related literature found by searching the keywords "melanoma chemoprevention," "nutrition and melanoma," "dietary botanicals and melanoma prevention," "green tea and melanoma," "vitamin D and melanoma," and "vitamin E and melanoma" in the PubMed database. Although randomized controlled trials of humans are lacking, basic science and epidemiologic studies show promising benefits of many natural products in chemoprevention for melanoma. Future studies, hopefully, will yield concrete answers and clarify the role of commonly available dietary nutrients in melanoma chemoprevention.

  3. Cutaneous Melanoma in Asians.

    PubMed

    Kim, Sang Yub; Yun, Sook Jung

    2016-09-01

    Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians. PMID:27689028

  4. Cutaneous Melanoma in Asians

    PubMed Central

    Kim, Sang Yub

    2016-01-01

    Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians.

  5. [Laboratory markers of melanoma progression].

    PubMed

    Bánfalvi, Teodóra; Edesné, Mariann B; Gergye, Mária; Udvarhelyi, Nóra; Orosz, Zsolt; Gilde, Katalin; Kremmer, Tibor; Ottó, Szabolcs; Tímár, József

    2003-01-01

    Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropriate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians. PMID:12704461

  6. Intraepidermal epidermotropic metastatic melanoma: a clinical and histopathological mimicker of melanoma in situ occurring in multiplicity.

    PubMed

    Lestre, Sara; João, Alexandre; Ponte, Pedro; Peixoto, Ana; Vieira, Joana; Teixeira, Manuel R; Fidalgo, Ana

    2011-06-01

    The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings. PMID:21352266

  7. A new understanding in the epidemiology of melanoma

    PubMed Central

    Erdei, Esther; Torres, Salina M

    2011-01-01

    The incidence of melanoma is continuing to increase worldwide. UV exposure is a known risk factor for melanoma. Geographic location is known to influence UV exposure and the distribution of the incidence of melanoma. Furthermore, epidemiologic data suggest that gender and genetics may influence the distribution of melanoma on the body surface and histopathologic characteristics of the lesion. This article describes what is known about the impact of gender, ethnicity and geography on the progression of melanoma. Advanced-stage cutaneous melanoma has a median survival time of less than 1 year. Surgical removal, radiotherapy, chemotherapy, targeted therapies and a variety of immunotherapies have been utilized in the treatment of melanoma. Current treatment strategies and the results of recent clinical trials are also discussed in this article. PMID:21080806

  8. Staged Radiosurgical Ablation for Choroid Melanoma: A Case Report with Emphasis on the Role of Patient Preparation, Treatment Planning, and Precision of Delivery

    PubMed Central

    Janiga, Piotr

    2016-01-01

    The aim of reporting this case of choroid melanoma of the left eye is to introduce the in-house-designed treatment planning protocol for fractionated radiosurgical ablation of an intraocular lesion. This is a clinical case with emphasis on treatment preparation and delivery using the Accuray CyberKnife Robotic Radiosurgery System (Accuray, Sunnyvale, CA, USA) for a patient immobilized with a head mask and our in-house-made eye fixation system. PMID:27335716

  9. Long-lasting multifunctional CD8+ T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination

    PubMed Central

    Wimmers, Florian; Aarntzen, Erik H. J. G.; Duiveman-deBoer, Tjitske; Figdor, Carl G.; Jacobs, Joannes F. M.; Tel, Jurjen; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Cytotoxic T cells are considered crucial for antitumor immunity and their induction is the aim of various immunotherapeutic strategies. High frequencies of tumor-specific CD8+ T cells alone, however, are no guarantee for long-term tumor control. Here, we analyzed the functionality of tumor-specific CD8+ T cells in melanoma patients upon dendritic cell vaccination by measuring multiple T cell effector functions considered crucial for anticancer immunity, including the expression of pro-inflammatory cytokines, chemokines and cytotoxic markers (IFNγ, TNFα, IL-2, CCL4, CD107a). We identified small numbers of multifunctional (polyfunctional) tumor-specific CD8+ T cells in several patients and dendritic cell therapy was able to improve the functionality of these pre-existing tumor-specific CD8+ T cells. Generated multifunctional CD8+ T cell responses could persist for up to ten years and within the same patient functionality could vary greatly for the different vaccination antigens. Importantly, after one cycle of DC vaccination highly functional CD8+ T cells were only detected in patients displaying prolonged overall survival. Our results shed light on the dynamics of multifunctional tumor-specific CD8+ T cells during metastatic melanoma and reveal a new feature of dendritic cell vaccination in vivo. PMID:26942087

  10. [Clinical aspect of new international gastric cancer staging system].

    PubMed

    Liang, Han

    2013-02-01

    The 7th UICC/AJCC Gastric Cancer TNM Staging System includes major revisions of pT and pN classification. The Japanese Classification and UICC/AJCC TNM System have reached consistency in staging of gastric cancer. There are some new topics of lymphadenectomy in the new guidelines. The new TNM system accepts the database from Japan and Korea and it will be more accurate to predict the prognosis of gastric cancer patients. The rationality of splenectomy, total bursectomy, dissection of No.13 and No.14 lymph nodes is still not very clear and needs more evidences. D2 lymphadenectomy is the recommended surgical approach both in Eastern and Western countries. The benefit of paraaortic lymphadenectmoy for selected patients needs further evidences as well. The international gastric cancer staging project will collect the data from 23 countries and the new staging system will be applicable worldwide. PMID:23446465

  11. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    PubMed

    Kircher, David A; Silvis, Mark R; Cho, Joseph H; Holmen, Sheri L

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  12. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

    PubMed Central

    Kircher, David A.; Silvis, Mark R.; Cho, Joseph H.; Holmen, Sheri L.

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  13. Molecular Classification of Melanoma

    Cancer.gov

    Tissue-based analyses of precursors, melanoma tumors and metastases within existing study populations to further understanding of the heterogeneity of melanoma and determine a predictive pattern of progression for dysplastic nevi.

  14. General Information about Melanoma

    MedlinePlus

    ... Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go to Health Professional Version Key ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  15. Testing Adjuvant Ipilimumab in Advanced Melanoma

    Cancer.gov

    In this clinical trial, patients with stage III or stage IV melanoma that has been completely resected will be randomly assigned to receive post-surgical treatment with either ipilimumab or high-dose interferon alfa-2b, the current standard of care.

  16. High LIFr expression stimulates melanoma cell migration and is associated with unfavorable prognosis in melanoma.

    PubMed

    Guo, Hongwei; Cheng, Yabin; Martinka, Magdalena; McElwee, Kevin

    2015-09-22

    Increased or decreased expression of LIF receptor (LIFr) has been reported in several human cancers, including skin cancer, but its role in melanoma is unknown. In this study, we investigated the expression pattern of LIFr in melanoma and assessed its prognostic value. Using tissue microarrays consisting of 441 melanomas and 96 nevi, we found that no normal nevi showed high LIFr expression. LIFr staining was significantly increased in primary melanoma compared to dysplastic nevi (P = 0.0003) and further increased in metastatic melanoma (P = 0.0000). Kaplan-Meier survival curve and univariate Cox regression analyses showed that increased expression of LIFr was correlated with poorer 5-year patient survival (overall survival, P = 0.0000; disease-specific survival, P = 0.0000). Multivariate Cox regression analyses indicated that increased LIFr expression was an independent prognostic marker for primary melanoma (P = 0.036). LIFr knockdown inhibited melanoma cell migration in wound healing assays and reduced stress fiber formation. LIFr knockdown correlated with STAT3 suppression, but not YAP, suggesting that LIFr activation might stimulate melanoma cell migration through the STAT3 pathway. Our data indicate that strong LIFr expression identifies potentially highly malignant melanocytic lesions at an early stage and LIFr may be a potential target for the development of early intervention therapeutics. PMID:26329521

  17. Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome.

    PubMed

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis.

  18. Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome.

    PubMed

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first-degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis. PMID:26892650

  19. Melanoma to the heart

    PubMed Central

    Hall, James A.; Fidone, Erica J.; Mack, Ryan; Metting, Austin L.

    2016-01-01

    Malignant melanoma is the third most common skin cancer yet has the highest mortality rate due to its predilection for metastasis. While the diagnosis of antemortem melanoma with cardiac metastasis is relatively uncommon, diagnosing malignant melanoma itself by first identifying a cardiac metastasis is even more rare. This vignette describes an antemortem diagnosis of melanoma in a 50-year-old woman through identification of metastasis to multiple sites, including the tricuspid valve. PMID:27695188

  20. Melanoma to the heart

    PubMed Central

    Hall, James A.; Fidone, Erica J.; Mack, Ryan; Metting, Austin L.

    2016-01-01

    Malignant melanoma is the third most common skin cancer yet has the highest mortality rate due to its predilection for metastasis. While the diagnosis of antemortem melanoma with cardiac metastasis is relatively uncommon, diagnosing malignant melanoma itself by first identifying a cardiac metastasis is even more rare. This vignette describes an antemortem diagnosis of melanoma in a 50-year-old woman through identification of metastasis to multiple sites, including the tricuspid valve.

  1. Cutaneous malignant melanoma: update on diagnostic and prognostic biomarkers.

    PubMed

    Abbas, Ossama; Miller, Daniel D; Bhawan, Jag

    2014-05-01

    The incidence of cutaneous malignant melanoma has rapidly increased in recent years in all parts of the world, and melanoma is a leading cause of cancer death. As even relatively small melanomas may have metastatic potential, accurate assessment of progression is critical. Although diagnosis of cutaneous malignant melanoma is usually based on histopathologic criteria, these criteria may at times be inadequate in differentiating melanoma from certain types of benign nevi. As for prognosis, tumor (Breslow) thickness, mitotic rate, and ulceration have been considered the most important prognostic indicators among histopathologic criteria. However, there are cases of thin primary melanomas that have ultimately developed metastases despite complete excision. Given this, an accurate assessment of melanoma progression is critical, and development of molecular biomarkers that identify high-risk melanoma in its early phase is urgently needed. Large-scale genomic profiling has identified considerable heterogeneity in melanoma and suggests subgrouping of tumors by patterns of gene expression and mutation will ultimately be essential to accurate staging. This subgrouping in turn may allow for more targeted therapy. In this review, we aim to provide an update on the most promising new biomarkers that may help in the identification and prognostication of melanoma. PMID:24803061

  2. Melanoma never says die.

    PubMed

    Haass, Nikolas K; Schumacher, Udo

    2014-07-01

    Drug resistance in melanoma is commonly attributed to ineffective apoptotic pathways. Targeting apoptosis regulators is thus considered a promising approach to sensitizing melanoma to therapy. In the previous issue of Experimental Dermatology, Plötz and Eberle discuss the role that apoptosis plays in melanoma progression and drug resistance and the utility of apoptosis-inducing BH3-mimetics as targeted therapy. There are a number of compounds in clinical development and the field seems close to translating recent findings into benefits for patients with melanoma. Thus, this viewpoint is timely and achieves a valuable summary of the current state of apoptosis-inducing therapy of melanoma.

  3. Melanoma resistance to photodynamic therapy: new insights

    PubMed Central

    Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.

    2012-01-01

    Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700–800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor. PMID:23152406

  4. Primary malignant melanoma

    PubMed Central

    Mısır, A. Ferhat; Durmuşlar, Mustafa C.; Zerener, Tamer; Gün, Banu D.

    2016-01-01

    Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period. PMID:27052289

  5. Clinical utilities and biological characteristics of melanoma sentinel lymph nodes

    PubMed Central

    Han, Dale; Thomas, Daniel C; Zager, Jonathan S; Pockaj, Barbara; White, Richard L; Leong, Stanley PL

    2016-01-01

    An estimated 73870 people will be diagnosed with melanoma in the United States in 2015, resulting in 9940 deaths. The majority of patients with cutaneous melanomas are cured with wide local excision. However, current evidence supports the use of sentinel lymph node biopsy (SLNB) given the 15%-20% of patients who harbor regional node metastasis. More importantly, the presence or absence of nodal micrometastases has been found to be the most important prognostic factor in early-stage melanoma, particularly in intermediate thickness melanoma. This review examines the development of SLNB for melanoma as a means to determine a patient’s nodal status, the efficacy of SLNB in patients with melanoma, and the biology of melanoma metastatic to sentinel lymph nodes. Prospective randomized trials have guided the development of practice guidelines for use of SLNB for melanoma and have shown the prognostic value of SLNB. Given the rapidly advancing molecular and surgical technologies, the technical aspects of diagnosis, identification, and management of regional lymph nodes in melanoma continues to evolve and to improve. Additionally, there is ongoing research examining both the role of SLNB for specific clinical scenarios and the ways to identify patients who may benefit from completion lymphadenectomy for a positive SLN. Until further data provides sufficient evidence to alter national consensus-based guidelines, SLNB with completion lymphadenectomy remains the standard of care for clinically node-negative patients found to have a positive SLN. PMID:27081640

  6. Serpine2, a potential novel target for combating melanoma metastasis

    PubMed Central

    Wu, Qi Wei

    2016-01-01

    Early stages of melanoma can be treated by surgical resection of tumor, but there is still no effective treatment once it is progressed to metastatic phases. Although growing family of both metastasis promoting and metastasis suppressor genes have been reported, the molecular mechanisms governing melanoma metastatic cascade are still not completely understood. Therefore, defining the molecules that govern melanoma metastasis may aid the development of more effective therapeutic strategies for combating cancer. In the present study, we found that Serpin Peptidase Inhibitor 2, Serpine2 was involved in the metastasis of melanoma cells. The requirement of Serpine2 in the migration of melanoma cells was confirmed by gene silencing and over-expression in vitro. Moreover, down-regulation of Serpine2 expression strikingly inhibited melanoma cellular metastasis in vivo. Finally, we found that Serpine2 promotes melanoma metastasis through the glycogen synthesis kinase 3β, GSK-3β signaling pathway. To conclude, our findings suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. PMID:27347308

  7. Autophagy- An emerging target for melanoma therapy.

    PubMed

    Ndoye, Abibatou; Weeraratna, Ashani T

    2016-01-01

    Melanoma accounts for only 5% of all cancers but is the leading cause of skin cancer death due to its high metastatic potential. Patients with metastatic melanoma have a 10-year survival rate of less than 10%. While the clinical landscape for melanoma is evolving rapidly, lack of response to therapies, as well as resistance to therapy remain critical obstacles for treatment of this disease. In recent years, a myriad of therapy resistance mechanisms have been unravelled, one of which is autophagy, the focus of this review. In advanced stages of malignancy, melanoma cells hijack the autophagy machinery in order to alleviate drug-induced and metabolic stress in the tumor microenvironment, thereby promoting resistance to multiple therapies, tumor cell survival, and progression.  Autophagy is an essential cellular process that maintains cellular homeostasis through the recycling of intracellular constituents. Early studies on the role of autophagy in cancer generated controversy as to whether autophagy was pro- or anti-tumorigenic. Currently, there is a consensus that autophagy is tumor-suppressive in the early stages of cancer and tumor-promoting in established tumors.  This review aims to highlight current understandings on the role of autophagy in melanoma malignancy, and specifically therapy resistance; as well as to evaluate recent strategies for therapeutic autophagy modulation. PMID:27583134

  8. MicroRNA dysregulation in melanoma.

    PubMed

    Latchana, Nicholas; Ganju, Akaansha; Howard, J Harrison; Carson, William E

    2016-09-01

    Melanoma is the deadliest form of skin cancer. Current challenges facing the management of melanoma include accurate prediction of individuals who will respond to adjuvant therapies as well as early detection of recurrences. These and other challenges have prompted investigation into biomarkers that could be used as diagnostic, prognostic and therapeutic aids. MicroRNAs (miRs) are small 19-22 nucleotide RNA inhibitors of protein translation. Over 800 different miRs are present within cells and importantly miR expression profiles may vary across different cells types and stages of malignancy. Unique expression profiles have been described for malignant melanoma; however, this work has yet to be translated into routine clinical practice. We highlight pertinent studies involving common miRs implicated in the oncogenesis of melanoma including miR-21, miR-125b, miR-150, miR-155, miR-205, and miR-211. In particular, emphasis is placed upon differential expression across different stages of melanoma progression, prognostic implications and potential mechanistic involvement. Focused efforts on inhibition of these miRs could be the most efficient method of translating preclinical endeavors into clinically meaningful applications. PMID:27566021

  9. Autophagy- An emerging target for melanoma therapy

    PubMed Central

    Ndoye, Abibatou; Weeraratna, Ashani T.

    2016-01-01

    Melanoma accounts for only 5% of all cancers but is the leading cause of skin cancer death due to its high metastatic potential. Patients with metastatic melanoma have a 10-year survival rate of less than 10%. While the clinical landscape for melanoma is evolving rapidly, lack of response to therapies, as well as resistance to therapy remain critical obstacles for treatment of this disease. In recent years, a myriad of therapy resistance mechanisms have been unravelled, one of which is autophagy, the focus of this review. In advanced stages of malignancy, melanoma cells hijack the autophagy machinery in order to alleviate drug-induced and metabolic stress in the tumor microenvironment, thereby promoting resistance to multiple therapies, tumor cell survival, and progression.  Autophagy is an essential cellular process that maintains cellular homeostasis through the recycling of intracellular constituents. Early studies on the role of autophagy in cancer generated controversy as to whether autophagy was pro- or anti-tumorigenic. Currently, there is a consensus that autophagy is tumor-suppressive in the early stages of cancer and tumor-promoting in established tumors.  This review aims to highlight current understandings on the role of autophagy in melanoma malignancy, and specifically therapy resistance; as well as to evaluate recent strategies for therapeutic autophagy modulation. PMID:27583134

  10. Malignant melanoma of the lacrimal sac.

    PubMed

    Yamade, S; Kitagawa, A

    1978-01-01

    A case of malignant melanoma of the lacrimal sac in a 41-year-old woman is reported, which is propably the 12th one in the world literature. Dacryocystectomy is advisable at a localized stage. The importance of early diagnosis is discussed. PMID:714368

  11. Melanoma with gastric metastases

    PubMed Central

    Wong, Katherine; Serafi, Sam W.; Bhatia, Abhijit S.; Ibarra, Irene; Allen, Elizabeth A.

    2016-01-01

    An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations. PMID:27609722

  12. Translational research in melanoma.

    PubMed

    Ray, Madhury; Farma, Jeffrey M; Hsu, Cary

    2013-10-01

    Recent breakthroughs in the fundamental understanding of the cellular and molecular basis of melanoma have culminated in new therapies with unquestionable efficacy. Immunotherapy and targeted therapy strategies have completely transformed the contemporary management of advanced melanoma. The translational research behind these developments is discussed, with an emphasis on immune checkpoint blockade and inhibition of the mitogen-activated protein kinase signaling pathway.

  13. Melanoma with gastric metastases.

    PubMed

    Wong, Katherine; Serafi, Sam W; Bhatia, Abhijit S; Ibarra, Irene; Allen, Elizabeth A

    2016-01-01

    An 81-year-old woman with a history of malignant melanoma who presented with dyspnea and fatigue was found to have metastases to the stomach detected on endoscopy. Primary cutaneous malignant melanoma with gastric metastases is a rare occurrence, and it is often not detected until autopsy because of its non-specific manifestations. PMID:27609722

  14. [Update on surgical treatment of primary and metastatic cutaneous melanoma].

    PubMed

    Zuluaga-Sepúlveda, María Alejandra; Arellano-Mendoza, Ivonne; Ocampo-Candiani, Jorge

    2016-01-01

    Melanoma is a common cutaneous tumour. It is of great importance due to its increasing incidence and aggressive behaviour, with metastasis to lymph nodes and internal organs. When suspecting melanoma, excisional biopsy should be performed to obtain complete histological information in order to determine the adverse factors such as ulceration, mitosis rate, and Breslow depth, which influence preoperative staging and provide data for sentinel lymph biopsy decision making. The indicated management for melanoma is wide local excision, observing recommended and well-established excision margins, depending on Breslow depth and anatomical location of the tumour. Therapeutic lymphadenectomy is recommended for patients with clinically or radiologically positive lymph nodes. This article reviews surgical treatment of melanoma, adverse histological factors, sentinel lymph node biopsy, and radical lymphadenectomy. Details are presented on special situations in which management of melanoma is different due to the anatomical location (plantar, subungual, lentigo maligna), or pregnancy.

  15. Time-resolved fluorescence lifetime for cutaneous melanoma detection

    PubMed Central

    Pires, Layla; Nogueira, Marcelo Saito; Pratavieira, Sebastião; Moriyama, Lilian Tan; Kurachi, Cristina

    2014-01-01

    Melanoma is the most aggressive skin cancer type. It is characterized by pigmented lesions with high tissue invasion and metastatic potential. The early detection of melanoma is extremely important to improve patient prognosis and survival rate, since it can progress to the deadly metastatic stage. Presently, the melanoma diagnosis is based on the clinical analysis of the macroscopic lesion characteristics such as shape, color, borders following the ABCD rules. The aim of this study is to evaluate the time-resolved fluorescence lifetime of NADH and FAD molecules to detect cutaneous melanoma in an experimental in vivo model. Forty-two lesions were analyzed and the data was classified using linear discriminant analysis, a sensitivity of 99.4%, specificity of 97.4% and accuracy of 98.4% were achieved. These results show the potential of this fluorescence spectroscopy for melanoma detection. PMID:25401022

  16. Circulating melanoma cells as a predictive biomarker.

    PubMed

    Karakousis, Giorgos; Yang, Ruifeng; Xu, Xiaowei

    2013-06-01

    The prognosis of patients with metastatic melanoma has improved significantly with targeted therapeutic agents and immunotherapies. Detection of early melanoma recurrence after treatment will be beneficial to switch patients who fail on one therapy to different modalities. Circulating tumor cells (CTCs) are cancer cells released by a tumor into the peripheral blood. These cells hold potential as prognostic, predictive, and pharmacodynamic biomarkers for treatment. In this issue, Khoja et al. report that melanoma CTCs can be detected using Melcam and high molecular weight melanoma-associated antibody. They found that in 101 stage IV melanoma patients, CTC numbers ranged between 0 and 36/7.5 ml blood; 26% of the patients had ≥ 2 CTCs at baseline. The CTC number (≥ 2 CTCs) at baseline was significantly prognostic for median overall survival (OS) in univariate and multivariate analysis. Patients receiving treatment where CTC numbers remained ≥ 2 CTCs during their treatment had shorter median OS than those who maintained <2 CTCs (7 vs. 10 months, hazard ratio 0.34, 95% confidence interval 0.14-0.81, log-rank test P=0.015). The implications of this work are substantial in counseling patients about their prognosis and in helping to assess responses to systemic therapies. PMID:23673501

  17. Tissue prognostic biomarkers in primary cutaneous melanoma.

    PubMed

    Mandalà, Mario; Massi, Daniela

    2014-03-01

    Cutaneous melanoma (CM) causes the greatest number of skin cancer-related deaths worldwide. Predicting CM prognosis is important to determine the need for further investigation, counseling of patients, to guide appropriate management (particularly the need for postoperative adjuvant therapy), and for assignment of risk status in groups of patients entering clinical trials. Since recurrence rate is largely independent from stages defined by morphological and morphometric criteria, there is a strong need for identification of additional robust prognostic factors to support decision-making processes. Most data on prognostic biomarkers in melanoma have been evaluated in tumor tissue samples by conventional morphology and immunohistochemistry (IHC) as well as DNA and RNA analyses. In the present review, we critically summarize main high-quality studies investigating IHC-based protein biomarkers of melanoma outcome according to Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)-derived criteria. Pathways have been classified and conveyed in the "biologic road" previously described by Hanahan and Weinberg. Data derived from genomic and transcriptomic technologies have been critically reviewed to better understand if any of investigated proteins or gene signatures should be incorporated into clinical practice or still remain a field of melanoma research. Despite a wide body of research, no molecular prognostic biomarker has yet been translated into clinical practice. Conventional tissue biomarkers, such as Breslow thickness, ulceration, mitotic rate and lymph node positivity, remain the backbone prognostic indicators in melanoma.

  18. [Melanoma secondary prevention].

    PubMed

    Suppa, M; Daxhelet, M; del Marmol, V

    2015-09-01

    Melanoma represents a major public health problem. Its incidence is constantly rising and the mortality rate can be frightfully important if the diagnosis is delayed. Melanoma also exerts a significant economical burden on the society. Therefore there is a need of concrete and pragmatic public health strategies in order to enhance melanoma prevention. Primary prevention of melanoma consists in avoiding excessive exposure to ultraviolet rays,'which represent the main risk factor for the disease occurrence. Secondary prevention is a synonym of melanoma early diagnosis and can be obtained by means of two methods : patients' self-examination and medical examination. Both these examinations must be routinely and thoroughly performed, must be based on the ABCDE rule and the ugly duckling sign, and ideally must be aided by the use of total-body photography. Current international guidelines suggest that all cutaneous screenings should be performed using dermoscopy, a non-invasive imaging technique that allows improving considerably the diagnostic performance. More sophisticated imaging techniques, such as confocal microscopy, are also available in specialised centres. The current scientific evidence supports the efficacy of melanoma primary and secondary prevention programs as a tool to decrease melanoma mortality. Many skin cancer prevention campaigns have been organised worldwide. The most famous and successful in Europe is Euromelanoma.

  19. SU-E-I-85: Exploring the 18F-Fluorodeoxyglucose PET Characteristics in Staging of Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Ma, C; Yin, Y

    2014-06-01

    Purpose: The aim of this study was to explore the characteristics derived from 18F-fluorodeoxyglucose (18F-FDG) PET image and assess its capacity in staging of esophageal squamous cell carcinoma (ESCC). Methods: 26 patients with newly diagnosed ESCC who underwent 18F-FDG PET scan were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, texture features and shape feature were considered. Taken the histopathologic examination as the gold standard, the extracted capacities of indices in staging of ESCC were assessed by Kruskal-Wallis test and Mann-Whitney test. Specificity and sensitivity for each of the studied parameters were derived using receiver-operating characteristic curves. Results: 18F-FDG SUVmax and SUVmean showed statistically significant capability in AJCC and TNM stages. Texture features such as ENT and CORR were significant factors for N stages(p=0.040, p=0.029). Both FDG PET Longitudinal length and shape feature Eccentricity (EC) (p≤0.010) provided powerful stratification in the primary ESCC AJCC and TNM stages than SUV and texture features. Receiver-operating-characteristic curve analysis showed that tumor textural analysis can capability M stages with higher sensitivity than SUV measurement but lower in T and N stages. Conclusion: The 18F-FDG image-derived characteristics of SUV, textural features and shape feature allow for good stratification AJCC and TNM stage in ESCC patients.

  20. [Issues around melanoma].

    PubMed

    Haanen, John

    2011-01-01

    Over the past 30 years little progress has been made in the treatment of patients with a metastatic melanoma. Recently there have been two new developments. One of these is ipilimumab, a monoclonal antibody that blocks the function of the protein cytotoxic T lymphocyte-associated antigen 4 (CTLA4) which inhibits activated T lymphocytes. This gives the immune system a chance to build up an immune response to the melanoma. The other development is vemurafenib, a small molecule that inhibits a mutated protein (BRAF) that occurs in many melanomas. The BRAF mutation leads to uninhibited proliferation.

  1. Intraoral malignant melanoma

    PubMed Central

    Babburi, Suresh; Subramanyam, R. V.; Aparna, V.; Sowjanya, P.

    2013-01-01

    Primary oral mucosal melanoma is a rare aggressive neoplasm and accounts for only 0.2-8% of all reported melanomas. It is a malignant neoplasm of melanocytes that may arise from a benign melanocytic lesion or de novo from melanocytes within normal skin or mucosa. It is considered to be the most deadly and biologically unpredictable of all human neoplasms, having the worst prognosis. In this article, we report a case of oral melanoma in a 52-year-old female patient with a chief complaint of black discolouration of the maxillary gingiva and palate. PMID:24249959

  2. Lymphangiogenesis and Anti-lymphangiogenesis in Cutaneous Melanoma.

    PubMed

    Raica, Marius; Jitariu, Adriana-Andreea; Cimpean, Anca Maria

    2016-09-01

    Cutaneous malignant melanoma is an aggressive tumor characterized by early lymph node metastasis and bad prognosis. Although the spread of tumor cells in the regional lymph nodes is very important in the staging, prognosis and therapeutic strategy of malignant melanoma, the mechanism(s) of initial lymphatic vessels invasion is are) not completely understood. In the present review, we analyze the main factors involved in melanoma-associated lymphangiogenesis, based on existing available evidence. Currently, there are no anti-lymphangiogenic drugs approved for clinical trials. On the other hand, inhibition of lymph node metastasis has been demonstrated in experimental models by inhibiting tumor-associated lymphangiogenesis. PMID:27630278

  3. Melanoma International Foundation

    MedlinePlus

    ... Exam Card Download a Patient Navigation Card Events, Webinars & Videos Events, Webinars & Videos Patient Experience Video Events Host an Event Past Webinars Upcoming Webinars Volunteer Blog Blog Melanoma? The Doctor ...

  4. Melanoma Epidemiology and Prevention.

    PubMed

    Berwick, Marianne; Buller, David B; Cust, Anne; Gallagher, Richard; Lee, Tim K; Meyskens, Frank; Pandey, Shaily; Thomas, Nancy E; Veierød, Marit B; Ward, Sarah

    2016-01-01

    The epidemiology of melanoma is complex, and individual risk depends on sun exposure, host factors, and genetic factors, and in their interactions as well. Sun exposure can be classified as intermittent, chronic, or cumulative (overall) exposure, and each appears to have a different effect on type of melanoma. Other environmental factors, such as chemical exposures-either through occupation, atmosphere, or food-may increase risk for melanoma, and this area warrants further study. Host factors that are well known to be important are the numbers and types of nevi and the skin phenotype. Genetic factors are classified as high-penetrant genes, moderate-risk genes, or low-risk genetic polymorphisms. Subtypes of tumors, such as BRAF-mutated tumors, have different risk factors as well as different therapies. Prevention of melanoma has been attempted using various strategies in specific subpopulations, but to date optimal interventions to reduce incidence have not emerged. PMID:26601858

  5. Anorectal melanoma. An update.

    PubMed

    Reina, Angel; Errasti, José; Espín, Eloy

    2014-10-01

    Anorectal melanoma is an uncommon and aggressive disease. Because the patients often present with non specific complaints, a high clinical suspicion is important to avoid a delayed diagnosis. Patients undergoing radical surgery have no significant survival difference compared to those undergoing wide local excision. Abdominoperineal resection should be reserved for selected patients in whom local excision is not technically possible or cannot obtain a clear margin. The indiscriminate use of groin dissection is not advisable in anorectal melanoma and should be use in selected cases. Systemic chemotherapy is generally a non effective treatment and continues be studied. Radiation therapy can be used as hypofractionated radiation therapy combined with local excision or in a palliative setting. The oncological outcomes in anorectal melanoma are very poor. The aim of the present study is to review clinicopathology features and management of anorectal melanoma.

  6. Melanoma and Hawaii's youth.

    PubMed

    Williams, Laura

    2004-03-01

    Hawaii's sandy beaches, warm crystal waters, and mild climate attract tourists and residents alike to enjoy hours of outdoor activities under the sun. As frequent participants of these sun related activities, Hawaii's youth are exposed to high levels and duration of ultraviolet radiation throughout their early lives. This study aims to define occurrence trends of cutaneous malignant melanoma in Hawaii in correlation to increased childhood ultraviolet exposure. This paper addresses trends in melanoma incidence during 1979-2002 for Hawaii residents < 25 years of age. Data obtained from this review were analyzed by age group and ethnicity. Results show that although the incidence of melanoma is increasing for Hawaii residents over 25 years of age, the rate of melanoma occurrence in Hawaii's youth (< 25 years) is not increasing. PMID:15124743

  7. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations

    PubMed Central

    Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-01-01

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression. PMID:27095580

  8. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations.

    PubMed

    Montagnani, Valentina; Benelli, Matteo; Apollo, Alessandro; Pescucci, Chiara; Licastro, Danilo; Urso, Carmelo; Gerlini, Gianni; Borgognoni, Lorenzo; Luzzatto, Lucio; Stecca, Barbara

    2016-05-24

    Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.

  9. Familial cutaneous melanoma.

    PubMed

    Hansson, Johan

    2010-01-01

    Approximately 5-10 % of all cutaneous melanomas occur in families with hereditary melanoma predisposition. Worldwide, approximately 20-40% of kindreds with familial elanoma harbor germline mutations in the CDKN2A gene, located on chromosome 9p21, which encodes two different proteins, p16INK4 and p14ARF, both involved in regulation of cell cycle progression and induction of senescence. In different populations several recurring CDKN2A founder mutations have been described. The risk of melanoma in CDKN2A mutations carriers varies between populations and is higher in regions with high sun exposure and high incidence of melanoma in the general population. Some CDKN2A mutations have been associated not only with melanoma but also with increased risk of other malignancies--most notably pancreatic carcinoma. A much smaller number of families have germline mutations in the CDK4 gene on chromosome 12q14, encoding a cyclin dependent kinase which normally interacts with p16INK4A. The management of families with hereditary melanoma is discussed. PMID:20687502

  10. Current State of Animal (Mouse) Modeling in Melanoma Research

    PubMed Central

    Kuzu, Omer F.; Nguyen, Felix D.; Noory, Mohammad A.; Sharma, Arati

    2015-01-01

    Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future. PMID:26483610

  11. Current State of Animal (Mouse) Modeling in Melanoma Research.

    PubMed

    Kuzu, Omer F; Nguyen, Felix D; Noory, Mohammad A; Sharma, Arati

    2015-01-01

    Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

  12. What Is Melanoma Skin Cancer?

    MedlinePlus

    ... that can become melanoma. They make a brown pigment called melanin , which gives the skin its tan ... to the sun, melanocytes make more of the pigment, causing the skin to tan or darken. Melanoma ...

  13. Preoperative nuclear scans in patients with melanoma

    SciTech Connect

    Au, F.C.; Maier, W.P.; Malmud, L.S.; Goldman, L.I.; Clark, W.H. Jr.

    1984-05-15

    One hundred forty-one liver scans, 137 brain scans, and 112 bone scans were performed in 192 patients with clinical Stage 1 melanoma. One liver scan was interpreted as abnormal; liver biopsy of that patient showed no metastasis. There were 11 suggestive liver scans; three of the patients with suggestive liver scans had negative liver biopsies. The remaining eight patients were followed from 4 to 6 years and none of those patients developed clinical evidence of hepatic metastases. All of the brain scans were normal. Five patients had suggestive bone scans and none of those patients had manifested symptoms of osseous metastases with a follow-up of 2 to 4.5 years. This study demonstrates that the use of preoperative liver, brain and bone scan in the evaluation of patients with clinical Stage 1 melanoma is virtually unproductive.

  14. Conforming to cancer staging, prognostic indicators and national treatment guidelines.

    PubMed

    Dykstra-Long, Gwendylen R

    2011-01-01

    Clinical cancer staging and prognostic indicators guide treatment planning, and as such the American College of Surgeons Commission on Cancer Commission on Cancer (ACoS CoC) and the American Joint Committee on Cancer (AJCC) have recognized this as quality patient care. Overton Brooks Veterans Administration (OBVAMC) developed an organizational policy and procedure, flow algorithms, treatment plan templates, and education strategies in order to conform to this quality care approach. The purpose of this article is to share this systematic approach that is able to support clinical and working cancer stage and prognostic indicators which have been recognized by national standard setting organizations as quality patient care.

  15. Culturing Uveal Melanoma Cells.

    PubMed

    Angi, Martina; Versluis, Mieke; Kalirai, Helen

    2015-04-01

    A major challenge in cancer research is the use of appropriate models with which to study a specific biological question. Cell lines have long been used to study cellular processes and the effects of individual molecules because they are easy to use, grow rapidly, produce reproducible results and have a strong track record in research. In uveal melanoma in particular, the absence of animal models that faithfully replicate the behavior of the human disease has propagated the generation and use of numerous cell lines by individual research groups. This in itself, however, can be viewed as a problem due to the lack of standardization when characterizing these entities to determine how closely they reflect the genetic and phenotypic characteristics of this disease. The alternative is to use in vitro primary cultures of cells obtained directly from uveal melanoma patient samples, but this too has its difficulties. Primary cell cultures are difficult to use, hard to obtain and can show considerable heterogeneity. In this article, we review the following: (1) the uveal melanoma cell lines that are currently available, discussing the importance of establishing a bank of those that represent the molecular heterogeneity of uveal melanoma; (2) the methods used to isolate and perform short-term cultures of primary uveal melanoma cells, and (3) the establishment of 3D tissue culture models that bridge the gap between 2D in vitro systems and in vivo models with which to dissect cancer biology and perform therapeutic screens. PMID:27171555

  16. Methods of Melanoma Detection.

    PubMed

    Leachman, Sancy A; Cassidy, Pamela B; Chen, Suephy C; Curiel, Clara; Geller, Alan; Gareau, Daniel; Pellacani, Giovanni; Grichnik, James M; Malvehy, Josep; North, Jeffrey; Jacques, Steven L; Petrie, Tracy; Puig, Susana; Swetter, Susan M; Tofte, Susan; Weinstock, Martin A

    2016-01-01

    Detection and removal of melanoma, before it has metastasized, dramatically improves prognosis and survival. The purpose of this chapter is to (1) summarize current methods of melanoma detection and (2) review state-of-the-art detection methods and technologies that have the potential to reduce melanoma mortality. Current strategies for the detection of melanoma range from population-based educational campaigns and screening to the use of algorithm-driven imaging technologies and performance of assays that identify markers of transformation. This chapter will begin by describing state-of-the-art methods for educating and increasing awareness of at-risk individuals and for performing comprehensive screening examinations. Standard and advanced photographic methods designed to improve reliability and reproducibility of the clinical examination will also be reviewed. Devices that magnify and/or enhance malignant features of individual melanocytic lesions (and algorithms that are available to interpret the results obtained from these devices) will be compared and contrasted. In vivo confocal microscopy and other cellular-level in vivo technologies will be compared to traditional tissue biopsy, and the role of a noninvasive "optical biopsy" in the clinical setting will be discussed. Finally, cellular and molecular methods that have been applied to the diagnosis of melanoma, such as comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), will be discussed. PMID:26601859

  17. Cutaneous melanoma mortality among the socioeconomically disadvantaged in Massachusetts.

    PubMed Central

    Geller, A C; Miller, D R; Lew, R A; Clapp, R W; Wenneker, M B; Koh, H K

    1996-01-01

    OBJECTIVES: To identify groups for melanoma prevention and early detection programs, this study explored the hypothesis that survival with cutaneous melanoma is disproportionately lower for persons of lower socioeconomic status. METHODS: Massachusetts Cancer Registry and Registry of Vital Records and Statistics data (1982 through 1987) on 3288 incident cases and 1023 deaths from cutaneous melanoma were analyzed. Mortality/incidence ratios were calculated and compared, predictors of late stage disease were examined with logistic regression analysis, and a proportional hazards regression analysis that used death registration as the outcome measure for incident cases was performed. RESULTS: Lower socioeconomic status was associated with a higher mortality/incidence ratio after adjustment for age and sex. For education, the mortality/incidence ratio was 0.37 in the lower group vs 0.25 in the higher group (rate ratio = 1.48, 95% confidence interval [CI] = 1.08, 2.03). Late stage disease was independently associated with lower income (rate ratio for lowest vs highest tertile = 1.64, 95% CI = 1.20, 2.25), and melanoma mortality among case patients was associated with lower education (rate ratio = 1.52, 95% CI = 1.09, 213). CONCLUSIONS: Melanoma patients of lower socioeconomic status may be more likely to die from their melanoma than patients of higher socioeconomic status. Low- SES communities may be appropriate intervention targets. PMID:8604786

  18. [Acral lentiginous melanoma: the current state of the problem].

    PubMed

    Myasnyankin, M Yu; Gafton, G I; Anisimov, V V; Matsko, D E; Imyanitov, E N; Semiletova, Yu V

    2015-01-01

    This review is aimed at the analysis the current state of acral lentiginous melanoma. This tumor has rather aggressive course and is the main cause of death in skin cancer patients. In Russia the incidence of melanoma during the period 2000-2010 increased from 3.18 to 3.95 cases per 100000 of population. The average annual growth rate was 1.99% and the total growth rate was 21.81%. Although skin melanoma is a visual tumor, more than one third of patients visit oncologists at advanced stages of the disease. Primary melanoma with localizations on the skin of fingers, interdigital spaces, soles, palms and nail plates is especially difficult for early diagnostics.

  19. C-Reactive Protein As a Marker of Melanoma Progression

    PubMed Central

    Fang, Shenying; Wang, Yuling; Sui, Dawen; Liu, Huey; Ross, Merrick I.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Royal, Richard E.; Lucci, Anthony; Schacherer, Christopher W.; Gardner, Julie M.; Reveille, John D.; Bassett, Roland L.; Wang, Li-E; Wei, Qingyi; Amos, Christopher I.; Lee, Jeffrey E.

    2015-01-01

    Purpose To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival. Patients and Methods Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Results Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression. Conclusion CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma. PMID:25779565

  20. Primary Malignant Vaginal Melanoma – Case Report and Review of the Literature

    PubMed Central

    Kühn, F.; Dieterich, M.; Klar, E.; Gerber, B.; Prinz, C.

    2012-01-01

    With fewer than 250 cases published worldwide, primary vaginal melanoma is an extremely rare malignant entity which is mostly diagnosed in advanced stages. The estimated incidence of vaginal melanoma is 0.026/100 000 women per year. The poor prognosis for advanced tumour stages and different therapies used in very limited numbers of patients require precise preoperative staging and a planned interdisciplinary therapeutic approach. PMID:25258467

  1. Dermoscopy of Nodular Melanoma: Review of the Literature and Report of 3 Cases.

    PubMed

    Đorđević Brlek, Zorica; Jurakić Tončić, Ružica; Radoš, Jaka; Marinović, Branka

    2016-08-01

    Nodular melanoma is the most aggressive subtype of melanoma, with rapid growth rate and metastatic potential. It is usually diagnosed at a locally advanced stage (Breslow thickness <2 mm) and is therefore associated with a poor prognosis. Nodular melanoma often does not fit the classic clinical ABCD criteria, but rather the EFG rule or 3 Cs criteria. Missing the diagnosis of nodular melanoma is a dermatologist's worst nightmare, especially since nodular melanomas can have a non-alarming clinical appearance and imitate a wide range of benign lesions. All evolving nodular lesions, despite their size, symmetry, and color, which cannot be confidently diagnosed as benign, should be excised in order to rule out nodular melanoma. Almost all melanoma-specific dermoscopic criteria are described in context of superficial spreading melanoma. Thus, physicians are not familiar and aware enough of dermoscopic features for early detection of nodular melanomas. Herein we present 3 cases of nodular melanomas from our Department and give a review of the current literature. PMID:27663921

  2. Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

    PubMed Central

    2013-01-01

    Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients. PMID:23731854

  3. Vitamins and Melanoma

    PubMed Central

    Russo, Irene; Caroppo, Francesca; Alaibac, Mauro

    2015-01-01

    A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamins in chemoprevention and therapy of melanoma could be encouraged if supported by pre-clinical and clinical evidence. PMID:26213971

  4. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

    This book contains the following 10 chapters: The role of oncogenes in the pathogenesis of malignant melanoma; Laminin and fibronectin modulate the metastatic activity of melanoma cells; Structure, function and biosynthesis of ganglioside antigens associated with human tumors derived from the neuroectoderm; Epidemiology of ocular melanoma; Malignant melanoma: Prognostic factors; Endocrine influences on the natural history of human malignant melanoma; Psychosocial factors associated with prognostic indicators, progression, psychophysiology, and tumor-host response in cutaneous malignant melanoma; Central nervous system metastases in malignant melanoma; Interferon trials in the management of malignant melanoma and other neoplasms: an overview; and The treatment of malignant melanoma by fast neutrons.

  5. Long-term Survival of Patients With Invasive Ultra-thin Cutaneous Melanoma

    PubMed Central

    Vecchiato, Antonella; Zonta, Elisa; Campana, Luca; Dal Bello, Giacomo; Rastrelli, Marco; Rossi, Carlo Riccardo; Alaibac, Mauro

    2016-01-01

    Abstract The incidence of cutaneous melanoma is increasing worldwide, especially for thin melanoma (Breslow ≤1 mm). Thin cutaneous melanoma has a favorable prognosis but there are few data about the prognosis of patients with ultra-thin cutaneous melanoma (Breslow ≤ 0.5 mm). Our aim was to investigate the disease-free survival among patients with invasive cutaneous melanoma with Breslow ≤ 0.5 mm after 10 years from the initial diagnosis. A retrospective review of 240 cutaneous melanoma patients with Breslow ≤ 0.5 mm was performed. Recurrence, death from cutaneous melanoma, and disease-free survival were all identified. In the whole group of patients, we observed only 2 deaths from cutaneous melanoma. Median follow-up was 13, 11 years. Among all 240 patients, 221 were alive and disease free, 2 died of cutaneous melanoma, 11 died of other non-neoplastic diseases, 5 died of other neoplastic diseases different from melanoma, and 1 patient had a local recurrence; therefore the 10-year melanoma survival rate was 99.6%. Our data indicate that death from cutaneous melanoma in the group of patients with Breslow ≤0.5 mm was a very rare event and that diagnosis at this stage dramatically decreases the risk of developing metastatic tumors to a <0.5% also after a 10-year period of follow-up. Limitation of the study includes the fact that other risk factors for melanoma, notably ulceration, and mitotic rate, were not evaluated. PMID:26765437

  6. Melanoma risk and survival among organ transplant recipients

    PubMed Central

    Robbins, Hilary A.; Clarke, Christina A.; Arron, Sarah T.; Tatalovich, Zaria; Kahn, Amy R.; Hernandez, Brenda Y.; Paddock, Lisa; Yanik, Elizabeth L.; Lynch, Charles F.; Kasiske, Bertram L.; Snyder, Jon; Engels, Eric A.

    2015-01-01

    Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked U.S. transplant-cancer registry data (1987–2010). We used standardized incidence ratios (SIRs) to compare incidence to the general population, and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (N=182) and non-recipients (N=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (N=519) was elevated (SIR=2.20, 95%CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95%CI 3.27–5.09). Risk of localized tumors was stable over time after transplantation, but higher with azathioprine maintenance therapy (IRR=1.35, 95%CI 1.03–1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95%CI 1.02–2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (HR 2.98, 95%CI 2.26–3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with ultraviolet radiation, while T-cell depleting induction therapies may promote late stage tumors. Our findings support sun safety practices and skin screening for transplant recipients. PMID:26270022

  7. Raman spectroscopy detects melanoma and the tissue surrounding melanoma using tissue-engineered melanoma models

    PubMed Central

    Yorucu, Ceyla; Lau, Katherine; Mittar, Shweta; Green, Nicola H.; Raza, Ahtasham; Rehman, Ihtesham Ur; MacNeil, Sheila

    2016-01-01

    ABSTRACT Invasion of melanoma cells from the primary tumor involves interaction with adjacent tissues and extracellular matrix. The extent of this interaction is not fully understood. In this study Raman spectroscopy was applied to cryo-sections of established 3D models of melanoma in human skin. Principal component analysis was used to investigate differences between the tumor and normal tissue and between the peri-tumor area and the normal skin. Two human melanoma cells lines A375SM and C8161 were investigated and compared in 3D melanoma models. Changes were found in protein conformations and tryptophan configurations across the entire melanoma samples, in tyrosine orientation and in more fluid lipid packing only in tumor dense areas, and in increased glycogen content in the peri-tumor areas of melanoma. Raman spectroscopy revealed changes around the perimeter of a melanoma tumor as well as detecting differences between the tumor and the normal tissue. PMID:27158185

  8. Melanoma of the Skin

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 76,380 % of All New Cancer Cases 4.5% Estimated Deaths in 2016 10,130 % of All Cancer ... of This Cancer : In 2013, there were an estimated 1,034,460 people living with melanoma of ...

  9. Spice Blocks Melanoma Growth

    ERIC Educational Resources Information Center

    Science Teacher, 2005

    2005-01-01

    Curcumin, the pungent yellow spice found in both turmeric and curry powders, blocks a key biological pathway needed for development of melanoma and other cancers, according to a study that appears in the journal Cancer. Researchers from The University of Texas M. D. Anderson Cancer Center demonstrate how curcumin stops laboratory strains of…

  10. Melanoma Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing melanoma cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  11. Dynamic contrast-enhanced MRI of ocular melanoma.

    PubMed

    Jiang, Xuyuan; Asbach, Patrick; Willerding, Gregor; Dulce, Miriam; Xu, Ke; Taupitz, Matthias; Hamm, Bernd; Erb-Eigner, Katharina

    2015-04-01

    Dynamic contrast-enhanced MRI is used for the assessment of microvasculature in several tumours. We aimed to assess the contrast signal enhancement characteristics of ocular melanoma. Forty patients with ocular melanoma were prospectively investigated with ocular MRI including dynamic contrast-enhanced sequences over a 13-month period. A region-of-interest analysis of the images was carried out to calculate signal enhancement characteristics after a contrast injection. Clinical follow-up data such as extraocular spread and development of liver metastasis were compared with the signal enhancement characteristics of the ocular melanoma. In 39 patients (98%), the ocular melanomas showed an early strong signal enhancement after contrast injection, resulting in a mean time of maximum enhancement of 49 s. Clinical follow-up was available in 28 patients (70%) and indicated that the peak signal intensity was significantly increased (P=0.039) in patients who developed extraocular spread or liver metastasis at a later stage. Ocular melanoma shows signal enhancement characteristics of hypervascular neoplasms. This study provides baseline curve pattern data that may be useful for assessing changes in vascularity, for example during therapy response. Furthermore, the study showed that a strong signal enhancement of the ocular melanoma might be linked to a less favourable prognosis.

  12. Socioeconomic and lifestyle factors and melanoma: a systematic review.

    PubMed

    Jiang, A J; Rambhatla, P V; Eide, M J

    2015-04-01

    Evidence of social determinants of disease and awareness of the impact of these factors on outcomes continues to increase. Social determinants include both socioeconomic and lifestyle factors. This review examines the interface between socioeconomic status (SES) and lifestyle and their effects on melanoma incidence and mortality. Lifestyle factors including occupation, occupational exposures, body mass index, marital status, smoking, recreational sun exposure and tanning were explored as they have a known relationship with melanoma. A remarkable association of SES with melanoma incidence and prognosis has been acknowledged worldwide. Melanoma incidence is increased in populations of higher SES, especially among the highly educated, while lower SES populations present with later-stage disease at time of diagnosis and display greater mortality. The aforementioned lifestyle factors are also related to SES, and have been shown internationally to affect melanoma incidence and mortality. This comprehensive systematic review suggests that lifestyle factors including occupation, occupational exposure, obesity, recreational sun exposure and tanning may explain the relationship between SES and melanoma.

  13. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  14. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. PMID:22212080

  15. Radiation Therapy and MK-3475 for Patients With Recurrent/Metastatic Head and Neck Cancer, Renal Cell Cancer, Melanoma, and Lung Cancer

    ClinicalTrials.gov

    2016-10-18

    Head and Neck Squamous Cell Carcinoma; Metastatic Renal Cell Cancer; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IV Lung Cancer; Stage IV Skin Melanoma

  16. Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network

    PubMed Central

    Li, Jian-Liang; Mazar, Joseph; Zhong, Cuncong; Faulkner, Geoffrey J.; Govindarajan, Subramaniam S.; Zhang, Zhan; Dinger, Marcel E.; Meredith, Gavin; Adams, Christopher; Zhang, Shaojie; Mattick, John S.; Ray, Animesh; Perera, Ranjan J.

    2013-01-01

    Metastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2, and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles, and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity. PMID:24129253

  17. Study Suggests Smaller Melanoma Excision Margins May Be Option for Some Patients

    Cancer.gov

    A randomized controlled trial of patients with stage IIA–C cutaneous melanoma thicker than 2-mm found that a 2-cm surgical resection margin is sufficient and is as safe for patients as a 4-cm margin.

  18. Alternative staging of regional lymph nodes in gastric cancer

    PubMed Central

    Szczepanik, Antoni M.; Paszko, Agata; Szura, Miroslaw; Scully-Horner, Thecla; Kulig, Jan

    2016-01-01

    The TNM pN stage based on the number of metastatic lymph nodes is an independent prognostic factor in gastric cancer. Many studies have highlighted the phenomenon of stage migration and problems in comparing groups of patients with different numbers of total lymph nodes harvested within TNM staging. The current version of UICC/AJCC and JGCA TNM classifications postulates a minimal number of 16 lymph nodes as the base for N stage determination. Alternative systems such as lymph node ratio (LNR), positive to negative lymph node ratio (PNLNR), and LOGODDS (or LODDS), were implemented to increase the quality of LN assessment. These methods have reached the background in the literature, but to date no standard approach according to the cut-offs for the stages has been implemented. LOGODDS is the method that most reflects the number of harvested lymph nodes. The rationale for alternative staging methods, their correlations, and limitations are presented. PMID:27713774

  19. Targeting BRAF in melanoma: biological and clinical challenges.

    PubMed

    Mandalà, Mario; Voit, Christiane

    2013-09-01

    Melanoma is an aggressive form of skin cancer that causes the greatest number of skin cancer-related deaths worldwide. In its early stages malignant melanoma can be cured by surgical resection, but once it has progressed to the metastatic stage it is extremely difficult to treat and does not respond to current therapies. A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk (MAPK) signal transduction pathway. The discovery of activating BRAF mutations in ∼50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. This review summarizes the critical role of BRAF in melanoma pathophysiology, the clinical and pathological determinants of BRAF mutation status and finally addresses the current state of the art of BRAF inhibitors. We further outline the most recent findings on the mechanisms that underlie intrinsic and acquired BRAF inhibitor resistance and describe ongoing preclinical and clinical studies designed to delay or abrogate the onset of therapeutic escape.

  20. In situ photoimmunotherapy for melanoma: preliminary clinical results

    NASA Astrophysics Data System (ADS)

    Naylor, Mark F.; Nordquist, Robert E.; Teauge, T. Kent; Perry, Lisa A.; Chen, Wei R.

    2006-02-01

    Although melanoma accounts for only 4% of skin cancer cases, it causes 79% of all skin cancer deaths. Patients with metastatic melanoma have a poor prognosis, and long term survival is only about 5% [1, 2]. Conventional therapies such as surgery and radiation therapy usually do not cure stage III or stage IV melanoma, while traditional chemotherapy is primarily palliative. Over the last decade we have been developing new methods for treating solid tumors like melanoma, first in animal models and now in humans. We present here preliminary results from a new technique that utilizes a combination of laser stimulation and drug therapy to stimulate brisk immunological responses in cases of advanced melanoma with cutaneous metastases. A high-power, near-infrared diode laser (805 nm) is used to kill tumors in situ and a topical toll-like receptor agonist (imiquimod cream, 5%) is used to intensify the resulting immunological response. This is essentially an in situ, tumor vaccine approach to treating solid tumors.

  1. Surgical treatment of advanced melanoma.

    PubMed

    Hussussian, Christopher J

    2010-01-01

    Primary surgical treatment should be considered for patients with metastatic melanoma. Because of the poor response of melanoma to chemotherapy or radiation therapy, surgery can be the best approach to quickly eliminate detectable disease and return the patient to normal activities. In properly selected patients, surgery can lead to significant palliation and prolongation of survival. This article reviews the principles of patient selection and the potential benefits of surgical management of melanoma metastatic to various sites. Novel adjuvant therapies are being developed to augment the benefits of surgical treatment of advanced melanoma in the future.

  2. The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation

    PubMed Central

    Lau, Eric; Feng, Yongmei; Claps, Giuseppina; Fukuda, Michiko N.; Perlina, Ally; Donn, Dylan; Jilaveanu, Lucia; Kluger, Harriet; Freeze, Hudson H.; Ronai, Ze’ev A.

    2016-01-01

    Melanoma is one of the most lethal skin cancers worldwide, primarily because of its propensity to metastasize. Thus, the elucidation of mechanisms that govern metastatic propensity is urgently needed. We found that protein kinase Cε (PKCε)–mediated activation of activating transcription factor 2 (ATF2) controls the migratory and invasive behaviors of melanoma cells. PKCε-dependent phosphorylation of ATF2 promoted its transcriptional repression of the gene encoding fucokinase (FUK), which mediates the fucose salvage pathway and thus global cellular protein fucosylation. In primary melanocytes and cell lines representing early-stage melanoma, the abundance of PKCε-phosphorylated ATF2 was low, thereby enabling the expression of FUK and cellular protein fucosylation, which promoted cellular adhesion and reduced motility. In contrast, increased expression of the gene encoding PKCε and abundance of phosphorylated, transcriptionally active ATF2 were observed in advanced-stage melanomas and correlated with decreased FUK expression, decreased cellular protein fucosylation, attenuated cell adhesion, and increased cell motility. Restoring fucosylation in mice either by dietary fucose supplementation or by genetic manipulation of murine Fuk expression attenuated primary melanoma growth, increased the number of intratumoral natural killer cells, and decreased distal metastasis in murine isograft models. Tumor microarray analysis of human melanoma specimens confirmed reduced fucosylation in metastatic tumors and a better prognosis for primary melanomas that had high abundance of fucosylation. Thus, inhibiting PKCε or ATF2 or increasing protein fucosylation in tumor cells may improve clinical outcome in melanoma patients. PMID:26645581

  3. FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential

    PubMed Central

    Romano, S; Staibano, S; Greco, A; Brunetti, A; Nappo, G; Ilardi, G; Martinelli, R; Sorrentino, A; Di Pace, A; Mascolo, M; Bisogni, R; Scalvenzi, M; Alfano, B; Romano, M F

    2013-01-01

    Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance. We hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion. In addition, FKBP51 induced some melanoma stem cell (MCSC) genes. Purified MCSCs expressed high EMT genes levels, suggesting that genetic programs of EMT and MCSCs overlap. Immunohistochemistry of samples from patients showed intense FKBP51 nuclear signal and cytoplasmic positivity for the stem cell marker nestin in extravasating melanoma cells and metastatic brains. In addition, FKBP51 targeting by small interfering RNA (siRNA) prevented the massive metastatic substitution of liver and lung in a mouse model of experimental metastasis. The present study provides evidence that the genetic programs of cancer stemness and invasiveness overlap in melanoma, and that FKBP51 plays a pivotal role in sustaining such a program. PMID:23559012

  4. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  5. The Role of Intralesional Therapies in Melanoma.

    PubMed

    Agarwala, Sanjiv S

    2016-05-01

    The US Food and Drug Administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. Recently, it approved the first intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. Several other intralesional therapies (PV-10, interleukin-12 electroporation, coxsackievirus A21 [CVA21]) are entering later-stage testing. Locally injected agents have clearly shown their ability to produce local responses that can be durable. The possibility that they also stimulate a regional and even systemic immune response is exciting, as this potential effect may have utility in combination regimens; such regimens are an area of active research. Favorable responses with minimal toxicities in monotherapy trials have led to the first melanoma studies of T-VEC in combination with the cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab and, separately, with the programmed death 1-blocking antibody pembrolizumab. Studies of PV-10 with pembrolizumab and of CVA21 with pembrolizumab are also being initiated. Preliminary analyses of the results of the first combination trials, which show higher response rates than with either agent alone, offer some optimism that these locoregional therapies will find application--as treatment for patients who cannot tolerate systemic immunotherapies, to alleviate locoregional morbidity, and perhaps even to "prime" the immune system.

  6. Cutaneous melanoma: new advances in treatment*

    PubMed Central

    Foletto, Michele Ceolin; Haas, Sandra Elisa

    2014-01-01

    Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life. PMID:24770508

  7. The gene expression signatures of melanoma progression

    PubMed Central

    Haqq, Christopher; Nosrati, Mehdi; Sudilovsky, Daniel; Crothers, Julia; Khodabakhsh, Daniel; Pulliam, Brian L.; Federman, Scot; Miller, James R.; Allen, Robert E.; Singer, Mark I.; Leong, Stanley P. L.; Ljung, Britt-Marie; Sagebiel, Richard W.; Kashani-Sabet, Mohammed

    2005-01-01

    Because of the paucity of available tissue, little information has previously been available regarding the gene expression profiles of primary melanomas. To understand the molecular basis of melanoma progression, we compared the gene expression profiles of a series of nevi, primary melanomas, and melanoma metastases. We found that metastatic melanomas exhibit two dichotomous patterns of gene expression, which unexpectedly reflect gene expression differences already apparent in comparing laser-capture microdissected radial and vertical phases of a large primary melanoma. Unsupervised hierarchical clustering accurately separated nevi and primary melanomas. Multiclass significance analysis of microarrays comparing normal skin, nevi, primary melanomas, and the two types of metastatic melanoma identified 2,602 transcripts that significantly correlated with sample class. These results suggest that melanoma pathogenesis can be understood as a series of distinct molecular events. The gene expression signatures identified here provide the basis for developing new diagnostics and targeting therapies for patients with malignant melanoma. PMID:15833814

  8. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  9. Immunobiology of primary murine melanomas.

    PubMed

    Donawho, C; Evans, R; Kripke, M L

    1992-10-01

    Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site. PMID:1445809

  10. New TNM staging system for esophageal cancer: what chest radiologists need to know.

    PubMed

    Hong, Su Jin; Kim, Tae Jung; Nam, Kyung Bum; Lee, In Sun; Yang, Hee Chul; Cho, Sukki; Kim, Kwhanmien; Jheon, Sanghoon; Lee, Kyung Won

    2014-10-01

    Esophageal cancer is a leading cause of cancer-related deaths worldwide, and the 5-year relative survival rate remains less than 20% in the United States. The treatment of esophageal cancer should be stage specific for better clinical outcomes. Recent treatment paradigms tend to involve a multimodality approach to management, which includes surgical resection and preoperative or definitive chemoradiation therapy. Accurate pretreatment staging of esophageal cancer is integral for assessing operability and determining a suitable treatment plan. The American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) have published the seventh edition of the staging manual for cancer in the esophagus and esophagogastric junction. Unlike the sixth edition, the revised staging manual is data driven and harmonized with the staging of stomach cancer. Improvements include new definitions for the anatomic classifications Tis, T4, regional lymph node, N, and M and the addition of nonanatomic cancer characteristics (histopathologic cell type, histologic grade, and cancer location). Given the recent increase in the incidence of adenocarcinoma of the distal esophagus, esophagogastric junction, and gastric cardia, the staging of tumors in the esophagogastric junction has been addressed. Radiologists must understand the details of the seventh edition of the AJCC-UICC staging system for esophageal cancer and use appropriate imaging modalities, such as computed tomography (CT), endoscopic ultrasonography, and positron emission tomography/CT, for initial staging.

  11. Risk of malignant melanoma in men with prostate cancer: Nationwide, population-based cohort study.

    PubMed

    Thomsen, Frederik B; Folkvaljon, Yasin; Garmo, Hans; Robinson, David; Loeb, Stacy; Ingvar, Christian; Lambe, Mats; Stattin, Pär

    2016-05-01

    An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1.09-1.27), and so had married men, men with high education and income, and men residing in southern Sweden. The strongest associations were observed for stage 0 melanoma in men with low-risk prostate cancer (HR 1.45, 1.14-1.86), high education (HR 1.87, 1.60-2.18) and top income (HR 1.61, 1.34-1.93), respectively, whereas there was no association between these factors and late-stage melanoma. Men with prostate cancer also had an increased risk of basal cell carcinoma (HR 1.18, 1.15-1.22). In conclusion, men with low-risk prostate cancer, high education, high income and residency in southern Sweden had an increased risk of early-stage melanoma.

  12. Melanoma and naevi: Incidence, interrelationships and implications

    SciTech Connect

    Elwood, J.M.

    1988-01-01

    This book contains 11 chapters. Some of the chapter titles are: Trend with Time of the Incidence of Malignant Melanoma of Skin in White Populations; Classical and Molecular Genetics of Malignant Melanoma and Dysplastic Naevi; Individuals at High Risk of Melanoma (with 1 color plate); Control of Melanoma in High-Risk Populations; and Frequency of Benign Pigmented Naevi in the General Population.

  13. Thermographic evaluation of early melanoma within the vascularized skin using combined non-Newtonian blood flow and bioheat models.

    PubMed

    Bhowmik, Arka; Repaka, Ramjee; Mishra, Subhash C

    2014-10-01

    A theoretical study on vascularized skin model to predict the thermal evaluation criteria of early melanoma using the dynamic thermal imaging technique is presented in this article. Thermographic evaluation of melanoma has been carried out during the thermal recovery of skin from undercooled condition. During thermal recovery, the skin has been exposed to natural convection, radiation, and evaporation. The thermal responses of melanoma have been evaluated by integrating the bioheat model for multi-layered skin with the momentum as well as energy conservation equations for blood flow. Differential changes in the surface thermal response of various melanoma stages except that of the early stage have been determined. It has been predicted that the thermal response due to subsurface blood flow overpowers the response of early melanoma. Hence, the study suggests that the quantification of early melanoma diagnosis using thermography has not reached a matured stage yet. Therefore, the study presents a systematic analysis of various intermediate melanoma stages to determine the thermal evaluation criteria of early melanoma. The comprehensive modeling effort made in this work supports the prediction of the disease outcome and relates the thermal response with the variation in patho-physiological, thermal and geometrical parameters.

  14. Sox4 Mediated Dicer Expression is Critical for Suppression of Melanoma Cell Invasion

    PubMed Central

    Jafarnejad, Seyed Mehdi; Ardekani, Gholamreza Safaee; Ghaffari, Mazyar; Martinka, Magdalena; Li, Gang

    2016-01-01

    We previously reported reduced expression of Sox4 in metastatic melanoma and its role in suppression of cell migration and invasion through inhibition of NF-κB p50. Sox4 can also bind to the promoter sequence of Dicer, a miRNA biogenesis factor. Interestingly, altered expression of Dicer was also observed in cancers. However, the potential mechanisms which regulate Dicer expression and its potential significance in melanoma progression are unknown. Here we studied the regulation of Dicer expression by Sox4 and its role in suppression of melanoma invasion. Our data showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least 2-fold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown. Furthermore, we examined the expression of Dicer protein in a large set of melanocytic lesions (n=504) at different stages by tissue microarray and found that Dicer expression is inversely correlated with melanoma progression (P < 0.0001). Consistently, reduced Dicer expression was correlated with a poorer overall and disease-specific 5-year survival of patients (P = 0.015 and 0.0029, respectively). In addition, we found a significant correlation between expression of Sox4 and Dicer proteins in melanoma biopsies (P = 0.009), further indicating the regulation of Dicer expression by Sox4. Finally, we revealed that knockdown of Sox4 induces a major change in the expression pattern of miRNAs in melanoma cells, mainly due to reduced expression of Dicer. Our results pinpoint the regulation of Dicer expression by Sox4 in melanoma and the critical role of Dicer in suppression of melanoma invasion. Our findings on Sox4 regulated miRNA biogenesis pathway may aid toward the development of novel targeted therapeutic approaches for melanoma. PMID:22689055

  15. Gamma-probe-guided lymph node localization in malignant melanoma.

    PubMed

    Alex, J C; Weaver, D L; Fairbank, J T; Rankin, B S; Krag, D N

    1993-10-01

    The initial draining lymph node (sentinel node) has been successfully localized using intraoperative vital dye mapping and reportedly is predictive of regional nodal metastases in Clinical- Stage 1 melanoma. In an animal model, we previously established the technique of gamma-probe-guided localization of the technetium-99 sulfur colloid labelled sentinel node and found its sensitivity equal to vital dye mapping. We now report our initial experience using gamma-probe-guided localization to identify and then surgically remove the first draining lymph node(s) in 10 malignant melanoma patients. Lymphoscintigraphy was used to confirm localization. We conclude that this technique: (a) reliably localizes the sentinel node draining the site of a primary melanoma, (b) allows the lymphatic bed to be checked intraoperatively verifying complete sentinel node biopsy, and (c) is relatively simple and can be performed under local anaesthesia.

  16. Skin lesion image segmentation using Delaunay Triangulation for melanoma detection.

    PubMed

    Pennisi, Andrea; Bloisi, Domenico D; Nardi, Daniele; Giampetruzzi, Anna Rita; Mondino, Chiara; Facchiano, Antonio

    2016-09-01

    Developing automatic diagnostic tools for the early detection of skin cancer lesions in dermoscopic images can help to reduce melanoma-induced mortality. Image segmentation is a key step in the automated skin lesion diagnosis pipeline. In this paper, a fast and fully-automatic algorithm for skin lesion segmentation in dermoscopic images is presented. Delaunay Triangulation is used to extract a binary mask of the lesion region, without the need of any training stage. A quantitative experimental evaluation has been conducted on a publicly available database, by taking into account six well-known state-of-the-art segmentation methods for comparison. The results of the experimental analysis demonstrate that the proposed approach is highly accurate when dealing with benign lesions, while the segmentation accuracy significantly decreases when melanoma images are processed. This behavior led us to consider geometrical and color features extracted from the binary masks generated by our algorithm for classification, achieving promising results for melanoma detection.

  17. An Association Between Glatiramer Acetate and Malignant Melanoma.

    PubMed

    Walker, John; Smylie, AnneLiese; Smylie, Michael

    2016-09-01

    A 43-year-old female receiving immunomodulatory therapy with glatiramer acetate (copaxone, GA) for relapsing, remitting multiple sclerosis was diagnosed with stage IIIB melanoma that recurred <7 months after resection and lymphadenectomy. In preparation for systemic therapy the patient discontinued GA, and shortly thereafter experienced spontaneous and complete clinical and radiographic resolution of her disease. The development and subsequent regression of melanoma in this patient may be due to the use and subsequent discontinuation of GA, and our discussion of the case includes the potential immunologic mechanisms that may provide an explanation for our findings. To the best of our knowledge, this case represents the first reported association between the immunomodulatory agent GA and malignant melanoma. PMID:27404942

  18. Skin lesion image segmentation using Delaunay Triangulation for melanoma detection.

    PubMed

    Pennisi, Andrea; Bloisi, Domenico D; Nardi, Daniele; Giampetruzzi, Anna Rita; Mondino, Chiara; Facchiano, Antonio

    2016-09-01

    Developing automatic diagnostic tools for the early detection of skin cancer lesions in dermoscopic images can help to reduce melanoma-induced mortality. Image segmentation is a key step in the automated skin lesion diagnosis pipeline. In this paper, a fast and fully-automatic algorithm for skin lesion segmentation in dermoscopic images is presented. Delaunay Triangulation is used to extract a binary mask of the lesion region, without the need of any training stage. A quantitative experimental evaluation has been conducted on a publicly available database, by taking into account six well-known state-of-the-art segmentation methods for comparison. The results of the experimental analysis demonstrate that the proposed approach is highly accurate when dealing with benign lesions, while the segmentation accuracy significantly decreases when melanoma images are processed. This behavior led us to consider geometrical and color features extracted from the binary masks generated by our algorithm for classification, achieving promising results for melanoma detection. PMID:27215953

  19. Major Changes in Systemic Therapy for Advanced Melanoma.

    PubMed

    Thompson, John A

    2016-05-01

    Over the past 5 years, a host of new agents have radically changed the therapeutic landscape in advanced melanoma; gone are the days when the only active agents were interferon and dacarbazine. Nearly 25 years ago, few patients with stage IV melanoma reached 2-year survival; today, these survival curves have risen substantially. At the NCCN 21st Annual Conference, John A. Thompson, MD, discussed updates with longer duration of patient follow-up for immune checkpoint therapies. He also reviewed some of the newer approvals in advanced melanoma, including the combination of ipilimumab and nivolumab, high-dose ipilimumab, the oncolytic virus therapy talimogene laherparepvec, and the molecularly targeted combination of the BRAF and MEK inhibitors vemurafenib and cobimetinib. PMID:27226502

  20. Clinical systemic lupeol administration for canine oral malignant melanoma

    PubMed Central

    YOKOE, INORU; AZUMA, KAZUO; HATA, KEISHI; MUKAIYAMA, TOSHIYUKI; GOTO, TAKAHIRO; TSUKA, TAKESHI; IMAGAWA, TOMOHIRO; ITOH, NORIHIKO; MURAHATA, YUSUKE; OSAKI, TOMOHIRO; MINAMI, SABURO; OKAMOTO, YOSHIHARU

    2015-01-01

    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperatively at various time points to treat these 11 COMM cases. Of the 11 subjects, 7 exhibited no local recurrence 180 days postoperatively and no severe adverse effects were observed in any of the cases. Furthermore, no distant metastasis was observed during the experimental period. Therefore, systemic lupeol may prevent local tumor progression and distant metastasis and may be a novel adjuvant treatment for the treatment of COMM. PMID:25469276

  1. Fully Regressive Melanoma: A Case Without Metastasis.

    PubMed

    Ehrsam, Eric; Kallini, Joseph R; Lebas, Damien; Khachemoune, Amor; Modiano, Philippe; Cotten, Hervé

    2016-08-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  2. Genomic investigations of posterior uveal melanoma.

    PubMed

    Hovland, Peter G; Trempe, Clement

    2005-01-01

    The specific genetic mechanisms responsible for the malignant behavior of uveal melanoma are not known. Unlike cutaneous melanoma, epidemiologic studies have not demonstrated a definitive germline form of uveal melanoma, though familial melanoma and racial predilections occur. Molecular cytogenetic characterization of uveal melanoma suggests that somatic deletions of chromosome 3 are associated with a worse prognosis. Microarray technology has been used to characterize uveal melanoma gene expression and may provide tests useful for determining prognosis. As an improved understanding of the cellular mechanisms used by uveal melanoma is gained, new opportunities to adapt or design therapeutic approaches may emerge.

  3. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors

    PubMed Central

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-01-01

    Abstract The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory. We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs. Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1–2, Ga, M0; stage II as T3, Ga, M0 or as T1–3, Gb, M0; stage III as T4, Ga–b, M0 and stage IV as any T, M1. The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05). Stratifying patients well

  4. An electrochemical immunosensing method for detecting melanoma cells.

    PubMed

    Seenivasan, Rajesh; Maddodi, Nityanand; Setaluri, Vijaysaradhi; Gunasekaran, Sundaram

    2015-06-15

    An electrochemical immunosensing method was developed to detect melanoma cells based on the affinity between cell surface melanocortin 1 receptor (MC1R) antigen and anti-MC1R antibody (MC1R-Ab). The MC1R-Abs were immobilized in amino-functionalized silica nanoparticles (n-SiNPs)-polypyrrole (PPy) nanocomposite modified on working electrode surface of screen-printed electrode (SPE). Cyclic voltammetry was employed, with the help of redox mediator ([Fe(CN)6](3-)), to measure the change in anodic oxidation peak current arising due to the specific interaction between MC1R antigens and MC1R-Abs when the target melanoma cells are present in the sample. Various factors affecting the sensor performance, such as the amount of MC1R-Abs loaded, incubation time with the target melanoma cells, the presence of interfering non-melanoma cells, were tested and optimized over different expected melanoma cell loads in the range of 50-7500 cells/2.5 mL. The immunosensor is highly sensitive (20 cells/mL), specific, and reproducible, and the antibody-loaded electrode in ready-to-use stage is stable over two weeks. Thus, in conjunction with a microfluidic lab-on-a-chip device our electrochemical immunosensing approach may be suitable for highly sensitive, selective, and rapid detection of circulating tumor cells (CTCs) in blood samples.

  5. [The reevaluation of neoangiogenesis indices in cutaneous melanoma].

    PubMed

    Marasà, S; Sciancalepore, G; Marasà, L

    2007-02-01

    The melanoma today represents one of more diffuse malignant neoplasm and known, object of numerous studies and you debate yourself, topic more and more puts into effect them, observed and estimated under more it varies aspects to you. Our study has been lead taking in consideration the process of neoangiogenesis, fundamental stage in the progression graduates them of the malignant melanoma, than it comes true through the release of VEGF and many other angiogenic molecules from part of the same neoplastic cells. The evolution of such process represents a critical moment for the development of whichever neoplasm, but in particular way in the melanoma it is in charge of the transition from the phase of horizontal increase to that one of vertical increase. We have therefore place the attention on the appraisal of objective indices of the vascularization as factor I prognosticate of the melanoma; particularly way we have correlated the indices of vascularisation in 54 cases of melanomas, all to III the level of Clark, and have obtained of turns out to you that confirm the possibility to insert between the prognostic factors determinants also those.

  6. An electrochemical immunosensing method for detecting melanoma cells

    PubMed Central

    Seenivasan, Rajesh; Maddodi, Nityanand; Setaluri, Vijaysaradhi; Gunasekaran, Sundaram

    2015-01-01

    An electrochemical immunosensing method was developed to detect melanoma cells based on the affinity between cell surface melanocortin 1 receptor (MC1R) antigen and anti-MC1R antibody (MC1R-Ab). The MC1R-Abs were immobilized in amino-functionalized silica nanoparticles (n-SiNPs)-polypyrrole (PPy) nanocomposite modified on working electrode surface of screen-printed electrode (SPE). Cyclic voltammetry was employed, with the help of redox mediator ([Fe(CN)6]3−), to measure the change in anodic oxidation peak current arising due to the specific interaction between MC1R antigens and MC1R-Abs when the target melanoma cells are present in the sample. Various factors affecting the sensor performance, such as the amount of MC1R-Abs loaded, incubation time with the target melanoma cells, the presence of interfering non-melanoma cells, were tested and optimized over different expected melanoma cell loads in the range of 50–7500 cells/2.5 mL. The immunosensor is highly sensitive (20 cells/mL), specific, and reproducible, and the antibody-loaded electrode in ready-to-use stage is stable over two weeks. Thus, in conjunction with a microfluidic lab-on-a-chip device our electrochemical immunosensing approach may be suitable for highly sensitive, selective, and rapid detection of circulating tumor cells (CTCs) in blood samples. PMID:25636023

  7. A Case of Choroidal Melanoma Metastatic to the Breast

    PubMed Central

    Taran-Munteanu, L.; Hartkopf, A.; Eigentler, T. K.; Vogel, U.; Brucker, S.; Taran, F. A.

    2016-01-01

    A 61-year-old woman developed blurred vision in her left eye in December 2006. A clinical diagnosis of choroidal melanoma was made. The patient underwent excision of the left lens, followed by vitrectomy and stereotactic radiotherapy. She remained systemically healthy until 50 months later when, during a CT scan done for staging purposes, a newly visible lump was noted in the lower quadrant of her left breast. Core needle biopsy of the lesion in the left breast was performed, and histologic examination revealed metastasis from the choroidal melanoma. The patient underwent breast-conserving surgery of the left breast. Definitive histological examination showed clear tumor margins in the resected specimen and one sentinel lymph node without evidence of metastatic cells. Twenty-nine months after surgery, a similar nodule was detected in the upper quadrant of the left breast. Core biopsy again showed metastatic melanoma, and similar breast-conserving surgery was performed. Systemic examination, including magnetic resonance imaging of the head and computed tomography of the pelvis, abdomen, and chest, was done regularly and revealed no significant findings. Solitary breast metastases from choroidal melanoma are extremely rare. Nevertheless, clinicians should be aware of this rare form of metastasis when treating patients with suspicious breast lesions and a history of choroidal melanoma. If solitary metastasis is confirmed, then breast-conserving surgery may be recommended. PMID:27239068

  8. Proteomic Findings in Melanoma

    PubMed Central

    Sengupta, Deepanwita; Tackett, Alan J

    2016-01-01

    Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate. PMID:27274624

  9. The embryonic morphogen, Nodal, is associated with channel-like structures in human malignant melanoma xenografts.

    PubMed

    McAllister, Josephine C; Zhan, Qian; Weishaupt, Carsten; Hsu, Mei-Yu; Murphy, George F

    2010-04-01

    Formation of channel-like structures, also termed vasculogenic mimicry (VM), describes the ability of aggressive melanoma cells to form PAS-positive anastomosing structures that correlate with tumor virulence. This phenomenon may indicate differentiation plasticity, a feature melanoma cells may share with stem cells in the developing embryo. Recent studies have indicated that VM and tumorigenicity of human malignant melanoma may depend on the signaling pathways of an embryonic morphogen, Nodal. However, given the secretory nature of Nodal protein and melanoma cell heterogeneity, it remains unclear whether the Nodal-expressing cells participate directly or indirectly in VM that is potentially related to tumorigenic growth. We have developed a humanized murine xenograft model in which developing human melanomas may be sequentially studied during early stages of tumorigenic growth within a physiological human dermal microenvironment. Nodal protein localized diffusely to melanoma cell membranes, with occasional foci of accentuated reactivity in patterns suggestive of channel formation. Similar findings were detected in a limited number of patient-derived tumors. In situ hybridization confirmed Nodal mRNA to be restricted to tumor cells within xenografts that formed arborizing networks in patterns consistent with VM. These data indicate that Nodal gene expression is associated with formation of VM-like structures in a physiologically relevant model of human melanoma tumorigenesis, and further support a key role for Nodal expression in the formation of channel-like structures. The humanized xenograft model should be useful in future studies to define the mechanistic pathways responsible for VM and melanoma progression.

  10. Use of sildenafil or other phosphodiesterase inhibitors and risk of melanoma

    PubMed Central

    Pottegård, Anton; Schmidt, Sigrún Alba Johannesdottir; Olesen, Anne Braae; Achacoso, Ninah; Van Den Eeden, Stephen K; Hallas, Jesper; Sørensen, Henrik Toft; Friis, Søren; Habel, Laurel A

    2016-01-01

    Background: Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. Methods: We conducted two parallel case–control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic health records. Identifying men with histologically verified melanoma (cases) matched on birth year to 10 cancer-free controls, we estimated odds ratios (OR) for melanoma associated with high use of PDEIs (⩾100 tablets filled), adjusting for available confounders. Results: We identified 7045 DNHR and 2972 KPNC cases with invasive melanoma. The adjusted OR for invasive melanoma associated with high PDEI use was 1.22 (95% confidence interval (CI), 0.99–1.49) in DNHR and 0.95 (95% CI, 0.78–1.14) in KPNC. Odds ratios were highest for localised invasive melanoma in DNHR (OR, 1.21) and melanoma in situ in KPNC (OR, 1.15), and lowest for non-localised disease in both populations (ORs 0.75 and 0.61, respectively). The increased ORs were slightly attenuated upon adjustment for markers of health-care utilisation. Conclusions: We found little evidence for a causal association between PDEI use and risk of melanoma. The marginally increased risk of early stage disease likely resulted from more frequent health-care contacts among PDEI users. PMID:27529513

  11. Recurrent inactivating RASA2 mutations in melanoma

    PubMed Central

    Arafeh, Rand; Qutob, Nouar; Emmanuel, Rafi; Keren-Paz, Alona; Madore, Jason; Elkahloun, Abdel; Wilmott, James S.; Gartner, Jared J.; Di Pizio, Antonella; Winograd-Katz, Sabina; Sindiri, Sivasish; Rotkopf, Ron; Dutton-Regester, Ken; Johansson, Peter; Pritchard, Antonia; Waddell, Nicola; Hill, Victoria K.; Lin, Jimmy C.; Hevroni, Yael; Rosenberg, Steven A.; Khan, Javed; Ben-Dor, Shifra; Niv, Masha Y.; Ulitsky, Igor; Mann, Graham J; Scolyer, Richard A.; Hayward, Nicholas K.; Samuels, Yardena

    2016-01-01

    Analysis of 501 melanoma exomes revealed RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings reveal RASA2 inactivation as a melanoma driver and highlight the importance of Ras GAPs in cancer. PMID:26502337

  12. Melanoma immunotherapy dominates the field.

    PubMed

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  13. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  14. miR-194 is a negative regulator of GEF-H1 pathway in melanoma.

    PubMed

    Guo, Bingyu; Hui, Qiang; Zhang, Yu; Chang, Peng; Tao, Kai

    2016-10-01

    The incidence and associated mortality of melanoma continues to increase worldwide. At present, there is no curative therapy for advanced stage of melanoma. It is necessary to find new indicators of prognosis and therapeutic targets. Increasing evidence shows that miRNA can provide potential candidate biomarkers for melanoma and therapeutic targets. GEF-H1, a regulator of RhoA, as oncogenic driver in melanoma, promotes the growth and invasion of melanoma. miR-194 is a tumor-suppressor gene in multiple tumors, such as bladder and non-small cell lung cancer, and clear cell renal cell carcinoma. In the present study, we demonstrated that GEF-H1 serves as target of miR-194. Overexpression of miR-194 downregulates the GEF-H1/RhoA pathway, inhibits melanoma cancer cell proliferation and metastasis. Furthermore, miR-194 expression is negatively associated with tumor-node-metastasis (TNM) stages. Briefly, our findings provided new theoretical basis for melanoma treatment. PMID:27573550

  15. Epigenomic landscape of melanoma progression to brain metastasis: unexplored therapeutic alternatives.

    PubMed

    Marzese, Diego M; Witz, Isaac P; Kelly, Daniel F; Hoon, Dave S B

    2015-01-01

    Melanoma brain metastasis is a complication with rising incidence. Despite the high rate of somatic mutations driving the initial stages of melanocyte transformation, the brain colonization requires a phenotypic reprogramming that is, in part, influenced by epigenomic modifications. This special report summarizes recent findings in the epigenomic landscape of melanoma progression to brain metastasis, with particular emphasis on the clinical utility of DNA methylation, chromatin modifications and ncRNA expression as theragnostic markers, as well as the significance of the metastatic microenvironment on melanoma brain metastasis epigenome.

  16. What's New in Research and Treatment of Melanoma Skin Cancer?

    MedlinePlus

    ... Topic Additional resources for melanoma skin cancer What’s new in melanoma skin cancer research? Research into the ... Melanoma Talking With Your Doctor After Treatment What`s New in Skin Cancer - Melanoma Research? Other Resources and ...

  17. Modern non-invasive diagnostic techniques in the detection of early cutaneous melanoma.

    PubMed

    Kardynal, Agnieszka; Olszewska, Malgorzata

    2014-03-31

    Over the past few years melanoma has grown into a disease of socio-economic importance due to the increasing incidence and persistently high mortality rates. Melanoma is a malignant tumor with a high tendency to metastasize. Therefore, an extremely important part of the therapeutic process is to identify the disease at an early stage: in situ or stage I. Many tools for early diagnosis of melanoma are available today, including dermoscopy, videodermoscopy and in vivo reflectance confocal microscopy. Other methods such as high frequency ultrasound, optical coherence tomography and electrical impedance spectroscopy may serve as additional diagnostic aids. Modern imaging techniques also allow the monitoring of melanocytic skin lesions over months or years to detect the moment of malignant transformation. This review summarizes the current knowledge about modern diagnostic techniques, which may aid early diagnosis of melanoma. PMID:24748903

  18. Circulating epigenetic biomarkers in melanoma.

    PubMed

    Xin, Yu; Li, Zheng; Chan, Matthew T V; Wu, William Ka Kei

    2016-02-01

    Recent researches have shed new light on the importance of epigenetic alterations, including promoter hypermethylation and microRNA dysregulation, in the initiation and progression of melanoma. The clinical utilization of circulating epigenetic markers in melanoma has also been investigated. In this review, we explored the literature and summarized the latest progress in the discovery of circulating epigenetic markers, namely methylated DNA and microRNAs, for non-invasive diagnosis of melanoma, as well as their measurability and predictability. We also discussed the utility of these epigenetic markers as novel prognostic and predictive markers and their association with melanoma clinical phenotypes, including recurrence and patients' survival. Large-cohort validations are warranted to maximize the clinical utilization of these markers. PMID:26662802

  19. What Does Melanoma Look Like?

    MedlinePlus

    ... that begins in melanocytes ( cells that make the pigment melanin ). Below are photos of melanoma that formed ... often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin. Color that ...

  20. Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma.

    PubMed

    Tian, Yongjing; Zhang, Xiuying; Hao, Yinghua; Fang, Zhengyu; He, Yanling

    2014-08-01

    Melanoma is a highly aggressive skin cancer with increasing incidence worldwide. Long noncoding RNAs (lncRNAs), a group of nonprotein-coding transcripts longer than 200 nucleotides, are pervasively transcribed in the genome and are emerging as new players in tumorigenesis. The primary objective of this study was to investigate the role of six cancer-related lncRNAs in pairs of melanoma and adjacent normal tissues (ANTs). A total of 63 primary melanoma, paired ANTs, and metastatic lesions were collected in a Chinese population. Real-time PCR analysis was carried out to compare a series of cancer-related lncRNAs among primary melanoma tissues, ANTs, and metastatic lesions. In in-vitro studies, transwell migration assay was carried out to estimate the migration abilities of melanoma cells with different expression levels of urothelial carcinoma-associated 1 (UCA1) or metastasis-associated lung adenocarcinoma transcript 1 (Malat-1) lncRNAs. We found that UCA1 and Malat-1 lncRNAs were markedly more increased in melanomas than in paired ANTs (P<0.05). Melanomas at later stages (stages 3-4) showed higher expression of UCA1 lncRNA than those at early stages (stages 1-2) (P=0.455). In melanomas with lymph node metastasis, the metastatic lesions had a relatively higher expression of Malat-1 lncRNA than in paired primary tumors (P=0.414). Knockdown of UCA1 or Malat-1 lncRNA could attenuate the migrational ability of melanoma cells in in-vitro studies. Increased expression of UCA1 and Malat-1 lncRNAs might have a correlation with melanoma metastasis.

  1. [Choroidal melanoma - evolution and prognosis].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  2. Discrepancies between two alternative staging systems (European Neuroendocrine Tumor Society 2006 and American Joint Committee on Cancer/Union for International Cancer Control 2010) of neuroendocrine neoplasms of the pancreas. A study of 50 cases.

    PubMed

    Liszka, Łukasz; Pająk, Jacek; Mrowiec, Sławomir; Zielińska-Pająk, Ewa; Gołka, Dariusz; Lampe, Paweł

    2011-04-15

    The aim of our study was to identify and describe potential inconsistencies between two alternative staging systems of pancreatic neuroendocrine neoplasms (pNENs)--the European Neuroendocrine Tumor Society (ENETS) system (2006) and the American Joint Committee on Cancer/Union for International Cancer Control (AJCC-UICC) system (2010). To address this issue, we performed a retrospective clinico-pathological study of 50 cases of pNENs. We found 9 (18%) cases of ENETS/AJCC-UICC discrepancies regarding the primary tumor stage. They included 7 cases of T2/T3 disagreement and 2 cases of T3/T4 disagreement. In addition, we discussed the issue of potential T1/T2 discrepancy (however, we did not observe any such a case). Another inconsistency was related to the application of different stage prognostic groupings between both systems. In conclusion, the discrepancies between ENETS and AJCC-UICC staging systems for pNENs are relatively frequent and heterogeneous. We believe that they should be rigorously recognized. This is necessary for the evaluation of prognostic factors and the effectiveness of therapeutic options used in patients with pNENs.

  3. Skin self-examination behaviors among individuals diagnosed with melanoma.

    PubMed

    Coups, Elliot J; Manne, Sharon L; Stapleton, Jerod L; Tatum, Kristina L; Goydos, James S

    2016-02-01

    Many melanoma patients do not regularly perform thorough skin self-examinations. We examined the extent to which melanoma patients conduct thorough skin self-examination, how they perform skin self-examination, and their related knowledge and self-efficacy. A sample of 176 individuals (61.5% response rate) diagnosed with primary pathologic stage 0-III cutaneous malignant melanoma at a single cancer center completed a written or telephone survey regarding their skin self-examination behaviors and associated factors. Almost all participants (98.9%) reported their race as white. Almost three-quarters (71.6%) of participants reported doing an examination in the past 2 months. However, only 14.2% had examined all areas of the body in the past 2 months. Few participants reported always using a full-length mirror (13.4%), hand-held mirror (11.3%), or having someone help (9.2%) when doing an examination. Having a higher level of education, greater knowledge of the ABCDE rule for detecting potential melanoma, higher skin self-examination self-efficacy, being shown how to do skin self-examination, and being shown what a suspicious mole would look like were all significantly associated with conducting more thorough skin self-examination. Most melanoma patients do not engage in regular, thorough skin self-examination, and when they do examine their skin they typically do not sufficiently utilize tools and techniques to facilitate a thorough examination and tracking of potentially suspicious moles. Efforts to promote skin self-examination among melanoma patients should focus on increasing knowledge and self-efficacy and providing education about the why, when, and how of conducting self-examination and mole tracking. PMID:26426762

  4. Skin self-examination behaviors among individuals diagnosed with melanoma.

    PubMed

    Coups, Elliot J; Manne, Sharon L; Stapleton, Jerod L; Tatum, Kristina L; Goydos, James S

    2016-02-01

    Many melanoma patients do not regularly perform thorough skin self-examinations. We examined the extent to which melanoma patients conduct thorough skin self-examination, how they perform skin self-examination, and their related knowledge and self-efficacy. A sample of 176 individuals (61.5% response rate) diagnosed with primary pathologic stage 0-III cutaneous malignant melanoma at a single cancer center completed a written or telephone survey regarding their skin self-examination behaviors and associated factors. Almost all participants (98.9%) reported their race as white. Almost three-quarters (71.6%) of participants reported doing an examination in the past 2 months. However, only 14.2% had examined all areas of the body in the past 2 months. Few participants reported always using a full-length mirror (13.4%), hand-held mirror (11.3%), or having someone help (9.2%) when doing an examination. Having a higher level of education, greater knowledge of the ABCDE rule for detecting potential melanoma, higher skin self-examination self-efficacy, being shown how to do skin self-examination, and being shown what a suspicious mole would look like were all significantly associated with conducting more thorough skin self-examination. Most melanoma patients do not engage in regular, thorough skin self-examination, and when they do examine their skin they typically do not sufficiently utilize tools and techniques to facilitate a thorough examination and tracking of potentially suspicious moles. Efforts to promote skin self-examination among melanoma patients should focus on increasing knowledge and self-efficacy and providing education about the why, when, and how of conducting self-examination and mole tracking.

  5. Psychosocial, clinical and demographic features related to worry in patients with melanoma

    PubMed Central

    Elliott, Faye; Kasparian, Nadine A.; Bishop, D. Timothy; Barrett, Jennifer H.; Newton-Bishop, Julia

    2016-01-01

    The aim of this study was to investigate clinical, demographic and psychosocial predictors of melanoma-related worry. A questionnaire-based study in a population-ascertained cohort of individuals diagnosed with melanoma in the previous 3–6 months was carried out to identify factors associated with worry about melanoma shortly after diagnosis. A total of 520 patients felt worried about their future with respect to melanoma and 1568 patients felt confident about their future with respect to melanoma. Worry was less likely in men with partners than women with partners [adjusted odds ratio (OR)=0.51, 95% confidence interval (CI) (0.39–0.67)], and increasing age was protective against worry [adjusted OR=0.96 per year, 95% CI (0.95–0.97)]. Worry was more likely for patients with stage III/IV melanoma [adjusted OR=1.90, 95% CI (1.41–2.56) compared with stages IB–IIC], melanoma arising in sun-protected sites (compared with a limb), no occupation (compared with workers), those who reported insufficient emotional support from healthcare providers [adjusted OR=2.20, 95% CI (1.56–3.09) compared with sufficient support], lower knowledge of melanoma [adjusted OR=4.50, 95% CI (2.82–7.18) compared with well informed], perceived financial hardship compared with no financial hardship and over three previous negative life events compared with none/one. Worry about melanoma outcomes after diagnosis is multifactorial in origin. PMID:27196629

  6. Melanoma therapy: Check the checkpoints.

    PubMed

    Furue, Masutaka; Kadono, Takafumi

    2016-02-01

    Recent mutational and translational studies have revealed that the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway plays a key role in melanomagenesis. Mutations in NRAS and BRAF are found in the majority of melanomas resulting in the formation of constitutively active NRAS and BRAF molecules, which leads to the proliferation and survival of melanoma cells through the activation of MEK/ERK signals. Inhibitors of BRAF or MEK significantly extend the progression-free survival and overall survival of melanoma patients compared with conventional chemotherapies. Combining BRAF and MEK inhibitors further enhances the clinical effectiveness. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is an immune checkpoint molecule that downregulates T-cell activation by binding to B7 (CD80/CD86) molecules on antigen-presenting cells. Programmed death receptor ligand 1 on melanoma cells negatively regulates T-cell function by binding to the programmed death-1 (PD-1) receptor on T cells. Antibodies against CTLA-4 and PD-1 also enhance the survival of melanoma patients. In this review, we summarize the clinical effectiveness and adverse events of the BRAF inhibitors, MEK inhibitors and anti-immune checkpoint antibodies in melanoma treatment.

  7. Racial differences in melanoma incidence.

    PubMed Central

    Crombie, I. K.

    1979-01-01

    The incidences of malignant melanoma recorded by 59 population-based cancer registries were investigated to determine the effects of racial and skin-colour differences. White populations exhibited a wide range of melanoma incidences and females commonly, though not invariably, had a higher incidence than males. Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates. No predominant sex difference emerged among non-whites. Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot. A clear negative correlation between degree of skin pigmentation and melanoma incidence emerged for the exposed body sites. These data provide strong support for the hypotheses that UV radiation is a major cause of malignant melanoma and that melanin pigmentation protects against it. Further research is required to elucidate the aetiology of melanoma of the sole of the foot. PMID:475965

  8. Impact of MAPK Pathway Activation in BRAF(V600) Melanoma on T Cell and Dendritic Cell Function.

    PubMed

    Ott, Patrick A; Bhardwaj, Nina

    2013-10-28

    Constitutive upregulation of the MAPK pathway by a BRAF(V600) mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAF(V600) mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 and programed death-1/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment. There is emerging preclinical and clinical evidence suggesting that MAPK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MAPK pathway inhibition in melanoma. The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs) are important in the induction of tumor-specific T cell responses, the impact of MAPK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAF(V600E) melanoma cells modulate DCs through the MAPK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/BRAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MAPK pathway inhibition affects the tumor immune response is needed.

  9. [Necessity of the development of a melanoma prevention program in Hungary - in the light of epidemiological data].

    PubMed

    Tóth, Veronika

    2016-03-01

    The prevention and the early diagnosis of melanoma malignum are essential because of the aggressive spreading and poor therapeutic response of the tumor. Since survival mainly depends on the tumor stage, in the first part of the Ph.D. thesis the stage distribution of melanomas was assessed in the melanoma patients treated at the Department of Dermatology, Dermatooncology and Venerology, Semmelweis University. This work filled a gap, because the Hungarian National Cancer Registry, similarly to other cancer registries, does not include the tumor stages. The results of the assessment showed that most of the patients (43.8%) belonged to stage IA, while only 0.4% of them were in stage IV. In comparison with international studies from Western Europe, Australia and the United States, the distribution of our patients was highly favorable concerning stages IA and IV. To assess the risk of melanoma among special work circumstances (Nuclear Power Plant of Paks) the Department of Dermatology, Dermatooncology and Venerology organized an oncodermatological screening. The results of the screening confirmed that melanoma incidence was not elevated among the nuclear industry workers compared to the general Hungarian population. Among the 556 examined workers we found one melanoma in situ, and the medical history of this patient suggested that UV exposure rather than ionizing radiation could have been the cause of this tumor. Our results also underline the necessity of analyzing skin effects of UV light to avoid false positive correlations. The risk of second primary cancers among melanoma survivors was also assessed in our Department. The findings suggest that the risk of all second primary tumors significantly, 11-15-times increased after having a former melanoma, compared to the general population. The higher risk was mostly caused by the elevated incidence of second primary melanoma and non-melanoma skin cancers. Besides skin tumors, the risk of some internal malignancies was

  10. Latitude and incidence of ocular melanoma.

    PubMed

    Yu, Guo-Pei; Hu, Dan-Ning; McCormick, Steven A

    2006-01-01

    We investigated the associations between latitude and the incidence of two different types of ocular melanoma, external ocular melanoma (exposed to sunlight) and internal melanoma (not exposed to sunlight), separately. Using 1992-2002 data from the Surveillance, Epidemiology, and End Results (SEER) Program of National Cancer Institute, we identified 2142 ocular melanoma cases in non-Hispanic whites, and then regressed the incidences of various types of ocular melanomas with latitude. Our analysis indicated that the higher the latitude (away from the equator, the less sun exposure), the lower the risk of external ocular melanoma (eyelid and conjunctival melanomas) among non-Hispanic whites (P for trend = 0.018). The incidence increased 2.48 fold from 47-48 degrees to 20-22 degrees. This trend is very similar to that of skin melanoma. The incidence of internal ocular melanoma (uveal melanoma) increased significantly with increasing latitudes (the less sun exposure, P for trend < 0.0001), it increased 4.91 fold from 20-22 degrees to 47-48 degrees. The latitudinal patterns of ocular melanomas may reflect the dual effects of sunlight exposure, i.e. a mutagenic effect of direct solar radiation on external ocular melanomas and a protective effect for internal uveal melanoma, which is similar to the sun radiation protective effects for various internal malignant tumors that are not exposed to the sunlight.

  11. Outcomes of Proton Beam Radiotherapy for Large Non-Peripapillary Choroidal and Ciliary Body Melanoma at TRIUMF and the BC Cancer Agency

    PubMed Central

    Weber, Britta; Paton, Katherine; Ma, Roy; Pickles, Tom

    2015-01-01

    Background and Purpose To report outcomes and toxicity after proton beam radiotherapy for non-peripapillary choroidal and ciliary body melanoma considered unsuitable for other eye-sparing therapies. Materials and Methods: An existing database of 77 patients with non-peripapillary tumors treated at TRIUMF, Canada, including patient, tumor, and treatment characteristics, was updated with ocular complications and follow-up status from chart reviews. Results Most of the patients had large tumors: 61% were T3/T4 tumors (AJCC classification), while 48% were large by the Collaborative Ocular Melanoma Study classification. The median thickness was 7.1 mm, and the ciliary body was involved in 35%. After 5 and 10 years, the actuarial ocular tumor control rate was 85 and 85%, metastasis-free survival was 72 and 57%, overall survival was 77 and 63%, the enucleation rate was 22 and 22%, and complete blindness was found in 38 and 38%, respectively. On univariate analysis, patients with ciliary body involvement had significantly worse metastasis-free survival and overall survival rates compared to patients without ciliary body involvement (p < 0.001). Conclusions Proton therapy for large anteriorly located tumors resulted in acceptable ocular tumor control and survival rates. The risk of blindness and severe toxicity requiring enucleation was low, and a substantial proportion of patients maintained useful vision. PMID:27171272

  12. Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research

    PubMed Central

    Bhatia, Parisha; Friedlander, Paul; Zakaria, Elmageed A.

    2015-01-01

    This review is intended to provide an updated role of molecular genetics and various targeted therapies that have been developed to treat advanced stages of melanoma. Because of the declining success in melanoma therapy, the curative treatment for advanced stage melanoma has been a challenge for clinicians. Several mutations such as N-RAS, p53, BRAF including mutant-BRAF that lead to activation of kinase pathway, are implicated in the development of malignant melanoma. However, the current literature depicts that the prognostic role of BRAF mutation in disease progression is still controversial. While its higher level in advanced stage disease is associated with decreased overall survival (OS), some studies show that it failed to confer as an independent prognostic predictor of the disease. This has also led researchers to accomplish newer therapeutic strategies that lead to improved disease-response and grant survival benefits. Vemurafenib, a BRAF inhibitor agent, is one of the few available targeted therapies that is FDA approved and provides promising results in metastatic disease. However, its resistance at an early stage is of great concern. Recent implementation of combinational therapies including “targeted therapy”, immunotherapy, and biological agents has appealed many researchers to define the adjunctive role of available therapies and their limitations in advanced stage and metastatic melanoma. This commends the need for future multi-institutional studies to confirm the clinical validity of different therapeutic strategies on a large scale population. PMID:25738144

  13. Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination

    PubMed Central

    Boudewijns, Steve; Koornstra, Rutger H. T.; Westdorp, Harm; Schreibelt, Gerty; van den Eertwegh, Alfons J. M.; Geukes Foppen, Marnix H.; Haanen, John B.; de Vries, I. Jolanda M.; Figdor, Carl G.; Bol, Kalijn F.; Gerritsen, Winald R.

    2016-01-01

    ABSTRACT Background: Ipilimumab has proven to be effective in metastatic melanoma patients. The purpose of this study was to determine the efficacy of ipilimumab in advanced melanoma patients who showed progressive disease upon experimental dendritic cell (DC) vaccination. Methods: Retrospective analysis of 48 stage IV melanoma patients treated with ipilimumab after progression upon DC vaccination earlier in their treatment. DC vaccination was given either as adjuvant treatment for stage III disease (n = 18) or for stage IV disease (n = 30). Ipilimumab (3 mg/kg) was administered every 3 weeks for up to 4 cycles. Results: Median time between progression upon DC vaccination and first gift of ipilimumab was 5.4 mo. Progression-free survival (PFS) rates for patients that received ipilimumab after adjuvant DC vaccination, and patients that received DC vaccination for stage IV melanoma, were 35% and 7% at 1 y and 35% and 3% at 2 y, while the median PFS was 2.9 mo and 3.1 mo, respectively. Median overall survival of patients pre-treated with adjuvant DC vaccination for stage III melanoma was not reached versus 8.0 mo (95% CI, 5.2–10.9) in the group pre-treated with DC vaccination for stage IV disease (HR of death, 0.36; p = 0.017). Grade 3 immune-related adverse events occurred in 19% of patients and one death (2%) was related to ipilimumab. Conclusions: Clinical responses to ipilimumab were found in a considerable number of advanced melanoma patients with progression after adjuvant DC vaccination for stage III disease, while the effect was very limited in patients who showed progression after DC vaccination for stage IV disease.

  14. Ipilimumab administered to metastatic melanoma patients who progressed after dendritic cell vaccination

    PubMed Central

    Boudewijns, Steve; Koornstra, Rutger H. T.; Westdorp, Harm; Schreibelt, Gerty; van den Eertwegh, Alfons J. M.; Geukes Foppen, Marnix H.; Haanen, John B.; de Vries, I. Jolanda M.; Figdor, Carl G.; Bol, Kalijn F.; Gerritsen, Winald R.

    2016-01-01

    ABSTRACT Background: Ipilimumab has proven to be effective in metastatic melanoma patients. The purpose of this study was to determine the efficacy of ipilimumab in advanced melanoma patients who showed progressive disease upon experimental dendritic cell (DC) vaccination. Methods: Retrospective analysis of 48 stage IV melanoma patients treated with ipilimumab after progression upon DC vaccination earlier in their treatment. DC vaccination was given either as adjuvant treatment for stage III disease (n = 18) or for stage IV disease (n = 30). Ipilimumab (3 mg/kg) was administered every 3 weeks for up to 4 cycles. Results: Median time between progression upon DC vaccination and first gift of ipilimumab was 5.4 mo. Progression-free survival (PFS) rates for patients that received ipilimumab after adjuvant DC vaccination, and patients that received DC vaccination for stage IV melanoma, were 35% and 7% at 1 y and 35% and 3% at 2 y, while the median PFS was 2.9 mo and 3.1 mo, respectively. Median overall survival of patients pre-treated with adjuvant DC vaccination for stage III melanoma was not reached versus 8.0 mo (95% CI, 5.2–10.9) in the group pre-treated with DC vaccination for stage IV disease (HR of death, 0.36; p = 0.017). Grade 3 immune-related adverse events occurred in 19% of patients and one death (2%) was related to ipilimumab. Conclusions: Clinical responses to ipilimumab were found in a considerable number of advanced melanoma patients with progression after adjuvant DC vaccination for stage III disease, while the effect was very limited in patients who showed progression after DC vaccination for stage IV disease. PMID:27622070

  15. Activation of Notch1 signaling is required for β-catenin–mediated human primary melanoma progression

    PubMed Central

    Balint, Klara; Xiao, Min; Pinnix, Chelsea C.; Soma, Akinobu; Veres, Imre; Juhasz, Istvan; Brown, Eric J.; Capobianco, Anthony J.; Herlyn, Meenhard; Liu, Zhao-Jun

    2005-01-01

    Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin–dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma. PMID:16239965

  16. Quantitative Histone Mass Spectrometry Identifies Elevated Histone H3 Lysine 27 (Lys27) Trimethylation in Melanoma.

    PubMed

    Sengupta, Deepanwita; Byrum, Stephanie D; Avaritt, Nathan L; Davis, Lauren; Shields, Bradley; Mahmoud, Fade; Reynolds, Matthew; Orr, Lisa M; Mackintosh, Samuel G; Shalin, Sara C; Tackett, Alan J

    2016-03-01

    Normal cell growth is characterized by a regulated epigenetic program that drives cellular activities such as gene transcription, DNA replication, and DNA damage repair. Perturbation of this epigenetic program can lead to events such as mis-regulation of gene transcription and diseases such as cancer. To begin to understand the epigenetic program correlated to the development of melanoma, we performed a novel quantitative mass spectrometric analysis of histone post-translational modifications mis-regulated in melanoma cell culture as well as patient tumors. Aggressive melanoma cell lines as well as metastatic melanoma were found to have elevated histone H3 Lys(27) trimethylation (H3K27me3) accompanied by overexpressed methyltransferase EZH2 that adds the specific modification. The altered epigenetic program that led to elevated H3K27me3 in melanoma cell culture was found to directly silence transcription of the tumor suppressor genes RUNX3 and E-cadherin. The EZH2-mediated silencing of RUNX3 and E-cadherin transcription was also validated in advanced stage human melanoma tissues. This is the first study focusing on the detailed epigenetic mechanisms leading to EZH2-mediated silencing of RUNX3 and E-cadherin tumor suppressors in melanoma. This study underscores the utility of using high resolution mass spectrometry to identify mis-regulated epigenetic programs in diseases such as cancer, which could ultimately lead to the identification of biological markers for diagnostic and prognostic applications. PMID:26621846

  17. Data Set for Pathology Reporting of Cutaneous Invasive Melanoma

    PubMed Central

    Judge, Meagan J.; Evans, Alan; Frishberg, David P.; Prieto, Victor G.; Thompson, John F.; Trotter, Martin J.; Walsh, Maureen Y.; Walsh, Noreen M.G.; Ellis, David W.

    2013-01-01

    An accurate and complete pathology report is critical for the optimal management of cutaneous melanoma patients. Protocols for the pathologic reporting of melanoma have been independently developed by the Royal College of Pathologists of Australasia (RCPA), Royal College of Pathologists (United Kingdom) (RCPath), and College of American Pathologists (CAP). In this study, data sets, checklists, and structured reporting protocols for pathologic examination and reporting of cutaneous melanoma were analyzed by an international panel of melanoma pathologists and clinicians with the aim of developing a common, internationally agreed upon, evidence-based data set. The International Collaboration on Cancer Reporting cutaneous melanoma expert review panel analyzed the existing RCPA, RCPath, and CAP data sets to develop a protocol containing “required” (mandatory/core) and “recommended” (nonmandatory/noncore) elements. Required elements were defined as those that had agreed evidentiary support at National Health and Medical Research Council level III-2 level of evidence or above and that were unanimously agreed upon by the review panel to be essential for the clinical management, staging, or assessment of the prognosis of melanoma or fundamental for pathologic diagnosis. Recommended elements were those considered to be clinically important and recommended for good practice but with lesser degrees of supportive evidence. Sixteen core/required data elements for cutaneous melanoma pathology reports were defined (with an additional 4 core/required elements for specimens received with lymph nodes). Eighteen additional data elements with a lesser level of evidentiary support were included in the recommended data set. Consensus response values (permitted responses) were formulated for each data item. Development and agreement of this evidence-based protocol at an international level was accomplished in a timely and efficient manner, and the processes described herein may

  18. Modeling Melanoma In Vitro and In Vivo

    PubMed Central

    Beaumont, Kimberley A.; Mohana-Kumaran, Nethia; Haass, Nikolas K.

    2013-01-01

    The behavior of melanoma cells has traditionally been studied in vitro in two-dimensional cell culture with cells adhering to plastic dishes. However, in order to mimic the three-dimensional architecture of a melanoma, as well as its interactions with the tumor microenvironment, there has been the need for more physiologically relevant models. This has been achieved by designing 3D in vitro models of melanoma, such as melanoma spheroids embedded in extracellular matrix or organotypic skin reconstructs. In vivo melanoma models have typically relied on the growth of tumor xenografts in immunocompromised mice. Several genetically engineered mouse models have now been developed which allow the generation of spontaneous melanoma. Melanoma models have also been established in other species such as zebrafish, which are more conducive to imaging and high throughput studies. We will discuss these models as well as novel techniques that are relevant to the study of the molecular mechanisms underlying melanoma progression. PMID:27429258

  19. Isolated Malignant Melanoma Metastasis to the Pancreas

    PubMed Central

    Krag, Christen; Geertsen, Poul; Jakobsen, Linda P.

    2013-01-01

    Summary: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field. PMID:25289269

  20. General Information about Intraocular (Uveal) Melanoma

    MedlinePlus

    ... Intraocular (Uveal) Melanoma Treatment (PDQ®)–Patient Version General Information About Intraocular (Uveal) Melanoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  1. Tool to Distinguish Moles from Melanoma

    Cancer.gov

    “Moles to Melanoma: Recognizing the ABCDE Features” presents photos that show changes in individual pigmented lesions over time, and describes the different appearances of moles, dysplastic nevi, and melanomas.

  2. Use of computed body tomography in malignant melanoma

    SciTech Connect

    Kostrubiak, I.; Whitley, N.O.; Aisner, J.; Goose, P.; DeLuca, R.R.; Didolkar, M.S.; Elias, E.G.

    1988-05-20

    Malignant melanoma has no predictable clinical behavior. The Breslow depth and Clark's level of invasion are important prognostic factors, but their prognostic values are overshadowed by the presence of regional lymph node metastasis (stage III disease). The authors reviewed the CT scans and charts of 67 patients who had a confirmed diagnosis of malignant melanoma. Excluding patients with stage I disease, all others had histological evidence of metastatic disease shown in one or more sites by biopsy or necropsy specimens. In addition, in some patients metastatic disease was documented by clinical course and follow-up study in sites such as the brain, lung, and liver, where biopsies were not performed. They tried to ascertain any change in the extent of disease or any alteration in therapy that was based on the findings on the CT scan.

  3. Donor transmission of melanoma following renal transplant.

    PubMed

    Chen, Kathryn T; Olszanski, Anthony; Farma, Jeffrey M

    2012-01-01

    Donor transmission of melanoma is one of the more common and lethal of recipient malignancies, often presenting with systemic disease. Although some patients may receive durable remission of melanoma following explantation of the allograft and withdrawal of immunosuppression, donor transmission of melanoma is fatal in most patients. Here we present a case of a 44-year-old male who developed metastatic melanoma following renal transplant.

  4. Can melanoma therapy change attitudes toward prevention and tanning?

    PubMed

    Konkolova, Radmila; Provaznikova, Doc Hana; Jirakova, Anna; Hercogova, Jana

    2014-01-01

    Malignant melanoma is the most lethal skin cancer whose incidence is increasing worldwide. Important is knowledge of risk factors, early diagnosis, long-term follow-up on confirmed melanoma cases and prevention. In this study, we tested melanoma patients' attitudes toward solar radiation and perception of the value of follow-up. The present cross-sectional epidemiological study was carried out in a group of patients diagnosed with stage I and II of malignant melanoma (n = 124). They were monitored for at least 1 year. The research was carried out by anonymous questionnaire. The results revealed that the respondents welcomed the opportunity of follow-up care. Its benefits were said to outweigh the inconvenience of repeated checkups. However, the esthetic importance of a suntan was still considered quite high. Substantial reserve was found in the use of sunscreen. The need for wide public education and the protection against excessive contact with solar radiation is evident. Regular monitoring seems to be just as important.

  5. Surgical management of primary and recurrent melanoma.

    PubMed

    Farma, Jeffrey M; Kulkarni, Nandini; Hsu, Cary

    2015-04-01

    Melanoma accounts for less than 2% of skin cancer cases but causes most skin cancer-related deaths. Surgery continues to be the cornerstone of treatment of melanoma and surgical principles are guided by data derived from clinical research. This article examines the evolution of surgical techniques for the diagnosis and treatment of primary and locally recurrent melanoma.

  6. Other targeted drugs in melanoma

    PubMed Central

    Rodón, Jordi; Karachaliou, Niki; Sánchez, Jesús; Santarpia, Mariacarmela; Viteri, Santiago; Pilotto, Sara; Teixidó, Cristina; Riso, Aldo; Rosell, Rafael

    2015-01-01

    Targeted therapy drugs are developed against specific molecular alterations on cancer cells. Because they are “targeted” to the tumor, these therapies are more effective and better tolerated than conventional therapies such as chemotherapy. In the last decade, great advances have been made in understanding of melanoma biology and identification of molecular mechanisms involved in malignant transformation of cells. The identification of oncogenic mutated kinases involved in this process provides an opportunity for development of new target therapies. The dependence of melanoma on BRAF-mutant kinase has provided an opportunity for development of mutation-specific inhibitors with high activity and excellent tolerance that are now being used in clinical practice. This marked a new era in the treatment of metastatic melanoma and much research is now ongoing to identify other “druggable” kinases and transduction signaling networking. It is expected that in the near future the spectrum of target drugs for melanoma treatment will increase. Herein, we review the most relevant potential novel drugs for melanoma treatment based on preclinical data and the results of early clinical trials. PMID:26605312

  7. Parotid involvement by desmoplastic melanoma.

    PubMed

    Jennings, T A; Okby, N T; Schroer, K R; Wolf, B C; Mihm, M C

    1996-08-01

    Desmoplastic malignant melanoma often arises in sun damaged skin of the head and neck and shows frequent neurotropism. Although metastatic melanoma frequently involve the parotid, direct spread to the parotid has been rarely reported. We evaluated five cases of desmoplastic malignant melanoma involving the parotid gland with clinical and pathological evidence of precursor cutaneous lesions in four of the five cases. The parotid involvement in four cases was tumoural, and three of these were not clinically suspected to be melanoma. The histological appearance in all five cases was that of a sarcomatoid tumour. Immunohistochemistry and electronmicroscopy performed on three of the cases showed only evidence of schwannian differentiation: the tumour cells were positive for S-100 protein and vimentin, and negative for cytokeratin and HMB-45. Electronmicroscopy showed no evidence of melanogenesis. All five tumours showed histological evidence of prominent neurotropism with one case demonstrating extension from overlying skin along cutaneous nerves to the superficial parotid. Thus, desmoplastic malignant melanoma may involve the parotid by neurotropic spread and can be pathologically indistinguishable from malignant schwannoma, a diagnosis which may be made erroneously in the absence of clinical information. PMID:8872151

  8. Melanoma Prevention Using Topical PBISe

    PubMed Central

    Chung, Chin-Ying; Madhunapantula, SubbaRao V.; Desai, Dhimant; Amin, Shantu; Robertson, Gavin P.

    2012-01-01

    Malignant melanoma is the deadliest form of skin cancer, known for its drug resistance and high metastatic potential. Deregulated PI3 and MAP kinase pathways promote early melanocytic lesion development and confer drug resistance. No agent exists to target these deregulated pathways to prevent cutaneous non-invasive melanocytic cells or invasive melanomas from developing into more aggressive widely disseminated metastatic disease. In this study, a selenium containing isosteric analogue of PBIT [S,S′-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea] called PBISe [Se,Se′-1,4-phenylenebis(1,2-ethanediyl)bis-isoselenourea] is shown to moderate these two major signaling pathways to prevent cutaneous melanocytic lesion or melanoma development. Topical application of PBISe retarded melanocytic lesion development in laboratory-generated skin by 70-80% and in animal skin by ∼50%. Mechanistically, prevention of lesion development occurred due to decreased Akt3 signaling, which increased MAP kinase pathway activity to inhibitory levels. The combined effect of targeting these pathways led to decreased cell proliferation and increased apoptotic cell death thereby preventing melanoma development. Thus, topically applied PBISe treatment has potential to prevent non-invasive melanocytic lesion and invasive metastatic melanoma development in skin. PMID:21367959

  9. Circulating Melanoma Cell Subpopulations: Their Heterogeneity and Differential Responses to Treatment.

    PubMed

    Gray, Elin S; Reid, Anna L; Bowyer, Samantha; Calapre, Leslie; Siew, Kelvin; Pearce, Robert; Cowell, Lester; Frank, Markus H; Millward, Michael; Ziman, Mel

    2015-08-01

    Metastatic melanoma is a highly heterogeneous tumor; thus, methods to analyze tumor-derived cells circulating in blood should address this diversity. Taking this into account, we analyzed, using multiparametric flow cytometry, the co-expression of the melanoma markers melanoma cell adhesion molecule and melanoma-associated chondroitin sulphate proteoglycan and the tumor-initiating markers ATP-binding cassette sub-family B member 5 (ABCB5), CD271, and receptor activator of NF-κβ (RANK) in individual circulating tumor cells (CTCs) from 40 late-stage (III-IV) and 16 early-stage (I-II) melanoma patients. CTCs were heterogeneous within and between patients, with limited co-expression between the five markers analyzed. Analysis of patient matched blood and metastatic tumors revealed that ABCB5 and RANK subpopulations are more common among CTCs than in the solid tumors, suggesting a preferential selection for these cells in circulation. Pairwise comparison of CTC subpopulations longitudinally before and 6-13 weeks after treatment initiation showed that the percentage of RANK(+) CTCs significantly increased in the patients undergoing targeted therapy (N=16, P<0.01). Moreover, the presence of ⩾5 RANK(+) CTCs in the blood of patients undergoing targeted therapies was prognostic of shorter progression-free survival (hazards ratio 8.73, 95% confidence interval 1.82-41.75, P<0.01). Taken together, our results provide evidence of the heterogeneity among CTC subpopulations in melanoma and the differential response of these subpopulations to targeted therapy.

  10. Evidence-based clinical practice guidelines on the use of sentinel lymph node biopsy in melanoma.

    PubMed

    Sondak, Vernon K; Wong, Sandra L; Gershenwald, Jeffrey E; Thompson, John F

    2013-01-01

    Sentinel lymph node biopsy (SLNB) was introduced in 1992 to allow histopathologic evaluation of the "sentinel" node, that is, the first node along the lymphatic drainage pathway from the primary melanoma. This procedure has less risk of complications than a complete lymphadenectomy, and if the sentinel node is uninvolved by tumor the likelihood a complete lymphadenectomy would find metastatic disease in that nodal basin is very low. SLNB is now widely used worldwide in the staging of melanoma as well as breast and Merkel cell carcinomas. SLNB provides safe, reliable staging for patients with clinically node-negative melanomas 1 mm or greater in thickness, with an acceptably low rate of failure in the sentinel node-negative basin. Evidence-based guidelines jointly produced by ASCO and the Society of Surgical Oncology (SSO) recommend SLNB for patients with intermediate-thickness melanomas and also state that SLNB may be recommended for patients with thick melanomas. Major remaining areas of uncertainty include the indications for SLNB in patients with thin melanomas, pediatric patients, and patients with atypical melanocytic neoplasms; the optimal radiotracers and dyes for lymphatic mapping; and the necessity of complete lymphadenectomy in all sentinel node-positive patients.

  11. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.

    PubMed

    Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A

    2015-01-01

    Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.

  12. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.

    PubMed

    Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A

    2015-01-01

    Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection. PMID:24907634

  13. Validation and Comparison of the 7th Edition of the American Joint Committee on Cancer Staging System and Other Prognostic Models to Predict Relapse-Free Survival in Asian Patients with Parotid Cancer

    PubMed Central

    Lu, Chang-Hsien; Liu, Chien-Ting; Chang, Pei-Hung; Yeh, Kun-Yun; Hung, Chia-Yen; Li, Shau-Hsuan; Lin, Yung-Chang; Yeh, Ta-Sen; Hung, Yung-Shin; Chou, Wen-Chi

    2016-01-01

    Purpose: Parotid cancer is a rare malignancy characterized by a heterogeneous histologic subtype and distinct biologic behavior. The present study aimed to externally validate and compare the performances of the American Joint Committee on Cancer (AJCC) staging system (7th Edition), Carrillo score, and Vander Poorten score in the prediction of tumor relapse probability in a large cohort of Asian parotid cancer patients. Methods: In total, 261 patients who underwent primary surgery for localized parotid cancer between 2002 and 2014 at the four affiliated hospitals of Chang Gung Memorial Hospital were identified. All patients were categorized into different prognostic groups defined by these three models for the comparison of associated relapse-free survival (RFS) rates. Results: The 5-year overall survival, cancer-specific survival, and RFS rates were 82.9%, 86.2%, and 77.5%, respectively. All three models were significantly powerful in discriminating between the tumors of patients in the lowest and highest risk groups. The c-statistic for predicting the 5-year RFS was 0.74 for the AJCC staging, 0.74 for the Vander Poorten score, and 0.62 for the Carrillo score. The AJCC staging and Vander Poorten score gave significantly high c-statistic values compared to the Carrillo score. Conclusion: Our data validated that all three models are significantly powerful in discriminating tumor relapse between patients in lowest and highest risk groups. The AJCC system and Vander Poorten score proved superior to the Carrillo score, and showed similar performances in discriminating between the 5-year RFS probabilities of low and high-risk Asian parotid cancer patients.

  14. Noninvasive Real-Time Automated Skin Lesion Analysis System for Melanoma Early Detection and Prevention

    PubMed Central

    Abuzaghleh, Omar; Barkana, Buket D.

    2015-01-01

    Melanoma spreads through metastasis, and therefore, it has been proved to be very fatal. Statistical evidence has revealed that the majority of deaths resulting from skin cancer are as a result of melanoma. Further investigations have shown that the survival rates in patients depend on the stage of the cancer; early detection and intervention of melanoma implicate higher chances of cure. Clinical diagnosis and prognosis of melanoma are challenging, since the processes are prone to misdiagnosis and inaccuracies due to doctors’ subjectivity. Malignant melanomas are asymmetrical, have irregular borders, notched edges, and color variations, so analyzing the shape, color, and texture of the skin lesion is important for the early detection and prevention of melanoma. This paper proposes the two major components of a noninvasive real-time automated skin lesion analysis system for the early detection and prevention of melanoma. The first component is a real-time alert to help users prevent skinburn caused by sunlight; a novel equation to compute the time for skin to burn is thereby introduced. The second component is an automated image analysis module, which contains image acquisition, hair detection and exclusion, lesion segmentation, feature extraction, and classification. The proposed system uses PH2 Dermoscopy image database from Pedro Hispano Hospital for the development and testing purposes. The image database contains a total of 200 dermoscopy images of lesions, including benign, atypical, and melanoma cases. The experimental results show that the proposed system is efficient, achieving classification of the benign, atypical, and melanoma images with accuracy of 96.3%, 95.7%, and 97.5%, respectively. PMID:27170906

  15. Validation of T Stage According to Depth of Invasion and N Stage Subclassification Based on Number of Metastatic Lymph Nodes for Distal Extrahepatic Bile Duct (EBD) Carcinoma

    PubMed Central

    Moon, Ahrim; Choi, Dong Wook; Choi, Seoung Ho; Heo, Jin Seok; Jang, Kee-Taek

    2015-01-01

    Abstract According to the current AJCC staging system, the T stage of distal extrahepatic bile duct carcinoma (EBD) is classified according to the extent of the tumor within or beyond the bile duct wall. However many invasive carcinoma accompany stromal desmoplasia that obscure lower boundary of bile duct wall; it is frequently difficult to clearly define the extent of tumors using the current T classification system. In this study, we validated an alternative T classification system by depth of invasion (DoI; T1: < 5 mm, T2: 5 to 12 mm, and T3: ≥ 12 mm). Specifically, we evaluated DoI in 114 cases of distal EBD carcinoma using digital scan images to achieve more objective measurements of tumor DoI. In addition, we evaluated the effect of the number of metastatic lymph nodes (LNs) as well as the number of total examined LNs on the survival rate in the same patient group, and performed a comparative analysis of these data to assess patient survival. We also analyzed 114 cases of distal EBD carcinoma using the current T and N classification of the AJCC staging system (7th edition). The T stage of the current AJCC staging system was not associated with significant differences in patient survival, especially between T2 and T3. However, T staging by DoI was associated with statistically significant differences in patient survival (P < 0.001 in DoI-1, P = 0.002 in DoI-2). With respect to N stage, we divided patients into 3 tiers comprising class 1 (no nodal metastasis), class 2 (1–3 nodal metastases), and class 3 (4 or more nodal metastases). In 3-tier classification analysis, the median survival times for classes 1, 2, and 3 were 79.2, 28.8, and 10.9 months, respectively. The difference in survival among the 3 classes was statistically significant (P < 0.001). We found the cut-off value of 11 LNs (1 to 10 vs ≥ 11) for N0 stage showed most significant difference (P = 0.007). We think at least 11 LNs should be examined for more

  16. High accuracy of family history of melanoma in Danish melanoma cases.

    PubMed

    Wadt, Karin A W; Drzewiecki, Krzysztof T; Gerdes, Anne-Marie

    2015-12-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma probands who reported 199 cases of melanoma in relatives, of which 135 cases where in first degree relatives. We confirmed the diagnosis of melanoma in 77% of all relatives, and in 83% of first degree relatives. In 181 probands we validated the negative family history of melanoma in 748 first degree relatives and found only 1 case of melanoma which was not reported in a 3 case melanoma family. Melanoma patients in Denmark report family history of melanoma in first and second degree relatives with a high level of accuracy with a true positive predictive value between 77 and 87%. In 99% of probands reporting a negative family history of melanoma in first degree relatives this information is correct. In clinical practice we recommend that melanoma diagnosis in relatives should be verified if possible, but even unverified reported melanoma cases in relatives should be included in the indication of genetic testing and assessment of melanoma risk in the family. PMID:26094006

  17. Medical management of malignant melanoma.

    PubMed

    Atkinson, Victoria

    2015-06-01

    The treatment and outcomes for people with metastatic melanoma have changed considerably in the past few years with the introduction of targeted anticancer drugs. About half of the patients with metastatic melanoma will have activating mutations in the BRAF gene. These people may benefit from a BRAF inhibitor (vemurafenib or dabrafenib) or a MEK inhibitor (trametinib). Addition of a MEK inhibitor to a BRAF inhibitor improves progression-free survival and alters the adverse effect profile. Ipilimumab is another drug indicated for metastatic melanoma. It works by altering the patient's own immune response to the tumour. Toxicities are common with these drugs and include arthralgias, fatigue, photosensitivity, squamous cell carcinomas, fever, diarrhoea, pruritus and immune-related adverse effects. PMID:26648623

  18. Cell Cycle Regulation and Melanoma.

    PubMed

    Xu, Wen; McArthur, Grant

    2016-06-01

    Dysregulation of cell cycle control is a hallmark of melanomagenesis. Agents targeting the G1-S and G2-M checkpoints, as well as direct anti-mitotic agents, have all shown promising preclinical activity in melanoma. However, in vivo, standalone single agents targeting cell cycle regulation have only demonstrated modest efficacy in unselected patients. The advent of specific CDK 4/6 inhibitors targeting the G1-S transition, with an improved therapeutic index, is a significant step forward. Potential synergy exists with the combination of CDK4/6 inhibitors with existing therapies targeting the MAPK pathway, particularly in subsets of metastatic melanomas such as NRAS and BRAF mutants. This reviews summaries of the latest developments in both preclinical and clinical data with cell cycle-targeted therapies in melanoma. PMID:27106898

  19. Epidemiology of invasive cutaneous melanoma

    PubMed Central

    MacKie, R. M.; Hauschild, A.; Eggermont, A. M. M.

    2009-01-01

    Data are presented on the current incidence of melanoma with recent and predicted future trends illustrating a likely continuing increase in incidence. Risk factors for developing melanoma are discussed, including current known melanoma susceptibility genes. Phenotypic markers of high-risk subjects include high counts of benign melanocytic naevi. Other risk factors considered include exposure to natural and artificial ultraviolet radiation, the effect of female sex hormones, socioeconomic status, occupation, exposure to pesticides and ingestion of therapeutic drugs including immunosuppressives and non-steroidal anti-inflammatory drugs. Aids to earlier diagnosis are considered, including public education, screening and use of equipment such as the dermatoscope. Finally, the current pattern of survival and mortality is described. PMID:19617292

  20. Recurrent inactivating RASA2 mutations in melanoma.

    PubMed

    Arafeh, Rand; Qutob, Nouar; Emmanuel, Rafi; Keren-Paz, Alona; Madore, Jason; Elkahloun, Abdel; Wilmott, James S; Gartner, Jared J; Di Pizio, Antonella; Winograd-Katz, Sabina; Sindiri, Sivasish; Rotkopf, Ron; Dutton-Regester, Ken; Johansson, Peter; Pritchard, Antonia L; Waddell, Nicola; Hill, Victoria K; Lin, Jimmy C; Hevroni, Yael; Rosenberg, Steven A; Khan, Javed; Ben-Dor, Shifra; Niv, Masha Y; Ulitsky, Igor; Mann, Graham J; Scolyer, Richard A; Hayward, Nicholas K; Samuels, Yardena

    2015-12-01

    Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer. PMID:26502337

  1. Melanoma: oncogenic drivers and the immune system

    PubMed Central

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio

    2015-01-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches. PMID:26605311

  2. The effect of sunscreen on melanoma risk.

    PubMed

    Mulliken, Jennifer S; Russak, Julie E; Rigel, Darrell S

    2012-07-01

    Total cumulative sun exposure is associated with the development of squamous cell and basal cell cancers, whereas intense intermittent sun exposure is associated with the development of melanoma. Exposure to UV radiation is the only known modifiable cause of melanoma, but the role of sunscreen in melanoma prevention remains somewhat controversial. This article discusses how UV radiation contributes to the pathogenesis of melanoma, how sunscreen modulates the action of UV radiation on the skin, and the effect of sunscreen on the risk of developing melanoma. A review of available sunscreen agents and their sun-protective properties is also included.

  3. Familial skin cancer syndromes: Increased melanoma risk.

    PubMed

    Ransohoff, Katherine J; Jaju, Prajakta D; Jaju, Prajaka D; Tang, Jean Y; Carbone, Michele; Leachman, Sancy; Sarin, Kavita Y

    2016-03-01

    Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings.

  4. Histological types of polypoid cutaneous melanoma II.

    PubMed

    Knezević, Fabijan; Duancić, Vjekoslav; Sitić, Sanda; Horvat-Knezević, Anica; Benković, Vesna; Ramić, Snjezana; Kostović, Kresimir; Ramljak, Vesna; Vrdoljak, Danko Velemir; Stanec, Mladen; Bozović, Angelina

    2007-12-01

    The aim of this study was to ascertain which histological types of melanoma can clinically and morphologically appear as polypoid melanomas. In 645 cases of primary cutaneous melanoma we have analyzed criteria for diagnosis of polypoid cutaneous melanoma and afterwards we have analyzed growth phase in each polypoid melanoma, histological type of atypical melanocytes, the number of epidermal ridges which are occupied by atypical melanocytes, and distribution according to age, sex and location, as well as the disease free survival. According to the criteria for polypoid melanomas we have found 147 (22.8%) polypoid cutaneous melanomas. Analyzing the growth phases, histological types of atypical melanocytes and the number of affected epidermal ridges in the group of polypoid melanomas we have ascertained 2 (1.4%) ALMs, 4 (2.8%) LMMs, 42 (28.6%) SSMs and 99 (67.2%) NMs. Our conclusion is that polypoid cutaneous melanomas are morphological forms of various histological melanoma types (ALM, LMM, SSM and NM) and they can all display polypoid morphological form. Polypoid cutaneous melanomas are most often of nodular histological type. PMID:18217457

  5. Curcumin Analog DM-1 in Monotherapy or Combinatory Treatment with Dacarbazine as a Strategy to Inhibit In Vivo Melanoma Progression

    PubMed Central

    Faião-Flores, Fernanda; Quincoces Suarez, José Agustín; Fruet, Andréa Costa; Maria-Engler, Silvya Stuchi; Pardi, Paulo Celso; Maria, Durvanei Augusto

    2015-01-01

    Malignant melanoma is a highly aggressive form of skin cancer with a high mortality rate if not discovered in early stages. Although a limited number of treatment options for melanoma currently exist, patients with a more aggressive form of this cancer frequently decline treatment. DM-1 is a sodium phenolate and curcumin analog with proven anticancer, anti-proliferative and anti-metastatic properties. In this paper, the DM-1 compound showed in vivo antitumor activity alone or in combination with chemotherapeutic DTIC in B16F10 melanoma-bearing mice. Beneficial effects such as melanoma tumor burden reduction with pyknotic nuclei, decreased nuclei/cytoplasmic ratio and nuclear degradation occurred after DM-1 treatment. No toxicological changes were observed in the liver, kidneys, spleen and lungs after DM-1 monotherapy or DTIC combined therapy. DTIC+DM-1 treatment induced the recovery of anemia arising from melanoma and immunomodulation. Both DM-1 treatment alone and in combination with DTIC induced apoptosis with the cleavage of caspase-3, -8 and -9. Furthermore, melanoma tumors treated with DM-1 showed a preferential apoptotic intrinsic pathway by decreasing Bcl-2/Bax ratio. Considering the chemoresistance exhibited by melanoma towards conventional chemotherapy drugs, DM-1 compound in monotherapy or in combination therapy provides a promising improvement in melanoma treatment with a reduction of side effects. PMID:25742310

  6. Melanoma incidence and frequency modulation (FM) broadcasting.

    PubMed

    Hallberg, Orjan; Johansson, Olle

    2002-01-01

    The incidence of melanoma has been increasing steadily in many countries since 1960, but the underlying mechanism causing this increase remains elusive. The incidence of melanoma has been linked to the distance to frequency modulation (FM) broadcasting towers. In the current study, the authors sought to determine if there was also a related link on a larger scale for entire countries. Exposure-time-specific incidence was extracted from exposure and incidence data from 4 different countries, and this was compared with reported age-specific incidence of melanoma. Geographic differences in melanoma incidence were compared with the magnitude of this environmental stress. The exposure-time-specific incidence from all 4 countries became almost identical, and they were approximately equal to the reported age-specific incidence of melanoma. A correlation between melanoma incidence and the number of locally receivable FM transmitters was found. The authors concluded that melanoma is associated with exposure to FM broadcasting.

  7. Video comparator system for early detection of cutaneous malignant melanoma

    NASA Astrophysics Data System (ADS)

    Craine, Eric R.; Craine, Brian L.

    1992-05-01

    The recognized incidence of cutaneous malignant melanoma in the United States is now rising faster than any other cancer, increasing by 83% from 1980 to 1987. Recent revelations that depletion of the earth's ozone layer is accelerating at a more rapid rate than previously believed can only exacerbate current projections for the increased incidence of this deadly disease. Because there is no good treatment for metastatic melanoma even small cancers often prove fatal if not detected early. Melanoma allowed to invade the subcutaneous tissue is associated with a five-year survival rate of only 44%. Ironically, few cancers provide a greater opportunity for early discovery and cure. Cutaneous melanoma is not only located where it is readily observed, but typically undergoes a `radial growth' phase prior to metastasis. During this phase the net growth is superficial and circumferential, gradually increasing the area of the lesion and changing its coloration. Screening measures for the early detection of melanoma must concentrate on two primary tasks: (1) detection of lesion changes indicative of the radial growth stage of malignancy and (2) alerting the patient and physician to the existence of a new or changed lesion on the skin. To accomplish these goals we have experimented with the applicability of a microcomputer based video imaging system which stores an image archive of historical reference images for each patient. With the acquisition of new images of the patient, easily registered with the archival images through a technique we have developed we are able to perform a blink comparison of the image pairs. This technique appears to be far more effective than currently used techniques for detecting changed lesions on a comprehensive basis.

  8. Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines.

    PubMed

    Jaworek-Korjakowska, Joanna

    2016-01-01

    Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions. PMID:27382567

  9. Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines

    PubMed Central

    2016-01-01

    Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions. PMID:27382567

  10. Skewed Differentiation of Circulating Vγ9Vδ2 T Lymphocytes in Melanoma and Impact on Clinical Outcome

    PubMed Central

    Toia, Francesca; Buccheri, Simona; Anfosso, Ampelio; Moschella, Francesco; Dieli, Francesco; Meraviglia, Serena; Cordova, Adriana

    2016-01-01

    Objective The aim of this study was to evaluate over time circulating γδ T lymphocytes in melanoma patients in terms of frequency, effector functions, and relationship with clinical stage and evolution, by comparing preoperative values to those obtained at a mean follow-up of 36 months or in the event of recurrence or disease progression, and to those of healthy controls. Also, we correlated the presence of tumor-infiltrating γδ T lymphocytes with clinical evolution of melanoma. Results Mean frequencies of circulating γδ T cells before and after melanoma removal were very similar and comparable to healthy subjects, but patients who progressed to stage III or IV showed a significantly decreased frequency of circulating Vγ9Vδ2 T cells. The distribution of Vγ9Vδ2 memory and effector subsets was similar in healthy subjects and melanoma patients at diagnosis, but circulating γδ T cells of patients after melanoma removal had a skewed terminally-differentiated effector memory phenotype. Highly suggestive of progressive differentiation toward a cytotoxic phenotype, Vγ9Vδ2T cells from patients at follow up had increased cytotoxic potential and limited cytokine production capability, while the opposite pattern was detected in Vγ9Vδ2T cells from patients before melanoma removal. Conclusions Follow-up data also showed that tumor infiltrating γδ T cells were significantly associated with lower mortality and relapse rates, suggesting that they may serve as a prognostic biomarker, for human melanoma. PMID:26915072

  11. Regional non-nodal metastases of cutaneous melanoma.

    PubMed

    Cascinelli, N; Bufalino, R; Marolda, R; Belli, F; Nava, M; Galluzzo, D; Santinami, M; Levene, A

    1986-06-01

    The authors studied the prognosis of patients with so called local recurrences, satellites and in-transit metastases from cutaneous melanoma on the basis of 291 patients. These are the 19.3% of the 1503 patients with stage I and II melanoma originally submitted to surgical treatment at the National Cancer Institute of Milano (Italy). The majority of patients were males (M/F = 0.7): 102 had local recurrence, 99 in-transit metastases, 24 satellites and 66 both local and in-transit metastases. Regional non-nodal metastases were not related with the site of origin, and inadequate treatment of primary. These metastases were more frequently observed in patients who were submitted to regional node dissection no matter whether in discontinuity or in continuity with primary tumor. The frequency of regional non-nodal metastases was found to increase with increasing thickness of primary melanoma or, in stage II patients, with the number of involved nodes. Local and in-transit metastases were related with prognostic criteria in the same way. The overall survival was very close between in-transit and local metastases. Similar survival rates were observed comparing regional non-nodes and disseminated cutaneous and subcutaneous metastases. The authors conclude that the distinction between local recurrences, satellites and in-transit metastases is artificial and that these metastatic events are not prognostically dissimilar from metastases in distant skin areas.

  12. [Malignant melanoma coexisting with pregnancy].

    PubMed

    Krasomski, G; Broniarczyk, D; Gładysiak, A

    1992-09-01

    An extremely rare case of melanoma amelanoticum coexisting with pregnancy has been discussed. Pregnant A. Ch., age 42, was admitted to the Polish Mother's Health Centre Memorial Hospital on the 22nd of August, 1990 with a diagnosis of the 5th pregnancy, the 2nd delivery, the 30th week of gestation, state after cesarean section. Suspected malignant melanoma. Stomach ulceration. Thrombophlebitis of left lower extremity. General condition--medium hard. For the last three days she did not report fetal movements, fetal heartbeat was not detected either. Us examination confirmed fetal death. On the 24th of August, 1990, spontaneous vaginal delivery terminated the pregnancy, giving a dead, macerated female fetus, body weight of 1500 g. On the 3rd day after delivery the patient died with growing circulation-respiratory insufficiency. Autopsy revealed melanoma malignum amelanoticum disseminatum. Neither an autopsy of the fetus nor histopathological examinations of the secundines were performed for the advanced maceration. The coexistence of pregnancy with malignant melanoma in this case brought a tragic end both for the mother and the fetus. PMID:1305602

  13. Solar radiation and cutaneous melanoma.

    PubMed

    Viola, M V; Houghton, A N

    1982-09-01

    Exposure to solar radiation has been widely implicated in the dramatic rise in the incidence of cutaneous melanoma throughout the world. The association may be more complex than originally suspected, involving such factors as sunspot-activity cycles and changes in the ozone layer affecting ultraviolet flux at the earth's surface. The evidence for these relationships is examined.

  14. Adjuvant therapy of malignant melanoma.

    PubMed

    Molife, R; Hancock, B W

    2002-10-01

    High risk surgically resected melanoma is associated with a less than 50% 5-year survival. Adjuvant therapy is an appropriate treatment modality in this setting, and is more likely to be effective as the tumour burden here is small. Clinical observations of spontaneous tumour regressions and a highly variable rate of disease progression suggest a role of the immune system in the natural history of melanoma. Biological agents have therefore been the subjects of numerous adjuvant studies. Early, randomised controlled trials (RCTs) of Bacillus Calmette-Guerin (BCG), levamisole, Corynebacterium parvum, chemotherapy, isolated limb perfusion (ILP), radiotherapy, transfer factor (TF), megestrol acetate and vitamin A yielded largely negative results. Current trials focus on vaccines and the interferons. To date the latter is the only therapy to have shown a significant benefit in the prospective randomised controlled phase III setting. This report represents a systematic review of studies in adjuvant therapy in melanoma. Data from ongoing studies is awaited before a role for adjuvant agents in high risk melanoma is confirmed. PMID:12399001

  15. [Mandibular metastasis of a cutaneous melanoma or metachronous amelanotic melanoma of the oral cavity? A case report and literature review].

    PubMed

    Vierne, C; Hardy, H; Guichard, B; Barat, M; Péron, J-M; Trost, O

    2014-08-01

    Primary and metastatic mandibular melanoma are extremely rare. We report the original case of a 55-year-old woman treated 16 years before for a cutaneous melanoma, and now presenting with a huge mandibular amelanotic melanoma. Was it an histologically different mandibular metastasis of the previous cutaneous melanoma, or a metachronous oral amelanotic melanoma?

  16. Localization of malignant melanoma using monoclonal antibodies

    SciTech Connect

    Wasselle, J.; Becker, J.; Cruse, W.; Espinosa, C.; Cox, C.; Reintgen, D. )

    1991-04-01

    Finding a screening test to evaluate patients with cancer for occult metastatic disease, as well as imaging all known disease, is a goal of research efforts. Twenty-nine evaluable patients with deeply invasive (stage I), regional nodal (stage II), or systemic (stage III) melanoma underwent imaging by administration of a preparation of the antimelanoma antibody labeled with technetium 99m. Scan results indicated that 28 of 32 confirmed metastatic sites were imaged with this technique (88% sensitivity). Analysis of the individual positive sites revealed that nodal basins and visceral metastases accounted for the highest percentage of metastatic sites imaged, with 14 (88%) of 16 nodal basin metastases and all four visceral metastases being detected through imaging. Occult nodal disease was detected in the iliac nodal chain in two of the 29 patients. The imaging of benign tumors and nodal basins not containing disease accounted for a confirmed false-positive rate of 21%. Three (10%) of the 29 scan results were confirmed to be false-negative. In vivo tumor localization with monoclonal antibodies showed a sensitivity similar to that of other roentgenographic procedures for identifying metastatic disease and was useful in two of three patients in identifying occult iliac nodal disease, a region that is difficult to evaluate with physical examination and other imaging modalities.

  17. Leser-Trelat sign in metastasized malignant melanoma.

    PubMed

    Siedek, Vanessa; Schuh, Theda; Wollenberg, Andreas

    2009-02-01

    The Leser-Trelat sign is defined as the association of multiple, eruptive seborrheic keratoses with an internal malignancy of a usually advanced stage. We report the case of malignant melanoma in an 82-year-old man covered with hundreds of greyish-dark seborrheic keratoses resembling a Christmas tree pattern, who was diagnosed with metastasized malignant melanoma involving the parotid gland and lymph nodes. Though the pathogenesis of Leser-Trelat sign is still unknown, spontaneous regression of the seborrheic keratoses following tumor reduction described in some cases argues for a paraneoplastic origin of this highly instructive clinical entity. Physicians should consider a workup for internal malignancy in patients presenting with multiple eruptive seborrheic keratoses.

  18. Genetic alterations of PTEN in human melanoma.

    PubMed

    Aguissa-Touré, Almass-Houd; Li, Gang

    2012-05-01

    The PTEN gene is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Inactivating mutations and deletions of the PTEN gene are found in many types of cancers, including melanoma. However, the exact frequency of PTEN alteration in melanoma is unknown. In this study, we comprehensively reviewed 16 studies on PTEN genetic changes in melanoma cell lines and tumor biopsies. To date, 76 PTEN alterations have been reported in melanoma cell lines and 38 PTEN alterations in melanoma biopsies. The rate of PTEN alterations in melanoma cell lines, primary melanoma, and metastatic melanoma is 27.6, 7.3, and 15.2%, respectively. Three mutations were found in both melanoma cell lines and biopsies. These mutations are scattered throughout the gene, with the exception of exon 9. A mutational hot spot is found in exon 5, which encodes the phosphatase activity domain. Evidence is also presented to suggest that numerous homozygous deletions and missense variants exist in the PTEN transcript. Studying PTEN functions and implications of its mutations and other genes could provide insights into the precise nature of PTEN function in melanoma and additional targets for new therapeutic approaches. PMID:22076652

  19. Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.

    PubMed

    Welinder, Charlotte; Jönsson, Göran B; Ingvar, Christian; Lundgren, Lotta; Baldetorp, Bo; Olsson, Håkan; Breslin, Thomas; Rezeli, Melinda; Jansson, Bo; Fehniger, Thomas E; Laurell, Thomas; Wieslander, Elisabet; Pawlowski, Krzysztof; Marko-Varga, György

    2014-01-01

    Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis. PMID:25333933

  20. Analysis of Alpha-Synuclein in Malignant Melanoma – Development of a SRM Quantification Assay

    PubMed Central

    Welinder, Charlotte; Jönsson, Göran B.; Ingvar, Christian; Lundgren, Lotta; Baldetorp, Bo; Olsson, Håkan; Breslin, Thomas; Rezeli, Melinda; Jansson, Bo; Fehniger, Thomas E.; Laurell, Thomas; Wieslander, Elisabet; Pawlowski, Krzysztof; Marko-Varga, György

    2014-01-01

    Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis. PMID:25333933

  1. Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion.

    PubMed

    Saunders, Lauren P; Ouellette, Amy; Bandle, Russ; Chang, William Chozen; Zhou, Hongwen; Misra, Raj N; De La Cruz, Enrique M; Braddock, Demetrios T

    2008-10-01

    Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffin-embedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma.

  2. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

    PubMed

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-07-01

    The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current

  3. Applications of a novel tumor-grading-metastasis staging system for pancreatic neuroendocrine tumors: An analysis of surgical patients from a Chinese institution.

    PubMed

    Yang, Min; Tan, Chun-Lu; Zhang, Yi; Ke, Neng-Wen; Zeng, Lin; Li, Ang; Zhang, Hao; Xiong, Jun-Jie; Guo, Zi-Heng; Tian, Bo-Le; Liu, Xu-Bao

    2016-07-01

    The ability to stratify patients with pancreatic neuroendocrine tumors (p-NETs) into prognostic groups has been hindered by the absence of a commonly accepted staging system. Both the 7th tumor-node-metastasis (TNM) staging guidelines by the American Joint Committee on Cancer (AJCC) and the 2010 grading classifications by the World Health Organization (WHO) were validated to be unsatisfactory.We aim to evaluate the feasibility of combining the latest AJCC and WHO criteria to devise a novel tumor-grading-metastasis (TGM) staging system. We also sought to examine the stage-specific survival rates and the prognostic value of this new TGM system for p-NETs.Data of 120 patients with surgical resection and histopathological diagnosis of p-NETs from January 2004 to February 2014 in our institution were retrospectively collected and analyzed. Based on the AJCC and WHO criteria, we replaced the stage N0 and N1 with stage Ga (NET G1 and NET G2) and Gb (NET G3 and MANEC) respectively, without changes of the definition of T or M stage. The present novel TGM staging system was grouped as follows: stage I was defined as T1-2, Ga, M0; stage II as T3, Ga, M0 or as T1-3, Gb, M0; stage III as T4, Ga-b, M0 and stage IV as any T, M1.The new TGM staging system successfully distributed 55, 42, 12, and 11 eligible patients in stage I to IV, respectively. Differences of survival compared stage I with III and IV for patients with p-NETs were both statistically significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001). Patients in stage I showed better a survival than those in stage II, whereas difference between stages III and IV was not notable (P = 0.001, P = 0.286, respectively). In multivariate models, when the TGM staging system was evaluated in place of the individual T, G, and M variables, this new criteria were proven to be an independent predictor of survival for surgically resected p-NETs (P < 0.05).Stratifying patients well, the current

  4. Caring for patients with melanoma in the primary care setting.

    PubMed

    Rea, Mary; Perrino, Laura; Sheets, Victoria; McDaniel, M Jane

    2014-07-01

    The incidence of melanoma is steadily rising and mortality continues to increase. This article describes types of melanoma and the role of primary care providers in the long-term management and follow-up of patients diagnosed with melanoma.

  5. Immune biomarkers are more accurate in prediction of survival in ulcerated than in non-ulcerated primary melanomas

    PubMed Central

    de Moll, Ellen H.; Fu, Yichun; Qian, Yingzhi; Perkins, Sara H.; Wieder, Shira; Gnjatic, Sacha; Remark, Romain; Bernardo, Sebastian G.; Moskalenko, Marina; Yao, Jonathan; Ferringer, Tammie; Chang, Rui; Chipuk, Jerry; Horst, Basil A.; Birge, Miriam B.; Phelps, Robert G.

    2015-01-01

    Introduction Ulcerated melanomas may have a unique biology and microenvironment. We test whether markers of immune infiltration correlate with clinical outcome in ulcerated compared to non-ulcerated primary melanoma tumors. Methods Sixty-two stage II–III cutaneous melanomas, 32 ulcerated and 30 non-ulcerated, were analyzed for tumor-infiltrating lymphocytes (TILs). Immunohistochemistry (IHC) was performed for CD2, a marker previously shown to correlate with overall survival (OS) and recurrence-free survival (RFS) in this patient population. IHC using antibody, VE1, to BRAF V600E was also performed on a subset of 41 tumors to assess the relationship of BRAF mutation to immune markers. Results We found, using Cox regression models, that the presence of TILs was associated with improved OS (p = 0.034) and RFS (p = 0.002) in ulcerated melanoma tumors, but not in non-ulcerated melanoma (p = 0.632, 0.416). CD2 expression also was correlated with improved OS (p = 0.021) and RFS (p = 0.001) in ulcerated melanoma, but no relationship was seen in non-ulcerated melanoma (p = 0.427, 0.682). In this small population, BRAF status did not correlate with TILs or CD2+ count. Conclusion Our data show that immune markers including TILs and CD2 count correlate more closely with survival in ulcerated melanomas than that in non-ulcerated melanomas. We propose that immune biomarkers may be particularly relevant to ulcerated, as compared to non-ulcerated, melanomas and that this merits study in larger populations. PMID:26076664

  6. Lymph node staging in colorectal cancer: Old controversies and recent advances

    PubMed Central

    Resch, Annika; Langner, Cord

    2013-01-01

    Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor node metastasis (TNM) system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer. For affected patients, the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen, several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging. These include changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected. Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression. Outcome prediction based on the lymph node ratio, defined as the number of positive lymph nodes divided by the total number of retrieved nodes, may be superior to the absolute numbers of involved nodes. Extracapsular invasion has been identified as additional prognostic factor. Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis. The clinical value of more recent technical advances, such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined. PMID:24379568

  7. Use of imiquimod for residual acral melanoma.

    PubMed

    Sue, Gloria R; Hanlon, Allison; Lazova, Rossitza; Narayan, Deepak

    2014-01-01

    Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins. The patients were then treated with topical imiquimod for 8 weeks after which a repeat biopsy of the affected region showed no evidence of residual melanoma in situ. The use of topical imiquimod cream should be considered in the management of residual melanoma in situ of the plantar surface of the foot. PMID:25188932

  8. Genetic and environmental melanoma models in fish

    PubMed Central

    Patton, E Elizabeth; Mitchell, David L; Nairn, Rodney S

    2010-01-01

    Experimental animal models are extremely valuable for the study of human diseases, especially those with underlying genetic components. The exploitation of various animal models, from fruitflies to mice, has led to major advances in our understanding of the etiologies of many diseases, including cancer. Cutaneous malignant melanoma is a form of cancer for which both environmental insult (i.e., UV) and hereditary predisposition are major causative factors. Fish melanoma models have been used in studies of both spontaneous and induced melanoma formation. Genetic hybrids between platyfish and swordtails, different species of the genus Xiphophorus, have been studied since the 1920s to identify genetic determinants of pigmentation and melanoma formation. Recently, transgenesis has been used to develop zebrafish and medaka models for melanoma research. This review will provide a historical perspective on the use of fish models in melanoma research, and an updated summary of current and prospective studies using these unique experimental systems. PMID:20230482

  9. The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis

    PubMed Central

    Ciarletta, P.; Foret, L.; Ben Amar, M.

    2011-01-01

    Cutaneous melanoma is disproportionately lethal despite its relatively low incidence and its potential for cure in the early stages. The aim of this study is to foster understanding of the role of microstructure on the occurrence of morphological changes in diseased skin during melanoma evolution. The authors propose a biomechanical analysis of its radial growth phase, investigating the role of intercellular/stromal connections on the initial stages of epidermis invasion. The radial growth phase of a primary melanoma is modelled within the multi-phase theory of mixtures, reproducing the mechanical behaviour of the skin layers and of the epidermal–dermal junction. The theoretical analysis takes into account those cellular processes that have been experimentally observed to disrupt homeostasis in normal epidermis. Numerical simulations demonstrate that the loss of adhesiveness of the melanoma cells both to the basal laminae, caused by deregulation mechanisms of adherent junctions, and to adjacent keratynocytes, consequent to a downregulation of E-cadherin, are the fundamental biomechanical features for promoting tumour initiation. Finally, the authors provide the mathematical proof of a long wavelength instability of the tumour front during the early stages of melanoma invasion. These results open the perspective to correlate the early morphology of a growing melanoma with the biomechanical characteristics of its micro-environment. PMID:20656740

  10. Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

    PubMed

    Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

    2010-07-01

    Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

  11. Pediatric melanoma, moles, and sun safety.

    PubMed

    Hawryluk, Elena B; Liang, Marilyn G

    2014-04-01

    Although pediatric melanoma is a rare disease, diagnosis and management of pigmented lesions in the pediatric population, particularly dysplastic nevi and Spitz nevi, can be challenging. In this article, we provide an overview of pigmented lesions in children, including melanoma and management of melanoma risk factors and melanocytic nevi in the pediatric population. Congenital melanocytic nevi, Spitz nevi, dysplastic and acquired nevi, and changes over time are reviewed. We discuss considerations for excision and management of pigmented lesions in children.

  12. Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model

    PubMed Central

    Acampora, Giovanni; Brown, David; Rees, Robert C.

    2016-01-01

    The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR

  13. Histone variants and melanoma: facts and hypotheses.

    PubMed

    Konstantinov, Nikifor K; Ulff-Møller, Constance J; Dimitrov, Stefan

    2016-07-01

    Melanoma is the most aggressive form of skin cancer with rising incidence and morbidity. Despite advances in treatment, the 10-yr survival for patients with metastatic disease is less than 10%. During the past few years, ongoing research on different epigenomic aberrations in melanoma has catalyzed better understanding of its pathogenesis and identification of new therapeutics. In our review, we will focus on the role of histone variants, key epigenetic players in melanoma initiation and progression. Specifically, incorporation of histone variants enables additional layers of chromatin structure, and here, we will describe how alterations in this epigenetic behavior impact melanoma.

  14. Emerging phytochemicals for prevention of melanoma invasion

    PubMed Central

    Jones, Virginia; Katiyar, Santosh K.

    2013-01-01

    Cutaneous malignant melanoma is the leading cause of death from skin diseases due to its propensity to metastasize. Once diagnosed with metastatic melanoma, most patients will die of their disease within 2 years. As suppression of metastases requires long-term interventions, potential anti-metastatic agents must not only be efficacious but also have low toxicity. Many phytochemicals used in traditional medicine have low toxicity and recent studies suggest that some are promising candidates for the prevention or treatment of metastatic melanoma. Here, we review the recent literature regarding phytochemicals that have shown inhibitory effects on melanoma cell migration or invasion. PMID:23474498

  15. Neutron capture therapy for melanoma

    SciTech Connect

    Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

    1988-01-01

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

  16. Malignant rectal melanoma. Case report.

    PubMed

    Morlino, Andrea; La Torre, Giuseppe; Vitagliano, Giulia; Cammarota, Aldo

    2015-03-26

    Il Melanoma Anorettale è una malattia rara e aggressiva ed è il terzo tipo più comune di melanoma maligno dopo quello della cute e della retina. Il sintomo più comune è il sanguinamento rettale, che è spesso scambiato per sanguinamento associato a emorroidi. La diagnosi è molto difficile, e quella iniziale può essere corretta solo in circa 80% dei casi. Il caso clinico che proponiamo riguarda un uomo di 71 anni giunto alla nostra osservazione per dolore anale, tenesmo rettale, sanguinamento. L’eplorazione rettale ci ha mostrato una neofromazione dolorosa, di colorito brunastro nel canale anale. La colonscopia e la endoscopia hanno evidenziato la presenza di una grande massa stenotica interessante il canale anale ed il retto con un diametro di circa 90 mm. La biopsia è positiva per melanoma a cellule maligne pigmentate. La TAC ha mostrato un ispessimento della parete rettale e linfonodi nel tessuto adiposo, nel distretto otturatore bilaterale e metastasi polmonari bilaterali. Il dato di laboratorio del Ca 19-9 è nei livelli normali. Il paziente è stato sottoposto a resezione addomino-perineale con dissezione linfonodale. Non ci sono studi dimostranti che la resezione radicale del melanoma primario ano-rettale è associata ad un miglioramento del controllo locale e della sopravvivenza. I pazienti con malattia localizzata dovrebbero essere sottoposti a escissione locale ogniqualvolta ciò sia tecnicamente fattibile. Il ruolo predominante del trattamento chemio radioterapico preoperatorio è quello di ridurre le recidive locoregionale e della cavità pelvica, e per ottenere un più alto tasso di conservazione dell’apparato sfinteriale. Inoltre facilita la rimozione delle potenziali micrometastasi e riduce le metastasi a distanza.

  17. The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

    SciTech Connect

    Serafino, A. Balestrieri, E.; Pierimarchi, P.; Matteucci, C.; Moroni, G.; Oricchio, E.; Rasi, G.; Mastino, A.; Spadafora, C.; Garaci, E.; Vallebona, P. Sinibaldi

    2009-03-10

    Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.

  18. Cutaneous melanoma frequencies and seasonal trend in 20 years of observation of a population characterised by excessive sun exposure

    PubMed Central

    Bonin, Serena; Albano, Antonio; di Meo, Nicola; Gatti, Alessandro; Stinco, Giuseppe; Zanconati, Fabrizio; Trevisan, Giusto

    2015-01-01

    Background Cutaneous melanoma is an aggressive form of skin cancer. It has become an increasingly common neoplasm in the most developed countries, especially among individuals of European origin. Patients and methods. Anonymous data of patients with cutaneous melanoma were collected from the diagnostic database of the University Hospital of Trieste from 1 January 1990 to 10 December 2013. Our study is based on a population which was constant over the period of observation; it was also well-defined and characterised by unrestrained sun exposure. Results The number of cutaneous melanomas increased during the period of observation with a seasonality trend and gender related differences both for anatomical sites distribution and stage of the disease. Moreover, 6% of our cohort developed multiple melanomas. Conclusions In a well-defined population devoted to excessive sun exposure the frequencies of skin melanomas roughly doubled from 1990 to 2013 following a seasonal trend. In that population, prevention efforts according to gender specific risk behaviour, as well as follow-up programmes both for evaluation of metastatic spreading and for early diagnosis of additional skin melanomas, are crucial due to gender specific differences and to the occurrence of multiple melanomas. PMID:26834525

  19. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  20. Melanoma arising after imiquimod use.

    PubMed

    Paul, Sharad P

    2014-01-01

    Imiquimod belongs to the class of 1H-imidazo-[4,5-c]quinolones-drugs originally developed as nucleoside analogues with the aim of finding new potential antiviral agents (Harrison et al., 1988). Indeed, Imiquimod was first released as treatment for genital warts before its actions against skin cancer were studied. Imiquimod is a relatively small sized molecule (Mr = 240.3) and is hydrophobic, allowing it to penetrate the skin epidermal barrier and therefore making it suitable for topical formulations (Gerster et al., 2005). Imiquimod has shown itself effective against skin cancers and precancerous lesions, especially basal cell cancers and actinic keratosis (Salasche et al., 2002, Beutner et al., 1999). There have been reports of Imiquimod being used as topical treatment against cutaneous metastases of melanoma and some authors have reported its use as first-line therapy against melanoma in situ (Smyth et al., 2011, Gagnon, 2011). We report a case of an invasive malignant melanoma arising de novo at the specific site of application of Imiquimod (Aldara cream 5%) for a biopsy-proven superficial BCC. Therefore while Imiquimod has added to our topical armamentarium against skin cancer, care must be exercised in prescribing this treatment and it is especially important to follow up patients regularly. PMID:25431597

  1. Melanoma: from mutations to medicine

    PubMed Central

    Tsao, Hensin; Chin, Lynda; Garraway, Levi A.; Fisher, David E.

    2012-01-01

    Melanoma is often considered one of the most aggressive and treatment-resistant human cancers. It is a disease that, due to the presence of melanin pigment, was accurately diagnosed earlier than most other malignancies and that has been subjected to countless therapeutic strategies. Aside from early surgical resection, no therapeutic modality has been found to afford a high likelihood of curative outcome. However, discoveries reported in recent years have revealed a near avalanche of breakthroughs in the melanoma field—breakthroughs that span fundamental understanding of the molecular basis of the disease all the way to new therapeutic strategies that produce unquestionable clinical benefit. These discoveries have been born from the successful fruits of numerous researchers working in many—sometimes-related, although also distinct—biomedical disciplines. Discoveries of frequent mutations involving BRAF(V600E), developmental and oncogenic roles for the microphthalmia-associated transcription factor (MITF) pathway, clinical efficacy of BRAF-targeted small molecules, and emerging mechanisms underlying resistance to targeted therapeutics represent just a sample of the findings that have created a striking inflection in the quest for clinically meaningful progress in the melanoma field. PMID:22661227

  2. Emerging technologies for the detection of melanoma: achieving better outcomes

    PubMed Central

    Herman, Cila

    2012-01-01

    Every year around 2.5–3 million skin lesions are biopsied in the US, and a fraction of these – between 50,000 and 100,000 – are diagnosed as melanoma. Diagnostic instruments that allow early detection of melanoma are the key to improving survival rates and reducing the number of unnecessary biopsies, the associated morbidity, and the costs of care. Advances in technology over the past 2 decades have enabled the development of new, sophisticated test methods, which are currently undergoing laboratory and small-scale clinical testing. This review highlights and compares some of the emerging technologies that hold the promise of melanoma diagnosis at an early stage of the disease. The needs for detection at different levels (patient, primary care, specialized care) are discussed, and three broad classes of instruments are identified that are capable of satisfying these needs. Technical and clinical requirements on the diagnostic instruments are introduced to aid the comparison and evaluation of new technologies. White- and polarized-light imaging, spatial and spectroscopic multispectral methods, quantitative thermographic imaging, confocal microscopy, Optical Coherence Tomography (OCT), and Terahertz (THZ) imaging methods are highlighted in light of the criteria identified in the review. Based on the properties, possibilities, and limitations of individual methods, those best suited for a particular setting are identified. Challenges faced in development and wide-scale application of novel technologies are addressed. PMID:23204850

  3. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

    PubMed

    Ascierto, Paolo A; Atkins, Michael; Bifulco, Carlo; Botti, Gerardo; Cochran, Alistair; Davies, Michael; Demaria, Sandra; Dummer, Reinhard; Ferrone, Soldano; Formenti, Silvia; Gajewski, Thomas F; Garbe, Claus; Khleif, Samir; Kiessling, Rolf; Lo, Roger; Lorigan, Paul; Arthur, Grant Mc; Masucci, Giuseppe; Melero, Ignacio; Mihm, Martin; Palmieri, Giuseppe; Parmiani, Giorgio; Puzanov, Igor; Romero, Pedro; Schilling, Bastian; Seliger, Barbara; Stroncek, David; Taube, Janis; Tomei, Sara; Zarour, Hassane M; Testori, Alessandro; Wang, Ena; Galon, Jérôme; Ciliberto, Gennaro; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena

    2015-11-30

    survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

  4. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

    PubMed

    Ascierto, Paolo A; Atkins, Michael; Bifulco, Carlo; Botti, Gerardo; Cochran, Alistair; Davies, Michael; Demaria, Sandra; Dummer, Reinhard; Ferrone, Soldano; Formenti, Silvia; Gajewski, Thomas F; Garbe, Claus; Khleif, Samir; Kiessling, Rolf; Lo, Roger; Lorigan, Paul; Arthur, Grant Mc; Masucci, Giuseppe; Melero, Ignacio; Mihm, Martin; Palmieri, Giuseppe; Parmiani, Giorgio; Puzanov, Igor; Romero, Pedro; Schilling, Bastian; Seliger, Barbara; Stroncek, David; Taube, Janis; Tomei, Sara; Zarour, Hassane M; Testori, Alessandro; Wang, Ena; Galon, Jérôme; Ciliberto, Gennaro; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena

    2015-01-01

    survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma. PMID:26619946

  5. Implications of age and conditional survival estimates for patients with melanoma.

    PubMed

    Banerjee, Mousumi; Lao, Christopher D; Wancata, Lauren M; Muenz, Daniel G; Haymart, Megan R; Wong, Sandra L

    2016-02-01

    Overall cancer incidence is decreasing, whereas melanoma cases are increasing. Conditional survival estimates offer a more accurate prognosis for patients the farther they are from time of diagnosis. The effect of age and stage on a melanoma patient's conditional survival estimate is unknown. Surveillance, Epidemiology, and End Results data were utilized to identify newly diagnosed cutaneous melanoma patients (N=95 041), from 1998 to 2005, with up to 12 years of follow-up. Estimates of disease-specific survival by stage and age were determined by Cox regression analysis and transformed to estimated conditional 5-year survival. Localized melanoma patients have an excellent 5-year survival at diagnosis and over subsequent years. For patients with localized and regional disease, an age effect is present for disease-specific mortality when comparing older patients (70-79 years) with younger patients (<30 years): hazard ratio (HR) for mortality 3.79 [95% confidence interval (CI) 3.01-4.84] and HR 2.36 (95% CI 1.93-2.91), respectively. No age effect difference is observed in disease-specific survival for advanced disease: HR 1.14 (95% CI 0.87-1.53). Over time, conditional survival estimates improve for older patients with localized and regional disease. This improvement is not seen in distant disease, neither is the age gradient. Disease-specific mortality and conditional survival for patients with localized and regional melanomas are initially impacted by older age, with effects dissipating over time. Age does not affect survival in patients with advanced disease. Understanding the conditional 5-year disease-specific survival of melanoma based on age and stage can help patients and physicians, informing decision-making about treatment and surveillance. PMID:26479218

  6. Implications of age and conditional survival estimates for patients with melanoma

    PubMed Central

    Banerjee, Mousumi; Lao, Christopher D.; Wancata, Lauren M.; Muenz, Daniel G.; Haymart, Megan R.; Wong, Sandra L.

    2016-01-01

    Objective Overall cancer incidence is decreasing while melanoma cases increase. Conditional survival estimates offer a more accurate prognosis for patients as they survive past diagnosis. It is unknown the effect age and stage has on a melanoma patient’s conditional survival estimate. Methods Surveillance, Epidemiology, End Results (SEER) data was utilized, identifying new diagnosis cutaneous melanoma patients (N=95,041), from 1998–2005, with up to 12 year follow up. Estimates of disease-specific survival by stage and age were determined by Cox regression and transformed to estimate conditional five-year survival. Results Localized melanoma patients have an excellent five-year survival at diagnosis and subsequent years. For patients with localized and regional disease, an age effect is present for disease-specific mortality when comparing older patients (70–79 years) to younger patients (<30 years): hazard ratio (HR) for mortality 3.79 (95% confidence interval (CI) 3.01–4.84) and HR 2.36 (95% CI 1.93–2.91), respectively. No age effect difference is observed in disease-specific survival for advanced disease: HR 1.14 (95% CI 0.87–1.53). Over time conditional survival estimates improve for older patients with localized and regional disease. This improvement is not seen in distant disease nor is the age gradient. Conclusions Disease-specific mortality and conditional survival for patients with localized and regional melanoma is initially impacted by older age with effects dissipating over time. Age does not affect survival in patients with advanced disease. Understanding the conditional five-year disease-specific survival of melanoma based on age and stage can help patients and physicians, informing decision making about treatment and surveillance. PMID:26479218

  7. Improving outcomes in patients with melanoma: strategies to ensure an early diagnosis

    PubMed Central

    Voss, Rachel K; Woods, Tessa N; Cromwell, Kate D; Nelson, Kelly C; Cormier, Janice N

    2015-01-01

    Patients with thin, low-risk melanomas have an excellent long-term prognosis and higher quality of life than those who are diagnosed at later stages. From an economic standpoint, treatment of early stage melanoma consumes a fraction of the health care resources needed to treat advanced disease. Consequently, early diagnosis of melanoma is in the best interest of patients, payers, and health care systems. This review describes strategies to ensure that patients receive an early diagnosis through interventions ranging from better utilization of primary care clinics, to in vivo diagnostic technologies, to new “apps” available in the market. Strategies for screening those at high risk due to age, male sex, skin type, nevi, genetic mutations, or family history are discussed. Despite progress in identifying those at high risk for melanoma, there remains a lack of general consensus worldwide for best screening practices. Strategies to ensure early diagnosis of recurrent disease in those with a prior melanoma diagnosis are also reviewed. Variations in recurrence surveillance practices by type of provider and country are featured, with evidence demonstrating that various imaging studies, including ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging, provide only minimal gains in life expectancy, even for those with more advanced (stage III) disease. Because the majority of melanomas are attributable to ultraviolet radiation in the form of sunlight, primary prevention strategies, including sunscreen use and behavioral interventions, are reviewed. Recent international government regulation of tanning beds is described, as well as issues surrounding the continued use artificial ultraviolet sources among youth. Health care stakeholder strategies to minimize UV exposure are summarized. The recommendations encompass both specific behaviors and broad intervention targets (eg, individuals, social spheres, organizations, celebrities

  8. Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma.

    PubMed

    Bernardo, Sebastian G; Moskalenko, Marina; Pan, Michael; Shah, Shaily; Sidhu, Harleen K; Sicular, Serge; Harcharik, Sara; Chang, Rui; Friedlander, Philip; Saenger, Yvonne M

    2013-02-01

    Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies. The most concerning side effects reported in clinical studies of ipilimumab fall into the category of immune-related adverse events, which include enterocolitis, dermatitis, thyroiditis, hepatitis, hypophysitis, uveitis, and others. During the course of routine clinical care at Mount Sinai Medical Center, frequent hepatotoxicity was noted when ipilimumab was administered at a dose of 3 mg/kg according to Food and Drug Administration (FDA) guidelines. To better characterize these adverse events, we conducted a retrospective review of the first 11 patients with metastatic melanoma treated with ipilimumab at the Mount Sinai Medical Center after FDA approval. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevation, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, each occurred in six of 11 cases (≥grade 1), a notably higher frequency than could be expected on the basis of the FDA licensing study where elevations were reported in 0.8 and 1.5% of patients for AST and ALT, respectively. Grade 3 elevations in AST occurred in three of 11 patients as compared with 0% in the licensing trial. All cases of transaminitis resolved when ipilimumab was temporarily withheld without administration of immunosuppressive medication. During routine clinical care of late-stage melanoma patients with ipilimumab, physicians should monitor patients closely for hepatotoxicity and be aware that toxicity rates may differ across populations during ipilimumab therapy.

  9. Melanoma Prognostic Model Using Tissue Microarrays and Genetic Algorithms

    PubMed Central

    Gould Rothberg, Bonnie E.; Berger, Aaron J.; Molinaro, Annette M.; Subtil, Antonio; Krauthammer, Michael O.; Camp, Robert L.; Bradley, William R.; Ariyan, Stephan; Kluger, Harriet M.; Rimm, David L.

    2009-01-01

    Purpose As a result of the questionable risk-to-benefit ratio of adjuvant therapies, stage II melanoma is currently managed by observation because available clinicopathologic parameters cannot identify the 20% to 60% of such patients likely to develop metastatic disease. Here, we propose a multimarker molecular prognostic assay that can help triage patients at increased risk of recurrence. Methods Protein expression for 38 candidates relevant to melanoma oncogenesis was evaluated using the automated quantitative analysis (AQUA) method for immunofluorescence-based immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a cohort of 192 primary melanomas collected during 1959 to 1994. The prognostic assay was built using a genetic algorithm and validated on an independent cohort of 246 serial primary melanomas collected from 1997 to 2004. Results Multiple iterations of the genetic algorithm yielded a consistent five-marker solution. A favorable prognosis was predicted by ATF2 ln(non-nuclear/nuclear AQUA score ratio) of more than –0.052, p21WAF1 nuclear compartment AQUA score of more than 12.98, p16INK4A ln(non-nuclear/nuclear AQUA score ratio) of ≤ −0.083, β-catenin total AQUA score of more than 38.68, and fibronectin total AQUA score of ≤ 57.93. Primary tumors that met at least four of these five conditions were considered a low-risk group, and those that met three or fewer conditions formed a high-risk group (log-rank P < .0001). Multivariable proportional hazards analysis adjusting for clinicopathologic parameters shows that the high-risk group has significantly reduced survival on both the discovery (hazard ratio = 2.84; 95% CI, 1.46 to 5.49; P = .002) and validation (hazard ratio = 2.72; 95% CI, 1.12 to 6.58; P = .027) cohorts. Conclusion This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy. PMID:19884546

  10. The Tumor-Log Odds of Positive Lymph Nodes-Metastasis Staging System, a Promising New Staging System for Gastric Cancer after D2 Resection in China

    PubMed Central

    Wang, Zhi-qiang; Ren, Chao; Wang, De-shen; Zhang, Dong-sheng; Luo, Hui-yan; Li, Yu-hong; Xu, Rui-hua

    2012-01-01

    Background In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the −2log likelihood and the hazard ratio. Results The cut points of lymph node ratio (LNR) were set as 0, 0–0.3, 0.3–0.6, 0.6–1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤−0.5, −0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions The TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection. PMID:22348125

  11. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound.

    PubMed

    Mishima, Y; Ichihashi, M; Tsuji, M; Hatta, S; Ueda, M; Honda, C; Suzuki, T

    1989-05-01

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

  12. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Tsuji, M.; Hatta, S.; Ueda, M.; Honda, C.; Suzuki, T.

    1989-05-01

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure.

  13. Surviving cutaneous melanoma: a clinical review of follow-up practices, surveillance, and management of recurrence.

    PubMed

    Mrazek, Amy A; Chao, Celia

    2014-10-01

    The number of melanoma survivors in the United States continues to steadily increase 2.6% per year, while death rates have remained stable over time. Although controversy exists regarding optimal surveillance strategies, recommendations for clinical monitoring are based on tumor stage, tumor phenotype, likelihood of recurrence, prognosis, risk factors, psychosocial impact of disease, and patient well-being. Management guidelines for recurrent disease depend on the type of recurrence: local, satellite/in-transit, regional, or distant metastasis. This article is a current review of the literature concerning melanoma survivorship.

  14. Towards multimodal detection of melanoma thickness based on optical coherence tomography and optoacoustics

    NASA Astrophysics Data System (ADS)

    Rahlves, M.; Varkentin, A.; Stritzel, J.; Blumenröther, E.; Mazurenka, M.; Wollweber, M.; Roth, B.

    2016-03-01

    Melanoma skin cancer has one of the highest mortality rates of all types of cancer if not detected at an early stage. The survival rate is highly dependent on its penetration depth, which is commonly determined by histopathology. In this work, we aim at combining optical coherence tomography and optoacoustic as a non-invasive all-optical method to measure the penetration depth of melanoma. We present our recent achievements to setup a handheld multimodal device and also results from first in vivo measurements on healthy and cancerous skin tissue, which are compared to measurements obtained by ultrasound and histopathology.

  15. Pattern of Melanoma Incidence in Miami, Florida

    PubMed Central

    Aldrich, Tim E.; Garcia, Norberto

    1981-01-01

    Although melanoma causes only 1.4 percent of cancers nationally, it accounts for 3.6 percent of cancers in southern Flordia. The authors conducted an incidence survey to determine if the distribution of melanoma was a function of population density, an outdoors lifestyle, or the presence of an older population. PMID:7277525

  16. Herramienta para distinguir lunares de melanoma.

    Cancer.gov

    “De lunares a melanoma: reconocimiento de las características ABCDE” presenta fotos que muestran cambios en lesions individuales pigmentadas con el tiempo, y describe las diferentes apariencias de lunares, de nevos displásicos y de melanomas.

  17. Update in genetic susceptibility in melanoma.

    PubMed

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2015-09-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual.

  18. Update in genetic susceptibility in melanoma.

    PubMed

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2015-09-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual. PMID:26488006

  19. Update in genetic susceptibility in melanoma

    PubMed Central

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep

    2015-01-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual. PMID:26488006

  20. Malignant melanoma of the anal canal: a case report

    PubMed Central

    Barbus, Roxana; Rancea, Alin; Fetica, Bogdan; Spârchez, Zeno

    2009-01-01

    This article is one case report of 49 year-old woman diagnosed with malignant melanoma of the anal canal. The tumor was detected at early stage and initially treated with local excision, followed by adjuvant interstitial brachytherapy. Since the patient complained of painful local ulceration and atypical cells were found at biopsy, abdominoperineal resection of the rectum was performed and a sterile specimen was obtained, proving the efficacy of adjuvant brachytherapy for local control. Patient is now considered disease free for 30 months after primary treatment.

  1. Dabrafenib in the treatment of metastatic or unresectable melanoma.

    PubMed

    Khoja, Leila; Hogg, David

    2015-03-01

    Dabrafenib is a potent inhibitor of mutant BRAF. Trials to date have shown it to be well tolerated, with significant activity in unresectable stage III or IV metastatic melanoma. Overall response rates of approximately 50% were seen in addition to improved progression-free and overall survival of 6 and 18 months, respectively. Preclinical studies suggested that combining BRAF and MEK inhibition would increase response rates and decrease toxicity. Clinical trials with the combination of dabrafenib and trametinib have improved progression-free and overall survival in interim analyses. Future improvements in responses and outcomes will depend on additional combination strategies, possibly employing immunotherapy. PMID:25711514

  2. Serum copper and zinc levels in melanoma patients

    SciTech Connect

    Fisher, G.L.; Spitler, L.E.; McNeill, K.L.; Rosenblatt, L.S.

    1981-04-01

    Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in malignant melanoma patients at various clinical stages. Copper levels were generally found to be elevated, reflecting the degree and extent of tumor activity. Zinc levels and, hence, SCL:SZL ratios did not reflect tumor activity. SCL appeared to prognosticate disease progression in that all patients whose values never declined below 150 ..mu..g/100 ml died during the course of the study. However, not all patients who died from tumor metastases displayed persistent elevations of SCL. Patients receiving BCG immunotherapy appeared to have higher SCL than untreated patients.

  3. Screening, early detection, education, and trends for melanoma: current status (2007-2013) and future directions: Part I. Epidemiology, high-risk groups, clinical strategies, and diagnostic technology.

    PubMed

    Mayer, Jonathan E; Swetter, Susan M; Fu, Teresa; Geller, Alan C

    2014-10-01

    While most cancers have shown both decreased incidence and mortality over the past several decades, the incidence of melanoma has continued to grow, and mortality has only recently stabilized in the United States and in many other countries. Certain populations, such as men >60 years of age and lower socioeconomic status groups, face a greater burden from disease. For any given stage and across all ages, men have shown worse melanoma survival than women, and low socioeconomic status groups have increased levels of mortality. Novel risk factors can help identify populations at greatest risk for melanoma and can aid in targeted early detection. Risk assessment tools have been created to identify high-risk patients based on various factors, and these tools can reduce the number of patients needed to screen for melanoma detection. Diagnostic techniques, such as dermatoscopy and total body photography, and new technologies, such as multispectral imaging, may increase the accuracy and reliability of early melanoma detection.

  4. Are some melanomas caused by artificial light?

    PubMed

    Kvaskoff, Marina; Weinstein, Philip

    2010-09-01

    The incidence rate of cutaneous melanoma has been increasing faster than that of any other cancer in white-skinned populations over the past decades. The main risk factors for melanoma (i.e. exposure to sunlight, naevus count, phototype, and family history of melanoma) may not wholly explain the epidemiological trends observed for this cancer. The light-at-night theory postulates that increasing use of artificial light-at-night may contribute to the increasing breast cancer incidence through suppressed secretion of melatonin (a hormone produced in the dark and inhibited by light, which regulates circadian rhythms). Here, we postulate that this theory may also apply to melanoma and that it may explain a part of this cancer burden. Consistent with our hypothesis is evidence from experimental studies suggesting a lightening effect of melatonin on frog skin and mammal hair during seasonal changes, its antioxidant and anti-carcinogenic effects in skin melanocytes, as well as the expression of melatonin receptors in melanocytes. Also, epidemiological data suggest lower melatonin concentrations in melanoma patients compared with controls; a potential therapeutic effect of melatonin in patients with metastatic disease; a higher prevalence of melanoma in pilots and aircrews, with increased risks with higher time zones travelled; and increased melanoma risks in office workers exposed to fluorescent lighting. Moreover, melanoma incidence and seasonal patterns are consistent with a reduction of melatonin secretion with intensity of exposure to light, although it remains difficult to distinguish the effect of melatonin disruption from that of sun exposure on the basis of ecological studies. Finally, the reported associations between hormonal factors and melanoma are consistent with melatonin inhibition increasing the risk of melanoma by increasing circulating oestrogen levels. Despite the existing suggestive evidence, the light-at-night hypothesis has never been directly tested

  5. Novel approaches in melanoma prevention and therapy.

    PubMed

    Grimaldi, Antonio M; Cassidy, Pamela B; Leachmann, Sancy; Ascierto, Paolo A

    2014-01-01

    The incidence of cutaneous melanoma has risen at a rate significantly higher than that for other malignancies. This increase persists despite efforts to educate the public about the dangers of excess exposure to UV radiation from both the sun and tanning beds. Melanoma affects a relatively younger population and is notorious for its propensity to metastasize and for its poor response to current therapeutic regimens. These factors make prevention an integral component to the goal of decreasing melanoma-related mortality. Transformation of melanocytes into malignant melanoma involves the interplay between genetic factors, UV exposure, and the tumor microenvironment. The roles of UV radiation in the etiology of melanoma are mediated by both direct damage of DNA through formation of photoproducts and production of reactive oxygen species (ROS). Many of the promising antioxidant agents under development for the prevention of melanoma are derived from foodstuffs. B-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases that plays a role in regulating the MAP kinase/ERKs signaling pathway. About 50 % of melanomas harbor activating BRAF mutations. BRAF mutations are found in 59 % of the melanomas arising in skin with intermittent sun exposure, such as trunk and arms, as compared with only 23 % of the acral melanomas, 11 % of mucosal melanomas, and 0 % of uveal melanomas. Two new agents, ipilimumab and vemurafenib, have been shown to improve outcome of advanced melanoma as presented at the plenary session of the 2011 annual meeting of the American Society of Clinical Oncology. Vemurafenib is the first personalized compound which demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) in metastatic melanoma harboring the BRAFV600 mutation and represents the first drug of a class that exerts its anti-proliferative activity through inhibition of a highly specific molecular target. GSK2118436 (dabrafenib), the

  6. Expression of miR-203 is decreased and associated with the prognosis of melanoma patients.

    PubMed

    Wang, Kai; Zhang, Zheng-Wen

    2015-01-01

    MicroRNAs (miRNAs or miRs) are a class of small, non-coding RNAs that can regulate the gene expression in various diseases. MicroRNA-203 (miRNA-203 or miR-203) has previously shown significant alteration in a number of cancers. However, the clinical value of miR-203 in melanoma is rarely reported. The present study aimed to clarify the expression pattern and prognostic role of miR-203 in melanoma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression level of miR-203 in 148 cases of melanoma tissues and adjacent non-cancerous tissues. Results showed that miR-203 expression was significantly decreased in melanoma tissues compared with that in adjacent non-cancerous tissues (P<0.05). Additionally, chi-square was performed to analyze the relationship between miR-203 and clinicopathological features and the down-regulation of miR-203 was significantly associated with tumor thickness and tumor stage (P<0.05). Moreover, Kaplan-Meier analysis showed that low miR-203 expression was associated with short overall survival time of patients. Multivariate analysis indicated that miR-203 could be an independent prognostic marker (P=0.003, HR=2.851, 95% CI=1.439-5.650) in melanoma This study for the first time provided evidence that miR-203 could be an independent potential prognostic marker for patients with melanoma, and might even become a new therapeutic target for the treatment of melanoma.

  7. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

    PubMed

    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients. PMID:26426764

  8. Cutaneous melanoma in genetically modified animals.

    PubMed

    Larue, Lionel; Beermann, Friedrich

    2007-12-01

    Cutaneous melanomas are tumors originating from skin melanocytes which are present in hair follicles, and interfollicular epidermal and dermal layers. Experimental work in model systems involves in silico, in vitro and in vivo analyses. Such models allow to mimick melanocytic aberrations characteristic of melanoma, and to potentially exploit novel therapies. Transgenic technologies can be used to modify specifically the genome of the model organism and thereby generate transgenic strains, and combinations of such strains, which may develop metastasizing melanoma. In such strains, metastasizing melanoma either arises spontaneously after a period of latency or requires additional physical or chemical induction. In this review, we summarize the work of currently available transgenic melanoma models and discuss the most recent progress in creating improved and/or inducible models reflecting the human disease.

  9. Solitary metachronous splenic metastasis from cutaneous melanoma

    PubMed Central

    Gavriilidis, Paschalis; Goupou, Eleni

    2012-01-01

    Melanoma has been found to metastasise to the spleen, usually in cases of disseminated disease. Solitary splenic metastasis from cutaneous melanoma is very rare. Herein we report the case of a 43-year-old man who developed solitary splenic metastasis from cutaneous melanoma. The patient was operated for T4b N1a Mo superficial spreading melanoma of the anterior thoracic wall. He subsequently underwent left axillary lymph node dissection due to a positive sentinel lymph node. The 33 retrieved lymph nodes were negative for metastasis. The patient received adjuvant therapy with high-dose interferon α-2b. After 27 months and during the follow-up visit an increasing lactate dehydrogenase serum level was observed. Furthermore, CT of the whole body revealed a solitary hypodense tumour of the spleen 9 cm×6 cm. Curative splenectomy was performed and the histopathological report confirmed metastatic melanoma to the spleen. PMID:23104633

  10. Arginine deprivation therapy for malignant melanoma

    PubMed Central

    Yoon, Jung-Ki; Frankel, Arthur E; Feun, Lynn G; Ekmekcioglu, Suhendan; Kim, Kevin B

    2013-01-01

    Despite recent development of promising immunotherapeutic and targeted drugs, prognosis in patients with advanced melanoma remains poor, and a cure for this disease remains elusive in most patients. The success of melanoma therapy depends on a better understanding of the biology of melanoma and development of drugs that effectively target the relevant genes or proteins essential for tumor cell survival. Melanoma cells frequently lack argininosuccinate synthetase, an essential enzyme for arginine synthesis, and as a result they become dependent on the availability of exogenous arginine. Accordingly, a therapeutic approach involving depletion of available arginine has been shown to be effective in preclinical studies. Early clinical studies have demonstrated sufficient antitumor activity to give rise to cautious optimism. In this article, the rationale for arginine deprivation therapy is discussed. Additionally, various strategies for depleting arginine are discussed and the preclinical and clinical investigations of arginine deprivation therapy in melanoma are reviewed. PMID:23293541

  11. Primary Bile Duct Melanoma Causing Obstructive Jaundice

    PubMed Central

    Addepally, Naga S.; Klair, Jagpal S.; Lai, Keith; Aduli, Farshad

    2016-01-01

    Malignant melanoma is one of the few malignancies that are well known for unusual behavior. Primary malignant melanoma usually originates from squamous epithelium of skin, mucous membranes, retina, and uvea. Although melanoma can metastasize to any part of the body, including biliary tract, primary malignant melanoma of bile ducts is an extremely rare entity. We present a 52-year-old man who presented with 5-month epigastric pain and 15-pound weight loss, with 1-week duration of jaundice, nausea/vomiting, pale stools, and dark urine, blood work suggested cholestatic jaundice. Imaging revealed a large perihilar/peripancreatic mass involving the portal vein and hepatic artery, and intrahepatic biliary dilation. Biliary brushings revealed neoplastic cells strongly suggestive of malignant melanoma. PMID:27807580

  12. Mechanisms of Melanoma Promotion by Ultraviolet Radiation.

    PubMed

    Rünger, Thomas M

    2016-09-01

    The mutagenic properties of ultraviolet radiation drive the initiation of melanoma. Induction of matrix metalloproteinases in melanoma cells by longwave UVA radiation, possibly via a Warburg-like effect, promotes melanoma invasiveness. This is one of several mechanisms by which ultraviolet radiation also promotes further growth of previously established melanomas. PMID:27542295

  13. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment.

    PubMed

    Sustarsic, Elahu G; Junnila, Riia K; Kopchick, John J

    2013-11-01

    Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute's NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma. PMID:24134847

  14. Hemorrhagic regression of melanoma metastases during therapeutic vaccination: a report of three cases.

    PubMed

    Pierret, Lauranne; Baren, Nicolas Van; Bonehill, Aude; Corthals, Jurgen; Van Nuffel, An M T; Heirman, Carlo; Roelandt, Truus; De Coninck, Arlette; Riet, Ivan Van; Degreef, Ellen; Goossens, Annieta; Verfaillie, Guy; Roseeuw, Diane; Thielemans, Kris; Neyns, Bart

    2009-12-01

    Melanoma metastases are characterized by pronounced neo-angiogenesis and spontaneous bleeding frequently occurring within central nervous system metastases. Clinically apparent spontaneous hemorrhage within subcutaneous melanoma metastases, however, is a rare event that coincides with progression of such metastases. We report, to our knowledge the first observation, on regression of subcutaneous metastases with hemorrhage of the overlying skin in three patients with stage IV melanoma who participated in clinical trials on therapeutic vaccination. In two patients, loss of arterial flow on Doppler ultrasound imaging was documented in the metastasis at the time of hematoma formation. One patient suffered from an intracranial hemorrhage in a subcentimetric brain metastasis coincident with the hemorrhagic regression of some of his skin metastases.

  15. In vivo molecular photoacoustic tomography of melanomas targeted by bio-conjugated gold nanocages

    PubMed Central

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher; Zhang, Qiang; Cobley, Claire M.; Gao, Feng; Xia, Younan; Wang, Lihong V.

    2010-01-01

    Early diagnosis, accurate staging, and image-guided resection of melanomas remain crucial clinical objectives for improving patient survival and treatment outcomes. Conventional techniques cannot meet this demand because of the low sensitivity, low specificity, poor spatial resolution, shallow penetration, and/or ionizing radiation. Here we overcome such limitations by combining high-resolution photoacoustic tomography (PAT) with extraordinarily optical absorbing gold nanocages (AuNCs). When bio-conjugated with [Nle4,D-Phe7]-α-melanocyte-stimulating hormone, the AuNCs can serve as a novel contrast agent for in vivo molecular PAT of melanomas with both exquisite sensitivity and high specificity. The bio-conjugated AuNCs enhanced contrast ~300% more than the control, PEGylated AuNCs. The in vivo PAT quantification of the amount of AuNCs accumulated in melanomas was further validated with inductively coupled plasma mass spectrometry (ICP-MS). PMID:20731439

  16. Brazilian guidelines for diagnosis, treatment and follow-up of primary cutaneous melanoma - Part II*

    PubMed Central

    Castro, Luiz Guilherme Martins; Bakos, Renato Marchiori; Duprat Neto, João Pedreira; Bittencourt, Flávia Vasques; Giacomo, Thais Helena Bello Di; Serpa, Sérgio Schrader; Messina, Maria Cristina de Lorenzo; Loureiro, Walter Refkalefsky; Macarenco, Ricardo Silvestre e Silva; Stolf, Hamilton Ometto; Gontijo, Gabriel

    2016-01-01

    The last Brazilian guidelines on melanoma were published in 2002. Development in diagnosis and treatment made updating necessary. The coordinators elaborated ten clinical questions, based on PICO system. A Medline search, according to specific MeSH terms for each of the 10 questions was performed and articles selected were classified from A to D according to level of scientific evidence. Based on the results, recommendations were defined and classified according to scientific strength. The present Guidelines were divided in two parts for editorial and publication reasons. In this second part, the following clinical questions were answered: 1) which patients with primary cutaneous melanoma benefit from sentinel lymph node biopsy? 2) Follow-up with body mapping is indicated for which patients? 3) Is preventive excision of acral nevi beneficious to patients? 4) Is preventive excision of giant congenital nevi beneficious to patients? 5) How should stages 0 and I primary cutaneous melanoma patients be followed? PMID:26982779

  17. Factors significantly increasing or inhibiting early stages of malignant melanoma (M.M.) and non-invasive evaluation of new treatment by ingestion and external application of optimal doses of the most effective anti-M.M. substances: haritaki, cilantro, vitamin D3, nori, EPA with DHA, & application of special (+) solar energy stored paper, which reduced the M.M. active area & asbestos rapidly.

    PubMed

    Omura, Yoshiaki; Jones, Marilyn; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2013-01-01

    Sterilizing the pre-cancer skin of malignant melanoma (M.M.) with 70% Isopropyl alcohol intensified malignancy & the malignant response extended to surrounding normal looking skin, while sterilizing with 80% (vodka) or 12% (plum wine) ethyl alcohol completely inhibited M.M. in the area (both effects lasted for about 90 minutes initially). Burnt food (bread, vegetables, meat, and fish), a variety of smoked & non-smoked fish-skin, many animal's skin, pepper, Vitamin C over 75 mg, mango, pineapple, coconut, almond, sugars, Saccharine & Aspartame, garlic, onion, etc & Electromagnetic field from cellular phones worsened M.M. & induced abnormal M.M. response of surrounding skin. We found the following factors inhibit early stage of M.M. significantly: 1) Increasing normal cell telomere, by taking 500 mg Haritaki, often reached between 400-1150 ng& gradually diminished, but the M.M. response was completely inhibited until normal cell telomeres are reduced to 150 ng, which takes 6-8 hours. More than 70 mg Vitamin C, Orange Juice, & other high Vitamin C containing substances shouldn't be taken because they completely inhibit the effects of Haritaki. 2) We found Chrysotile asbestos & Tremolite asbestos (% of the Chrysotile amount) coexist. A special Cilantro tablet was used to remove asbestos & some toxic metals. 3) Vitamin D3 400 I.U. has a maximum inhibiting effect on M.M. but 800 I.U. or higher promotes malignancy. 4) Noricontaining Iodine, etc., was used. 5) EPA 180 mm with DHA 120 mg was most effectively used after metastasis to the surrounding skin was eliminated. When we combined 1 Cilantro tablet & Vitamin D3 400 I.U. withsmall Nori pieces & EPA with DHA, the effect of complete inhibition of M.M. lasted 9-11 hours. When these anti-M.M.substances (Haritaki, Vitamin D3, Cilantro, Nori, EPA. with DHA) were taken together, the effect lasted 12-14 hoursand M.M. involvement in surrounding normal-looking skin disappeared rapidly & original dark brown or black are as

  18. Aberrant CpG methylation of the TFAP2A gene constitutes a mechanism for loss of TFAP2A expression in human metastatic melanoma

    PubMed Central

    Hallberg, Andrea R; Vorrink, Sabine U; Hudachek, Danielle R; Cramer-Morales, Kimberly; Milhem, Mohammed M; Cornell, Robert A; Domann, Frederick E

    2014-01-01

    Metastatic melanoma is a deadly treatment-resistant form of skin cancer whose global incidence is on the rise. During melanocyte transformation and melanoma progression the expression profile of many genes changes. Among these, a gene implicated in several steps of melanocyte development, TFAP2A, is frequently silenced; however, the molecular mechanism of TFAP2A silencing in human melanoma remains unknown. In this study, we measured TFAP2A mRNA expression in primary human melanocytes compared to 11 human melanoma samples by quantitative real-time RT-PCR. In addition, we assessed CpG DNA methylation of the TFAP2A promoter in these samples using bisulfite sequencing. Compared to primary melanocytes, which showed high TFAP2A mRNA expression and no promoter methylation, human melanoma samples showed decreased TFAP2A mRNA expression and increased promoter methylation. We further show that increased CpG methylation correlates with decreased TFAP2A mRNA expression. Using The Cancer Genome Atlas, we further identified TFAP2A as a gene displaying among the most decreased expression in stage 4 melanomas vs. non-stage 4 melanomas, and whose CpG methylation was frequently associated with lack of mRNA expression. Based on our data, we conclude that TFAP2A expression in human melanomas can be silenced by aberrant CpG methylation of the TFAP2A promoter. We have identified aberrant CpG DNA methylation as an epigenetic mark associated with TFAP2A silencing in human melanoma that could have significant implications for the therapy of human melanoma using epigenetic modifying drugs. PMID:25625848

  19. Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

    SciTech Connect

    Sustarsic, Elahu G.; Junnila, Riia K.; Kopchick, John J.

    2013-11-08

    Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includes 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on

  20. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature.

    PubMed

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5-29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10-15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  1. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature

    PubMed Central

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5–29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10–15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  2. Perfusion and infusion for melanoma in-transit metastases in the era of effective systemic therapy.

    PubMed

    Grünhagen, Dirk J; Kroon, Hidde M; Verhoef, Cornelis

    2015-01-01

    The management of melanoma in-transit metastases (IT-mets) is challenging. For many years, the absence of effective systemic therapy has prompted physicians to focus on regional therapies for melanoma confined to the limb. The introduction of isolated limb perfusion (ILP) and isolated limb infusion (ILI) has enabled effective delivery of cytotoxic drugs in an isolated circuit, so as to overcome systemic toxicity and maximize local response. Both techniques have evolved over years and both tumor necrosis factor (TNF)-alpha-based ILP and ILI have distinct indications. The development of new systemic treatment options for patients with melanoma in the past decade has shed a new light on melanoma therapy. The present manuscript focuses on the modern role of ILI and ILP in the treatment of patients with melanoma with in-transit metastases in the era of effective systemic therapy. The response and control rates of ILI/ILP are still superior to rates achieved with systemic agents. The extent of disease in patients with stage III disease, however, warrants effective systemic treatment to prolong survival. There is great potential in combining rapid response therapy such as ILI/ILP with systemic agents for sustainable response. Trial results are eagerly awaited. PMID:25993219

  3. Host kinin B1 receptor plays a protective role against melanoma progression.

    PubMed

    Maria, Andrea G; Dillenburg-Pilla, Patrícia; Reis, Rosana I; Floriano, Elaine M; Tefé-Silva, Cristiane; Ramos, Simone G; Pesquero, João B; Nahmias, Clara; Costa-Neto, Claudio M

    2016-01-01

    Melanoma is a very aggressive tumor that arises from melanocytes. Late stage and widely spread diseases do not respond to standard therapeutic approaches. The kallikrein-kinin system (KKS) participates in biological processes such as vasodilatation, pain and inflammatory response. However, the role of KKS in tumor formation and progression is not completely understood. The role of the host kinin B1 receptor in melanoma development was evaluated using a syngeneic melanoma model. Primary tumors and metastasis were respectively induced by injecting B16F10 melanoma cells, which are derived from C57BL/6 mice, subcutaneously or in the tail vein in wild type C57BL/6 and B1 receptor knockout mice (B1(-/-)). Tumors developed in B1(-/-) mice presented unfavorable prognostic factors such as increased incidence of ulceration, higher levels of IL-10, higher activation of proliferative pathways such as ERK1/2 and Akt, and increased mitotic index. Furthermore, in the metastasis model, B1(-/-) mice developed larger metastatic colonies in the lung and lower CD8(+)immune effector cells when compared with WT animals. Altogether, our results provide evidences that B1(-/-) animals developed primary tumors with multiple features associated with poor prognosis and unfavorable metastatic onset, indicating that the B1 receptor may contribute to improve the host response against melanoma progression. PMID:26898917

  4. Host kinin B1 receptor plays a protective role against melanoma progression

    PubMed Central

    Maria, Andrea G.; Dillenburg-Pilla, Patrícia; Reis, Rosana I.; Floriano, Elaine M.; Tefé-Silva, Cristiane; Ramos, Simone G.; Pesquero, João B.; Nahmias, Clara; Costa-Neto, Claudio M.

    2016-01-01

    Melanoma is a very aggressive tumor that arises from melanocytes. Late stage and widely spread diseases do not respond to standard therapeutic approaches. The kallikrein-kinin system (KKS) participates in biological processes such as vasodilatation, pain and inflammatory response. However, the role of KKS in tumor formation and progression is not completely understood. The role of the host kinin B1 receptor in melanoma development was evaluated using a syngeneic melanoma model. Primary tumors and metastasis were respectively induced by injecting B16F10 melanoma cells, which are derived from C57BL/6 mice, subcutaneously or in the tail vein in wild type C57BL/6 and B1 receptor knockout mice (B1−/−). Tumors developed in B1−/− mice presented unfavorable prognostic factors such as increased incidence of ulceration, higher levels of IL-10, higher activation of proliferative pathways such as ERK1/2 and Akt, and increased mitotic index. Furthermore, in the metastasis model, B1−/− mice developed larger metastatic colonies in the lung and lower CD8+immune effector cells when compared with WT animals. Altogether, our results provide evidences that B1−/− animals developed primary tumors with multiple features associated with poor prognosis and unfavorable metastatic onset, indicating that the B1 receptor may contribute to improve the host response against melanoma progression. PMID:26898917

  5. Advances in Personalized Targeted Treatment of Metastatic Melanoma and Non-Invasive Tumor Monitoring

    PubMed Central

    Klinac, Dragana; Gray, Elin S.; Millward, Michael; Ziman, Mel

    2013-01-01

    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management. PMID:23515890

  6. Diagnostic and therapeutic approaches in Italian hospitals: adjuvant and metastatic therapy in melanoma.

    PubMed

    Chiarion-Sileni, Vanna; Guida, Michele; Romanini, Antonella; Bernengo, Maria Grazia; Ascierto, Paolo; Queirolo, Paola; Mandalà, Mario; Maio, Michele; Ferraresi, Virginia; Stanganelli, Ignazio; Testori, Alessandro; Ridolfi, Ruggero

    2013-01-01

    Melanoma incidence and mortality rates are rising in Italy, indicating that more effective treatments are required both in the adjuvant and metastatic settings. We analyzed clinical practices in the adjuvant and metastatic settings by conducting a nationwide survey of clinicians responsible for managing melanoma treatment and follow-up in a representative sample of Italian hospitals. 95% of participating hospitals completed the panel of questions on adjuvant and metastatic treatment, making it likely that these results give a realistic picture of treatment and follow-up of melanoma patients in Italy. In low-volume hospitals (<25 new melanoma diagnoses yearly) adjuvant therapy was significantly more used than in large-volume hospitals for patients in stage III and IV (82 versus 66% and 56 versus 30%, respectively), and only 11% of patients were enrolled in clinical trials. In the metastatic setting dacarbazine was the preferred first-line treatment (32%) followed by polychemotherapy (23%); 12% of patients were enrolled in clinical trials and less than 10% received interleukin-2, usually subcutaneously. The information provided by this study was used by the Italian Melanoma Intergroup to improve the quality of care and to redirect financial resources. PMID:23736267

  7. SERPINB1 expression is predictive for sensitivity and outcome of cisplatin-based chemotherapy in melanoma

    PubMed Central

    Willmes, Christoph; Kumar, Rajiv; Becker, Jürgen C.; Fried, Isabella; Rachakonda, P. Sivaramakrishna; Poppe, Lidia M.; Hesbacher, Sonja; Schadendorf, Dirk; Sucker, Antje

    2016-01-01

    Despite of highly effective new therapeutic strategies, chemotherapy still is an important treatment option in metastatic melanoma. Since predictors of chemotherapy response are rare, drugs and regimens are currently chosen arbitrarily. The present study was aimed at the identification of molecular markers predicting the outcome of chemotherapy in melanoma. Tumor biopsies from metastatic lesions were collected from 203 stage IV melanoma patients prior to chemotherapy onset and used for gene expression profiling (n = 6; marker identification set), quantitative real-time PCR (n = 127; validation set 1), and immunohistochemistry on tissue microarrays (n = 70; validation set 2). The results were correlated to the tumors' in-vitro chemosensitivity and to the patients' in-vivo chemotherapy outcome. SERPINB1 was found to correlate to the in-vitro sensitivity to cisplatin-containing chemotherapy regimens (p = 0.005). High SERPINB1 gene expression was associated with favorable tumor response (p = 0.012) and prolonged survival (p = 0.081) under cisplatin-based chemotherapy. High SERPINB1 protein expression in tumor tissue from cisplatin-treated patients was associated with a favorable survival (p = 0.011), and proved as an independent predictor of survival (p = 0.008) by multivariate analysis. We conclude, that SERPINB1 expression, although not functionally involved, is predictive for the outcome of cisplatin-based chemotherapy in melanoma, and thus may be useful to personalize melanoma chemotherapy. PMID:26799424

  8. Perfusion and infusion for melanoma in-transit metastases in the era of effective systemic therapy.

    PubMed

    Grünhagen, Dirk J; Kroon, Hidde M; Verhoef, Cornelis

    2015-01-01

    The management of melanoma in-transit metastases (IT-mets) is challenging. For many years, the absence of effective systemic therapy has prompted physicians to focus on regional therapies for melanoma confined to the limb. The introduction of isolated limb perfusion (ILP) and isolated limb infusion (ILI) has enabled effective delivery of cytotoxic drugs in an isolated circuit, so as to overcome systemic toxicity and maximize local response. Both techniques have evolved over years and both tumor necrosis factor (TNF)-alpha-based ILP and ILI have distinct indications. The development of new systemic treatment options for patients with melanoma in the past decade has shed a new light on melanoma therapy. The present manuscript focuses on the modern role of ILI and ILP in the treatment of patients with melanoma with in-transit metastases in the era of effective systemic therapy. The response and control rates of ILI/ILP are still superior to rates achieved with systemic agents. The extent of disease in patients with stage III disease, however, warrants effective systemic treatment to prolong survival. There is great potential in combining rapid response therapy such as ILI/ILP with systemic agents for sustainable response. Trial results are eagerly awaited.

  9. Recovery of a cell surface fetal antigen from circulating immune complexes of melanoma patients.

    PubMed

    Wong, J H; Aguero, B; Gupta, R K; Morton, D L

    1988-01-01

    A well-characterized 69.5 x 10(3) dalton glycoprotein fetal antigen (FA), isolated from the spent culture medium of a melanoma cell line, UCLA-SO-14 (M14), was utilized to characterize the antigen component of circulating immune complexes (CIC) from melanoma patients. Ten serum samples from five patients with stage II melanoma at 1 and 4 months prior to the clinical detection of recurrent disease were selected for study. The CIC were dissociated with low pH and ultrafiltered through a 100 x 10(3) dalton exclusion limit membrane. The low pH treatment resulted in an increase in antibody titer in eight of ten serum samples. The antibody activity in membrane immunofluorescence was quantitatively inhibited by the filtered antigen fraction and purified FA, suggesting the presence of anti-FA antibodies in the treated serum, which possibly were complexed with FA in the untreated sample. As determined by competitive inhibition in an enzyme-linked immunosorbent assay, the filtrate (antigen fraction) contained an antigen that was immunologically similar to FA. These results clearly demonstrate that FA, expressed on the cell surface of melanoma cells, is present in CIC of selected melanoma patients.

  10. Adoptive immunotherapy of advanced melanoma.

    PubMed

    Shapira-Frommer, Ronnie; Schachter, Jacob

    2012-09-01

    Adoptive cell therapy (ACT) has emerged as an effective therapy for patients with metastatic melanoma. Since the first introduction of the protocol in 1988 [1], major improvements have been achieved with response rates of 40%-72% among patients who were resistant to previous treatment lines. Both cell product and conditioning regimen are major determinants of treatment efficacy; therefore, developing ACT protocols explore diverse ways to establish autologous intra-tumoral lymphocyte cultures or peripheral effector cells as well as different lymphodepleting regimens. While a proof of feasibility and a proof of concept had been established with previous published results, ACT will need to move beyond single-center experiences, to confirmatory, multi-center studies. If ACT is to move into widespread practice, it will be necessary to develop reproducible high quality cell production methods and accepted lymphodepleting regimen. Two new drugs, ipilimumab (Yervoy, Bristol-Myers Squibb) and vemurafenib (Zelboraf, Roche), were approved in 2011 for the treatment of metastatic melanoma based on positive phase III trials. Both drugs show a clear overall survival benefit, so the timing of when to use ACT will need to be carefully thought out. In contrast to these 2 new, commercially available outpatient treatments, ACT is a personally-specified product and labor-intensive therapy that demands both acquisition of high standard laboratory procedures and close clinical inpatient monitoring during treatment. It is unique among other anti-melanoma treatments, providing the potential for a durable response following a single, self-limited treatment. This perspective drives the efforts to make this protocol accessible for more patients and to explore modifications that may optimize treatment results.

  11. Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report.

    PubMed

    Ozgun, Alpaslan; Tuncel, Tolga; Emirzeoglu, Levent; Celik, Serkan; Bilgi, Oguz; Haholu, Abdullah; Urhan, Muammer; Karagoz, Bulent

    2015-01-01

    Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously. PMID:25436010

  12. Variability in melanoma post-treatment surveillance practices by country and physician specialty: A systematic review

    PubMed Central

    Cromwell, Kate D.; Ross, Merrick I.; Xing, Yan; Gershenwald, Jeffrey E.; Royal, Richard E.; Lucci, Anthony; Lee, Jeffrey E.; Cormier, Janice N.

    2013-01-01

    Background There are no evidence-based guidelines for surveillance of patients with melanoma following surgical treatment. We performed a systematic review to identify current stage-specific surveillance practices for patients with melanoma by country and physician specialty. Methods Three major medical indices, MEDLINE, the Cochrane Library database, and Scopus, were reviewed to identify articles published in January 1970 to October 2011 that included detailed information about surveillance of patients with melanoma after initial surgical treatment. Data on surveillance intervals and recommended evaluation were extracted and categorized by country and, when reported, physician specialty. Results One hundred four articles from 10 countries and 4 physician specialties (dermatology, surgical oncology, medical oncology, and general practice) met the inclusion criteria, including 43 providing specific patient-level data. The articles showed wide variation with respect to surveillance intervals and recommended evaluations. Variation was greatest for patients with stage I disease, for whom follow-up frequency ranged from 1 to 6 visits per year during years 1 and 2 after treatment. All 4 physician specialties agreed that for years 1–3, the follow-up frequency should be 4 times per year for all patients. For years 4 and 5, surgical oncologists recommended 2 follow-up visits per year, whereas general practitioners, dermatologists, and medical oncologists recommended 4 visits per year. Recommended imaging and laboratory evaluations were most intense in the United Kingdom and most minimalist in The Netherlands. While general practitioners did not recommend routine laboratory or imaging tests for surveillance, all other specialties utilized both in their surveillance practice. Self skin-examination was recommended for surveillance in all countries and by all practitioner specialties. Conclusions There is significant intercountry and interspecialty variation in surveillance

  13. Epigenetic inactivation of tumor suppressor genes in serum of patients with cutaneous melanoma.

    PubMed

    Marini, Alessandra; Mirmohammadsadegh, Alireza; Nambiar, Sandeep; Gustrau, Annett; Ruzicka, Thomas; Hengge, Ulrich R

    2006-02-01

    Small amounts of cell-free DNA circulate in both healthy and diseased human blood, while increased concentrations of DNA are present in the serum of cancer patients. Tumor-specific mutations or epigenetic modifications have predominantly been detected in tissue specimens. The purpose of this study was to investigate methylation of five different genes involved in tumor suppression and DNA repair (suppressors of cytokine signaling 1 and 2 (SOCS1, SOCS2)), Ras-association domain family protein 1A (RASSF1a), D-type p16(INK4a) cyclin-dependent kinase inhibitor (CDKN), and O6-methylguanine DNA-methyltransferase (MGMT)) in the serum of 100 patients using methylation-specific PCR. In all, 41 melanoma patients (stage I = 18; stage II = 10; stage III/IV = 13), 13 healthy controls without nevi, and 10 individuals with more than 15 nevi of >5 mm in size were investigated. For comparison, sera from patients with other skin tumors (nine basal cell cancers, five Kaposi's sarcoma), different metastasized cancers (five breast cancers, five colon cancers), and several chronic inflammatory diseases (n = 12) were also analyzed. In addition, we examined if methylation was involved in silencing transcription of these genes in 12 melanoma specimens. SOCS1, SOCS2, RASSF1a, CDKN2a, and MGMT were methylated in 75, 43, 64, 75, and 64% of melanoma samples, respectively. Of the 41 melanoma patients, 83% had one hypermethylated gene, while 66, 51, and 41% had two, three, or four hypermethylated genes, respectively. Also, 20% of these patients showed hypermethylation for all genes, while only 17% showed no methylation. Importantly, the methylation profile of the selected genes from melanoma patients was distinct from the other analyzed tumors. Transcription of SOCS1, SOCS2, CDKN2a, and RASSF1a genes was significantly reduced in fresh melanoma samples, while MGMT showed a 12-fold upregulation at the messenger ribonucleic acid level (P < 0.001). Our findings suggest that epigenetic silencing of

  14. In Situ Measurement of miR-205 in Malignant Melanoma Tissue Supports its Role as a Tumor Suppressor MicroRNA

    PubMed Central

    Hanna, Jason A.; Hahn, Lewis; Agarwal, Seema; Rimm, David L.

    2012-01-01

    Oncogenic and tumor suppressing miRNAs have emerged as key regulators of gene expression in many types of cancer including melanoma. We utilized quantitative in situ hybridization (qISH) to evaluate the tumor suppressing properties of miRNA, miR-205 in a population of human tumors. We hypothesize decreased miR-205 would be associated with more aggressive tumors. Multiplexing miR-205 qISH with immunofluorescent assessment of S100/GP100 allowed us to quantitatively evaluate miR-205 expression using the AQUA method of quantitative immunofluorescence. The specificity of the assay was validated using blocking oligos and transfected cell lines as controls. Outcomes were assessed on the Yale Melanoma Discovery Cohort consisting of 105 primary melanoma specimens and validated on an independent set of 206 primary melanomas (Yale Melanoma Validation Cohort). Measurement of melanoma cell miR-205 levels shows a significantly shorter melanoma specific survival in patients with low expression. Multivariate analysis shows miR-205 levels are significantly independent of stage, age, gender and Breslow depth. Low levels of melanoma cell miR-205 expression as quantified by ISH show worse outcome, supporting the role of miR-205 as a tumor suppressor miRNA. The quantification of miR205 in situ suggests potential for the use of miRNAs in future prognostic or predictive models. PMID:22890556

  15. Melanoma susceptibility genes and risk assessment.

    PubMed

    Marzuka-Alcalá, Alexander; Gabree, Michele Jacobs; Tsao, Hensin

    2014-01-01

    Familial melanoma accounts for approximately a tenth of all melanoma cases. The most commonly known melanoma susceptibility gene is the highly penetrant CDKN2A (p16INK4a) locus, which is transmitted in an autosomal dominant fashion and accounts for approximately 20-50 % of familial melanoma cases. Mutated p16INK4a shows impaired capacity to inhibit the cyclin D1-CDK4 complex, allowing for unchecked cell cycle progression. Mutations in the second protein coded by CDKN2A, p14ARF, are much less common and result in proteasomal degradation of p53 with subsequent accumulation of DNA damage as the cell progresses through the cell cycle without a functional p53-mediated DNA damage response. Mutations in CDK4 that impair the inhibitory interaction with p16INK4a also increase melanoma risk but these mutations are extremely rare. Genes of the melanin biosynthetic pathway, including MC1R and MITF, have also been implicated in melanomagenesis. MC1R variants were traditionally thought to increase risk for melanoma secondary to intensified UV-mediated DNA damage in the setting of absent photoprotective eumelanin. Accumulation of pheomelanin, which appears to have a carcinogenic effect regardless of UV exposure, may be a more likely mechanism. Impaired SUMOylation of the E318K variant of MITF results in increased transcription of genes that confer melanocytes with a pro-malignant phenotype. Mutations in the tumor suppressor BAP1 enhance the metastatic potential of uveal melanoma and predispose to cutaneous/ocular melanoma, atypical melanocytic tumors, and other internal malignancies (COMMON syndrome). Genome-wide association studies have identified numerous low-risk alleles. Although several melanoma susceptibility genes have been identified, risk assessment tools have been developed only for the most common gene implicated with hereditary melanoma, CDKN2A. MelaPRO, a validated model that relies on Mendelian inheritance and Bayesian probability theories, estimates carrier

  16. Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011

    PubMed Central

    Chen, Haiyan; Cai, Yibo; Liu, Yue; He, Jinjie; Hu, Yeting; Xiao, Qian; Hu, Wangxiong; Ding, Kefeng

    2016-01-01

    Abstract Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM. We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery. We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision. This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis. PMID:26886623

  17. Primary malignant melanoma of oral cavity: A tertiary care center experience

    PubMed Central

    Kumar, Vijay; Vishnoi, Jeewan Ram; Kori, Channabasappa G.; Gupta, Sameer; Misra, Sanjeev; Akhtar, Naseem

    2015-01-01

    Background: Primary mucosal malignant melanoma is an extremely rare, aggressive neoplasm accounting for 0.5% of all oral malignancies. Any pigmented lesion in oral cavity should have an index of suspicion, which should be investigated to detect the disease at an early stage and managed appropriately. Melanomas tend to invade locally into the tissue or metastasize more commonly than other malignant tumors of the oral cavity. Materials and Methods: We report a retrospective case series of eight patients suffering from primary oral malignant melanoma treated in our department between 2012 and 2014. The details were recorded from the departmental computerized database and patients on follow-up. Results: There were six male and two female patients with a mean age of 46.8 years. Hard palate was the most common affected site in oral cavity. Pigmented lesion\\ulcer was the most common presenting symptom. Majority of patients (5 patients) were diagnosed with Stage III (distant metastasis), two patients in Stage II, and one patient in Stage I. Three patients were treated with definitive surgery and five patients with palliative chemotherapy in view of distant disease. Following surgery, two of them required adjuvant chemoradiotherapy in view of nodal spread. Patients had a mean follow-up of 10.5 months (range: 8–26 months). Patients treated with definitive surgery had a mean survival rate of 16 months (range: 10–26 months), with local recurrence in one patient. Metastatic melanoma patients treated with palliative chemotherapy had a mean disease control rate of 5 months (range 5–9 months). Conclusion: Oral melanoma carries dismal prognosis with a 5-year survival rate of 5–20%. Early detection of the lesion, proper evaluation, and appropriate treatment are very important to cure the disease. PMID:27390490

  18. A new melanoma diagnosis active support system.

    PubMed

    Fiorini, R A; Dacquino, G; Laguteta, G

    2004-01-01

    The aim of this paper is to present the operational performance of a new MDASS (Melanoma Diagnosis Active Support System) prototype able to distil optimal knowledge from acquired data to automatically capture and reliably discriminate and quantify the stage of disease evolution. Automated classification dermatoscopical parameters can be divided into two main classes: Size Descriptor (point size, local, and global) and Intrinsic Descriptor (morphological, geometrical, chromatic, others). Usually elementary geometric shape robust and effective characterization, invariant to environment and optical geometry transformations, on a rigorous mathematical level is a key and computational intensive problem. MDASS uses GEOGINE (GEOmetrical enGINE), a state-of-the-art OMG (Ontological Model Generator) based on n-D Tensor Moment Invariants for shape/texture effective description. MDASS main results show robust disease classification procedure with distillation of minimal reference grids for pathological cases and they ultimately achieve effective early diagnosis of melanocytic lesion. System results are validated by carefully designed experiments with certified clinical reference database. Overall system operational performance is presented. Finally, MDASS error analysis and computational complexity are addressed and discussed. PMID:17270962

  19. CD82 suppresses CD44 alternative splicing-dependent melanoma metastasis by mediating U2AF2 ubiquitination and degradation

    PubMed Central

    Fu, Ailing; Zhu, Huifeng; Ren, Qiao; Wang, Bochu; Xu, Xingran; Bai, Huiyuan; Dong, Cheng

    2016-01-01

    Melanoma is one of the most lethal forms of skin cancer due to its early metastatic spread. The variant form of CD44 (CD44v), a cell surface glycoprotein, is highly expressed on metastatic melanoma. The mechanisms of regulation of CD44 alternative splicing in melanoma and its pathogenic contributions are so far poorly understood. Here, we investigated the expression level of CD44 in a large set of melanocytic lesions at different stages. We found that the expression of CD44v8-10 and a splicing factor, U2AF2, is significantly increased during melanoma progression, while CD82/KAI1, a tetraspanin family of tumor suppressor, is reduced in metastatic melanoma. CD44v8-10 and U2AF2 expressions which are negatively correlated with CD82 levels are dramatically elevated in primary melanoma compared with dysplastic nevi and further increased in metastatic melanoma. We also showed that patients with higher CD44v8-10 and U2AF2 expression levels tended to have shorter survival. By using both in vivo and in vitro assays, we demonstrated that CD82 inhibits the production of CD44v8-10 on melanoma. Mechanistically, U2AF2 is a downstream target of CD82 and in malignant melanoma facilitates CD44v8-10 alternative splicing. U2AF2-mediated CD44 isoform switch is required for melanoma migration in vitro and lung and liver metastasis in vivo. Notably, overexpression of CD82 suppresses U2AF2 activity by inducing U2AF2 ubiquitination. In addition, our data suggested that enhancement of melanoma migration by U2AF2-dependent CD44v8-10 splicing is mediated by Src/FAK/RhoA activation and formation of stress fibers as well as CD44-E-selectin binding reinforcement. These findings uncovered a hitherto unappreciated function of CD82 in severing the linkage between U2AF2-mediated CD44 alternative splicing and cancer aggressiveness, with potential prognostic and therapeutic implications in melanoma. PMID:27041584

  20. Immunohistochemical Expression of Leptin in Non Melanoma Skin Cancer

    PubMed Central

    Farag, Azza G.A.; El-Dien, Marwa Mohammed Serag

    2016-01-01

    Introduction Obesity in adults is associated with numerous health disorders including some forms of cancer. Various epidemiological studies have found a link between excess adiposity and malignant melanoma; however, the association with non melanoma skin cancer is questionable. Leptin is a hormone produced mainly by the adipose tissue and its serum level may reflect body mass index. Leptin is reported to promote proliferation and angiogenesis and deregulate apoptosis, therefore facilitates the process of carcinogenesis. Aim The current study tried to assess leptin localization and expression in non melanoma skin cancer to verify its possible role in pathogenesis of this cancer. Materials and Methods This study was carried out on 13 Basal Cell Carcinoma (BCC) cases and 14 Squamous Cell Carcinoma (SCC) cases together with 19 normal skin biopsies as a control group using immunohistochemical method. Results Leptin was expressed in 52.6% of the normal epidermis with pure cytoplasmic and both cytoplasmic and nuclear staining patterns. All cases of SCC (100%) and two cases of BCC (15.4%) showed leptin expression in tumour cells whereas nuclear expression was in favour of SCC. Stromal expression of leptin was seen in both SCC (57.1%) and BCC (38.5%) without significant differences. Percentage of leptin expression by tumour cells in SCC showed positive linear correlation with tumour size (p=0.02) and microvessel density (p=0.000). Stromal expression of leptin in SCC was associated with large tumour size (p=0.04), advanced stage (p=0.01) and tumours arising in sites other than head and neck (p=0.01). Conclusion Leptin could have a more important role in pathogenesis of cutaneous SCC rather than BCC that may reflect the trivial role of obesity in induction of BCC. The expression of leptin by tumour and stromal cells of SCC could co-operate in its progression by promoting angiogenesis with subsequently acquiring large tumour size and then advanced stage. PMID:27656540

  1. Sentinel node identification by scintigraphic methods in cutaneous melanoma.

    PubMed

    Dias Moreira, R; Altino de Almeida, S; Maliska Guimarães, C M; Resende, J F; Gutfilen, B; Barbosa da Fonseca, L M

    2005-06-01

    In melanoma patients lymph node metastasis is an important prognostic factor that indicates the need for therapeutic lymph node dissection. Preoperative lymphoscintigraphy mapping associated with radioguided sentinel lymph node biopsy has become a well established procedure for cutaneous melanoma patients without clinically detectable lymph node metastases (stage I, II). This technique is a versatile way of characterizing the lymphatic basin at risk for metastases and identifying involved lymph nodes. The purpose of the present study was to examine the reproducibility of lymphoscintigraphy and sentinel lymph node biopsy in detecting micro metastases in cutaneous melanoma. The study was a single-institution prospective analysis of 74 melanoma patients, with primary tumors having Breslow thickness > 0.7 mm, who underwent lymphoscintigraphies between May 2002 and September 2003. Technetium-99m sulfur colloid was injected intradermally at the primary tumor site and dynamic images were obtained for 40 minutes. Two observers evaluated the images. One to two weeks after the first lymphoscintigraphy, radioguided lymph node biopsy was performed. For the biopsy, technetium-99m sulfer colloid was injected intradermally in the same manner as performed before. Lymph nodes were identified and removed with the aid of a gamma ray detecting probe (GDP), and were submitted to histopathological analysis. The histopathological analysis of the sentinel lymph nodes collected during surgery was performed in a sequential manner. First, frozen sections were analyzed during surgery. The lymph nodes considered negative by frozen section were analyzed by H&E staining. Subsequently, the slides considered negative with H&E were sent for immunohistochemical analysis. Lymphoscintigraphy identified at least one sentinel lymph node in all patients. Sentinel node biopsy detected metastases in 20 patients (27.2%). In all cases the lymph node basins identified during lymphoscintigraphy were found to

  2. Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis

    PubMed Central

    Xing, Yan; Chang, George J.; Hu, Chung-Yuan; Askew, Robert L.; Ross, Merrick I.; Gershenwald, Jeffrey E.; Lee, Jeffrey E.; Mansfield, Paul F.; Lucci, Anthony; Cormier, Janice N.

    2009-01-01

    Background Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision-making. Methods Patients with melanoma and at least 5 years of follow-up were identified from the Surveillance Epidemiology and End Results (SEER) registry (1988–2000). Using the methods of Kaplan and Meier, stage-specific 5-year CS estimates were independently calculated for survivors for each year following diagnosis. Stage-specific multivariate Cox regression models including baseline survivor functions were used to calculate adjusted melanoma-specific CS for different subgroups of patients further stratified by age, gender, race, marital status, anatomic tumor location, and tumor histology. Results Five-year CS estimates for stage I patients remained constant at 97% annually, while for patients with stages II, III and IV disease, 5-year CS estimates from time 0 (diagnosis) to 5 years improved from 72% to 86%, 51% to 87%, and 19% to 84%, respectively. Multivariate CS analysis revealed that differences in stages II through IV CS based on age, gender and race decreased over time. Conclusions Five-year melanoma-specific CS estimates improve dramatically over time for survivors with advanced stages of disease. These prognostic data are critical to patients for both treatment and non-treatment related life decisions. PMID:20187100

  3. A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.

    PubMed

    Kaufman, Charles K; Mosimann, Christian; Fan, Zi Peng; Yang, Song; Thomas, Andrew J; Ablain, Julien; Tan, Justin L; Fogley, Rachel D; van Rooijen, Ellen; Hagedorn, Elliott J; Ciarlo, Christie; White, Richard M; Matos, Dominick A; Puller, Ann-Christin; Santoriello, Cristina; Liao, Eric C; Young, Richard A; Zon, Leonard I

    2016-01-29

    The "cancerized field" concept posits that cancer-prone cells in a given tissue share an oncogenic mutation, but only discreet clones within the field initiate tumors. Most benign nevi carry oncogenic BRAF(V600E) mutations but rarely become melanoma. The zebrafish crestin gene is expressed embryonically in neural crest progenitors (NCPs) and specifically reexpressed in melanoma. Live imaging of transgenic zebrafish crestin reporters shows that within a cancerized field (BRAF(V600E)-mutant; p53-deficient), a single melanocyte reactivates the NCP state, revealing a fate change at melanoma initiation in this model. NCP transcription factors, including sox10, regulate crestin expression. Forced sox10 overexpression in melanocytes accelerated melanoma formation, which is consistent with activation of NCP genes and super-enhancers leading to melanoma. Our work highlights NCP state reemergence as a key event in melanoma initiation.

  4. Wavelengths effective in induction of malignant melanoma

    SciTech Connect

    Setlow, R.B.; Grist, E.; Thompson, K.; Woodhead, A.D. )

    1993-07-15

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented back-cross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. The authors irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and score the irradiated animals for melanomas 4 months later. They used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. They interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths >320 nm-the UV-A and visible spectral regions. 25 refs., 4 figs., 1 tab.

  5. Wavelengths Effective in Induction of Malignant Melanoma

    NASA Astrophysics Data System (ADS)

    Setlow, Richard B.; Grist, Eleanor; Thompson, Keith; Woodhead, Avril D.

    1993-07-01

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented backcross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. We irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and scored the irradiated animals for melanomas 4 months later. We used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. We interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths > 320 nm-the UV-A and visible spectral regions.

  6. Immunotherapy for advanced melanoma: fulfilling the promise.

    PubMed

    Gogas, Helen; Polyzos, Aristidis; Kirkwood, John

    2013-12-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past thirty years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes failed to show significant improvement in overall survival. Recent advances and in-depth understanding of the biology of melanoma, have contributed in the development of new agents. Based on the molecular and immunological background of the disease, the new drugs have shown benefit in overall and progression free survival. As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:23725878

  7. Whole Body Melanoma Transcriptome Response in Medaka

    PubMed Central

    Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K.; Postlethwait, John; Warren, Wesley C.

    2015-01-01

    The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. PMID

  8. Whole Body Melanoma Transcriptome Response in Medaka.

    PubMed

    Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K; Postlethwait, John; Warren, Wesley C

    2015-01-01

    The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. PMID

  9. Malignant melanoma--a genetic overview.

    PubMed

    Bloethner, S; Scherer, D; Drechsel, M; Hemminki, K; Kumar, R

    2009-11-01

    Malignant melanoma, a potentially lethal skin neoplasm, is characterized by a complex and heterogeneous etiology. Both incidences and deaths associated with melanoma are increasing in Caucasian populations. While exposure to ultraviolet radiation through sun-exposure is the major risk factor; the host factors including skin type and number of moles are critical in predisposition. The CDKN2A is a high penetrance melanoma susceptibility gene as carriers of the mutations are predisposed to the disease within familial settings. The gene is also somatically altered to varying degrees in sporadic melanoma. The CDK4 gene due to occurrence of activation mutations in a few families worldwide represents another melanoma susceptibility locus. The variants within the melanocortin receptor 1 (MC1R) gene, which encodes a melanocyte specific surface receptor with a key role in pigmentation, are associated with high risk phenotypes and increased risk of melanoma. Melanoma tumors are characterized by activation of the RAS-RAF-MEK-ERK pathway through either autocrine growth factor stimulation or oncogenic mutations in the B-RAF or N-RAS genes. Somatic mutations in the B-RAF gene are complemented by those in the N-RAS gene and represent the major genetic alterations. The mutations in the B-RAF gene in melanoma due to occurrence in melanocytic nevi represent early events that additionally require loss of cell cycle inhibitors like CDKN2A for melanoma progression and development. The sequence of events points to the cooperative collaboration between different genetic pathways in tumor development that can be and are being used as targets for developing specific therapeutic agents. PMID:20096196

  10. Primary Retroperitoneal Melanoma Presented in a Rare Extracutaneous Site for Malignant Melanoma

    PubMed Central

    Alsharedi, Mohamed; Zgheib, Nadim Bou; Khelfa, Yousef; Raufi, Ali; Elmsherghi, Nabiha; Lebowicz, Yehuda

    2016-01-01

    Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature. PMID:27746882

  11. [Treatment of BRAF-mutated metastatic melanoma].

    PubMed

    Boyles, Tessa Bystrup; Svane, Inge Marie; Bastholt, Lars; Schmidt, Henrik

    2016-08-29

    Melanoma is an aggressive form of skin cancer which is the cause of a great number of skin cancer-related deaths worldwide and about 300 deaths in Denmark. After several years of failure of treatment of metastatic melanoma, the development of BRAF- and later MEK inhibitors was considered revolutionary. Treatment with BRAF inhibitors alone and especially in combination with a MEK inhibitor improves outcome for patients with BRAF V600-mutated metastatic melanoma. However, even when treated with the combination of the inhibitors, many patients develop acquired resistance within a year. PMID:27592869

  12. Axillary Silicone Granulomas in Patients With Melanoma.

    PubMed

    Fernández Canedo, M I; Blázquez Sánchez, N; Valdés Solís, P; de Troya Martín, M

    2016-05-01

    Subcutaneous lesions may be detected during follow-up of patients with melanoma. The main entities that should be contemplated in the differential diagnosis in such cases are in-transit and regional lymph node metastases. We describe 2 cases of women with breast implants who developed palpable subcutaneous lesions in the axillary region during follow-up of melanoma. In both cases, the ultrasound study showed diffuse hyperechoic signals forming the characteristic snowstorm sign in the subcutaneous tissue. Ultrasound proved to be a key diagnostic tool for ruling out melanoma-related disease, such as in-transit metastases and regional lymph node metastases. PMID:26626499

  13. Myeloid Cells' Evasion of Melanoma Immunity

    PubMed Central

    Wang, Jun; Chen, Lieping

    2015-01-01

    An immune-suppressive role of myeloid-derived suppressor cells (MDSCs) in melanoma has long been speculated, whereas molecular mechanisms underlying this role are not well understood. Here, Chung and colleagues show that dendritic cell-associated, heparan sulfate proteoglycans-dependent integrin ligand (DC-HIL), a cell surface immune-modulatory molecule, is highly expressed on tumor-associated MDSCs. Genetic ablation or antibody blockade of DC-HIL delays the growth of transplantable B16 melanoma in syngeneic mice, which is accompanied by enhanced antitumor T-cell activities. These findings support a role for DC-HIL in immune evasion within the melanoma microenvironment. PMID:25318429

  14. Axillary Silicone Granulomas in Patients With Melanoma.

    PubMed

    Fernández Canedo, M I; Blázquez Sánchez, N; Valdés Solís, P; de Troya Martín, M

    2016-05-01

    Subcutaneous lesions may be detected during follow-up of patients with melanoma. The main entities that should be contemplated in the differential diagnosis in such cases are in-transit and regional lymph node metastases. We describe 2 cases of women with breast implants who developed palpable subcutaneous lesions in the axillary region during follow-up of melanoma. In both cases, the ultrasound study showed diffuse hyperechoic signals forming the characteristic snowstorm sign in the subcutaneous tissue. Ultrasound proved to be a key diagnostic tool for ruling out melanoma-related disease, such as in-transit metastases and regional lymph node metastases.

  15. Immunotherapy for advanced melanoma: future directions.

    PubMed

    Valpione, Sara; Campana, Luca G

    2016-02-01

    As calculated by the meta-analysis of Korn et al., the prognosis of metastatic melanoma in the pretarget and immunological therapy era was poor, with a median survival of 6.2 and a 1-year life expectancy of 25.5%. Nowadays, significant advances in melanoma treatment have been gained, and immunotherapy is one of the promising approaches to get to durable responses and survival improvement. The aim of the present review is to highlight the recent innovations in melanoma immunotherapy and to propose a critical perspective of the future directions of this enthralling oncology subspecialty.

  16. Gene signature of the metastatic potential of cutaneous melanoma: too much for too little?

    PubMed

    Tímár, József; Gyorffy, Balázs; Rásó, Erzsébet

    2010-08-01

    It was expected that with the advent of genomics, oncology may defeat the deadliest forms of cancer including malignant melanoma, but the past years have indicated that this is not the case. Despite the stunning success of genomics in defining markers or gene signatures for breast cancer prognosis and predicting therapies, there is virtually no progression in malignant melanoma. This is happening when experimental oncology or metastasis research is using several rodent and human melanoma models, when our knowledge on the metastatic cascade is actually derived from these models. Our critical analysis of these studies revealed several factors which might be responsible for this failure. First, it is evident, that these studies must be based on rigorous sample collection and basic pathological considerations, where divergent histological types of melanoma cannot be analysed universally. Secondly, without following basic consideration of metastasis biology, the majority of these studies were rarely based on primary tumors but frequently on various types of regional metastases. Third, successful expression profiling studies on other tumors such as breast cancer, provided evidences that the homogeneity of the patient cohort at least by clinicopathological stage is a critical element when defining prognostic signatures. Four studies attempted to define the prognostic signature of skin melanoma but only one based the study on the primary tumor resulting in heterogenous signatures with a minimal overlap (MCM3 and NFKBIZ). Four study attempted to define the invasiveness-signature in the primary tumor based on thickness or growth pattern discrimination identifying a 9-gene overlap which proved to be different from the prognostic signatures. On the other hand, seven studies analyzed various types of metastatic tissues (rarely visceral-, mostly cutaneous or lymphatic metastases) to define the metastasis-signatures, again with minimal overlap (AQP3, LGALS7 and SFN). Using seven

  17. Descriptive epidemiology of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe.

    PubMed

    Mallone, S; De Vries, E; Guzzo, M; Midena, E; Verne, J; Coebergh, J W; Marcos-Gragera, R; Ardanaz, E; Martinez, R; Chirlaque, M D; Navarro, C; Virgili, G

    2012-05-01

    the studied rare cancer types. Therefore, maximising quality of life is particularly important in treatment of uveal melanoma. As regards mucosal melanomas, the centralisation of treatment to a select number of specialist centres as well as the establishment of expert pathology panels should be promoted. The geographical differences in incidence and survival should be further investigated analysing the centre of treatment, the stage at diagnosis and the treatment.

  18. Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

    PubMed Central

    Goldenberg, Alina; Vujic, Igor; Sanlorenzo, Martina; Ortiz-Urda, Susana

    2015-01-01

    Introduction Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair). Whites have a 27-fold higher incidence of melanoma than African-Americans (AA), but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods Qualitative review of the literature. Results Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. PMID:26346576

  19. Melanoma Disparities among US Hispanics: Use of the Social Ecological Model to Contextualize Reasons for Inequitable Outcomes and Frame a Research Agenda.

    PubMed

    Harvey, Valerie M; Oldfield, Charlene W; Chen, Jarvis T; Eschbach, Karl

    2016-01-01

    Cutaneous melanoma is a significant public health concern, accounting for thousands of deaths annually in the US. Early detection and diagnosis are critical given the poor prognosis and limited treatment options of advanced-stage disease. While non-Hispanic whites have higher incidence rates of melanoma, Hispanics are typically diagnosed at later disease stages and suffer higher morbidity and mortality. Currently, there is a paucity of literature investigating the root causes underlying these trends among Hispanics. Given that Hispanics are the most rapidly expanding demographic segment in the US, it is essential for cancer control efforts to elucidate the major determinants of their poor melanoma outcomes. Herein, we use the social ecological model as a framework to explore the multitude of influences on melanoma disparities among Hispanics and provide recommendations for planning future studies and interventions. PMID:27651954

  20. Melanoma Disparities among US Hispanics: Use of the Social Ecological Model to Contextualize Reasons for Inequitable Outcomes and Frame a Research Agenda

    PubMed Central

    Oldfield, Charlene W.; Chen, Jarvis T.; Eschbach, Karl

    2016-01-01

    Cutaneous melanoma is a significant public health concern, accounting for thousands of deaths annually in the US. Early detection and diagnosis are critical given the poor prognosis and limited treatment options of advanced-stage disease. While non-Hispanic whites have higher incidence rates of melanoma, Hispanics are typically diagnosed at later disease stages and suffer higher morbidity and mortality. Currently, there is a paucity of literature investigating the root causes underlying these trends among Hispanics. Given that Hispanics are the most rapidly expanding demographic segment in the US, it is essential for cancer control efforts to elucidate the major determinants of their poor melanoma outcomes. Herein, we use the social ecological model as a framework to explore the multitude of influences on melanoma disparities among Hispanics and provide recommendations for planning future studies and interventions.

  1. Melanoma Disparities among US Hispanics: Use of the Social Ecological Model to Contextualize Reasons for Inequitable Outcomes and Frame a Research Agenda

    PubMed Central

    Oldfield, Charlene W.; Chen, Jarvis T.; Eschbach, Karl

    2016-01-01

    Cutaneous melanoma is a significant public health concern, accounting for thousands of deaths annually in the US. Early detection and diagnosis are critical given the poor prognosis and limited treatment options of advanced-stage disease. While non-Hispanic whites have higher incidence rates of melanoma, Hispanics are typically diagnosed at later disease stages and suffer higher morbidity and mortality. Currently, there is a paucity of literature investigating the root causes underlying these trends among Hispanics. Given that Hispanics are the most rapidly expanding demographic segment in the US, it is essential for cancer control efforts to elucidate the major determinants of their poor melanoma outcomes. Herein, we use the social ecological model as a framework to explore the multitude of influences on melanoma disparities among Hispanics and provide recommendations for planning future studies and interventions. PMID:27651954

  2. Melanoma cell galectin-1 ligands functionally correlate with malignant potential*

    PubMed Central

    Yazawa, Erika M.; Geddes-Sweeney, Jenna E.; Cedeno-Laurent, Filiberto; Walley, Kempland C.; Barthel, Steven R.; Opperman, Matthew J.; Liang, Jennifer; Lin, Jennifer Y.; Schatton, Tobias; Laga, Alvaro C.; Mihm, Martin C.; Qureshi, Abrar A.; Widlund, Hans R.; Murphy, George F.; Dimitroff, Charles J.

    2015-01-01

    Galectin-1 (Gal-1)-binding to Gal-1 ligands on immune and endothelial cells can influence melanoma development through dampening anti-tumor immune responses and promoting angiogenesis. However, whether Gal-1 ligands are functionally expressed on melanoma cells to help control intrinsic malignant features remains poorly understood. Here, we analyzed expression, identity and function of Gal-1 ligands in melanoma progression. Immunofluorescent analysis of benign and malignant human melanocytic neoplasms revealed that Gal-1 ligands were abundant in severely-dysplastic nevi as well as in primary and metastatic melanomas. Biochemical assessments indicated that melanoma cell adhesion molecule (MCAM) was a major Gal-1 ligand on melanoma cells that was largely dependent on its N-glycans. Other melanoma cell Gal-1 ligand activity conferred by O-glycans was negatively regulated by α2,6 sialyltransferase ST6GalNAc2. In Gal-1-deficient mice, MCAM-silenced (MCAMKD) or ST6GalNAc2-overexpressing (ST6O/E) melanoma cells exhibited slower growth rates, underscoring a key role for melanoma cell Gal-1 ligands and host Gal-1 in melanoma growth. Further analysis of MCAMKD or ST6O/E melanoma cells in cell migration assays indicated that Gal-1 ligand-dependent melanoma cell migration was severely inhibited. These findings provide a refined perspective on Gal-1 – melanoma cell Gal-1 ligand interactions as contributors to melanoma malignancy. PMID:25756799

  3. Genetic Engineering of T cells to Target HERV-K, an Ancient Retrovirus on Melanoma

    PubMed Central

    Krishnamurthy, Janani; Rabinovich, Brian A.; Mi, Tiejuan; Switzer, Kirsten C.; Olivares, Simon; Maiti, Sourindra N.; Plummer, Joshua B.; Singh, Harjeet; Kumaresan, Pappanaicken R.; Huls, Helen M.; Wang-Johanning, Feng; Cooper, Laurence J.N.

    2015-01-01

    Purpose The human endogenous retrovirus (HERV-K) envelope (env) protein is a tumor- associated antigen expressed on melanoma, but not normal cells. This study was designed to engineer a chimeric antigen receptor (CAR) on T cell surface, such that they target tumors in advanced stages of melanoma. Experimental Design Expression of HERV-K protein was analyzed in 220 melanoma samples (with various stages of disease) and 139 normal organ donor tissues using immuno-histochemical (IHC) analysis. HERV-K env-specific CAR derived from mouse monoclonal antibody was introduced into T cells using the transposon-based Sleeping Beauty (SB) system. HERV-K env-specific CAR+ T cells were expanded ex vivo on activating and propagating cells (AaPC), and characterized for CAR expression and specificity. This includes evaluating the HERV-K-specific CAR+ T cells for their ability to kill A375-SM metastasized tumors in a mouse xenograft model. Results We detected HERV-K env protein on melanoma, but not in normal tissues. After electroporation of T cells and selection on HERV-K+ AaPC, over 95% of genetically-modified T cells expressed the CAR with an effector memory phenotype and lysed HERV-K env+ tumor targets in an antigen specific manner. Even though there is apparent shedding of this TAA from tumor cells which can be recognized by HERV-K env-specific CAR+ T cells, we observed a significant anti-tumor effect. Conclusion Adoptive cellular immunotherapy with HERV-K env-specific CAR+ T cells represents a clinically-appealing treatment strategy for advanced-stage melanoma and provides an approach for targeting this TAA on other solid tumors. PMID:25829402

  4. A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2016-01-01

    Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately. PMID:26918446

  5. Malignant potential of cells isolated from lymph node or brain metastases of melanoma patients and implications for prognosis.

    PubMed

    Zhang, R D; Price, J E; Schackert, G; Itoh, K; Fidler, I J

    1991-04-15

    We studied the correlation between the formation of brain metastasis and the malignant growth potential of seven human melanoma cell lines, isolated from lymph node metastases (A375-SM, TXM-1, DM-4) or from brain metastases (TXM-13, TXM-18, TXM-34, TXM-40), and the potential of three variants of the mouse K-1735 melanoma. Growth rates in different concentrations of fetal bovine serum and colony-forming efficiency in semisolid agarose were measured, and the tumorigenicity and metastatic ability were determined in nude mice (for the human melanoma cell lines) or in C3H/HeN mice (for the K-1735 variants). The ability to form brain metastasis was tested by injection of cells into the carotid artery. A high colony-forming efficiency in agarose, especially at concentrations of agarose greater than 0.6%, corresponded with high tumor take rates, rapid tumor growth rates, and metastatic colonization of the lungs of the recipient mice. For the human melanomas, the lymph node metastasis-derived cells were more tumorigenic and metastatic than the brain metastasis-derived cells. In the K-1735 mouse melanoma, the tumorigenic and metastatic behavior of the cells after i.v. and s.c. injection corresponded with growth in agarose cultures. However, for growth in the brain after intracarotid injection, the different melanoma cell lines showed similar frequencies of tumor take, regardless of tumorigenicity in other sites of the recipient mice, although mice given injections of brain metastasis-derived cells survived longer than mice given injections of lymph node metastasis (human melanoma) or lung metastasis (K-1735 M-2)-derived cell lines. The results from the human and mouse melanoma cell lines show that the brain metastasis-derived cell lines were not more malignant than the lymph node or lung metastasis-derived cells. These data imply that the production of brain metastasis is not always the final stage of a metastatic cascade. PMID:1826230

  6. Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes

    PubMed Central

    Fang, Shenying; Wang, Yuling; Chun, Yun S; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; Cormier, Janice N; Royal, Richard E; Lucci, Anthony; Schacherer, Christopher W; Reveille, John D; Chen, Wei; Sui, Dawen; Bassett, Roland L; Wang, Li-E; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey E

    2015-01-01

    Recent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10−38); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10−9). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00–2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11–3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome. PMID:25848976

  7. How Is Melanoma Skin Cancer Diagnosed?

    MedlinePlus

    ... medicine doctor injects a small amount of a radioactive substance into the area of the melanoma. After ... one or more sentinel lymph nodes. Once the radioactive area has been marked, the patient is taken ...

  8. Updates in Therapy for Advanced Melanoma.

    PubMed

    Singh, Bhavana P; Salama, April K S

    2016-01-15

    Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5-10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

  9. Cutaneous Melanoma: A Population Health Problem.

    PubMed

    Warren, Hermine

    2015-01-01

    Cutaneous melanoma (CM), generally referred to as melanoma, has been identified as an overall population health problem. Examination of evidence-based research revealed a strong correlation between CM and tanning bed usage, specifically by young females. For these reasons, a preliminary research question/hypothesis was structured that proposed examining different geographical locations, and whether the relationship between melanoma and tanning bed exposure by young females would be affected. Epidemiologic principles will be utilized to provide guidelines and tools for comprehensively examining this health issue and how it might affect morbidity and mortality within the populations where occurrences are identified. Furthermore, to understand some of the contributing factors of this disease, melanoma was discussed in terms of person, place, time, and how tanning bed exposure may significantly heighten CM as a potentially fatal health problem.

  10. Isolated pancreatic metastasis from melanoma. Case report.

    PubMed

    Portale, T R; Di Benedetto, V; Mosca, F; Trovato, M A; Scuderi, M G; Puleo, S

    2011-03-01

    Pancreas is frequently site of isolated metastasis, approximately in the 40% of cases in patient with previous history of malignant neoplasia, more frequently from renal cell carcinoma. The melanoma metastasis can also interest the pancreas in case of disseminated disease (50% of the cases); more rarely the pancreas is site of isolated metastases from melanoma. The treatment of the pancreatic metastases from melanoma is controversial: the therapeutic choices are few and the role of surgery is not well defined. If the metastasis are confined to the pancreas, the surgical treatment can be useful for better long time survival. We report a rare case of melanoma with pancreatic isolated metastasi in a patient with a previous melanotic metastasis to the inguinal lymph nodes without evidence of primitive tumor.

  11. Pembrolizumab for Ipilimumab-Resistant Melanoma

    Cancer.gov

    KEYNOTE-002 was designed to test the safety and efficacy of two doses of pembrolizumab compared with chemotherapy in patients with ipilimumab-resistant melanoma; interim results show that pembrolizumab improves progression-free survival for these patients

  12. The state of melanoma: challenges and opportunities.

    PubMed

    Merlino, Glenn; Herlyn, Meenhard; Fisher, David E; Bastian, Boris C; Flaherty, Keith T; Davies, Michael A; Wargo, Jennifer A; Curiel-Lewandrowski, Clara; Weber, Michael J; Leachman, Sancy A; Soengas, Maria S; McMahon, Martin; Harbour, J William; Swetter, Susan M; Aplin, Andrew E; Atkins, Michael B; Bosenberg, Marcus W; Dummer, Reinhard; Gershenwald, Jeffrey E; Halpern, Allan C; Herlyn, Dorothee; Karakousis, Giorgos C; Kirkwood, John M; Krauthammer, Michael; Lo, Roger S; Long, Georgina V; McArthur, Grant; Ribas, Antoni; Schuchter, Lynn; Sosman, Jeffrey A; Smalley, Keiran S; Steeg, Patricia; Thomas, Nancy E; Tsao, Hensin; Tueting, Thomas; Weeraratna, Ashani; Xu, George; Lomax, Randy; Martin, Alison; Silverstein, Steve; Turnham, Tim; Ronai, Ze'ev A

    2016-07-01

    The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas - diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts as per the current status, challenges, and opportunities in the four respective areas. The current state and immediate and long-term needs of the melanoma field, from basic research to clinical management, are presented in the following report.

  13. Nivolumab-Based Treatments for Advanced Melanoma

    Cancer.gov

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  14. [Molecular alterations in melanoma and targeted therapies].

    PubMed

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology.

  15. [Molecular alterations in melanoma and targeted therapies].

    PubMed

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology. PMID:25776766

  16. Pembrolizumab superior to ipilimumab in melanoma.

    PubMed

    2015-06-01

    In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab yielded significantly better treatment outcomes than ipilimumab.

  17. Immunotherapy in a rare case of primary pelvic retroperitoneal melanoma.

    PubMed

    Talag, Maria Monica; Alsharedi, Mohamed; Bou Zgheib, Nadim; Lebowicz, Yehuda

    2016-01-01

    Recent advances in novel immunotherapeutic and targeted therapeutic agents have increased treatment options in patients with advanced metastatic melanoma. However, evidence in the literature on whether or not extracutaneous melanoma will acquire an equivalent advantage from these therapies is very scarce. In general, extracutaneous melanomas are rare and aggressive melanomas, which are clinically and biologically unique, with higher incidence of metastatic disease and poor prognosis. In this case report, we present a very rare case of a 54-year-old woman with primary pelvic retroperitoneal melanoma treated with an anti-PD-1 antibody, pembrolizumab. Furthermore, we explore the role of novel immunotherapies in the treatment of advanced melanoma. PMID:27624447

  18. Thigmotropism of malignant melanoma cells.

    PubMed

    Quatresooz, Pascale; Piérard-Franchimont, Claudine; Noël, Fanchon; Piérard, Gérald E

    2012-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called "accretive" growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread. PMID:22203839

  19. A systematic review of automated melanoma detection in dermatoscopic images and its ground truth data

    NASA Astrophysics Data System (ADS)

    Ali, Abder-Rahman A.; Deserno, Thomas M.

    2012-02-01

    Malignant melanoma is the third most frequent type of skin cancer and one of the most malignant tumors, accounting for 79% of skin cancer deaths. Melanoma is highly curable if diagnosed early and treated properly as survival rate varies between 15% and 65% from early to terminal stages, respectively. So far, melanoma diagnosis is depending subjectively on the dermatologist's expertise. Computer-aided diagnosis (CAD) systems based on epiluminescense light microscopy can provide an objective second opinion on pigmented skin lesions (PSL). This work systematically analyzes the evidence of the effectiveness of automated melanoma detection in images from a dermatoscopic device. Automated CAD applications were analyzed to estimate their diagnostic outcome. Searching online databases for publication dates between 1985 and 2011, a total of 182 studies on dermatoscopic CAD were found. With respect to the systematic selection criterions, 9 studies were included, published between 2002 and 2011. Those studies formed databases of 14,421 dermatoscopic images including both malignant "melanoma" and benign "nevus", with 8,110 images being available ranging in resolution from 150 x 150 to 1568 x 1045 pixels. Maximum and minimum of sensitivity and specificity are 100.0% and 80.0% as well as 98.14% and 61.6%, respectively. Area under the receiver operator characteristics (AUC) and pooled sensitivity, specificity and diagnostics odds ratio are respectively 0.87, 0.90, 0.81, and 15.89. So, although that automated melanoma detection showed good accuracy in terms of sensitivity, specificity, and AUC, but diagnostic performance in terms of DOR was found to be poor. This might be due to the lack of dermatoscopic image resources (ground truth) that are needed for comprehensive assessment of diagnostic performance. In future work, we aim at testing this hypothesis by joining dermatoscopic images into a unified database that serves as a standard reference for dermatology related research in

  20. Imaging of ocular melanoma metastasis.

    PubMed

    Balasubramanya, Rashmi; Selvarajan, Santosh Kumar; Cox, Mougnyan; Joshi, Ganesh; Deshmukh, Sandeep; Mitchell, Donald G; O'Kane, Patrick

    2016-09-01

    Ocular melanoma is the most common adult primary intraocular tumour. Although <1% of patients have metastatic disease at the time of initial diagnosis, most will develop metastasis at varying lengths of time. Metastasis surveillance is therefore critical in the follow-up of patients with ocular melanoma. Liver is the most common site of metastasis and prognosis is based on the treatment of liver metastasis. Hence, imaging of liver metastasis is vital. MRI is the most specific modality for imaging liver metastasis and is at least as sensitive as CT. Extrahepatic metastasis such as retroperitoneal nodules and bone metastases are also better evaluated on MRI. Gadolinium-based contrast agents are extremely helpful for detecting liver lesions. In particular, newer hepatobiliary contrast agents which offer an additional hepatobiliary phase of excretion help in the detection of even tiny liver metastases. Diffusion-weighted imaging is helpful when an i.v. contrast cannot be administered. Treated lesions are also better evaluated with MRI. CT is useful for evaluating lung nodules, large liver metastasis or in patients in whom MRI is medically contraindicated. The disadvantage lies in its inability to detect small liver metastasis and the radiation dose involved. The lesions treated with iodized oil as part of chemoembolization procedures can be followed on CT. Ultrasound can be used only for detecting hepatic metastases. However, it is heavily operator dependent, technically challenging and time consuming especially in patients who are large. Extrahepatic metastasis cannot be seen on ultrasound. Its utility is primarily for the biopsy of liver lesions. Positron emission tomography (PET)-CT can detect lung nodules and large liver lesions but is insensitive to small liver lesions. Moreover, the high radiation dose is a major disadvantage. PMID:27168029

  1. Melanoma immunotherapy: past, present, and future.

    PubMed

    Saleh, Farid; Renno, Waleed; Klepacek, Ivo; Ibrahim, Ghada; Asfar, Sami; Dashti, Hussein; Romero, Pedro; Dashti, Ali; Behbehani, Abdullah

    2005-01-01

    The incidence of cancer and its related morbidity and mortality remain on the increase in both developing and developed countries. Cancer remains a huge burden on the health and social welfare sectors worldwide and its prevention and cure remain two golden goals that science strives to achieve. Among the treatment options for cancer that have emerged in the past 100 years, cancer vaccine immunotherapy seems to present a promising and relatively safer approach as compared to chemotherapy and radiotherapy. The identification of different tumour antigens in the last fifteen years using a variety of techniques, together with the molecular cloning of cytotoxic T lymphocytes (CTLs)- and tumour infiltrating lymphocytes (TILs)-defined tumour antigens allowed more refining of the cancer vaccines that are currently used in different clinical trials. In a proportion of treated patients, some of these vaccines have resulted in partial or complete tumour regression, while they have increased the disease-free survival rate in others. These outcomes are more evident now in patients suffering from melanoma. This review provides an update on melanoma vaccine immunotherapy. Different cancer antigens are reviewed with a detailed description of the melanoma antigens discovered so far. The review also summarises clinical trials and individual clinical cases in which some of the old and current methods to vaccinate against or treat melanoma were used. These include vaccines made of autologous or allogenic melanoma tumour cells, melanoma peptides, recombinant bacterial or viral vectors, or dendritic cells. PMID:16248801

  2. Phytochemicals for the Management of Melanoma

    PubMed Central

    Pal, Harish Chandra; Hunt, Katherine Marchiony; Diamond, Ariana; Elmets, Craig A.; Afaq, Farrukh

    2016-01-01

    Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma. PMID:26864554

  3. Generation and analysis of zebrafish melanoma models.

    PubMed

    Wojciechowska, S; van Rooijen, E; Ceol, C; Patton, E E; White, R M

    2016-01-01

    The rapid emergence of the zebrafish as a cancer model has been aided by advances in genetic, chemical, and imaging technologies. Melanoma in particular highlights both the power and challenges associated with cancer modeling in zebrafish. This chapter focuses on the lessons that have emerged from the melanoma models as paradigmatic of what will apply to nearly all cancer models in the zebrafish system. We specifically focus on methodologies related to germline and mosaic transgenic melanoma generation, and how these can be used to deeply interrogate additional cooperating oncogenes or tumor suppressors. These transgenic tumors can in turn be used to generate zebrafish-specific, stable melanoma cell lines which can be fluorescently labeled, modified by cDNA/CRISPR techniques, and used for detailed in vivo imaging of cancer progression in real time. These zebrafish melanoma models are beginning to elucidate both cell intrinsic and microenvironmental factors in melanoma that have broader implications for human disease. We envision that nearly all of the techniques described here can be applied to other zebrafish cancer models, and likely expanded beyond what we describe here. PMID:27312504

  4. Phytochemicals for the Management of Melanoma.

    PubMed

    Pal, Harish Chandra; Hunt, Katherine Marchiony; Diamond, Ariana; Elmets, Craig A; Afaq, Farrukh

    2016-01-01

    Melanoma claims approximately 80% of skin cancer-related deaths. Its life-threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3-carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma. PMID:26864554

  5. Prediction of positron emission tomography/computed tomography (PET/CT) positivity in patients with high-risk primary melanoma

    PubMed Central

    Danielsen, Maria; Kjaer, Andreas; Wu, Max; Martineau, Lea; Nosrati, Mehdi; Leong, Stanley PL; Sagebiel, Richard W; III, James R Miller; Kashani-Sabet, Mohammed

    2016-01-01

    Positron emission tomography/computed tomography (PET/CT) is an important tool to identify occult melanoma metastasis. To date, it is controversial which patients with primary cutaneous melanoma should have staging PET/CT. In this retrospective analysis of more than 800 consecutive patients with cutaneous melanoma, we sought to identify factors predictive of PET/CT positivity in the setting of newly-diagnosed high-risk primary melanoma to determine those patients most appropriate to undergo a PET/CT scan as part of their diagnostic work up. 167 patients with newly-diagnosed high-risk primary cutaneous melanoma underwent a PET/CT scan performed as part of their initial staging. Clinical and histologic factors were evaluated as possible predictors of melanoma metastasis identified on PET/CT scanning using both univariate and multivariate logistic regression. In all, 32 patients (19.2%) had a positive PET/CT finding of metastatic melanoma. In more than half of these patients (56.3%), PET/CT scanning identified disease that was not detectable on clinical examination. Mitotic rate, tumor thickness, lymphadenopathy, and bleeding were significantly predictive of PET/CT positivity. A combinatorial index constructed from these factors revealed a significant association between number of high-risk factors observed and prevalence of PET/CT positivity, which increased from 5.8% (with the presence of 0-2 factors) to 100.0%, when all four factors were present. These results indicate that combining clinical and histologic prognostic factors enables the identification of patients with a higher likelihood of a positive PET/CT scan. PMID:27766186

  6. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  7. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems

    PubMed Central

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-01-01

    Abstract In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs. The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05). The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could

  8. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  9. Melanoma

    MedlinePlus

    ... are essential for reducing exposure to harmful ultraviolet (UV) light. These protective measures are especially important in children because 80% of our lifetime exposure to UV light occurs before age 18. Once a month, you ...

  10. Melanoma

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  11. Melanoma

    MedlinePlus

    ... following tips can also help: Apply high-quality sunscreen with a sun protection factor (SPF) rating of ... a short time. Apply a large amount of sunscreen on all exposed areas, including ears and feet. ...

  12. Melanoma

    MedlinePlus

    ... edges are ragged, blurred or irregular Color - the color is uneven and may include shades of black, brown and tan Diameter - there is a change in size, usually an increase Evolving - the mole has changed over the past ...

  13. Radiotherapy to Control Limited Melanoma Progression Following Ipilimumab

    PubMed Central

    Kropp, Lauren M.; De Los Santos, Jennifer F.; McKee, Svetlana B.

    2016-01-01

    Durable local control of irradiated cancer and distant abscopal effects are presumably immune mediated. To evaluate the role of radiotherapy (RT) for limited progression after anti-CTLA4 checkpoint inhibition, medical records of all patients with surgically incurable stage III or IV melanoma from a single institution who received ipilimumab as first-line immunotherapy and subsequent RT were reviewed. Sixteen patients who received RT to all sites of limited melanoma progression were analyzed. Eight patients with an incomplete initial response to ipilimumab received RT to new or progressive disease, whereas the remaining 8 patients with a complete initial response to ipilimumab received RT to sites of subsequent recurrence. The median interval from ipilimumab initiation to start of RT was 30 weeks (range, 15–130 wk), a timeframe where delayed response to ipilimumab is rare. The RT dose was predominantly 30 Gy in 5 fractions (41%) or 36 Gy in 6 fractions (26%). Brain radiation was limited to stereotactic radiosurgery in a single patient. The median local control with RT was 31.4 months. The median disease control was 18.7 months, defined as the interval from completion of RT to the start of additional systemic therapy known to impact survival (anti-programmed death-1 or targeted BRAF therapy), hospice enrollment, or death. The overall survival at 1 and 2 years was 87% and 61%, respectively. Seven patients (44%) had no evidence of melanoma at median follow-up of 29.5 months since completion of RT with no additional therapy. This series supports use of RT to limited sites of progression following ipilimumab as an alternative to other systemic treatments such as anti-programmed death-1 antibodies. PMID:27662339

  14. Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma.

    PubMed

    Hayashibe, K; Mishima, Y; Ferrone, S

    1991-08-01

    The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution.

  15. Human melanoma cells transplanted into zebrafish proliferate, migrate, produce melanin, form masses and stimulate angiogenesis in zebrafish.

    PubMed

    Haldi, Maryann; Ton, Christopher; Seng, Wen Lin; McGrath, Patricia

    2006-01-01

    In this research, we optimized parameters for xenotransplanting WM-266-4, a metastatic melanoma cell line, including zebrafish site and stage for transplantation, number of cells, injection method, and zebrafish incubation temperature. Melanoma cells proliferated, migrated and formed masses in vivo. We transplanted two additional cancer cell lines, SW620, a colorectal cancer cell line, and FG CAS/Crk, a pancreatic cancer cell line and these human cancers also formed masses in zebrafish. We also transplanted CCD-1092Sk, a human fibroblast cell line established from normal foreskin and this cell line migrated, but did not proliferate or form masses. We quantified the number of proliferating melanoma and normal skin fibroblasts by dissociating xenotransplant zebrafish, dispensing an aliquot of CM-DiI labeled human cells from each zebrafish onto a hemocytometer slide and then visually counting the number of fluorescently labeled cancer cells. Since zebrafish are transparent until approximately 30 dpf, the interaction of labeled melanoma cells and zebrafish endothelial cells (EC) can be visualized by whole-mount immunochemical staining. After staining with Phy-V, a mouse anti-zebrafish monoclonal antibody (mAb) that specifically labels activated EC and angioblasts, using immunohistology and 2-photon microscopy, we observed activated zebrafish EC embedded in human melanoma cell masses. The zebrafish model offers a rapid efficient approach for assessing human cancer cells at various stages of tumorigenesis. PMID:17051341

  16. AC-93253 triggers the downregulation of melanoma progression markers and the inhibition of melanoma cell proliferation.

    PubMed

    Karwaciak, Iwona; Gorzkiewicz, Michal; Ryba, Katarzyna; Dastych, Jaroslaw; Pulaski, Lukasz; Ratajewski, Marcin

    2015-07-01

    A major challenge in anti-melanoma therapy is to develop treatments that are effective for advanced melanoma patients. Unfortunately, the currently used regimens are not efficient and have unsatisfactory effects on disease progression, thus increasing the pressure to develop new, profitable drugs and to identify new molecular targets. Here, we show for the first time that AC-93253, a SIRT2 inhibitor, exerts a negative effect on the expression of a set of genes involved in the progression and chemoresistance (e.g., oncogenes, apoptosis-related genes, ABC transporter genes, and cell cycle control genes) of melanoma cells. Furthermore, melanoma cells exposed to AC-93253 and doxorubicin displayed altered biological responses, including apoptosis and proliferation, compared to cells exposed to single treatments. Taken together, we conclude that the usage of AC-93253 in combined therapy could be a promising strategy for melanoma patients.

  17. Standard melanoma-associated markers do not identify the MM127 metastatic melanoma cell line

    PubMed Central

    Haridas, Parvathi; McGovern, Jacqui A.; Kashyap, Abhishek S.; McElwain, D. L. Sean; Simpson, Matthew J.

    2016-01-01

    Reliable identification of different melanoma cell lines is important for many aspects of melanoma research. Common markers used to identify melanoma cell lines include: S100; HMB-45; and Melan-A. We explore the expression of these three markers in four different melanoma cell lines: WM35; WM793; SK-MEL-28; and MM127. The expression of these markers is examined at both the mRNA and protein level. Our results show that the metastatic cell line, MM127, cannot be detected using any of the commonly used melanoma-associated markers. This implies that it would be very difficult to identify this particular cell line in a heterogeneous sample, and as a result this cell line should be used with care. PMID:27087056

  18. Extra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases

    PubMed Central

    Kraehn, G M; Utikal, J; Udart, M; Greulich, K M; Bezold, G; Kaskel, P; Leiter, U; Peter, R U

    2001-01-01

    Amplification and overexpression of the c-myc gene have been associated with neoplastic transformation in a plethora of malignant tumours. We applied interphase fluorescence in situ hybridization (FISH) with a locus-specific probe for the c-myc gene (8q24) in combination with a corresponding chromosome 8 α-satellite probe to evaluate genetic alterations in 8 primary melanomas and 33 advanced melanomas and compared it to 12 melanocytic nevi, 7 safety margins and 2 cases of normal skin. Additionally, in metaphase spreads of 7 melanoma cell lines a whole chromosome 8 paint probe was used. We investigated the functionality of the c-myc gene by detecting c-myc RNA expression with RT-PCR and c-myc protein by immunohistochemistry. 4/8 primary melanomas and 11/33 melanoma metastases showed additional c-myc signals relative to the centromere of chromosome 8 copy number. None of the nevi, safety margins or normal skin samples demonstrated this gain. In 2/7 melanoma cell lines (C32 and WM 266–4) isochromosome 8q formation with a relative gain of c-myc copies and a loss of 8p was observed. The highest c-myc gene expression compared to GAPDH was found in melanoma metastases (17.5%). Nevi (6.6%) and primary melanomas (5.0%) expressed the c-myc gene on a lower level. 72.7% of the patients with c-myc extra copies had visceral melanoma metastases (UICC IV), patients without c-myc gain in 35.0% only. The collective with additional c-myc copies also expressed the gene on a significantly higher level. These results indicate that a c-myc gain in relation to the centromere 8 copy number might be associated with advanced cutaneous melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11139316

  19. Our experience of melanoma thickness as a predictor of outcome of sentinel node biopsy.

    PubMed

    Homolak, Damir; Vucetić, Borki; Puljiz, Zvonimir; Blajć, Iva; Vurnek Zivković, Maja; Situm, Mirna

    2008-10-01

    All follow up protocols for patients with malignant melanoma (MM) are oriented to early detection of metastases. As most of the relapses happened in regional lymph nodes, special attention is given to this region, using different diagnostic tools. Sentinel lymph node biopsy (SLNB) is generally accepted method in determining status of lymph nodes in MM patients, in their staging. This method provides valuable prognostic information, facilitates early therapeutical lymphadenectomy and so provides good base for identification of those patients who are candidates for different adjuvant modalities of treatment. (In 2001 American Joint Committee on Cancer introduced new staging system for melanoma patients which presents good frame for prognosis and therapeutical approach. Inclusion of new criteria will allow better and more individualized prognosis and treatment.) The most important predictor of SLNB outcome is thickness of tumor according to Breslow, while there is no sufficient data to show correlation with other factors. We retrospectively studded 431 patients, out of which SLNB was performed on 188. Forty patients or 21.3% had positive lymph nodes. Our results showed strong correlation of tumor thickness and Clark level of invasion with SLNB outcome. Metastatic lymph nodes were founded in all acral-lentiginous melanoma patients, followed by nodular melanoma--55.6% and superficial spreading melanoma--14.1%. Results showed statistically significant predilection of positive SLNB in male patients and no correlation of positive SLNB with histological type of tumor. On the contrary, it showed significant correlation with development of metastases. Thus our results are similar to other comparable studies. PMID:19138008

  20. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  1. Spontaneous melanoma formation in nonhybrid Xiphophorus.

    PubMed

    Schartl, A; Malitschek, B; Kazianis, S; Borowsky, R; Schartl, M

    1995-01-01

    Melanoma in hybrids of Xiphophorus is due to the unrestricted activity of a cellular oncogene locus, Tu, encoding the growth factor receptor gene Xmrk. In nonhybrid parental fish, Tu is controlled by a tumor suppressor gene. Thus, its restricted activity leads there only to a nonmalignant, species- and population-specific macromelanophore spot pattern. Prompted by enigmatic reports on nonhybrid Xiphophorus with pigmentation abnormalities resembling melanoma, we have studied pigmentation in descendants of wild-caught fish and purebred laboratory stocks derived from wild populations. Whereas most stocks exhibiting macromelanophore patterns never developed pigmentation abnormalities, an exceptional situation for some nonhybrids was found. In X. variatus carrying the macromelanophore pattern "punctatus-2" and in X. cortezi with "spotted caudal," expressivity of the pigmentation gene ranges from a few black spots to extreme melanosis and eventually to malignant melanoma. In X. maculatus with the mutant pigmentation gene striped" carrying in addition the micromelanophore pattern "anal fin black" or "lower comet," testosterone-dependent melanoma develop originating from the corresponding micromelanophore pattern. The tumors are highly malignant and express a melanoma-associated antigen. Overexpression of the Xmrk oncogene appears as the underlying molecular mechanism for tumor induction. These findings clearly demonstrate that tumors can also develop in purebred wild-type fish. The classical model for formation of hereditary melanoma in Xiphophorus hybrids does not explain the development of melanoma in the absence of hybridization. However, their existence gives additional support to the reasoning that the Xmrk oncogene associated with the macromelanophore locus is potentially injurious. PMID:7805027

  2. Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

    PubMed

    Dudek, Maxine C; Wong, Kaitlyn E; Bassa, Lotfi M; Mora, Maria Carmen; Ser-Dolansky, Jennifer; Henneberry, Jean M; Crisi, Giovanna M; Arenas, Richard B; Schneider, Sallie S

    2015-12-01

    Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin β1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma. PMID:26159852

  3. Participants' perceptions of a peer-helper, telephone-based social support intervention for melanoma patients.

    PubMed

    Rudy, R R; Rosenfeld, L B; Galassi, J P; Parker, J; Schanberg, R

    2001-01-01

    This descriptive study investigated perceptions of a peer-helper, telephone-based, social support intervention for melanoma patients receiving immunotherapy. Participants were 59 male and female Stage 3 or4 melanoma patients (helpees) at a Comprehensive Cancer Center and 29 former patients (helpers). Helpers were matched with helpees about to begin immunotherapy based on the site of the melanoma, age, and, when possible, biological sex. The intervention consisted of 2 required telephone contacts initiated by the helper before the helpee's first and second immunotherapy treatments. The reactions to this social support intervention were assessed using surveys and telephone interviews with both open- and closed-ended questions. Results indicated that (a) helpees became more sensitive and open to available social support in their environment; (b) helpers and helpees thought the intervention was effective; and (c) the telephone, as a medium for providing support, was a satisfactory substitute for face-to-face interaction. Limitations of the study and future directions for telephone-based support programs for melanoma patients are discussed.

  4. Unexpected reduction of mortality rates from melanoma in males living in central Italy.

    PubMed

    Crocetti, E; Carli, Paolo

    2003-04-01

    A registry-based study has been carried out in central Italy to investigate cutaneous melanoma incidence and mortality trends. The incidence of invasive (1492 cases analysed) and in situ (224 cases) cutaneous melanomas increased significantly from 1985 to 1997, in both genders. The increase of invasive tumours was mainly due to 'thin' (stage at diagnosis was worse for males than females at the beginning of the analysed period, therefore the former had more possibilities for improvement than females. This may partially explain this finding since mortality rates among females were also quite low during the late 1980s. However, the stable incidence rates of the thick forms of melanoma make this finding largely unexpected, and difficult to understand assuming that in the last decade no 'clear-cut' improvements in survival have been documented as a result of new treatments in advanced melanomas.

  5. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy

    PubMed Central

    Niezgoda, Anna; Niezgoda, Piotr; Czajkowski, Rafał

    2015-01-01

    The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015. PMID:26171394

  6. Artesunate in the treatment of metastatic uveal melanoma--first experiences.

    PubMed

    Berger, Thomas G; Dieckmann, Detlef; Efferth, Thomas; Schultz, Erwin S; Funk, Jens-Oliver; Baur, Andreas; Schuler, Gerold

    2005-12-01

    Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future. PMID:16273263

  7. Acral Melanoma in Chinese: A Clinicopathological and Prognostic Study of 142 cases

    PubMed Central

    Lv, Jiaojie; Dai, Bo; Kong, Yunyi; Shen, Xuxia; Kong, Jincheng

    2016-01-01

    Acral melanoma (AM), as a peculiar subgroup of melanoma, is rare in Caucasians but has higher incidence in Asians. Large series of study on AM with clinicopathological features and prognostic factors is still limited, especially in Asian population. We retrospectively collected clinical, pathological and follow-up data of 142 AM cases. All patients were Chinese, with the age ranging from 24 to 87 years (mean 62.0; median 62.0). The Breslow thickness of primary lesions ranged from 0.6 to 16.3 mm (mean 4.9; median 3.7). 85.9% of the patients had acral lentiginous histologic subtype. Plantar was the most frequently involved site, followed by heels. Statistically, duration of the lesion before diagnosis (≤2.5 years), Breslow thickness >4.0 mm (T4), high mitotic index (>15 mm−2), presence of vascular invasion, regional lymph node metastasis at diagnosis and pathologic stage (II/III/IV) were found to be independent prognostic factors in both univariate and multivariate analyses. The prognosis of AM in Chinese is extremely poor. Our 5- and 10-year disease-specific survival (DSS) rates were 53.3% and 27.4%, respectively. Therefore, AM in Asians represents a more biologically aggressive melanoma subtype and is thought to carry a worse prognosis when compared with other races or cutaneous melanomas in other anatomic sites. PMID:27545198

  8. Ascertaining serum levels of trace elements in melanoma patients using PIXE and HR-ICPMS

    NASA Astrophysics Data System (ADS)

    Bernardes, S.; Tabacniks, M. H.; Santos, I. D. A. O.; Oliveira, A. F.; Shie, J. N.; Sarkis, J. E. S.; Oliveira, T.

    2014-01-01

    Melanoma is a serious and deadly form of skin cancer. However, patients' chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at São Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.

  9. Solar radiation and malignant melanoma of the skin.

    PubMed

    Houghton, A N; Viola, M V

    1981-10-01

    Several observations suggest that a majority of cases of malignant melanoma of the skin are linked to sun exposure. Evidence includes higher occurrence of melanoma on anatomic areas heavily exposed during recreation, development of melanoma more frequently in lightly pigmented persons, and correlation of melanoma incidence and mortality with proximity to the equator. The role of the sun exposure in the pathogenesis of melanoma remains unclear, however. Many cases of melanoma may be related to heavy doses of solar radiation received during recreation. Chronic sun exposure is not so clearly linked to the development of melanoma (except in the uncommon lentigo maligna variety). Sunspot cycles have been associated with changes in melanoma incidence; an excess of melanoma cases has been observed every 9 to 12 years after peak sunspot activity. These excess cases may be caused by more intense exposure to solar ultraviolet radiation during sunspot maxima, perhaps related to changes in the stratospheric ozone layer. These epidemiologic and clinical clues suggest that many cases of melanoma are related to sun exposure triggering the appearance of clinically evident melanoma. In this regard, solar radiation behaves as a cocarcinogen or promoter, rather than a dose-dependent carcinogen. These observations also suggest that other factors may be involved in the pathogenesis of melanoma, e.g., nevi, heredity, or exposure to chemical carcinogens.

  10. Indium-111 labeled anti-melanoma monoclonal antibodies

    DOEpatents

    Srivastava, S.C.; Fawwaz, R.A.; Ferrone, S.

    1984-04-30

    A monoclonal antibody to a high molecular weight melanoma-associated antigen was chelated and radiolabeled with indium-111. This material shows high affinity for melanoma and thus can be used in the detection, localization and imaging of melanoma. 1 figure.

  11. Immunotherapy of metastatic melanoma by reversal of immune suppression

    SciTech Connect

    Biggs, M.W.; Eiselein, J.E.

    1997-01-01

    Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

  12. Community Perceptions of Specific Skin Features of Possible Melanoma

    ERIC Educational Resources Information Center

    Baade, Peter D.; Balanda, Kevin P.; Stanton, Warren R.; Lowe, John B.; Del Mar, Chris B.

    2004-01-01

    Background: Melanoma can be curable if detected early. One component of detecting melanoma is an awareness of the important features of the disease. It is currently not clear which features the community view as indicative of melanoma. Objective: To investigate which features of the skin members of an urban community believe may indicate skin…

  13. Solar radiation and malignant melanoma of the skin

    SciTech Connect

    Houghton, A.N.; Viola, M.V.

    1981-01-01

    Several observations suggest that a majority of cases of malignant melanoma of the skin are linked to sun exposure. Evidence includes higher occurrence of melanoma on anatomic areas heavily exposed during recreation, development of melanoma more frequently in lightly pigmented persons, and correlation of melanoma incidence and mortality with proximity to the equator. The role of the sun exposure in the pathogenesis of melanoma remains unclear, however. Many cases of melanoma may be related to heavy doses of solar radiation received during recreation. Chronic sun exposure is not so clearly linked to the development of melanoma (except in the uncommon lentigo maligna variety). Sunspot cycles have been associated with changes in melanoma incidence; an excess of melanoma cases has been observed every 9 to 12 years after peak sunspot activity. These excess cases may be caused by more intense exposure to solar ultraviolet radiation during sunspot maxima, perhaps related to changes in the stratospheric ozone layer. These epidemiologic and clinical clues suggest that many cases of melanoma are related to sun exposure triggering the appearance of clinically evident melanoma. In this regard, solar radiation behaves as a cocarcinogen or promoter, rather than a dose-dependent carcinogen. These observations also suggest that other factors may be involved in the pathogenesis of melanoma, e.g., nevi, heredity, or exposure to chemical carcinogens.

  14. Sun exposure and melanoma prognostic factors

    PubMed Central

    GANDINI, SARA; MONTELLA, MAURIZIO; AYALA, FABRIZIO; BENEDETTO, LUCIA; ROSSI, CARLO RICCARDO; VECCHIATO, ANTONELLA; CORRADIN, MARIA TERESA; DE GIORGI, VINCENZO; QUEIROLO, PAOLA; ZANNETTI, GUIDO; GIUDICE, GIUSEPPE; BORRONI, GIOVANNI; FORCIGNANÒ, ROSACHIARA; PERIS, KETTY; TOSTI, GIULIO; TESTORI, ALESSANDRO; TREVISAN, GIUSTO; SPAGNOLO, FRANCESCO; ASCIERTO, PAOLO A.

    2016-01-01

    Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P<0.001) and absence of ulceration (P=0.009), following multiple adjustments for factors such as sociodemographic status, speciality of doctor performing the diagnosis and season of diagnosis. Sunbed exposure and sun exposure during peak hours of sunlight were not significantly associated with Breslow thickness and ulceration. Holidays with sun exposure were associated with favorable CM prognostic factors, whereas no association was identified between sunbed use and sun exposure during peak hours of sunlight with favorable CM prognostic factors. However, the results of the

  15. Non-surgical treatment of canine oral malignant melanoma: A case study of the application of complementary alternative medicine

    PubMed Central

    ITOH, HIROYASU; MUKAIYAMA, TOSHIYUKI; GOTO, TAKAHIRO; HATA, KEISHI; AZUMA, KAZUO; TSUKA, TAKASHI; OSAKI, TOMOHIRO; IMAGAWA, TOMOHIRO; OKAMOTO, YOSHIHARU

    2014-01-01

    This report describes a dog with a clinical stage III oral malignant melanoma that was treated with complementary alternative medicine (CAM). The CAM included high temperature hyperthermia, dendritic cell therapy and lupeol injections. Surgery, radiation and chemotherapy were not performed. Two months after the start of treatment, the tumor disappeared and after six months, the follow-up examinations revealed no recurrence or metastasis of the tumor. Quality of life (QOL) of the dog was maintained; therefore, the application of CAM may be an effective treatment for canine oral malignant melanoma. The effective application of CAM has the potential to prolong life and maintain an excellent QOL for pets. PMID:24932241

  16. Antioxidants can increase melanoma metastasis in mice.

    PubMed

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-01

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression.

  17. Animal Eye Models for Uveal Melanoma

    PubMed Central

    Cao, Jinfeng; Jager, Martine J.

    2015-01-01

    Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models. PMID:27172424

  18. Animal Eye Models for Uveal Melanoma.

    PubMed

    Cao, Jinfeng; Jager, Martine J

    2015-04-01

    Animal models play an important role in understanding tumor growth and may be used to develop novel therapies against human malignancies. The significance of the results from animal experiments depends on the selection of the proper model. Many attempts have been made to create appropriate animal models for uveal melanoma and its characteristic metastatic behavior. One approach is to use transgenic animal models or to implant tumor cells. A variety of tumor types have been used for this purpose: tumor cells, such as Greene melanoma, murine B16 melanoma, and human uveal melanoma cells, may be implanted in the eyes of hamsters, rats, rabbits, and mice, among others. Various inoculation routes, including into the anterior chamber and posterior compartment, and retro-orbitally, have been applied to obtain tumor growth mimicking ocular uveal melanoma. However, when we choose animal models, we must be conscious of many disadvantages, such as variable tumor growth, or the need for immunosuppression in xenogeneic grafts. In this paper, we will discuss the various eye models. PMID:27172424

  19. The Epidemiology, Prevention, and Detection of Melanoma

    PubMed Central

    Riker, Adam I.; Zea, Nicolas; Trinh, Tan

    2010-01-01

    We are seeing a record number of newly diagnosed skin cancers worldwide, with the incidence of melanoma increasing at a faster rate than almost all other cancers. As clinicians, we will have, by far, the greatest impact on reducing this incidence through better methods of early detection of melanoma and proven prevention methods and techniques. The medical community must enhance its efforts to increase its training of new health care personnel who are capable of diagnosing and treating this record number of patients with skin cancer. We must also try to increase the access to our limited number of dermatologists and provide novel ways of patient education such as through skin self-examinations, total body photography, and improved education for our children. By providing easier access to skin examinations, we will increase our chances of detecting melanoma in its earliest and most curable form. The dangers of indoor tanning beds and salons must be transparent to those that use them, focusing on expanding the oversight of such facilities by our local and federal governmental agencies while establishing legislation in several states to further limit their use to our youth, who are especially at high risk for developing melanoma in the future. This review will focus on the epidemiology, prevention, and detection of melanoma. PMID:21603359

  20. A Landscape of Driver Mutations in Melanoma

    PubMed Central

    Hodis, Eran; Watson, Ian R.; Kryukov, Gregory V.; Arold, Stefan T.; Imielinski, Marcin; Theurillat, Jean-Philippe; Nickerson, Elizabeth; Auclair, Daniel; Li, Liren; Place, Chelsea; DiCara, Daniel; Ramos, Alex H.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey; Voet, Douglas; Saksena, Gordon; Stransky, Nicolas; Onofrio, Robert C.; Winckler, Wendy; Ardlie, Kristin; Wagle, Nikhil; Wargo, Jennifer; Chong, Kelly; Morton, Donald L.; Stemke-Hale, Katherine; Chen, Guo; Noble, Michael; Meyerson, Matthew; Ladbury, John E.; Davies, Michael A.; Gershenwald, Jeffrey E.; Wagner, Stephan N.; Hoon, Dave S.B.; Schadendorf, Dirk; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Garraway, Levi A.; Chin, Lynda

    2012-01-01

    SUMMARY Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic ultraviolet (UV) light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19 and ARID2), three of which - RAC1, PPP6C and STK19 - harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis. PMID:22817889

  1. Microwave plaque thermoradiotherapy for choroidal melanoma.

    PubMed Central

    Finger, P. T.

    1992-01-01

    Microwave thermoradiotherapy was used as a primary treatment for 44 patients with choroidal melanoma. An episcleral dish-shaped microwave antenna was placed beneath the tumour at the time of plaque brachytherapy. While temperatures were measured at the sclera, the tumour's apex was targeted to receive a minimum of 42 degrees C for 45 minutes. In addition, the patients received full or reduced doses of plaque radiotherapy. No patients have been lost to follow-up. Two eyes have been enucleated: one for rubeotic glaucoma, and one for uveitic glaucoma. Though six patients have died, only one death was due to metastatic choroidal melanoma (39 months after treatment). Clinical observations suggest that the addition of microwave heating to plaque radiation therapy of choroidal melanoma has been well tolerated. There has been a 97.7% local control rate (with a mean follow-up of 22.2 months). We have reduced the minimum tumour radiation dose (apex dose) to levels used for thermoradiotherapy of cutaneous melanomas (50 Gy/5000 rad). Within the range of this follow-up period no adverse effects which might preclude the use of this microwave heat delivery system for treatment of choroidal melanoma have been noted. Images PMID:1622949

  2. Impact of melanoma genetic test reporting on perceived control over melanoma prevention.

    PubMed

    Aspinwall, Lisa G; Stump, Tammy K; Taber, Jennifer M; Kohlmann, Wendy; Leaf, Samantha L; Leachman, Sancy A

    2015-10-01

    To determine whether receiving melanoma genetic test results undermines perceived control over melanoma prevention, control-related beliefs were examined among 60 adults from melanoma-prone families receiving CDKN2A/p16 test results (27 unaffected noncarriers, 15 unaffected carriers, 18 affected carriers; response rate at 2 years = 64.9 % of eligible respondents). Multilevel modeling of perceived control ratings over a 2-year period revealed significant variation in individual trajectories: most participants showed increases (45 %) or no change (38.3 %), while 16.7 % showed decreases. At the group level, noncarriers reported sustained increases through the 2-year follow-up (ps < .05); unaffected carriers reported significant short-term increases (ps < .05); and affected carriers reported no change. Participants in all groups continued to rate photoprotection as highly effective in reducing melanoma risk and reported decreased beliefs that carrying the p16 mutation would inevitably lead to the development of melanoma. Qualitative responses immediately following counseling and test reporting corroborated these findings, as 93 % indicated it was possible to either prevent (64.9 %) or decrease the likelihood (28.1 %) of future melanomas. Thus, genetic test reporting does not generally undermine perceived control over melanoma prevention, though variability in response to positive results warrants future study.

  3. An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

    PubMed

    Kirby, L C; Banerjee, A; Augustine, T; Douglas, J F

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation. PMID:27484276

  4. Targeting Nitric Oxide Signaling with nNOS Inhibitors As a Novel Strategy for the Therapy and Prevention of Human Melanoma

    PubMed Central

    Yang, Zhen; Misner, Bobbye; Ji, Haitao; Poulos, Thomas L.; Silverman, Richard B.; Meyskens, Frank L.

    2013-01-01

    Abstract Aims: Our previous studies have shown that nitric oxide (NO) plays an important role in increasing the invasion and proliferation of human melanoma cells, suggesting that targeting NO signaling may facilitate therapy and prevention. Neuronal nitric oxide synthase (nNOS) is present in melanocytes, a cell type that originates from the neural crest. The aims of this study were to determine the role of nNOS in melanoma progression and the potential antitumor effects of novel synthesized nNOS inhibitors. Results: In vitro studies demonstrated abundant expression of nNOS in melanoma compared to melanocytes, which was inducible by ultraviolet radiation and was associated with increased NO generation. nNOS was also detected in melanoma biopsies that increased with disease stage. Knockdown of nNOS in melanoma cells diminished L-arginine-induced NO production; the metastatic capacity was also reduced as well as the levels of MMP-1, Bcl-2, JunD, and APE/Ref-1. Similar inhibition of NO and invasion potential was observed utilizing novel, highly selective nNOS inhibitors. In three-dimensional human skin reconstructs, the nNOS inhibitor cpd8 effectively reversed the melanoma overgrowth stimulated by NO stress. Innovation: Our work lays the foundation for development of clinical “drug-like” nNOS inhibitors as a new and promising strategy for the chemoprevention of early melanoma progression and the inhibition of secondary melanoma in high-risk individuals. Conclusion: Based on our observations, we propose that nNOS in melanoma results in constitutive overproduction of NO, which stimulates proliferation and increases invasion potential, leading to subsequent development of metastases. Antioxid. Redox Signal. 19, 433–447. PMID:23199242

  5. Assessment of melanoma extent and melanoma metastases invasion using electron paramagnetic resonance and bioluminescence imaging.

    PubMed

    Godechal, Quentin; Defresne, Florence; Danhier, Pierre; Leveque, Philippe; Porporato, Paolo Ettore; Sonveaux, Pierre; Baurain, Jean-François; Feron, Olivier; Gallez, Bernard

    2011-01-01

    The clinical outcome of melanoma depends on the local and distant spread of the disease at the time of diagnosis, as the estimated 5-year survival rate is about 100% for superficial melanoma diagnosed early, but less than 10% for melanoma that has disseminated to major organs such as lungs. There is a crucial need for new effective methods for the detection and the characterization of melanomas. In the pre-clinical setting, this will help to understand the factors that contribute to the malignancy while the transfer into the clinic will contribute to an early effective treatment of patients. Melanoma lesions can be detected by electron paramagnetic resonance (EPR) using paramagnetic properties of melanin pigments. As part of the development of EPR imaging to characterize melanomas, we evaluated in the present study the usefulness of EPR to report on the extension of lung metastases by comparing the method with bioluminescence imaging using B16 melanoma cells expressing luciferase. B16 melanoma cells were injected subcutaneously or intravenously in C57/BL6 mice. The primary tumors or the lung colonization by melanoma cells was measured after several delay periods to obtain several degrees of invasiveness. The animals were measured in-vivo with bioluminescence after i.v. injection of luciferin. The primary tumors or lungs were then excised. After freeze-drying, the content of melanin in lungs was measured and imaged by EPR at 9 GHz. We observed a direct relationship between the EPR intensity and the bioluminescence intensity. Another tumor model (KHT sarcoma), non-pigmented but expressing luciferase, was used to confirm that the EPR signal was directly linked to the melanin pigment present in the tumors. PMID:21861288

  6. Gene expression analyses of primary melanomas reveal CTHRC1 as an important player in melanoma progression

    PubMed Central

    Eriksson, Johanna; Le Joncour, Vadim; Nummela, Pirjo; Jahkola, Tiina; Virolainen, Susanna; Laakkonen, Pirjo; Saksela, Olli; Hölttä, Erkki

    2016-01-01

    Melanoma is notorious for its high tendency to metastasize and its refractoriness to conventional treatments after metastasis, and the responses to most targeted therapies are short-lived. A better understanding of the molecular mechanisms behind melanoma development and progression is needed to develop more effective therapies and to identify new markers to predict disease behavior. Here, we compared the gene expression profiles of benign nevi, and non-metastatic and metastatic primary melanomas to identify any common changes in disease progression. We identified several genes associated with inflammation, angiogenesis, and extracellular matrix modification to be upregulated in metastatic melanomas. We selected one of these genes, collagen triple helix repeat containing 1 (CTHRC1), for detailed analysis, and found that CTHRC1 was expressed in both melanoma cells and the associated fibroblasts, as well as in the endothelium of tumor blood vessels. Knockdown of CTHRC1 expression by shRNAs in melanoma cells inhibited their migration in Transwell assays and their invasion in three-dimensional collagen and Matrigel matrices. We also elucidated the possible down-stream effectors of CTHRC1 by gene expression profiling of the CTHRC1-knockdown cells. Our analyses showed that CTHRC1 is regulated coordinately with fibronectin and integrin β3 by the pro-invasive and -angiogenic transcription factor NFATC2. We also found CTHRC1 to be a target of TFGβ and BRAF. These data highlight the importance of tumor stroma in melanoma progression. Furthermore, CTHRC1 was recognized as an important mediator of melanoma cell migration and invasion, providing together with its regulators—NFATC2, TGFβ, and BRAF—attractive therapeutic targets against metastatic melanomas. PMID:26918341

  7. MicroRNA-199a-5p inhibits tumor proliferation in melanoma by mediating HIF-1α.

    PubMed

    Yang, Xinghua; Lei, Shaorong; Long, Jianhong; Liu, Xiaojin; Wu, Qizhen

    2016-06-01

    The expression of hypoxia-inducible factor 1α (HIF-1α) is often abundant in human cancer and it is associated with poor prognosis. The present study aimed to investigate its regulation by microRNA (miRNA). The expression of miRNA-199a-5p (miR-199a-5p) in melanoma was detected by quantitative polymerase chain reaction on samples from 25 melanoma patients. The target of miR-199a-5p was predicted and demonstrated by a dual‑luciferase reporter system. The effects of miR-199a-5p on melanoma cells were assayed in B16 and HME1 melanoma cell lines. Furthermore, the potential of miR‑199a‑5p as a therapeutic target was illustrated in xenograft nude mice models. Low expression of miR‑199a‑5p in tumor melanoma tissue samples from patients was associated with high histological grade and advanced tumor stage. The 3'-untranslated region of HIF‑1α was identified as a target of miR‑199a‑5p by Targetscan software. The dual-luciferase reporter assay demonstrated that miR‑199a‑5p transfection of mimics decreased the luciferase activity significantly (P<0.05). In the B16 and HME1 cell lines, overexpression of miR‑199a‑5p suppressed cell proliferation and arrested the cell cycle in the G1 phase. In vivo overexpression of miR‑199a‑5p significantly suppressed xenograft growth and downregulated the expression of HIF‑1α (P<0.05). The results from the present study suggest that miR‑199a‑5p suppressed melanoma proliferation via HIF‑1α, suggesting it may be a potential therapeutic target for melanoma treatment. PMID:27122154

  8. Report from the Melanoma Independent Board First Melanoma MIB Conference, 21–22 October 2013

    PubMed Central

    Testori, A; Ascierto, P; Chiarion Sileni, V; De Lorenzo, F; Pelicci, PG; Rossi, CR

    2014-01-01

    The Melanoma Independent Board (MIB) held its first conference from 21 to 22 October, 2013, in Rome, Italy. Like the MIB itself, the conference brought together specialists from all aspects of cancer care: doctors, patient associations, journalists, and representatives from local government, hospitals, and pharma to encourage an interdisciplinary discussion on the future of melanoma. It was hoped that the conference would be an opportunity for all participants to see and understand each other’s points of view. In memoriam of melanoma pioneer Natalie Cascinelli, the conference focussed on innovation and sustainability as well as the latest drug developments. PMID:25075214

  9. Bioelectric Applications for Treatment of Melanoma

    PubMed Central

    Beebe, Stephen J.; Schoenbach, Karl H.; Heller, Richard

    2010-01-01

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma. PMID:24281185

  10. Conjunctival malignant melanoma in a horse.

    PubMed

    Moore, C.P.; Collins, B.K.; Linton, L.L.; Collier, L.L.

    2000-01-01

    A case of malignant melanoma originating from the conjunctiva of a horse is reported. The tumor exhibited locally aggressive behavior as evidenced clinically by recurrence following two treatment episodes including surgical excision on each occasion and one application of cryotherapy. The orbit was subsequently exenterated and histologically malignant conjunctival melanoma was confirmed. Histopathologic features included variable pigmentation with amelanotic sites demonstrating marked cellular and nuclear pleomorphism with high numbers of mitotic figures. Cords of neoplastic cells invaded the sclera and cornea. Following exenteration, the horse exhibited no recurrence of the tumor for five years before being lost to follow-up. To our knowledge, this is the first report of primary malignant conjunctival melanoma in a horse.

  11. Proton beam radiotherapy of uveal melanoma

    PubMed Central

    Damato, Bertil; Kacperek, Andrzej; Errington, Doug; Heimann, Heinrich

    2013-01-01

    Proton beam radiotherapy of uveal melanoma can be administered as primary treatment, as salvage therapy for recurrent tumor, and as neoadjuvant therapy prior to surgical resection. The physical properties of proton beams make it possible to deliver high-doses of radiation to the tumor with relative sparing of adjacent tissues. This form of therapy is effective for a wider range of uveal melanoma than any other modality, providing exceptionally-high rates of local tumor control. This is particularly the case with diffuse iris melanomas, many of which are unresectable. The chances of survival, ocular conservation, visual preservation and avoidance of iatrogenic morbidity depend greatly on the tumor size, location and extent. When treating any side-effects and/or complications, it is helpful to consider whether these are the result of collateral damage or persistence of the irradiated tumor (‘toxic tumor syndrome’). PMID:24227980

  12. Genetic determinants of cutaneous melanoma predisposition.

    PubMed

    Udayakumar, Durga; Mahato, Bisundev; Gabree, Michele; Tsao, Hensin

    2010-09-01

    In the last 2 decades, advances in genomic technologies and molecular biology have accelerated the identification of multiple genetic loci that confer risk for cutaneous melanoma. The risk alleles range from rarely occurring, high-risk variants with a strong familial predisposition to low-risk to moderate-risk variants with modest melanoma association. Although the high-risk alleles are limited to the CDKN2A and CDK4 loci, the authors of recent genome-wide association studies have uncovered a set of variants in pigmentation loci that contribute to low risk. A biological validation of these new findings would provide greater understanding of the disease. In this review we describe some of the important risk loci and their association to risk of developing cutaneous melanoma and also address the current clinical challenges in CDKN2A genetic testing. PMID:21051013

  13. Bioelectric applications for treatment of melanoma.

    PubMed

    Beebe, Stephen J; Schoenbach, Karl H; Heller, Richard

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  14. Pembrolizumab for the treatment of melanoma.

    PubMed

    Kumar, Sanjeev Srinivas; McNeil, Catriona Mairi

    2015-01-01

    The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. In particular, blockade of programmed cell death protein 1 (PD-1) in advanced melanoma has proven to be a most promising new anticancer strategy. Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies.

  15. Ensemble approach for differentiation of malignant melanoma

    NASA Astrophysics Data System (ADS)

    Rastgoo, Mojdeh; Morel, Olivier; Marzani, Franck; Garcia, Rafael

    2015-04-01

    Melanoma is the deadliest type of skin cancer, yet it is the most treatable kind depending on its early diagnosis. The early prognosis of melanoma is a challenging task for both clinicians and dermatologists. Due to the importance of early diagnosis and in order to assist the dermatologists, we propose an automated framework based on ensemble learning methods and dermoscopy images to differentiate melanoma from dysplastic and benign lesions. The evaluation of our framework on the recent and public dermoscopy benchmark (PH2 dataset) indicates the potential of proposed method. Our evaluation, using only global features, revealed that ensembles such as random forest perform better than single learner. Using random forest ensemble and combination of color and texture features, our framework achieved the highest sensitivity of 94% and specificity of 92%.

  16. Advances in noninvasive imaging of melanoma.

    PubMed

    Menge, Tyler D; Pellacani, Giovanni

    2016-03-01

    Melanoma is the most dangerous type of skin cancer and its incidence has risen sharply in recent decades. Early detection of disease is critical for improving patient outcomes. Any pigmented lesion that is clinically concerning must be removed by biopsy for morphologic investigation on histology. However, biopsies are invasive and can cause significant morbidity, and their accuracy in detecting melanoma may be limited by sampling error. The advent of noninvasive imaging devices has allowed for assessment of intact skin, thereby minimizing the need for biopsy; and these technologies are increasingly being used in the diagnosis and management of melanoma. Reflectance confocal microscopy, optical coherence tomography, ultrasonography, and multispectral imaging are noninvasive imaging techniques that have emerged as diagnostic aids to physical exam and/or conventional dermoscopy. This review summarizes the current knowledge about these techniques and discusses their practical applications and limitations. PMID:26963113

  17. Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

    SciTech Connect

    Rades, Dirk; Setter, Cornelia; Dahl, Olav; Schild, Steven E.; Noack, Frank

    2011-06-01

    Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells

  18. L1CAM from human melanoma carries a novel type of N-glycan with Galβ1-4Galβ1- motif. Involvement of N-linked glycans in migratory and invasive behaviour of melanoma cells.

    PubMed

    Hoja-Łukowicz, Dorota; Link-Lenczowski, Paweł; Carpentieri, Andrea; Amoresano, Angela; Pocheć, Ewa; Artemenko, Konstantin A; Bergquist, Jonas; Lityńska, Anna

    2013-04-01

    Dramatic changes in glycan biosynthesis during oncogenic transformation result in the emergence of marker glycans on the cell surface. We analysed the N-linked glycans of L1CAM from different stages of melanoma progression, using high-performance liquid chromatography combined with exoglycosidase sequencing, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, and lectin probes. L1CAM oligosaccharides are heavily sialylated, mainly digalactosylated, biantennary complex-type structures with galactose β1-4/3-linked to GlcNAc and with or without fucose α1-3/6-linked to GlcNAc. Hybrid, bisected hybrid, bisected triantennary and tetraantennary complex oligosaccharides, and β1-6-branched complex-type glycans with or without lactosamine extensions are expresses at lower abundance. We found that metastatic L1CAM possesses only α2-6-linked sialic acid and the loss of α2-3-linked sialic acid in L1CAM is a phenomenon observed during the transition of melanoma cells from VGP to a metastatic stage. Unexpectedly, we found a novel monoantennary complex-type oligosaccharide with a Galβ1-4Galβ1- epitope capped with sialic acid residues A1[3]G(4)2S2-3. To our knowledge this is the first report documenting the presence of this oligosaccharide in human cancer. The novel and unique N-glycan should be recognised as a new class of human melanoma marker. In functional tests we demonstrated that the presence of cell surface α2-3-linked sialic acid facilitates the migratory behaviour and increases the invasiveness of primary melanoma cells, and it enhances the motility of metastatic cells. The presence of cell surface α2-6-linked sialic acid enhances the invasive potential of both primary and metastatic melanoma cells. Complex-type oligosaccharides in L1CAM enhance the invasiveness of metastatic melanoma cells. PMID:22544341

  19. Oxidative burst of neutrophils against melanoma B16-F10.

    PubMed

    Zivkovic, Morana; Poljak-Blazi, Marija; Zarkovic, Kamelija; Mihaljevic, Danijela; Schaur, Rudolf Joerg; Zarkovic, Neven

    2007-02-01

    Intensive oxidative burst was determined by chemiluminescence of peripheral blood neutrophils of mice that were intramuscularly injected with melanoma B16-F10 and/or subcutaneously with Sephadex G-200. The neutrophils from papula developed at the site of Sephadex injection were cytotoxic for the B16-F10 cells in vitro. However, survival of Sephadex injected tumour-bearing mice was lower than of control animals bearing B16-F10, while their tumours grew faster and were less necrotic. Thus, it is likely that injection of Sephadex distracted the neutrophils from the tumour allowing faster progression of the tumour, indicating that neutrophils may have an important role in the host defence against malignant cells in the early stage of tumour development.

  20. Immunotherapy for melanoma: the good, the bad, and the future.

    PubMed

    Poehlein, Christian H; Rüttinger, Dominik; Ma, Jun; Hu, Hong-Ming; Urba, Walter J; Fox, Bernard A

    2005-09-01

    The past 20 years have seen remarkable advances in our understanding of the molecular and cellular processes controlling the development of an anticancer immune response. These advances have spawned a renaissance in the field of cancer immunotherapy, the original targeted therapy, during which investigators have pushed the envelope and translated promising strategies into investigational therapeutics in patients with cancer. An approach that combined nonmyeloablative lymphodepleting chemotherapy with adoptive transfer of tumor-specific CD4 and CD8 T cells exhibited an initial objective response rate of 51% for patients with stage IV melanoma. Although this strategy is extremely challenging, one can expect technological advances that may simplify this approach and further improve outcome.

  1. Immunotherapy for Melanoma: Current Status and Perspectives

    PubMed Central

    Alexandrescu, Doru T.; Ichim, Thomas E.; Riordan, Neil H.; Marincola, Francesco M.; Nardo, Anna Di; Kabigting, Filamer D.; Dasanu, Constantin A.

    2012-01-01

    Summary Immunotherapy is an important modality in the therapy of patients with malignant melanoma. As our knowledge about this disease continues to expand, so does the immunotherapeutic armamentarium. Nevertheless, successful preclinical models do not always translate into clinically meaningful results. The authors give a comprehensive analysis of most recent advances in the immune anti-melanoma therapy, including interleukins, interferons, other cytokines, adoptive immunotherapy, biochemotherapy, as well as the use of different vaccines. We also present the fundamental concepts behind various immune enhancement strategies, passive immunotherapy, as well as the use of immune adjuvants. This review brings into discussion the results of newer and older clinical trials, as well as potential limitations and drawbacks seen with the utilization of various immune therapies in malignant melanoma. Development of novel therapeutic approaches, along with optimization of existing therapies, continues to hold a great promise in the field of melanoma therapy research. Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma. The need to engineer better immune interactions and to boost positive feedback loops appear crucial for the future of melanoma therapy, which ultimately resides in our understanding of the complexity of immune responses in this disease. PMID:20551839

  2. Swimming and the risk of cutaneous melanoma.

    PubMed

    Nelemans, P J; Rampen, F H; Groenendal, H; Kiemeney, L A; Ruiter, D J; Verbeek, A L

    1994-10-01

    Recreational exposure to the sun may not explain fully current trends in melanoma incidence. The hypothesis was examined whether carcinogens in water play a role in the development of cutaneous melanoma. In a case-control study, 128 melanoma patients and 168 patients with other types of malignancy completed a detailed questionnaire on aquatic leisure time activities. All relative risk estimates were adjusted for age, gender, educational level, pigmentation characteristics, and exposure to sun habits. Regular swimming during the summer months in swimming pools and in open waters such as rivers and seas before the age of 15 years, was associated with odds ratios of 2.20 (95% confidence interval (CI), 1.05-4.62) and 2.41 (95% CI, 1.04-5.58), respectively, compared with no swimming at all or swimming in relatively unpolluted waters, such as lakes and fens. Melanoma patients learned to swim at a younger age; compared with those who never learned to swim or who learned to swim after the age of 12 years, the odds ratio was 1.87 (95% CI, 0.91-3.78) for those who learned to swim at ages 9-12 years, and 2.22 (95% CI, 1.16-4.26) for those who learned to swim before 9 years of age. Compared with persons who had no swimming certificates, an odds ratio of 1.25 (95% CI, 0.71-2.23) was found for persons with one or two certificates, and an odds ratio of 2.96 (95% CI, 1.25-6.96) for persons with three or more certificates. The positive association between a history of swimming and melanoma risk suggests that carcinogenic agents in water, possibly chlorination by products, play a role in melanoma aetiology. PMID:7858410

  3. In vivo melanoma depth detection by a handheld photoacoustic microscope

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Xing, Wenxin; Maslov, Konstantin I.; Cornelius, Lynn A.; Wang, Lihong V.

    2015-03-01

    We developed a handheld photoacoustic microscope (PAM) to detect melanoma and determine tumor depth in nude mice in vivo. Compared to our previous PAM system for melanoma imaging, a new light delivery mechanism is introduced to improve light penetration. We show that melanomas with 4.1 mm and 3.3 mm thicknesses can be successfully detected in phantom and in vivo experiments, respectively. With its deep melanoma imaging ability and novel handheld design, this system is promising for clinical melanoma diagnosis, prognosis, and surgical planning for patients at the bedside.

  4. Historical summary and recommendations on Melanoma in the LLNL workforce

    SciTech Connect

    Moore, D.H. II; Hatch, F.

    1994-12-01

    This document provides a historical summary and recommendations on melanoma in the Lawrence Livermore National Laboratory (LLNL) workforce. Melanoma of the skin comprises about 3.5% of the incidence (38,000 new cases in 1991) and 1.7% of the mortality (8500 deaths in 1991) of all cancer in the U.S. However, for several decades it has shown the fastest rate of increase of any cancer site. The following areas are discussed: background and recognition of increased melanoma at LLNL, history of melanoma studies at LLNL, results from occupational factors study, overall conclusion on increased melanoma incidence, and recommendations for future management.

  5. Genetic Testing in the Multidisciplinary Management of Melanoma.

    PubMed

    Rashid, Omar M; Zager, Jonathan S

    2015-10-01

    Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma.

  6. Intratumoral expression of cyclooxygenase-2 (COX-2) is a negative prognostic marker for patients with cutaneous melanoma.

    PubMed

    Kuźbicki, Łukasz; Lange, Dariusz; Stanek-Widera, Agata; Chwirot, Barbara W

    2016-10-01

    Because of the well-known heterogeneity of melanomas, prognosis of the disease is often difficult to assess even for lesions classified in similar stages. The aim of this study was to assess the usefulness of COX-2 as a melanoma prognostic marker and to establish an optimum algorithm for analysis of COX-2 expression levels in lesions of interest. Expression of COX-2 was detected immunohistochemically in standard sections of formalin-fixed paraffin-embedded tissue samples of 85 primary melanomas, 36 lymph node metastases, and five skin metastases including 39 cases of paired primary and metastatic lesions obtained from the same patient. Enhanced expression of COX-2 in primary melanomas is an indicator of poorer prognosis. A significant correlation was found between high expression of COX-2 in primary lesions and shorter survival. The enhancement of COX-2 expression is also positively correlated with other prognostic factors such as tumor thickness and infiltration level, ulceration, high mitotic index, more invasive histologic type, vertical growth phase, and lymph node metastasis. On the whole, the results suggest that intratumoral expression of COX-2 is a strong negative prognostic marker for patients with melanoma. Moreover, our work shows that a simple and objective immunohistochemical scoring algorithm involving the determination of only a percentage fraction of positively stained cells is sufficient to obtain the prognostic information.

  7. Clinicopathologic features of incident and subsequent tumors in patients with multiple primary cutaneous melanomas

    PubMed Central

    Murali, Rajmohan; Goumas, Chris; Kricker, Anne; From, Lynn; Busam, Klaus J.; Begg, Colin B.; Dwyer, Terence; Gruber, Stephen B.; Kanetsky, Peter A.; Orlow, Irene; Rosso, Stefano; Thomas, Nancy E.; Berwick, Marianne; Scolyer, Richard A.; Armstrong, Bruce K.

    2011-01-01

    Background 0.6–12.7% of patients with primary cutaneous melanoma will develop additional melanomas. Pathologic features of tumors in patients with multiple primary cutaneous melanomas have not been well described. In this large international multi-center case-control study, we compared the clinicopathologic features of a subsequent melanoma with the preceding (usually the first) melanoma in patients with multiple primary cutaneous melanomas, and with those of melanomas in patients with single primary cutaneous melanomas. Methods Multiple primary melanoma (cases) and single primary invasive melanoma (controls) patients from the Genes, Environment and Melanoma (GEM) study were included if their tumors were available for pathologic review and confirmed as melanoma. Clinicopathologic characteristics of invasive subsequent and first melanomas in cases and invasive single melanomas in controls were compared. Results 473 pairs comprising a subsequent and a first melanoma and 1989 single melanomas were reviewed. Forward stepwise regression modeling in 395 pairs with complete data showed that, compared to first melanomas, subsequent melanomas were: more commonly contiguous with a dysplastic nevus; more prevalent on the head/neck and legs than other sites; and thinner. Compared with single primary melanomas, subsequent melanomas were also more likely to be: associated with a contiguous dysplastic nevus; more prevalent on the head/neck and legs; and thinner. The same differences were observed when subsequent melanomas were compared with single melanomas. First melanomas were more likely than single melanomas to have associated solar elastosis and no observed mitoses. Conclusions Thinner subsequent than first melanomas suggest earlier diagnosis, perhaps due to closer clinical scrutiny. The association of subsequent melanomas with dysplastic nevi is consistent with the latter being risk factors or risk markers for melanoma. PMID:21913010

  8. Malignant Melanoma Arising in Red Tattoo Ink

    PubMed Central

    Duff, Gerald; McKenna, Dermot; Regan, Padraic James

    2015-01-01

    We report the case of a 33-year-old male who presented with a malignant melanoma on his anterior chest wall. The lesion was only found in the red ink pigment of the tattoo, as were several in-transit dermal metastases. Possible explanations include a pre-existing lesion which was seeded with red ink or the possibility of the red ink causing an inflammatory reaction leading to malignant transformation. This is the first reported case of a melanoma developing in the red ink pigment of a multi-colored tattoo. PMID:26217569

  9. Clinicopathologic characteristics and management trends of cutaneous invasive and in situ melanoma in older patients: a retrospective analysis of the National Cancer Data Base

    PubMed Central

    Shrestha, Rajesh; Krishnamurthy, Jairam; Mosalpuria, Kailash; Loberiza, Fausto R.; Ganti, Apar Kishor; Silberstein, Peter T.

    2015-01-01

    Background: The incidence of melanoma in older patients is on the rise. Prior studies have shown disparities in surgical management and poor survival of older patients with melanoma. Methods: This is a retrospective study of adult patients diagnosed with cutaneous invasive and in situ melanoma between 2000 and 2011 in the National Cancer Data Base. Characteristics and management of older patients (≥60 years) were compared with younger patients (20–59 years) using χ2 testing. Results: Of 476,623 total cases, 54% (n = 258,153) were diagnosed among older patients. The reported cases in the older patients increased by 1.74-fold between 2000 and 2011. The majority were white (96%), men (65%), with early-stage disease (76% stage 0-II), and superficial spreading melanoma histology (39%). Older patients, compared with younger patients, were more likely to be men (65% versus 49%, p < 0.0001), and have in situ melanoma (28% versus 21%, p < 0.0001); less likely to have nodal metastases (7% versus 9%, p < 0.0001), receive care in academic centers (30% versus 35%, p < 0.0001), undergo wide excision or major amputation for stage I–III disease (68% versus 72%, p < 0.0001) and systemic therapy for stage III (18% versus 45%, p < 0.0001) and IV disease (30% versus 50%, p < 0.0001). Conclusion: Older patients with melanoma are less likely to receive care in academic centers, undergo wide excision for stage I–III disease and receive systemic therapy for stage III–IV disease. Particularly, the utilization of systemic therapy is markedly low. This disparity is particularly important with the availability of less intense more effective therapies. PMID:25553079

  10. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    PubMed Central

    Beutler, Bryce D.; Cohen, Philip R.

    2015-01-01

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis. PMID:26083934

  11. Defining the dermoscopic characteristics of fast-growing cutaneous melanomas.

    PubMed

    Tejera-Vaquerizo, Antonio; Arias-Santiago, Salvador; Nagore, Eduardo; Martín-Cuevas, Paula; Orgaz-Molina, Javier; Traves, Victor; Herrera-Acosta, Enrique; Naranjo-Sintes, Ramón; Guillén, Carlos; Herrera-Ceballos, Enrique

    2015-06-01

    A high growth rate in melanomas has been associated with a more aggressive phenotype and worse survival. The aim of this study was to define the dermoscopic characteristics associated with this type of cutaneous melanoma. We carried out a retrospective study of 132 cutaneous melanomas, analyzing certain clinical characteristics and the most important dermoscopic variables related to the melanomas. Fast-growing melanomas were considered to be those with a growth rate of more than 0.5 mm per month. Fast-growing melanomas more often lacked an atypical network, were symmetrical, presented ulceration, and were hypopigmented. The dermoscopic vascular pattern often showed atypical irregular vessels and milky-red areas. The association of these two is a specific characteristic. Fast-growing melanomas have a characteristic phenotype and dermoscopy can be useful for their identification.

  12. Epidermotropic Metastatic Melanoma with Perilesional Depigmentation in an Indian Male

    PubMed Central

    Doshi, Bhavana; Mahajan, Sunanda; Khopkar, Uday S; Kharkar, Vidya; Agarwal, Prachi

    2013-01-01

    Melanoma is a rare form of cutaneous malignancy encountered in the dark skin population. Epidermotropic metastatic melanoma is a rare form of cutaneous metastatic melanoma which can mimic primary melanoma on histopathology. Hence its differentiation is of immense prognostic importance. The occurrence of rim of depigmentation around the primary cutaneous melanoma has previously been reported to portend a bad prognosis. The occurrence of vitiligo like lesions in patients with metastatic melanoma in comparison has a better prognosis. However the occurrence of depigmentation around the secondaries is rare and its importance is not well known. Hence we wish to report a case of epidermotropic metastatic melanoma with perilesional depigmentation in a 78 year old Indian male. PMID:24082190

  13. Melanoma Cells Break Down LPA to Establish Local Gradients That Drive Chemotactic Dispersal

    PubMed Central

    Muinonen-Martin, Andrew J.; Susanto, Olivia; Zhang, Qifeng; Smethurst, Elizabeth; Faller, William J.; Veltman, Douwe M.; Kalna, Gabriela; Lindsay, Colin; Bennett, Dorothy C.; Sansom, Owen J.; Herd, Robert; Jones, Robert; Machesky, Laura M.; Wakelam, Michael J. O.; Knecht, David A.; Insall, Robert H.

    2014-01-01

    The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient. PMID:25313567

  14. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options.

    PubMed

    Metcalfe, Lucy Va; O'Brien, Peter J; Papakonstantinou, Stratos; Cahalan, Stephen D; McAllister, Hester; Duggan, Vivienne E

    2013-01-01

    A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thoracic radiography, cytological examination of the pleural fluid and a fine needle aspirate of a thoracic mass led to a presumptive diagnosis of malignant melanoma and this was confirmed at post mortem examination. Further metastatic spread to the central nervous system and right guttural pouch was also identified. In conclusion this case manifests the potential malignant behaviour of equine melanomas, and a review of proposed therapies for melanoma treatment highlights the therapeutic options and current areas of research. PMID:24196087

  15. Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011: A Population-Based SEER Analysis.

    PubMed

    Chen, Haiyan; Cai, Yibo; Liu, Yue; He, Jinjie; Hu, Yeting; Xiao, Qian; Hu, Wangxiong; Ding, Kefeng

    2016-02-01

    Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis.

  16. Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011: A Population-Based SEER Analysis.

    PubMed

    Chen, Haiyan; Cai, Yibo; Liu, Yue; He, Jinjie; Hu, Yeting; Xiao, Qian; Hu, Wangxiong; Ding, Kefeng

    2016-02-01

    Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis. PMID:26886623

  17. Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer

    ClinicalTrials.gov

    2013-01-09

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Melanoma; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer

  18. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile.

    PubMed

    Larsen, Ann-Cathrine

    2016-05-01

    conjunctival melanomas were BRAF-mutated, and the incidence of BRAF mutations was constant over time. BRAF-mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations. In univariate analysis, distant metastatic disease was associated with BRAF mutations. No prognostic associations with BRAF mutations were identified in multivariate analyses. MicroRNA expression analysis revealed 25 tumour-specific microRNAs in conjunctival melanoma. Five possibly oncogenic miRNAs (miR-20b-5p, miR-146b-5p, miR-146a-5p, miR-506-3p and miR-509-3p) were up-regulated. Seven microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) were significantly and simultaneously up-regulated in both stage T1 and stage T2 tumours, and were associated with increased tumour thickness. The expression of the 25 tumour-specific microRNAs did not differ significantly between conjunctival melanoma and oral or nasal mucosal melanoma. In conclusion, the incidence of conjunctival melanoma increased in the Danish population from 1960 to 2012. From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, it is evident that conjunctival melanoma is closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma. PMID:27192168

  19. Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling.

    PubMed

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Recent advances in cancer genomics have enabled the discovery of many cancer-predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype