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Sample records for advanced melanoma technique

  1. Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

    Directory of Open Access Journals (Sweden)

    Helena Kupcova Skalnikova

    2017-12-01

    Full Text Available Melanoma is a skin cancer with permanently increasing incidence and resistance to therapies in advanced stages. Reports of spontaneous regression and tumour infiltration with T-lymphocytes makes melanoma candidate for immunotherapies. Cytokines are key factors regulating immune response and intercellular communication in tumour microenvironment. Cytokines may be used in therapy of melanoma to modulate immune response. Cytokines also possess diagnostic and prognostic potential and cytokine production may reflect effects of immunotherapies. The purpose of this review is to give an overview of recent advances in proteomic techniques for the detection and quantification of cytokines in melanoma research. Approaches covered span from mass spectrometry to immunoassays for single molecule detection (ELISA, western blot, multiplex assays (chemiluminescent, bead-based (Luminex and planar antibody arrays, ultrasensitive techniques (Singulex, Simoa, immuno-PCR, proximity ligation/extension assay, immunomagnetic reduction assay, to analyses of single cells producing cytokines (ELISpot, flow cytometry, mass cytometry and emerging techniques for single cell secretomics. Although this review is focused mainly on cancer and particularly melanoma, the discussed techniques are in general applicable to broad research field of biology and medicine, including stem cells, development, aging, immunology and intercellular communication.

  2. Management of advanced melanoma

    International Nuclear Information System (INIS)

    Nathanson, L.

    1986-01-01

    This book presents papers on the subject of management of advanced melanoma. The topics covered are: non-investigational cytotoxic agents; high-dosage chemotherapy in antologous bone marrow transplantation; Radiotherapy of melanomas; hyperthermia; ureal melanoma; surgical treatment of recurrent a metastatic melanoma; role of interferons in management of melanoma and molecular genetics of melanoma

  3. Advanced Melanoma Facebook Live Event

    Science.gov (United States)

    In case you missed it, watch this recent Facebook Live event about the current state of research and treatment for advanced stage melanoma. To learn more, see our evidence-based information about skin cancer, including melanoma.

  4. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

    Full Text Available Abstract Serum lactate dehydrogenase (LDH is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS, we subsequently determined using tissue microarray (TMA analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.

  5. Immunotherapy for advanced melanoma: future directions.

    Science.gov (United States)

    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.

  6. Systematic review of psychosocial outcomes for patients with advanced melanoma.

    Science.gov (United States)

    Dunn, Jeff; Watson, Maggie; Aitken, Joanne F; Hyde, Melissa K

    2017-11-01

    New advanced melanoma therapies are associated with improved survival; however, quality of survivorship, particularly psychosocial outcomes, for patients overall and those treated with newer therapies is unclear. Synthesize qualitative and quantitative evidence about psychosocial outcomes for advanced (stage III/IV) melanoma patients. Five databases were searched (01/01/1980 to 31/01/2016). Inclusion criteria were as follows: advanced melanoma patients or sub-group analysis; assessed psychosocial outcomes; and English language. Fifty-two studies met review criteria (4 qualitative, 48 quantitative). Trials comprise mostly medical not psychosocial interventions, with psychosocial outcomes assessed within broader quality of life measures. Patients receiving chemotherapy or IFN-alpha showed decreased emotional and social function and increased distress. Five trials of newer therapies appeared to show improvements in emotional and social function. Descriptive studies suggest that patients with advanced, versus localized disease, had decreased emotional and social function and increased distress. Contributors to distress were largely unexplored, and no clear framework described coping/adjustment trajectories. Patients with advanced versus localized disease had more supportive care needs, particularly amount, quality, and timing of melanoma-related information, communication with and emotional support from clinicians. Limitations included: lack of theoretical underpinnings guiding study design; inconsistent measurement approaches; small sample sizes; non-representative sampling; and cross-sectional design. Quality trial evidence is needed to clarify the impact of treatment innovations for advanced melanoma on patients' psychosocial well-being. Survivorship research and subsequent translation of that knowledge into programs and services currently lags behind gains in the medical treatment of advanced melanoma, a troubling circumstance that requires immediate and focused

  7. ADVANCED UVEAL MELANOMA WITH SUBDURAL METASTASIS MIMICKING MENINGEOMA - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Predrag Kovačević

    2011-03-01

    Full Text Available Uveal melanoma is a rare malignancy. Its clinical course is highly agressive. At thetime of diagnosis, extraocular extension is present in most of the cases.We present a case of 69-year-old white man admitted for sharp orbital pain. Advanced uveal melanoma was diagnosed. We found black-colored tumor rotruding from the left eye and multiple cutaneous metastases on the scalp. CT scan revealed intracranial tumor mimicking meningeoma in the left parietal region. Lymhogenous metastases were not found and other hematogenous metastases were excluded. After biopsy of the eye tumor and excisional biopsy of one skin tumor, the uveal melanoma was diagnosed and the left orbital exenteration and extirpation of intracranial tumor were performed. The reconstruction was performed using galeacutaneous flap harvested from craniotomy flap. Postoperative course was uneventful and the patient was released from pain. He refused the additional oncological treatment. After four months, he died of liver metastatic disease.The uveal melanoma is highly aggressive malignancy and isolated subdural metastasis is quite rare. The reconstruction with transposed galeacutaneous flap is versatile and secure technique after orbital exenteration.

  8. Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

    OpenAIRE

    Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

    2018-01-01

    Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

  9. Nivolumab-Based Treatments for Advanced Melanoma

    Science.gov (United States)

    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.

  10. Humanistic burden of disease for patients with advanced melanoma in Canada.

    Science.gov (United States)

    Cheung, Winson Y; Bayliss, Martha S; White, Michelle K; Stroupe, Angela; Lovley, Andrew; King-Kallimanis, Bellinda L; Lasch, Kathryn

    2018-06-01

    Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach. Many patients' journeys began with the startling diagnosis of an invasive disease and a vastly shortened life expectancy. By the time they reached an advanced stage of melanoma, these patients' overall functioning and quality of life had been greatly diminished by this quickly progressing cancer. The impact was described in terms of physical pain and disability, emotional distress, diminished interactions with friends and family, and burden on caregivers. Our findings provide evidence of signs, symptoms, and functional impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and social) confirm and expand on those reported in the existing clinical literature. Primary care physicians should be better trained to identify melanomas early. Oncology care teams can improve on their current approaches for helping patients navigate treatment options, with information about ancillary services to mitigate disease impacts on HRQL, such as mental health and social supports, as well as employment or financial support services.

  11. Advances in Immunotherapy for Melanoma: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Carmen Rodríguez-Cerdeira

    2017-01-01

    Full Text Available Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

  12. A challenging case of ocular melanoma.

    Science.gov (United States)

    Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

    2015-01-01

    Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

  13. Ipilimumab in advanced melanoma: reports of long-lasting responses.

    Science.gov (United States)

    Farolfi, Alberto; Ridolfi, Laura; Guidoboni, Massimo; Nicoletti, Stefania Vittoria Luisa; Piciucchi, Sara; Valmorri, Linda; Costantini, Matteo; Scarpi, Emanuela; Amadori, Dino; Ridolfi, Ruggero

    2012-06-01

    Patients with metastatic melanoma have a poor prognosis; the results of chemotherapy remain unsatisfactory. Ipilimumab, an anticytotoxic T lymphocyte-associated antigen-4 antibody, has shown promising results in several clinical trials. In this report, advanced melanoma patients receiving ipilimumab were scored according to novel immune-related response criteria (irRC) in an attempt to capture additional response patterns and to avoid premature treatment cessation. Thirty-six heavily pretreated metastatic melanoma patients recieved ipilimumab within five international clinical trials at our Institution from May 2006 to August 2008. Disease progression was defined as an increase in tumor burden by at least 25% compared with the nadir, irrespective of any initial increase in baseline lesions or the appearance of new lesions. We report unusually long-lasting responses in patients treated with ipilimumab 10 mg/kg. An overall response was observed in six out of 30 patients (20%), a complete response in three (10%), and disease control in 11 (37%), which seemed to be of a long duration (median of 16 months; complete response 36+, 34+, and 41+ months). All irRC patterns seemed to be strongly associated with an improvement in overall survival. Interestingly, we found a correlation between the presence of a grade 3/4 immune-related adverse event and responses, time to progression, and overall survival. Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, supporting the need for further irRC validation.

  14. Rapid BRAF mutation tests in patients with advanced melanoma : Comparison of immunohistochemistry, Droplet Digital PCR, and the Idylla Mutation Platform

    NARCIS (Netherlands)

    Bisschop, Cornelis; Ter Elst, Arja; Bosman, Lisette J; Platteel, Inge; Jalving, Mathilde; van den Berg, Anke; Diepstra, Arjan; van Hemel, Bettien; Diercks, Gilles F H; Hospers, Geke A P; Schuuring, Ed

    BRAF mutational testing has become a common practice in the diagnostic process of patients with advanced melanoma. Although time-consuming, DNA sequencing techniques are the current gold standard for mutational testing. However, in certain clinical situations, a rapid test result is required. In

  15. Clinical utility of nivolumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Asmar R

    2016-02-01

    Full Text Available Ramsey Asmar,1 Jessica Yang,1 Richard D Carvajal1,2 1Department of Medicine, College of Physicians and Surgeons, 2Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA Abstract: Melanomas are highly immunogenic tumors that evade the immune system by exploiting innate checkpoint pathways, rendering effector T-cells anergic. The immunotherapeutic approach of checkpoint inhibition can restore and invigorate endogenous antitumor T-cell responses and has become an important treatment option for patients with advanced melanoma. The CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab have been shown to induce durable responses and improve overall survival in metastatic, refractory melanoma. Optimization and validation of pretreatment biomarkers to predict response to these agents is a crucial area of ongoing research. Combination immunotherapy has recently demonstrated superior response rates compared to monotherapy; further investigation is needed to refine combinatorial strategies. Keywords: nivolumab, immune checkpoint inhibitors, PD-1, melanoma

  16. Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Mélanie Saint-Jean

    2018-01-01

    Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

  17. Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

    Science.gov (United States)

    Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

    2017-11-01

    Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

  18. Non-invasive spectroscopic techniques in the diagnosis of non-melanoma skin cancer

    Science.gov (United States)

    Drakaki, E.; Sianoudis, IA; Zois, EN; Makropoulou, M.; Serafetinides, AA; Dessinioti, C.; Stefanaki, E.; Stratigos, AJ; Antoniou, C.; Katsambas, A.; Christofidou, E.

    2017-11-01

    The number of non-melanoma skin cancers is increasing worldwide and has become an important health and economic issue. Early detection and treatment of skin cancer can significantly improve patient outcome. Therefore there is an increase in the demand for proper management and effective non-invasive diagnostic modalities in order to avoid relapses or unnecessary treatments. Although the gold standard of diagnosis for non-melanoma skin cancers is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of non-melanoma skin cancers include high-definition optical coherence tomography, fluorescence spectroscopy, oblique incidence diffuse reflectance spectrometry among others spectroscopic techniques. Our findings establish how those spectrometric techniques can be used to more rapidly and easily diagnose skin cancer in an accurate and automated manner in the clinic.

  19. Patient and Oncology Nurse Preferences for the Treatment Options in Advanced Melanoma: A Discrete Choice Experiment.

    Science.gov (United States)

    Liu, Frank Xiaoqing; Witt, Edward A; Ebbinghaus, Scot; DiBonaventura Beyer, Grace; Basurto, Enrique; Joseph, Richard W

    2017-10-25

    Understanding the perceptions of patients and oncology nurses about the relative importance of benefits and risks associated with newer treatments of advanced melanoma can help to inform clinical decision-making. The aims of this study were to quantify and compare the views of patients and oncology nurses regarding the importance of attributes of treatments of advanced melanoma. A discrete choice experiment (DCE) was conducted in US-based oncology nurses and patients diagnosed with advanced melanoma. Patients and nurses were enlisted through online panels. In a series of scenarios, respondents had to choose between 2 hypothetical treatments, each with 7 attributes: mode of administration (MoA), dosing schedule (DS), median duration of therapy (DoT), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and grade 3 or 4 adverse events (AEs). Hierarchical Bayesian logistic regression models were used to estimate preference weights. A total of 200 patients with advanced melanoma and 150 oncology nurses participated. The relative importance estimates of attributes by patients and nurses, respectively, were as follows: OS, 33% and 28%; AEs, 29% and 26%; ORR, 25% and 27%; PFS, 12% and 15%; DS, 2% and 3%; DoT, 0% and 0%; and MoA, 0% and 0%. Both patients and oncology nurses valued OS, ORR, and AEs as the most important treatment attributes for advanced melanoma, followed by PFS, whereas DS, DoT, and MoA were given less value in their treatment decisions. Oncology nurses and patients have similar views on important treatment considerations for advanced melanoma, which can help build trust in shared decision-making.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  20. Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

    Czech Academy of Sciences Publication Activity Database

    Kupcová Skalníková, Helena; Čížková, Jana; Červenka, Jakub; Vodička, Petr

    2017-01-01

    Roč. 18, č. 12 (2017), č. článku 2697. E-ISSN 1422-0067 R&D Projects: GA ČR GA16-05534S; GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : cytokine * cancer * melanoma * secretome * proteomics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemical research methods Impact factor: 3.226, year: 2016

  1. Intensity-Modulated Radiotherapy Triggers Onset of Bullous Pemphigoid in a Patient with Advanced Melanoma Treated with Nivolumab

    Directory of Open Access Journals (Sweden)

    Kayo Tanita

    2018-02-01

    Full Text Available Since the efficacy of ipilimumab on nivolumab-resistant advanced melanoma is extremely low, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma is needed. Although several supportive therapies that enhance the antitumor immune response of anti-PD-1 antibodies have already been reported, unexpected immune-related adverse events were detected at the same time. In this report, we describe a patient with advanced melanoma treated with nivolumab followed by intensity-modulated radiotherapy, which might have triggered bullous pemphigoid (BP. Although several cases of BP developing in anti-PD-1 antibody-treated patients have already been reported, in this report, we shed light on the possible pathogenesis of BP developing in a patient treated with nivolumab through M2 macrophages.

  2. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  3. Melanoma during pregnancy

    DEFF Research Database (Denmark)

    de Haan, Jorine; Lok, Christianne A; de Groot, Christianne J M

    2017-01-01

    The management of melanoma during pregnancy is challenging as maternal benefits and fetal risks need to be balanced. Here, we present an overview of the incidence, the demographic and clinical characteristics and the treatment modalities used. After analysis of obstetric, fetal and maternal outcome......, recommendations for clinical practice are provided. From the 'International Network on Cancer, Infertility and Pregnancy' database, pregnant patients with melanoma were identified and analysed. Sixty pregnancies were eligible for analysis. Fifty percent of the patients presented with advanced melanoma during...... pregnancy (14 stage III and 16 stage IV), and 27% were diagnosed with recurrent melanoma. Surgery was the main therapeutic strategy during pregnancy. Only four patients with advanced melanoma were treated during pregnancy with systemic therapy (n=1) or radiotherapy (n=3). Premature delivery was observed...

  4. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  5. Monosomy 3 by FISH in uveal melanoma: variability in techniques and results.

    Science.gov (United States)

    Aronow, Mary; Sun, Yang; Saunthararajah, Yogen; Biscotti, Charles; Tubbs, Raymond; Triozzi, Pierre; Singh, Arun D

    2012-09-01

    Tumor monosomy 3 confers a poor prognosis in patients with uveal melanoma. We critically review the techniques used for fluorescence in situ hybridization (FISH) detection of monosomy 3 in order to assess variability in practice patterns and to explain differences in results. Significant variability that has likely affected reported results was found in tissue sampling methods, selection of FISH probes, number of cells counted, and the cut-off point used to determine monosomy 3 status. Clinical parameters and specific techniques employed to report FISH results should be specified so as to allow meta-analysis of published studies. FISH-based detection of monosomy 3 in uveal melanoma has not been performed in a standardized manner, which limits conclusions regarding its clinical utility. FISH is a widely available, versatile technology, and when performed optimally has the potential to be a valuable tool for determining the prognosis of uveal melanoma. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

  7. Confirming the timing of phase-based costing in oncology studies: a case example in advanced melanoma.

    Science.gov (United States)

    Atkins, Michael; Coutinho, Anna D; Nunna, Sasikiran; Gupte-Singh, Komal; Eaddy, Michael

    2018-02-01

    The utilization of healthcare services and costs among patients with cancer is often estimated by the phase of care: initial, interim, or terminal. Although their durations are often set arbitrarily, we sought to establish data-driven phases of care using joinpoint regression in an advanced melanoma population as a case example. A retrospective claims database study was conducted to assess the costs of advanced melanoma from distant metastasis diagnosis to death during January 2010-September 2014. Joinpoint regression analysis was applied to identify the best-fitting points, where statistically significant changes in the trend of average monthly costs occurred. To identify the initial phase, average monthly costs were modeled from metastasis diagnosis to death; and were modeled backward from death to metastasis diagnosis for the terminal phase. Points of monthly cost trend inflection denoted ending and starting points. The months between represented the interim phase. A total of 1,671 patients with advanced melanoma who died met the eligibility criteria. Initial phase was identified as the 5-month period starting with diagnosis of metastasis, after which there was a sharp, significant decline in monthly cost trend (monthly percent change [MPC] = -13.0%; 95% CI = -16.9% to -8.8%). Terminal phase was defined as the 5-month period before death (MPC = -14.0%; 95% CI = -17.6% to -10.2%). The claims-based algorithm may under-estimate patients due to misclassifications, and may over-estimate terminal phase costs because hospital and emergency visits were used as a death proxy. Also, recently approved therapies were not included, which may under-estimate advanced melanoma costs. In this advanced melanoma population, optimal duration of the initial and terminal phases of care was 5 months immediately after diagnosis of metastasis and before death, respectively. Joinpoint regression can be used to provide data-supported phase of cancer care durations, but

  8. Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle.

    Science.gov (United States)

    Gutman, Haim; Ben-Ami, Eytan; Shapira-Frommer, Roni; Schachter, Jacob

    2012-08-01

    Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this

  9. New developments in the management of advanced melanoma - role of pembrolizumab

    DEFF Research Database (Denmark)

    Improta, Giuseppina; Leone, Isabella; Donia, Marco

    2015-01-01

    Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed...... inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma....

  10. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2015-02-01

    Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.

  11. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

    DEFF Research Database (Denmark)

    Burgdorf, S K; Fischer, A; Claesson, M H

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.......Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...

  12. Melanoma risk perception and prevention behavior among African-Americans: the minority melanoma paradox

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    Goldenberg A

    2015-08-01

    Full Text Available Alina Goldenberg,1 Igor Vujic,2,3 Martina Sanlorenzo,2,4 Susana Ortiz-Urda2 1Department of Internal Medicine/Dermatology, University of California, San Diego, 2Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA; 3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; 4Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy 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. Keywords: acral, advanced, African-American, disparity, melanoma, survival

  13. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

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    Jinah Kim

    Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

  14. PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV

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    Diwakar Davar

    2015-01-01

    Full Text Available On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1 inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma. Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV, and/or human immunodeficiency virus (HIV infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials.

  15. Fulminant Diabetes in a Patient with Advanced Melanoma on Nivolumab

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    Nora Chokr

    2018-01-01

    Full Text Available Background. Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case. A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise. He was started on nivolumab and ipilimumab. After the third dose, he developed a generalized rash and was prescribed high-dose prednisone. Labs revealed potassium 9.5 mmol/L, sodium 127 mmol/L, bicarbonate 31 mmol, arterial blood pH 7.14, and beta-hydroxybutyrate 13.7 mmol/L. He was diagnosed with diabetic ketoacidosis. Hemoglobin A1C was 6.9%. C-peptide was undetectable (<0.1 ng/ml. Glutamic acid decarboxylase autoantibodies, zinc transporter 8 autoantibodies, insulin autoantibodies, islet antigen 2 autoantibodies, and islet cell antibodies were all negative. Conclusion. Anti-PD-1 immunotherapy is effective in cancers refractory to standard chemotherapy. These agents can precipitate autoimmune disorders. As the use of anti-PD-1 agents is expected to rise, physicians should be educated about the potential side effects. We recommend conducting routine blood glucose checks in patients on these agents.

  16. Biatrial Cardiac Metastases in a Patient with Uterine Cervix Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Caglayan Geredeli

    2015-01-01

    Full Text Available Primary malignant melanomas of uterine cervix are quite rarely seen neoplasms, and long-life prognosis of patients with this disease is poor. Immunohistochemical methods and exclusion of other primary melanoma sites are used to confirm the diagnosis. As with other melanomas, cervix malignant melanomas may also cause cardiac metastases. Cardiac metastases are among rarely seen but more commonly encountered cases, compared to primary cardiac tumors. Here, we present a case of biatrial cardiac metastases in a 73-year-old patient with uterine cervix malignant melanomas. The patient underwent echocardiography, cardiac magnetic resonance imaging, and computed tomography. Our report shows the importance of advanced diagnostic techniques, such as cardiac magnetic resonance, not only for the detection of cardiac masses, but for a better anatomic definition and tissue characterization. Although the cases of malignant melanomas leading to multiple cardiac metastasis were reported in literature, the metastatic concurrence of malignant melanomas in both right and left atriums is quite rarely encountered as metastatic malignant melanomas. Also, another intriguing point in our case is that the primary lesion of our case was stemmed from uterine cervix, but not skin.

  17. A linac-based stereotactic irradiation technique of uveal melanoma

    International Nuclear Information System (INIS)

    Dieckmann, Karin; Bogner, Joachim; Georg, Dietmar; Zehetmayer, Martin; Kren, Gerhard; Poetter, Richard

    2001-01-01

    Purpose: To describe a stereotactic irradiation technique for uveal melanomas performed at a linac, based on a non-invasive eye fixation and eye monitoring system. Methods: For eye immobilization a light source system is integrated in a standard stereotactic mask system in front of the healthy eye: During treatment preparation (computed tomography/magnetic resonance imaging) as well as for treatment delivery, patients are instructed to gaze at the fixation light source. A mini-video camera monitors the pupil center position of the diseased eye. For treatment planning and beam delivery standard stereotactic radiotherapy equipment is used. If the pupil center deviation from a predefined 'zero-position' exceeds 1 mm (for more than 2 s), treatment delivery is interrupted. Between 1996 and 1999 60 patients with uveal melanomas, where (i) tumor height exceeded 7 mm, or (ii) tumor height was more than 3 mm, and the central tumor distance to the optic disc and/or the macula was less than 3 mm, have been treated. A total dose of 60 or 70 Gy has been given in 5 fractions within 10 days. Results: The repositioning accuracy in the mask system is 0.47±0.36 mm in rostral-occipital direction, 0.75±0.52 mm laterally, and 1.12±0.96 mm in vertical direction. An eye movement analysis performed for 23 patients shows a pupil center deviation from the 'zero' position<1 mm in 91% of all cases investigated. In a theoretical analysis, pupil center deviations are correlated with GTV 'movements'. For a pupil center deviation of 1 mm (rotation of the globe of 5 degree sign ) the GTV is still encompassed by the 80% isodose in 94%. Conclusion: For treatments of uveal melanomas, linac-based stereotactic radiotherapy combined with a non-invasive eye immobilization and monitoring system represents a feasible, accurate and reproducible method. Besides considerable technical requirements, the complexity of the treatment technique demands an interdisciplinary team continuously dedicated to this

  18. Vaccines against advanced melanoma.

    Science.gov (United States)

    Blanchard, Tatiana; Srivastava, Pramod K; Duan, Fei

    2013-01-01

    Research shows that cancers are recognized by the immune system but that the immune recognition of tumors does not uniformly result in tumor rejection or regression. Quantitating the success or failure of the immune system in tumor elimination is difficult because we do not really know the total numbers of encounters of the immune system with the tumors. Regardless of that important issue, recognition of the tumor by the immune system implicitly contains the idea of the tumor antigen, which is what is actually recognized. We review the molecular identity of all forms of tumor antigens (antigens with specific mutations, cancer-testis antigens, differentiation antigens, over-expressed antigens) and discuss the use of these multiple forms of antigens in experimental immunotherapy of mouse and human melanoma. These efforts have been uniformly unsuccessful; however, the approaches that have not worked or have somewhat worked have been the source of many new insights into melanoma immunology. From a critical review of the various approaches to vaccine therapy we conclude that individual cancer-specific mutations are truly the only sources of cancer-specific antigens, and therefore, the most attractive targets for immunotherapy. Published by Elsevier Inc.

  19. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

    Science.gov (United States)

    Topalian, Suzanne L; Sznol, Mario; McDermott, David F; Kluger, Harriet M; Carvajal, Richard D; Sharfman, William H; Brahmer, Julie R; Lawrence, Donald P; Atkins, Michael B; Powderly, John D; Leming, Philip D; Lipson, Evan J; Puzanov, Igor; Smith, David C; Taube, Janis M; Wigginton, Jon M; Kollia, Georgia D; Gupta, Ashok; Pardoll, Drew M; Sosman, Jeffrey A; Hodi, F Stephen

    2014-04-01

    Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

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

    Directory of Open Access Journals (Sweden)

    Joanna Jaworek-Korjakowska

    2016-01-01

    Full Text Available 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.

  1. Safety, immunogenicity, and early evidence of antitumor response with the use of the vaccine formulation NeuGcGM3 / VSSPs in patients with advanced melanoma

    International Nuclear Information System (INIS)

    Osorio Rodríguez, Marta de la Caridad

    2014-01-01

    Introduction. Melanoma is now considered an epidemic around the world. Its high lethality, constitutes a serious problem despite the continuous pharmacological and technological advances. NeuGcGM3/VSSP is a vaccine formulation containing ganglioside NeuGcGM3 incorporated in the acting of Neisseria meningitidis. It may be a choice therapeutic given this ganglioside in primary melanoma expression and immunogenicity and safety demonstrated by this vaccine in advanced breast cancer. This study evaluated the safety, immunogenicity and the anti-tumor response in patients with advanced melanoma to manage it via IM or SC. Material and methods: The expression of ganglioside in primary melanomas and its metastases was identified by immunohistochemical methods with the AcM 14F7 (anti-NGCGM3). 2 clinical trials Phase Ib/IIa escalation of doses with NeuGcGM3 /VSSP were conducted in patients with melanoma Advanced IM and SC routes. Safety and anti-tumour response were evaluated with the CTC and RECIST criteria. The statistical analysis was performed with the SPSS statistical package. Results: NeuGcGM3 is expressed in primary tumors and the studied lymph nodes metastases. NeuGcGM3/VSSP was safely managed by the SC and IM, roads without limiting toxicity. Immunogenic with IgM and IgG isotype antibody response resulted in 75% patients. There was anti-tumoral response in 38.5% with increase in median SV mainly associated with anti-tumor response. The appearance of vitiligo and the response of antibodies against other not present in the vaccine formulation gangliosides may be considered a manifestation of immune restoration. Conclusions. NeuGcGM3/VSSP managed IM and SC in patients with advanced melanoma was safe, immunogenic and antitumor activity associated with overall survival advantage. (author)

  2. [Molecular and immunohistochemical diagnostics in melanoma].

    Science.gov (United States)

    Schilling, B; Griewank, K G

    2016-07-01

    To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

  3. Chimeric Monoclonal Antibody Cetuximab Targeting Epidermal Growth Factor-Receptor in Advanced Non-Melanoma Skin Cancer.

    Science.gov (United States)

    Wollina, Uwe; Tchernev, Georgi; Lotti, Torello

    2018-01-25

    Non-melanoma skin cancer (NMSC) is the most common malignancy in humans. Targeted therapy with monoclonal antibody cetuximab is an option in case of advanced tumor or metastasis. We present and update of the use of cetuximab in NMSC searching PUBMED 2011-2017. The monoclonal antibody cetuximab against epidermal growth factor receptor (EGFR) has been investigated for its use in NMSC during the years 2011 to 2017 by a PUBMED research using the following items: "Non-melanoma skin cancer AND cetuximab," "cutaneous squamous cell carcinoma AND cetuximab," and "basal cell carcinoma AND cetuximab", and "cetuximab AND skin toxicity". Available data were analyzed including case reports. Current evidence of cetuximab efficacy in NMSC was mainly obtained in cutaneous SCC and to a lesser extend in BCC. Response rates vary for neoadjuvant, adjuvant, mono- and combined therapy with cetuximab. Management of cutaneous toxicities is necessary. Guidelines are available. Cetuximab is an option for recurrent or advanced NMSC of the skin. It seems to be justified particularly in very high-risk tumors. There is a need for phase III trials.

  4. Contemporary Management of Early-Stage Melanoma: A Systematic Review.

    Science.gov (United States)

    Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

    2017-05-01

    The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

  5. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung

    2012-02-01

    Full Text Available Abstract Advanced malignant melanoma remains a challenging cancer. Over the past year, there have been 3 agents approved for treatment of melanoma by Food and Drug Administration. These include pegylated interferon alpha-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for treatment of unresectable or metastatic melanoma. This review will also update on the development of novel agents, including tyrosine kinase inhibitors and adoptive cellular therapy.

  6. Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

    Directory of Open Access Journals (Sweden)

    Ballardini Michela

    2006-08-01

    Full Text Available Abstract Background We present our experience of therapeutic vaccination using dendritic cells (DC pulsed with autologous tumor antigens in patients with advanced melanoma. Methods Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL or – homogenate (ATH and 50 μg/ml of keyhole limpet hemocyanin (KLH. The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC (range 4.5 – 82 × 106 and the remaining 13 intradermally with in vitro matured DC (mDC (range 1.2–26 × 106. Subcutaneous interleukin-2 (3 × 106 IU was administered from days 3 to 7 of each treatment cycle. Results Three of the 8 iDC patients obtained stabilizations (SD, each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months, 1 partial response (3 months, 2 mixed responses (6 and 12 months and 3 SD (9, 7+, and 3+ months. Overall responses (OR were observed in 4/21 (19% patients, or 4/13 (30.7% considering mDC treatment only. 10/21 (47.6% patients showed non progressive disease (NPD, with 7/13 (53.8% cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH test to ATL/ATH and/or KLH correlated with increased overall survival (OS. Median OS was 24 months (range 3 – 45 for the 10 DTH-positive (1 iDC and 9 mDC and 5 months (range 3–14 for the 11 DTH-negative patients (P in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75% and clinical outcome (70%. Conclusion Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

  7. Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients.

    Science.gov (United States)

    Ridolfi, Ruggero; Petrini, Massimiliano; Fiammenghi, Laura; Stefanelli, Monica; Ridolfi, Laura; Ballardini, Michela; Migliori, Giuseppe; Riccobon, Angela

    2006-08-16

    We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 microg/ml of autologous-tumor-lysate (ATL) or -homogenate (ATH) and 50 microg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC) (range 4.5-82 x 10(6)) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 x 10(6)). Subcutaneous interleukin-2 (3 x 10(6) IU) was administered from days 3 to 7 of each treatment cycle. Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SD (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3-45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival.

  8. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma

    NARCIS (Netherlands)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J. A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with

  9. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    NARCIS (Netherlands)

    Ribas, A.; Kefford, R.; Marshall, Martin; Punt, C.J.A.; Haanen, J.B.; Marmol, M.; Garbe, C.; Gogas, H.; Schachter, J.; Linette, G.; Lorigan, P.; Kendra, K.L.; Maio, M.; Trefzer, U.; Smylie, M.; McArthur, G.A.; Dreno, B.; Nathan, P.D.; Mackiewicz, J.; Kirkwood, J.M.; Gomez-Navarro, J.; Huang, B.; Pavlov, D.; Hauschild, A.

    2013-01-01

    PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients

  10. Successful Treatment of Nivolumab-Resistant Multiple In-Transit Melanomas with Ipilimumab and Topical Imiquimod

    Directory of Open Access Journals (Sweden)

    Taku Fujimura

    2018-01-01

    Full Text Available Simultaneous or sequential, planned administration of ipilimumab could significantly enhance the antitumor effects of nivolumab in advanced melanoma patients. On the other hand, the efficacy of ipilimumab for nivolumab-resistant advanced melanoma is extremely poor. Therefore, additional supportive therapy for anti-PD-1 antibody therapy-resistant advanced melanoma has been widely investigated. In this report, we describe a case of multiple in-transit melanomas developing in a nivolumab-resistant patient successfully treated with ipilimumab in combination with imiquimod. Our present case suggested a possible therapy for nivolumab-resistant multiple in-transit melanomas using ipilimumab in combination with topical imiquimod.

  11. First-line treatment of metastatic melanoma: role of nivolumab

    Directory of Open Access Journals (Sweden)

    Force J

    2017-02-01

    Full Text Available Jeremy Force,1 April KS Salama,1,2 1Division of Hematology/Oncology, Duke University Medical Center, Durham, NC, USA; 2Division of Medical Oncology, Duke University Medical Center, Durham, NC, USA Abstract: Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes. Keywords: PD-1, immunotherapy, pembrolizumab, PD-L1, resistance, checkpoint, BRAF

  12. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available 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.

  13. Phase III Randomized Clinical Trial Comparing Tremelimumab With Standard-of-Care Chemotherapy in Patients With Advanced Melanoma

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A.; Punt, Cornelis J.A.; Haanen, John B.; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L.; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A.; Dreno, Brigitte; Nathan, Paul D.; Mackiewicz, Jacek; Kirkwood, John M.; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-01-01

    Purpose In phase I/II trials, the cytotoxic T lymphocyte–associated antigen-4–blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients and Methods Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). Results In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. Conclusion This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma. PMID:23295794

  14. Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.

    Science.gov (United States)

    Ribas, Antoni; Kefford, Richard; Marshall, Margaret A; Punt, Cornelis J A; Haanen, John B; Marmol, Maribel; Garbe, Claus; Gogas, Helen; Schachter, Jacob; Linette, Gerald; Lorigan, Paul; Kendra, Kari L; Maio, Michele; Trefzer, Uwe; Smylie, Michael; McArthur, Grant A; Dreno, Brigitte; Nathan, Paul D; Mackiewicz, Jacek; Kirkwood, John M; Gomez-Navarro, Jesus; Huang, Bo; Pavlov, Dmitri; Hauschild, Axel

    2013-02-10

    In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy. Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine). In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor. This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.

  15. Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2001-06-01

    In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

  16. [Clinical and economic evaluation of the introduction of the combinazion trametinib + dabrafenib in the management of advanced melanoma in the Italian market

    Directory of Open Access Journals (Sweden)

    Lorenzo Pradelli

    2016-12-01

    Full Text Available Melanoma is the most aggressive type of all skin cancers. In Italy the incidence is increasing both in men and in women with 13,800 new cases expected in 2016. The advanced melanoma therapy has changed in recent years with the use of immunotherapy and targeted therapies. In particular, treatment with BRAF inhibitors in patients with advanced BRAF V600 mutated melanoma has shown high rates of rapid response and survival. Due to development of acquired resistance with disease progression the rapid response observed with BRAF inhibitor therapy is not long lasting. Combining a BRAF inhibitor with a MEK inhibitor may help to delay the development of resistance and to enhance the antitumor activities with a further increase in the response and survival rate. Trametinib, an inhibitor of MEK kinases, and dabrafenib, an inhibitor of BRAF kinase, have authorizations as monotherapies and in combination with each other for treating adults with unresectable or metastatic melanoma with BRAF V600 mutation. Purpose of this report is to describe the combination in terms of clinical efficacy, safety, and economic impact. In particular, a cost-effectiveness analysis and a budget impact analysis were performed in order to evaluate the combination versus monotherapy and the financial sustainability of trametinib + dabrafenib on the Italian market. [In Italian

  17. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Ocular melanoma: Detection using iodine-123-iodoamphetamine and SPECT imaging

    International Nuclear Information System (INIS)

    Dewey, S.H.; Leonard, J.C.

    1990-01-01

    Uptake of iodine-123-iodoamphetamine has been demonstrated in malignant melanoma using planar imaging techniques and has been used to detect an ocular melanoma at 12 hr postinjection. Using SPECT technique, an ocular melanoma is identified in a 64-yr-old male at 1 hr postinjection

  19. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  20. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  1. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    Pacheco, Ivan; Buzea, Cristina; Tron, Victor

    2011-11-01

    Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

  2. Melanoma genetics and the development of rational therapeutics.

    Science.gov (United States)

    Chudnovsky, Yakov; Khavari, Paul A; Adams, Amy E

    2005-04-01

    Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. No current treatments substantially enhance patient survival once metastasis has occurred. This review focuses on recent insights into melanoma genetics and new therapeutic approaches being developed based on these advances.

  3. Cross-cultural development of a quality-of-life measure for patients with melanoma : Phase 3 testing of an EORTC Melanoma Module

    NARCIS (Netherlands)

    Winstanley, J.B.; Young, T.; Boyle, F.M.; Bergenmar, M.; Bottomley, A.; Burmeister, .; Campana, L.G.; Garioch, J.J.; King, M.; Nikolic, D.V.; van de Poll-Franse, L.V.; Saw, R.; Thompson, J.F.; White, E.G.; European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group, The

    2015-01-01

    Melanoma is an increasingly common skin cancer worldwide. Recent treatment advances have provided patients and healthcare professionals (HCPs) with choices where quality of life (QoL) and toxicity are important considerations. A melanoma-specific QoL questionnaire is being developed in a

  4. Pediatric melanoma: incidence, treatment, and prognosis

    Directory of Open Access Journals (Sweden)

    Saiyed FK

    2017-04-01

    Full Text Available Faiez K Saiyed,1 Emma C Hamilton,1 Mary T Austin,1,2 1Department of Pediatric Surgery, McGovern Medical School, 2Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The purpose of this review is to outline recent advancements in diagnosis, treatment, and prevention of pediatric melanoma. Despite the recent decline in incidence, it continues to be the deadliest form of skin cancer in children and adolescents. Pediatric melanoma presents differently from adult melanoma; thus, the traditional asymmetry, border irregularity, color variegation, diameter >6 mm, and evolution (ABCDE criteria have been modified to include features unique to pediatric melanoma (amelanotic, bleeding/bump, color uniformity, de novo/any diameter, evolution of mole. Surgical and medical management of pediatric melanoma continues to derive guidelines from adult melanoma treatment. However, more drug trials are being conducted to determine the specific impact of drug combinations on pediatric patients. Alongside medical and surgical treatment, prevention is a central component of battling the incidence, as ultraviolet (UV-related mutations play a central role in the vast majority of pediatric melanoma cases. Aggressive prevention measures targeting sun safety and tanning bed usage have shown positive sun-safety behavior trends, as well as the potential to decrease melanomas that manifest later in life. As research into the field of pediatric melanoma continues to expand, a prevention paradigm needs to continue on a community-wide level. Keywords: melanoma, pediatric, adolescent, childhood

  5. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

  6. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  7. Melanoma survivorship: research opportunities.

    Science.gov (United States)

    Oliveria, Susan A; Hay, Jennifer L; Geller, Alan C; Heneghan, Maureen K; McCabe, Mary S; Halpern, Allan C

    2007-03-01

    The rising incidence and mortality rates of melanoma, the most fatal form of skin cancer, are among the greatest increases of all preventable cancers over the past decade. However, because of recent advances in early detection, secondary prevention efforts, and treatment, the number of melanoma survivors is increasing. Little research has been conducted on melanoma survivors and important opportunities exist for research in this understudied population. Here, we outline the important research opportunities related to the study of melanoma survivorship and summarize the paucity of literature currently available. A computerized literature search was performed of the MEDLINE database of the National Library of Medicine from 1966-2005. The scope of the search was limited to those studies published in English. The search was conducted using the following MeSH headings: melanoma, neoplasms, skin neoplasms, survival, and survival rate. The reference lists of relevant book chapters and review articles were further reviewed, and printed materials from recent scientific meetings addressing this topic were obtained. Several factors that affect melanoma survivors warrant further study, including: physiologic long-term effects; psychosocial, behavioral, and cognitive factors; demographic characteristics; surveillance practices; recurrences, secondary primaries, and other cancers; family members of survivors; and economic issues, access to health care/life insurance. Understanding recurrence and second primary cancer risk, psychosocial and cognitive characteristics, behaviors, surveillance patterns, economic sequelae, and family issues of melanoma survivors is important from a public health standpoint to promote the health and well-being of this cohort. Melanoma is an understudied cancer, and the incidence and mortality of this disease are increasing. Describing the long term burden of this cancer and identifying factors that contribute to them will facilitate efforts to develop

  8. Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.

    Science.gov (United States)

    Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; van Baren, Nicolas; Lucas, Sophie; Kvistborg, Pia; Thielemans, Kris; Neyns, Bart

    2016-04-20

    Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma. Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point. The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma. © 2016 by American Society of Clinical Oncology.

  9. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    International Nuclear Information System (INIS)

    Li Xiaosong; Hode, Tomas; Guerra, Maria C; Ferrel, Gabriela L; Nordquist, Robert E; Chen, Wei R

    2011-01-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  10. Precision Medicine and PET/Computed Tomography in Melanoma.

    Science.gov (United States)

    Mena, Esther; Sanli, Yasemin; Marcus, Charles; Subramaniam, Rathan M

    2017-10-01

    Recent advances in genomic profiling and sequencing of melanoma have provided new insights into the development of the basis for molecular biology to more accurately subgroup patients with melanoma. The development of novel mutation-targeted and immunomodulation therapy as a major component of precision oncology has revolutionized the management and outcome of patients with metastatic melanoma. PET imaging plays an important role in noninvasively assessing the tumor biological behavior, to guide individualized treatment and assess response to therapy. This review summarizes the recent genomic discoveries in melanoma in the era of targeted therapy and their implications for functional PET imaging. Published by Elsevier Inc.

  11. Surgical reconstruction with pedicle flap of advance after excision of facial melanoma in a dog - Case report

    Directory of Open Access Journals (Sweden)

    Bruna Bristot Colombo

    2016-06-01

    Full Text Available ABSTRACT. Colombo B.B., Kuci C.C., Gehrcke M.I., de Souza L.P., Colodel M.M., Gerber J., Salbego F.Z., de Moraes A.N. & Oleskovicz N. [Surgical reconstruction with pedicle flap of advance after excision of facial melanoma in a dog - Case report.] Reconstrução cirúrgica com retalho pediculado de avanço após exérese de melanoma cutâneo facial em um cão - Relato de caso. Revista Brasileira de Medicina Veterinária, 38(2:128-132, 2016. Programa de Pós- -Graduação em Ciência Animal, Universidade do Estado de Santa Catarina, Av. Luís de Camões, 2090, Conta Dinheiro, Lages, SC 88520-000, Brasil. E-mail: brucolombo@hotmail.com The reconstructive surgery has been growing in veterinary medicine, whether in reconstruction tissue caused by trauma or even when there is an extensive tumor resection. This report aims to discuss about a female dog, assisted at the Teaching Hospital of an Educational Institution, which had an ulcerated nodule in the lateral portion of nasal flow plan, with suggestive diagnosis of malignant melanoma, concluded through cytology and referred for surgery. After resection of the tumor, the incision of skin and subcutaneous divulsion for production pedicle flap of advance. After surgery, it was applied with a padded bandage and gauze sheath on the face of the animal. During both the post-operative immediate period and in the following days the retail tissue showed rosy and healthy, with no sign of necrosis or dehiscence. The animal was observed until the day 30 after surgery, where there was local hair growth and good aesthetic appearance, which leads to the conclusion that the pedicle flap advance was an appropriate choice in this case, solving the matter about the animal’s health and looking from the owner’s point of view.

  12. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    Science.gov (United States)

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  13. Real-world healthcare costs of ipilimumab in patients with advanced cutaneous melanoma in The Netherlands.

    Science.gov (United States)

    Franken, Margreet G; Leeneman, Brenda; Jochems, Anouk; Schouwenburg, Maartje G; Aarts, Maureen J B; van Akkooi, Alexander C J; van den Berkmortel, Franchette W P J; van den Eertwegh, Alfonsus J M; de Groot, Jan Willem B; van der Hoeven, Koos J M; Hospers, Geke A P; Kapiteijn, Ellen; Koornstra, Rutger; Kruit, Wim H J; Louwman, Marieke W J; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; Vreugdenhil, Gerard; Wouters, Michel W J M; van Zeijl, Michiel; Haanen, John B A G; Uyl-de Groot, Carin A

    2018-07-01

    There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to individual patient resource use. A total of 807 patients who were diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice. The mean (median) episode duration was 6.27 (4.61) months (computed from the start of ipilimumab until the start of a next treatment, death, or the last date of follow-up). The average total healthcare costs amounted to &OV0556;81 484, but varied widely (range: &OV0556;18 131-&OV0556;160 002). Ipilimumab was by far the most important cost driver (&OV0556;73 739). Other costs were related to hospital admissions (&OV0556;3323), hospital visits (&OV0556;1791), diagnostics and imaging (&OV0556;1505), radiotherapy (&OV0556;828), and surgery (&OV0556;297). Monthly costs for resource use other than ipilimumab were &OV0556;1997 (SD: &OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared with previously-treated patients (n=463; &OV0556;85 081 vs. &OV0556;78 811). Although patients with colitis (n=106) had higher costs for resource use other than ipilimumab (&OV0556;11 426) compared with patients with other types of immune-related adverse events (n=90; &OV0556;9850) and patients with no immune-related adverse event (n=611; &OV0556;6796), they had lower total costs (&OV0556;76 075 vs. &OV0556;87 882 and &OV0556;81 480, respectively). In conclusion, this nation-wide study provides valuable insights into the healthcare costs of advanced cutaneous melanoma patients who were treated with ipilimumab in clinical practice. Most of the costs were attributable to ipilimumab, but the costs and its distribution varied considerably across subgroups.

  14. Nivolumab in the treatment of malignant melanoma: review of the literature

    Directory of Open Access Journals (Sweden)

    Mashima E

    2015-08-01

    Full Text Available Emi Mashima, Akiha Inoue, Yumiko Sakuragi, Takashi Yamaguchi, Natsuko Sasaki, Yoko Hara, Daisuke Omoto, Shun Ohmori, Sanehito Haruyama, Yu Sawada, Manabu Yoshioka, Daisuke Nishio, Motonobu Nakamura Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. Keywords: monoclonal antibody, PD-1, PD-L1

  15. The Role of Regional Therapies for in-Transit Melanoma in the Era of Improved Systemic Options

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Emmanuel [Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Skitzki, Joseph, E-mail: joseph.skitzki@roswellpark.org [Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States); Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263 (United States)

    2015-07-01

    The incidence of melanoma has been increasing at a rapid rate, with 4%–11% of all melanoma recurrences presenting as in-transit disease. Treatments for in-transit melanoma of the extremity are varied and include surgical excision, lesional injection, regional techniques and systemic therapies. Excision to clear margins is preferred; however, in cases of widespread disease, this may not be practical. Historically, intralesional therapies were generally not curative and were often used for palliation or as adjuncts to other therapies, but recent advances in oncolytic viruses may change this paradigm. Radiation as a regional therapy can be quite locally toxic and is typically relegated to disease control and symptom relief in patients with limited treatment options. Regional therapies such as isolated limb perfusion and isolated limb infusion are older therapies, but offer the ability to treat bulky disease for curative intent with a high response rate. These techniques have their associated toxicities and can be technically challenging. Historically, systemic therapy with chemotherapies and biochemotherapies were relatively ineffective and highly toxic. With the advent of novel immunotherapeutic and targeted small molecule agents for the treatment of metastatic melanoma, the armamentarium against in-transit disease has expanded. Given the multitude of options, many different combinations and sequences of therapies can be offered to patients with in-transit extremity melanoma in the contemporary era. Reported response and survival rates of the varied treatments may offer valuable information regarding treatment decisions for patients with in-transit melanoma and provide rationale for these decisions.

  16. Advanced in-flight measurement techniques

    CERN Document Server

    Lawson, Nicholas; Jentink, Henk; Kompenhans, Jürgen

    2013-01-01

    The book presents a synopsis of the main results achieved during the 3 year EU-project "Advanced Inflight Measurement Techniques (AIM)" which applied advanced image based measurement techniques to industrial flight testing. The book is intended to be not only an overview on the AIM activities but also a guide on the application of advanced optical measurement techniques for future flight testing. Furthermore it is a useful guide for engineers in the field of experimental methods and flight testing who face the challenge of a future requirement for the development of highly accurate non-intrusive in-flight measurement techniques.

  17. Metastasis of Ciliary Body Melanoma to the Contralateral Eye: A Case Report and Review of Uveal Melanoma Literature

    Directory of Open Access Journals (Sweden)

    Nouritza M. Torossian

    2015-01-01

    Full Text Available Many types of cancers metastasize to the eye. However, uveal melanoma metastasizing to the contralateral choroid is very rare. We report the case of a 68-year-old man with history of treated uveal melanoma of the right eye that developed metastasis to the liver and the choroid of the left eye. Ten years earlier, he was diagnosed to have uveal melanoma of the right eye and was initially treated with plaque radiotherapy. Two years later, upon progression of the disease in the right eye he had enucleation of the eye. We describe the patient’s clinical history, the diagnosis of recurrent disease in the contralateral eye, therapy of the left eye, and systemic metastasis. In addition, we reviewed the published medical literature and described the recent advances in the management of uveal melanoma.

  18. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

    DEFF Research Database (Denmark)

    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  19. Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study.

    Science.gov (United States)

    Nakamura, Yasuhiro; Tanaka, Ryota; Asami, Yuri; Teramoto, Yukiko; Imamura, Taichi; Sato, Sayuri; Maruyama, Hiroshi; Fujisawa, Yasuhiro; Matsuya, Taisuke; Fujimoto, Manabu; Yamamoto, Akifumi

    2017-02-01

    Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P = 0.027). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95% confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047, respectively). At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit (P = 0.28). The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome. © 2016 Japanese Dermatological Association.

  20. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  1. Future perspectives in melanoma research

    Directory of Open Access Journals (Sweden)

    Paolo A. Ascierto

    2016-11-01

    Full Text Available Abstract The sixth “Melanoma Bridge Meeting” took place in Naples, Italy, December 1st–4th, 2015. The four sessions at this meeting were focused on: (1 molecular and immune advances; (2 combination therapies; (3 news in immunotherapy; and 4 tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS and overall survival (OS of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC, renal cell carcinoma (RCC, bladder cancer, and Hodgkin’s disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4 and the programmed cell death-1 (PD-1 and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.; adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs, chimeric

  2. Phase I study of GC1008 (fresolimumab: a human anti-transforming growth factor-beta (TGFβ monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    John C Morris

    Full Text Available In advanced cancers, transforming growth factor-beta (TGFβ promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks.GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.Clinicaltrials.gov NCT00356460.

  3. Proteomic Analysis of Laser Microdissected Melanoma Cells from Skin Organ Cultures

    Science.gov (United States)

    Hood, Brian L.; Grahovac, Jelena; Flint, Melanie S.; Sun, Mai; Charro, Nuno; Becker, Dorothea; Wells, Alan; Conrads, Thomas P

    2010-01-01

    Gaining insights into the molecular events that govern the progression from melanoma in situ to advanced melanoma, and understanding how the local microenvironment at the melanoma site influences this progression, are two clinically pivotal aspects that to date are largely unexplored. In an effort to identify key regulators of the crosstalk between melanoma cells and the melanoma-skin microenvironment, primary and metastatic human melanoma cells were seeded into skin organ cultures (SOCs), and grown for two weeks. Melanoma cells were recovered from SOCs by laser microdissection and whole-cell tryptic digests analyzed by nanoflow liquid chromatography-tandem mass spectrometry with an LTQ-Orbitrap. The differential protein abundances were calculated by spectral counting, the results of which provides evidence that cell-matrix and cell-adhesion molecules that are upregulated in the presence of these melanoma cells recapitulate proteomic data obtained from comparative analysis of human biopsies of invasive melanoma and a tissue sample of adjacent, non-involved skin. This concordance demonstrates the value of SOCs for conducting proteomic investigations of the melanoma microenvironment. PMID:20459140

  4. lncRNA H19 predicts poor prognosis in patients with melanoma and regulates cell growth, invasion, migration and epithelial–mesenchymal transition in melanoma cells

    Directory of Open Access Journals (Sweden)

    Shi G

    2018-06-01

    Full Text Available Gaofeng Shi,1,2 Hu Li,2 Fengshan Gao,2 Qian Tan1 1Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Plastic Surgery, the Affiliated Wuxi No 4 People’s Hospital of Jiangnan University, Wuxi, People’s Republic of China Introduction: Melanoma is a deadly malignancy and the poor prognosis of patients with advanced disease is relatively poor. Recent studies indicate that long non-coding RNAs are involved in the pathogenesis of malignant melanoma. This study aims to investigate the role of the long non-coding RNA H19 in melanoma and to explore the underlying molecular mechanisms. Materials and methods: The expression levels of H19 in clinical samples and melanoma cells were determined by quantitative real-time PCR. The cell growth and cell metastasis were assessed by Cell Counting Kit 8, cell invasion and wound healing assays. Cell apoptosis and cell cycle were determined by flow cytometry. Protein levels were determined by Western blotting assay. Results: H19 was highly expressed in melanoma tissues compared to normal adjacent skin tissues, and the tissue expression level of H19 from melanoma patients with metastasis was significantly higher than that from patients without distant metastasis. In addition, the high expression of H19 in melanoma tissues was associated with advanced tumor invasion and TNM stage, distal metastasis, lymph node metastasis and shorter overall survival in patients with melanoma. The in vitro functional assays showed that knockdown of H19 inhibited cell growth, invasion and migration and also induced cell apoptosis as well as G0/G1 arrest in melanoma cells. Further quantitative real-time PCR and Western blot experiments showed that knockdown of H19 differentially regulated the epithelial–mesenchymal transition (EMT-related gene expressions and reversed EMT in melanoma cell lines. Knockdown of H19 suppressed in vivo tumor growth and modulated the

  5. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

    NARCIS (Netherlands)

    Weber, J.; Mandala, M.; Vecchio, M.; Gogas, H.J.; Arance, A.M.; Cowey, C.L.; Dalle, S.; Schenker, M.; Chiarion-Sileni, V.; Marquez-Rodas, I.; Grob, J.J.; Butler, M.O.; Middleton, M.R.; Maio, M.; Atkinson, V.; Queirolo, P.; Gonzalez, R.; Kudchadkar, R.R.; Smylie, M.; Meyer, N.; Mortier, L.; Atkins, M.B.; Long, G.V.; Bhatia, S.; Lebbe, C.; Rutkowski, P.; Yokota, K.; Yamazaki, N.; Kim, T.M.; Pril, V. de; Sabater, J.; Qureshi, A.; Larkin, J.; Ascierto, P.A.; Koornstra, R.H.; et al.,

    2017-01-01

    BACKGROUND: Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher

  6. Principles of modern radar advanced techniques

    CERN Document Server

    Melvin, William

    2012-01-01

    Principles of Modern Radar: Advanced Techniques is a professional reference for practicing engineers that provides a stepping stone to advanced practice with in-depth discussions of the most commonly used advanced techniques for radar design. It will also serve advanced radar academic and training courses with a complete set of problems for students as well as solutions for instructors.

  7. Review of advanced imaging techniques

    Directory of Open Access Journals (Sweden)

    Yu Chen

    2012-01-01

    Full Text Available Pathology informatics encompasses digital imaging and related applications. Several specialized microscopy techniques have emerged which permit the acquisition of digital images ("optical biopsies" at high resolution. Coupled with fiber-optic and micro-optic components, some of these imaging techniques (e.g., optical coherence tomography are now integrated with a wide range of imaging devices such as endoscopes, laparoscopes, catheters, and needles that enable imaging inside the body. These advanced imaging modalities have exciting diagnostic potential and introduce new opportunities in pathology. Therefore, it is important that pathology informaticists understand these advanced imaging techniques and the impact they have on pathology. This paper reviews several recently developed microscopic techniques, including diffraction-limited methods (e.g., confocal microscopy, 2-photon microscopy, 4Pi microscopy, and spatially modulated illumination microscopy and subdiffraction techniques (e.g., photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy. This article serves as a primer for pathology informaticists, highlighting the fundamentals and applications of advanced optical imaging techniques.

  8. Seven Non-melanoma Features to Rule Out Facial Melanoma

    Directory of Open Access Journals (Sweden)

    Philipp Tschandl

    2017-08-01

    Full Text Available Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p < 0.001. Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8% and seborrhoeic keratosis (74.3% and lower for actinic keratosis (61.4% and lichenoid keratosis (25.6%. Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

  9. The patterns of melanoma presentation in Rijeka region.

    Science.gov (United States)

    Pavlović-Ružić, Ira; Jonjić, Nives; Zamolo, Gordana; Zuvić-Butorac, Marta; Katunarić, Miljenko; Pečanić, Sanja

    2013-01-01

    There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people.

  10. Clinical significance of the molecular detection of melanoma cells circulating in the peripheral blood in melanoma patients.

    Science.gov (United States)

    Konstantopoulos, K; Psatha, M; Kalotychou, V; Frangia, N; Ioannovits, I; Meletis, I; Loukopoulos, D

    2001-06-01

    Blood circulating melanoma cells may be important for the spread of the disease. The current methods are not sensitive in detecting micro metastases. Tyrosinase mRNA can be detected in peripheral blood by a molecular test. As tyrosinase is expressed only in melanocytes and melanocytes normally do not circulate in the blood, the test may prove reliable in detecting circulating melanoma cells. we used a reverse-transcription polymerase chain reaction (RT-PCR) detecting tyrosinase mRNA in the blood. A prospective investigation in melanoma patients undergoing surgery was conducted; follow-up duration was 12 months. University Department Laboratory and Melanoma Clinic of a Tertiary Hospital. a total of 27 Greek patients with a diagnosis of malignant melanoma at different stages of the disease; 12 months follow-up after surgery. Samples form 12 healthy volunteers and 13 patients with chronic myelogenous leukemia served as controls. none. none. We detected mRNA tyrosinase in the peripheral blood in 16 out of 27 melanoma patients studied. No tyrosinase mRNA was detected in any of the 25 samples from the controls. Two of the 16 positive cases developed a metastasis within the next 12 months following testing. The other 14 positive cases remain metastasis free for this period, as also did the test negative cases. Detection of blood circulating melanoma cells by a RT-PCR technique, may be helpful in defining melanoma patients who are at risk for the spread of the disease.

  11. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    Hook, R.R.; Berkelhammer, J.; Hamby, C.V.

    1986-01-01

    Sinclair(S-1) miniature swine spontaneously develop melanomas which have many biologic and histologic features in common with human superficial spreading melanoma. Host control of this neoplasm was indicated by the high incidence of spontaneous regression, a decrease in tumor development with age and a decrease in progressive growth of the tumor as age of tumor development increases. Immunologic mechanisms were implicated in host control by histologic observation of a mononuclear inflammatory infiltration of tumors which lead to depigmentation and fibrosis. In vitro immunologic studies revealed that leukocytes from melanoma swine were sensitized specifically to a tumor associated antigen like substance present in extracts of cutaneous melanomas and cultured swine melanoma cells and that melanoma swine leukocytes were cytotoxic for swine melanoma cells. Furthermore, these studies suggested the existence of a common cross reactive, melanoma associated antigen shared by human and swine melanomas. Antigenic analyses of swine melanomas with mouse monoclonal antibodies developed to a single swine melanoma cell culture and with rabbit antisera developed to pooled extracts of cutaneous melanomas demonstrated the presence of tumor associated antigens in swine melanoma cell culture and cutaneous melanomas. The failure of mouse monoclonal antibodies to detect antigens in cutaneous melanoma extracts and the failure of rabbit antisera to detect antigens in melanoma cell culture extracts suggested a differential in antigen expression between swine melanoma cells grown in vitro and in vivo

  12. Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Rosie [School of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Olson, Adam [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Singh, Bhavana [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Thomas, Samantha; Wolf, Steven [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Bhavsar, Nrupen A. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Hanks, Brent A. [Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, Joseph K. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Salama, April K.S., E-mail: april.salama@duke.edu [Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2016-09-01

    Purpose: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. Methods and Materials: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. Results: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non–immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non–statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. Conclusions: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

  13. Major amputation for intractable extremity melanoma after failure of isolated limb perfusion

    NARCIS (Netherlands)

    Kapma, M. R.; Vrouenraets, B. C.; Nieweg, O. E.; van Geel, A. N.; Noorda, E. M.; Eggermont, A. M. M.; Kroon, B. B. R.

    2005-01-01

    AIM: The aim of this study was to analyse indications and results of amputation for intractable extremity melanoma after failure of isolated limb perfusion (ILP). METHODS: Between 1978 and 2001, 451 patients with loco-regional advanced extremity melanoma underwent 505 ILPs. Amputation of the

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

    Science.gov (United States)

    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.

  15. Malignant melanoma of the oral cavity: Report of two cases

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2014-01-01

    Full Text Available Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female.

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

    Science.gov (United States)

    2018-05-15

    Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  17. Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

    Science.gov (United States)

    Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

    2017-12-01

    Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

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

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → 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-γ and TGF-β 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    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.

  20. Ocular Melanoma

    Science.gov (United States)

    ... is Ocular Melanoma? Leer en Español: ¿Qué es el melanoma ocular? Written By: Daniel Porter Reviewed By: Robert H Janigian Jr MD Sep. 01, 2017 Ocular melanoma (melanoma in or around the eye) is a type of cancer that develops in the cells that produce pigment. ...

  1. Advanced Techniques in Biophysics

    CERN Document Server

    Arrondo, José Luis R

    2006-01-01

    Technical advancements are basic elements in our life. In biophysical studies, new applications and improvements in well-established techniques are being implemented every day. This book deals with advancements produced not only from a technical point of view, but also from new approaches that are being taken in the study of biophysical samples, such as nanotechniques or single-cell measurements. This book constitutes a privileged observatory for reviewing novel applications of biophysical techniques that can help the reader enter an area where the technology is progressing quickly and where a comprehensive explanation is not always to be found.

  2. Primary Malignant Melanoma of the Esophagus

    OpenAIRE

    Oya Yonal; Duygu Ibrisim; Yıldıran Songur; Yılmaz Cakaloglu; Koray Tuncer; Hale Kırımlıoglu; Sadakat Ozdil

    2013-01-01

    Primary malignant melanoma of the esophagus (PMME) comprises only 0.1?0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ...

  3. Communication about melanoma and risk reduction after melanoma diagnosis.

    Science.gov (United States)

    Rodríguez, Vivian M; Berwick, Marianne; Hay, Jennifer L

    2017-12-01

    Melanoma patients are advised to perform regular risk-reduction practices, including sun protection as well as skin self-examinations (SSEs) and physician-led examinations. Melanoma-specific communication regarding family risk and screening may promote such behaviors. To this end, associations between patients' melanoma-specific communication and risk reduction were examined. Melanoma patients (N = 169) drawn from a population-based cancer registry reported their current risk-reduction practices, perceived risk of future melanoma, and communication with physicians and relatives about melanoma risk and screening. Patients were, on average, 56 years old and 6.7 years' post diagnosis; 51% were male, 93% reported "fair/very fair" skin color, 75% completed at least some college, and 22% reported a family history of melanoma. Patients reported varying levels of regular (always/nearly always) sun protection: sunscreen use (79%), shade seeking (60%), hat use (54%), and long-sleeve shirt use (30%). Only 28% performed thorough SSE regularly, whereas 92% reported undergoing physician-led skin examinations within the past year. Participants who were female, younger, and had a higher perceived risk of future melanoma were more likely to report past communication. In adjusted analyses, communication remained uniquely associated with increased sunscreen use and SSE. Encouraging melanoma patients to have a more active role in discussions concerning melanoma risk and screening with relatives and physicians alike may be a useful strategy to promote 2 key risk-reduction practices post melanoma diagnosis and treatment. Future research is needed to identify additional strategies to improve comprehensive risk reduction in long-term melanoma patients. Copyright © 2016 John Wiley & Sons, Ltd.

  4. A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

    Directory of Open Access Journals (Sweden)

    Clemens Krepler

    2017-11-01

    Full Text Available Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX. Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  6. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  7. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): Novel gene therapeutic for metastatic melanoma

    International Nuclear Information System (INIS)

    Fisher, Paul B.; Sarkar, Devanand; Lebedeva, Irina V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su Zaozhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

    2007-01-01

    A potentially less toxic approach for cancer therapy comprises induction of tumor cells to lose growth potential irreversibly and terminally differentiate. Combining this scheme termed 'differentiation therapy of cancer' with subtraction hybridization to human melanoma cells resulted in the cloning of melanoma differentiation associated (mda) genes displaying elevated expression as a consequence of induction of terminal differentiation. One originally novel gene, mda-7, was found to display elevated expression in normal melanocytes and nevi with progressive loss of expression as a consequence of melanoma development and progression to metastasis. Based on structure, biochemical properties and chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a member of the expanding IL-10 family of cytokines. In vitro cell culture and in vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell death (apoptosis) in multiple human cancers (including melanomas), without harming normal cells, and promotes profound anti-tumor activity in nude mice containing human tumor xenografts. Based on these remarkable properties, a Phase I clinical trial was conducted to test the safety of administration of mda-7/IL-24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and to promote significant clinical activity, particularly in the context of patients with metastatic melanoma. These results provide an impetus for further clinical studies and document a central paradigm of cancer therapy, namely translation of basic science from the 'bench to the bedside.'

  8. GPNMB expression in uveal melanoma: a potential for targeted therapy.

    Science.gov (United States)

    Williams, Michelle D; Esmaeli, Bita; Soheili, Aydin; Simantov, Ronit; Gombos, Dan S; Bedikian, Agop Y; Hwu, Patrick

    2010-06-01

    Uveal melanoma is an aggressive disease without effective adjuvant therapy for metastases. Despite genomic differences between cutaneous and uveal melanomas, therapies based on shared biological factors could be effective against both tumor types. High expression of glycoprotein-NMB (GPNMB) in cutaneous melanomas led to the development of CDX-011 (glembatumumab vedotin), a fully human monoclonal antibody against the extracellular domain of GPNMB conjugated to the cytotoxic microtubule toxin monomethylauristatin E. Ongoing phase II trials suggest that CDX-011 has activity against advanced cutaneous melanomas. To determine the potential role of CDX-011 in uveal melanomas, we studied their GPNMB expression. Paraffin-embedded tissues from 22 uveal melanomas treated by enucleation from 2004-2007 at one institution were evaluated immunohistochemically for expression of GPNMB using biotinylated CDX-011 (unconjugated) antibody. Melanoma cells were evaluated for percentage and intensity of expression. Spectral imaging was used in one case with high melanin content. Clinical data were reviewed. Twelve women and 10 men with a median age of 58.7 years (range: 28-83 years) were included. Eighteen of 21 tumors evaluated immunohistochemically (85.7%) expressed GPNMB in 10-90% of tumor cells with variable intensity (5 tumors, 1+; 11, 2+; and 2, 3+). Eleven of 18 tumors (61.1%) expressed GPNMB in >or=50% of cells. Spectral imaging showed diffuse CDX-011 (unconjugated) reactivity in the remaining case. Uveal melanoma, like cutaneous melanoma, commonly expresses GPNMB. Ongoing clinical trials of CDX-011 should be extended to patients with metastatic uveal melanoma to determine potential efficacy in this subset of patients with melanoma.

  9. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  10. Racial and ethnic variations in incidence and survival of cutaneous melanoma in the United States, 1999-2006.

    Science.gov (United States)

    Wu, Xiao-Cheng; Eide, Melody J; King, Jessica; Saraiya, Mona; Huang, Youjie; Wiggins, Charles; Barnholtz-Sloan, Jill S; Martin, Nicolle; Cokkinides, Vilma; Miller, Jacqueline; Patel, Pragna; Ekwueme, Donatus U; Kim, Julian

    2011-11-01

    Most melanoma studies use data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program or individual cancer registries. Small numbers of melanoma cases have limited in-depth analyses for all racial and ethnic groups. We sought to describe racial and ethnic variations in melanoma incidence and survival. Incidence for invasive melanoma and 5-year melanoma-specific survival were calculated for whites, blacks, American Indians/Alaskan Natives, Asians/Pacific Islanders (API), and Hispanics using data from 38 population-based cancer registries. Incidence rates of melanoma were significantly higher for females than males among whites and Hispanics under 50 years of age and APIs under 40 years of age. White and black patients were older (median age: 59-63 years) compared with Hispanics, American Indians/Alaskan Natives, and API (median age: 52-56 years). The most common histologic type was acral lentiginous melanoma among blacks and superficial spreading melanoma among all other racial and ethnic groups. Hispanics had the highest incidence rate of acral lentiginous melanoma, significantly higher than whites and API. Nonwhites were more likely to have advanced and thicker melanomas at diagnosis and lower melanoma-specific survival compared with whites. Over 50% of melanoma cases did not have specified histology. The numbers of nonwhite patients were still relatively small despite broad population coverage (67% of United States). Racial and ethnic differences in age at melanoma diagnosis, anatomic sites, and histologic types suggest variations in etiologic pathways. The high percentages of advanced and thicker melanomas among nonwhites highlight the need to improve melanoma awareness for all race and ethnicity in the United States. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  11. From dysplastic nevus to melanoma: functional proteomic approach for the identification of bio markers

    International Nuclear Information System (INIS)

    De Pol, A.

    2009-01-01

    The project ultimately aims to identify bio markers from serum or other biological fluids helpful for early diagnosis of melanoma. Parametric analysis combined with advanced skin imaging technology, such as con focal microscopy, is directed to the identification of different types of benign melanocyte lesions, as well as to the characterization of different melanomas and dysplastic nevi, in order to understand different tumour progression behaviours and to identify possible melanoma precursors

  12. Does Melanoma Begin in a Melanocyte Stem Cell

    International Nuclear Information System (INIS)

    Hoerter, J. D.; Bradley, P.; Casillas, A.; Chambers, D.; Weiswasser, B.; Clements, L.; Gilbert, S.; Jiao, A.

    2012-01-01

    What is the cellular origin of melanoma? What role do melanocyte stem cells (MSC) and other melanocyte precursors play in the development of melanoma? Are MSCs and other latent melanocyte precursors more susceptible to solar radiation? These and many other questions can be very effectively addressed using the zebra fish model. Zebra fish have a robust regenerative capability, permitting the study of how MSCs are regulated and recruited at specific times and places to generate the pigment pattern following fin amputation or melanocyte ablation. They can be used to determine the effects of environmental radiation on the proliferation, survival, repair, and differentiation of MSCs. Our lab is using zebra fish to investigate how UVA- (320-400nm) and UVB- (290-320nm) induced damage to MSCs may contribute to the development of melanoma. A review is given of MSCs in zebrafish as well as experimental techniques and drugs for manipulating MSC populations. These techniques can be used to design experiments to help answer many questions regarding the role of MSCs or melanocyte precursors in the formation of melanoma stem cells and tumors following exposure to UVA/UVB radiation.

  13. Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7 th2010"

    Directory of Open Access Journals (Sweden)

    Maio Michele

    2011-03-01

    Full Text Available Abstract Progress in understanding the molecular basis of melanoma has made possible the identification of molecular targets with important implications in clinical practice. In fact, new therapeutic approaches are emerging from basic science and it will be important to implement their rapid translation into clinical practice by active clinical investigation. The first meeting of Melanoma Research: a bridge Naples-USA, organized by Paolo A. Ascierto (INT, Naples, Italy and Francesco Marincola (NIH, Bethesda, USA took place in Naples, on 6-7 December 2010. This international congress gathered more than 30 international and Italian faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive discussion across Institutions belonging to Government, Academy and Pharmaceutical Industry, in order to stimulate new approaches in basic, translational and clinical research. Four topics of discussion were identified: New pathways in Melanoma, Biomarkers, Clinical Trials and New Molecules and Strategies.

  14. Sentinel node biopsy for melanoma: a study of 241 patients

    DEFF Research Database (Denmark)

    Chakera, Annette Hougaard; Drzewiecki, Krzysztof Tadeusz; Jakobsen, Annika Loft

    2004-01-01

    The aim of this study was to evaluate the sentinel node biopsy (SNB) technique for melanoma using both radiocolloid and blue dye in 241 clinically N0 patients with melanomas >1.0 mm, or thinner lesions exhibiting regression/ulceration. We showed that an increase in injected radioactivity increased...

  15. Intratumor and Intertumor Heterogeneity in Melanoma

    Directory of Open Access Journals (Sweden)

    Tomasz M. Grzywa

    2017-12-01

    Full Text Available Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

  16. Impact of MAPK Pathway Activation in BRAFV600 Melanoma on T Cell and Dendritic Cell Function

    Directory of Open Access Journals (Sweden)

    Patrick A. Ott

    2013-10-01

    Full Text Available Constitutive upregulation of the MAPK pathway by a BRAFV600 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 BRAFV600 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. BRAFV600E 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.

  17. Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

    International Nuclear Information System (INIS)

    Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

    2011-01-01

    Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

  18. Dermoscopic appearance of an amelanotic mucosal melanoma

    Science.gov (United States)

    Blum, Andreas; Beck-Zoul, Ulrike; Held, Laura; Haase, Sylvie

    2016-01-01

    Background Hypomelanotic or amelanotic melanomas are challenging to identify, especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal melanomas have been reported to be structureless zones with the presence of blue, gray, or white colors. Case A female in her seventies noted a new lesion on the inside of her right labia that first appeared two months prior. Her past medical history was significant for rheumatoid arthritis requiring ongoing treatment with methotrexate for 20 years and adalimumab for 10 years. After no response to two weeks of local treatment for suspected herpes simplex infection, her gynecologist performed a skin biopsy. Based on the histopathological diagnosis of an amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to dermatology for further assessment. Polarized dermoscopy revealed a distinct asymmetric, sharply demarcated homogenous white papule (4 × 5 mm) as well as polymorphous vessels. Conclusion Dermoscopy may aid in the diagnosis of amelanotic mucosal melanomas. Our case revealed a structureless white area and polymorphous vessels. Additional clues to the diagnosis were the advanced age of the patient and the clinical presentation of a new lesion. PMID:27867742

  19. Pregnancy and melanoma.

    Science.gov (United States)

    Driscoll, Marcia S; Martires, Kathryn; Bieber, Amy Kalowitz; Pomeranz, Miriam Keltz; Grant-Kels, Jane M; Stein, Jennifer A

    2016-10-01

    Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. FUTURE PERSPECTIVES IN MELANOMA RESEARCH. Meeting report from the “Melanoma Research: a bridge from Naples to the World. Napoli, December 5th–6 th2011”

    Directory of Open Access Journals (Sweden)

    Ascierto Paolo A

    2012-07-01

    Full Text Available Abstract After more than 30 years, landmark progress has been made in the treatment of cancer, and melanoma in particular, with the success of new molecules such as ipilimumab, vemurafenib and active specific immunization. After the first congress in December 2010, the second edition of “Melanoma Research: a bridge from Naples to the World” meeting, organized by Paolo A. Ascierto (INT, Naples, Italy, Francesco M. Marincola (NIH, Bethesda, USA, and Nicola Mozzillo (INT, Naples, Italy took place in Naples, on 5–6 December 2011. We have identified four new topics of discussion: Innovative Approaches in Prevention, Diagnosis and Surgical Treatment, New Pathways and Targets in Melanoma: An Update about Immunotherapy, and Combination Strategies. This international congress gathered more than 30 international faculty members and was focused on recent advances in melanoma molecular biology, immunology and therapy, and created an interactive atmosphere which stimulated discussion of new approaches and strategies in the field of melanoma.

  1. Diagnosis of Malignant Melanoma of Skin Cancer Types

    Directory of Open Access Journals (Sweden)

    Abbas Hassin Alasadi

    2017-08-01

    Full Text Available Malignant melanoma is a kind of skin cancer that begins in melanocytes. It can influence on the skin only, or it may expand to the bones and organs. It is less common, but more serious and aggressive than other types of skin cancer. Malignant Melanoma can happen anywhere on the skin, but it is widespread in certain locations such as the legs in women, the back and chest in men, the face, the neck, mouth, eyes, and genitals. In this paper, a proposed algorithm is designed for diagnosing malignant melanoma types by using digital image processing techniques. The algorithm consists of four steps: preprocessing, separation, features extraction, and diagnosis. A neural network (NN used to diagnosis malignant melanoma types. The total accuracy of the neural network was 100% for training and 93% for testing. The evaluation of the algorithm is done by using sensitivity, specificity, and accuracy. The sensitivity of NN in diagnosing malignant melanoma types was 95.6%, while the specificity was 92.2% and the accuracy was 93.9%. The experimental results are acceptable.

  2. GPU PRO 3 Advanced rendering techniques

    CERN Document Server

    Engel, Wolfgang

    2012-01-01

    GPU Pro3, the third volume in the GPU Pro book series, offers practical tips and techniques for creating real-time graphics that are useful to beginners and seasoned game and graphics programmers alike. Section editors Wolfgang Engel, Christopher Oat, Carsten Dachsbacher, Wessam Bahnassi, and Sebastien St-Laurent have once again brought together a high-quality collection of cutting-edge techniques for advanced GPU programming. With contributions by more than 50 experts, GPU Pro3: Advanced Rendering Techniques covers battle-tested tips and tricks for creating interesting geometry, realistic sha

  3. Intratumor and Intertumor Heterogeneity in Melanoma.

    Science.gov (United States)

    Grzywa, Tomasz M; Paskal, Wiktor; Włodarski, Paweł K

    2017-12-01

    Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Classical and molecular genetics of malignant melanoma and dysplastic naevi

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

    The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

  5. New diagnostics for melanoma detection: from artificial intelligence to RNA microarrays.

    Science.gov (United States)

    Ahlgrimm-Siess, Verena; Laimer, Martin; Arzberger, Edith; Hofmann-Wellenhof, Rainer

    2012-07-01

    Early detection of melanoma remains crucial to ensuring a favorable prognosis. Dermoscopy and total body photography are well-established noninvasive aids that increase the diagnostic accuracy of dermatologists in their daily routine, beyond that of a naked-eye examination. New noninvasive diagnostic techniques, such as reflectance confocal microscopy, multispectral digital imaging and RNA microarrays, are currently being investigated to determine their utility for melanoma detection. This review presents emerging technologies for noninvasive melanoma diagnosis, and discusses their advantages and limitations.

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

    Directory of Open Access Journals (Sweden)

    Voss RK

    2015-11-01

    Full Text Available Rachel K Voss,1 Tessa N Woods,1 Kate D Cromwell,1 Kelly C Nelson,2 Janice N Cormier1 1Department of Surgical Oncology, 2Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: 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

  7. Impact of {sup 18}F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis

    Energy Technology Data Exchange (ETDEWEB)

    Forschner, Andrea; Keim, Ulrike; Eigentler, Thomas Kurt; Garbe, Claus [Eberhard-Karls-University Tuebingen, Department of Dermatology, Tuebingen (Germany); Olthof, Susann-Cathrin; Gueckel, Brigitte; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Martus, Peter [Eberhard-Karls-University Tuebingen, Department of Clinical Epidemiology and Applied Biostatistics, Tuebingen (Germany); Vach, Werner [University Freiburg, Institute of Medical Biometry and Statistics, Freiburg (Germany); Fougere, Christian la [Eberhard-Karls-University Tuebingen, Department of Nuclear Medicine and Clinical Molecular Imaging, Tuebingen (Germany)

    2017-08-15

    To evaluate the influence of {sup 18}F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT. Management changes after PET/CT were classified as major and minor changes. A subgroup of 107 patients (stage I, N = 5; stage II, N = 3; stage III, N = 42; stage IV, N = 57) was planned for complete metastasectomy initially, based on conventional imaging. Management changes and outcome were evaluated by linkage with the information obtained from patients' medical records. In 28 of 107 patients (26%), the surgical treatment plan remained unchanged after PET/CT. In 24 patients (22%), minor changes were performed, such as enlargement or reduction of the surgical field. In 55 patients (51%, 95% CI 42%-61%) major changes of the intended treatment plan occurred; of those, 20 patients (19%) were classified to be tumor-free with PET/CT, 32 patients (30%) were found to have multiple previously unrecognized metastases and had to be treated by systemic therapy, three patients (3%) had to be changed to palliative radiotherapy or isolated extremity perfusion. The 1-year and 2-year overall survival (OS) in patients with complete metastasectomy (N = 52) was 90% and 79%, respectively. Systemically treated patients (N = 32) resulted in 1-year OS of 72% and 2-year OS of 61%. Eleven of 32 patients (34%) with systemic therapy experienced a complete response. Until December 2016, all 20 patients classified as tumor-free by PET/CT were alive. The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes

  8. Impact of "1"8F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis

    International Nuclear Information System (INIS)

    Forschner, Andrea; Keim, Ulrike; Eigentler, Thomas Kurt; Garbe, Claus; Olthof, Susann-Cathrin; Gueckel, Brigitte; Nikolaou, Konstantin; Pfannenberg, Christina; Martus, Peter; Vach, Werner; Fougere, Christian la

    2017-01-01

    To evaluate the influence of "1"8F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT. Management changes after PET/CT were classified as major and minor changes. A subgroup of 107 patients (stage I, N = 5; stage II, N = 3; stage III, N = 42; stage IV, N = 57) was planned for complete metastasectomy initially, based on conventional imaging. Management changes and outcome were evaluated by linkage with the information obtained from patients' medical records. In 28 of 107 patients (26%), the surgical treatment plan remained unchanged after PET/CT. In 24 patients (22%), minor changes were performed, such as enlargement or reduction of the surgical field. In 55 patients (51%, 95% CI 42%-61%) major changes of the intended treatment plan occurred; of those, 20 patients (19%) were classified to be tumor-free with PET/CT, 32 patients (30%) were found to have multiple previously unrecognized metastases and had to be treated by systemic therapy, three patients (3%) had to be changed to palliative radiotherapy or isolated extremity perfusion. The 1-year and 2-year overall survival (OS) in patients with complete metastasectomy (N = 52) was 90% and 79%, respectively. Systemically treated patients (N = 32) resulted in 1-year OS of 72% and 2-year OS of 61%. Eleven of 32 patients (34%) with systemic therapy experienced a complete response. Until December 2016, all 20 patients classified as tumor-free by PET/CT were alive. The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes, preventing

  9. Relevance of serum biomarkers associated with melanoma during follow-up of anti-CTLA-4 immunotherapy.

    Science.gov (United States)

    Felix, Joana; Cassinat, Bruno; Porcher, Raphael; Schlageter, Marie-Hélène; Maubec, Eve; Pages, Cécile; Baroudjian, Barouyr; Homyrda, Laurence; Boukouaci, Wahid; Tamouza, Ryad; Bagot, Martine; Caignard, Anne; Toubert, Antoine; Lebbé, Céleste; Moins-Teisserenc, Hélène

    2016-11-01

    Metastatic melanoma is a rapidly spreading cancer whose prognosis remains poor although important therapy advances in recent years. Ipilimumab, an anti-CTLA-4 immunotherapy used in advanced melanoma, is an effective immunotherapy alone or combined with other agents but with few predictive biomarkers of response. Here, we sought to analyze the potential of S100B, MIA, soluble MICA, anti-MICA antibodies and LDH as serum biomarkers of response and survival in a cohort of 77 advanced melanoma patients subjected to ipilimumab. Lower levels of S100B, and LDH at baseline and at weeks 3 and 6 correlated to a better response and survival. After multivariate analysis LDH maintained its independence at baseline and week 6, whereas S100B might be a useful tool for anti-CTLA-4 treatment monitoring after the first two doses of ipilimumab (W6). In addition, higher sMICA serum levels at baseline were associated with less frequency of irAEs. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Metastatic melanoma causing double small intestinal intussusception: diagnosis by computed tomography

    International Nuclear Information System (INIS)

    Bortolucci, G.; Garcia, M.; Dalcim, L.; Dias, I.; Teshirogi, E.

    2011-01-01

    Full text: Introduction: Metastases from malignant melanoma to the gastrointestinal tract are uncommon. Often found in jejunum and ileum, they are responsible for up to 7% of complications pre mortem. These metastases manifest with bleeding, perforation, obstruction or intussusception and require immediate surgery. Intussusception is a rare finding in the report described and is presented in a double into distinct segments. History and Physical Examination: M.H.C.S, female, 50 years, presenting 3 cm ulcerated lesion in the calcaneous region of the right foot with two years of evolution, no signs of infection or neoplastic permeation shores. Surgical excision of the lesion was performed and histopathologic analysis showed non-classifiable malignant melanoma. Submitted material to immunohistochemistry showed that markers of antigens Melan A and HMB45 positive, favoring the diagnosis of malignant melanoma. Tumor resection with expanding margins and selective inguinal lymphadenectomy through the technique of sentinel node, with rates equal to V Clark and Breslow thickness of 1.3 cm. Patient presented with acute abdominal obstruction treated surgically. Despite an uneventful post-operative, brain metastases developed, and patient is currently undergoing chemotherapy. Complementary Exams: Contrasted abdominal CT showing distension of the small bowel and an image suggestive of double intussusception. Treatment and Results: Indicated that laparotomy confirmed the presence of double intussusception in small intestine, the first being 110 cm from the angle of Treitz with a palpable tumor mass and dilatation of the upstream and the second character equal to 220 cm of the same, treated with bowel resection followed by end anastomosis. The diagnosis of malignant melanoma was confirmed by immunohistochemical analysis of surgical specimens. Discussion/Conclusion: Metastatic lesions in the gastrointestinal tract are often asymptomatic or nonspecific. The diagnosis should be

  11. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali

    2012-01-01

    Full Text Available The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group.

  12. Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

    Science.gov (United States)

    Andtbacka, Robert H I; Kaufman, Howard L; Collichio, Frances; Amatruda, Thomas; Senzer, Neil; Chesney, Jason; Delman, Keith A; Spitler, Lynn E; Puzanov, Igor; Agarwala, Sanjiv S; Milhem, Mohammed; Cranmer, Lee; Curti, Brendan; Lewis, Karl; Ross, Merrick; Guthrie, Troy; Linette, Gerald P; Daniels, Gregory A; Harrington, Kevin; Middleton, Mark R; Miller, Wilson H; Zager, Jonathan S; Ye, Yining; Yao, Bin; Li, Ai; Doleman, Susan; VanderWalde, Ari; Gansert, Jennifer; Coffin, Robert S

    2015-09-01

    Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC-treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma. © 2015 by

  13. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

    Full Text Available 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.

  14. Economic burden of advanced melanoma in France, Germany and the UK: a retrospective observational study (Melanoma Burden-of-Illness Study).

    Science.gov (United States)

    Grange, Florent; Mohr, Peter; Harries, Mark; Ehness, Rainer; Benjamin, Laure; Siakpere, Obukohwo; Barth, Janina; Stapelkamp, Ceilidh; Pfersch, Sylvie; McLeod, Lori D; Kaye, James A; Wolowacz, Sorrel; Kontoudis, Ilias

    2017-12-01

    The aim of this study was to estimate the cost-of-illness associated with completely resected stage IIIB/IIIC melanoma with macroscopic lymph node involvement, overall and by disease phase, in France, Germany and the UK. This retrospective observational study included patients aged older than or equal to 18 years first diagnosed with stage IIIB/IIIC cutaneous melanoma between 1 January 2009 and 31 December 2011. Data were obtained from medical records and a patient survey. Direct costs, indirect costs and patient out-of-pocket expenses were estimated in euros (€) (and British pounds, £) by collecting resource use and multiplying by country-specific unit costs. National annual costs were estimated using national disease prevalence from the European cancer registry and other published data. Forty-nine centres provided data on 558 patients (58.2% aged <65 years, 53.6% stage IIIB disease at diagnosis). The mean follow-up duration was 27 months (France), 26 months (Germany) and 22 months (UK). The mean total direct cost per patient during follow-up was €23 582 in France, €32 058 in Germany and €37 970 (£31 123) in the UK. The largest cost drivers were melanoma drugs [mean €14 004, €21 269, €29 750 (£24 385), respectively] and hospitalization/emergency treatment [mean: €6634, €6950, €3449 (£2827), respectively]. The total mean indirect costs per patient were €129 (France), €4,441 (Germany) and €1712 (£1427) (UK). Estimates for annual national direct cost were €13.1 million (France), €30.2 million (Germany) and €27.8 (£22.8) million (UK). The economic burden of stage IIIB/IIIC melanoma with macroscopic lymph node involvement was substantial in all three countries. Total direct costs were the highest during the period with distant metastasis/terminal illness.

  15. Advanced malignant melanoma during pregnancy: technical description of sentinel lymph node biopsy followed by radical lymph node dissection

    Directory of Open Access Journals (Sweden)

    Alberto Julius Alves Wainstein

    2015-12-01

    Full Text Available Abstract Introduction: melanoma is a very aggressive cancer, with increasing incidence, and is currently the fifth most common cancer in men and the sixth most common in women in the United States. Melanoma is not unusual in pregnancy, with an estimated occur-rence rate of 1:1.000. Although not the most common cancer in pregnancy, melanoma is the tumor with the highest incidence ofplacenta and fetus metastases. Description: a 29-year-old lady, 4 weeks after conception underwent resection of an atypical pigmented lesion after a diagnosis of stage T4b melanoma. At 16 weeks she underwent a broad local excision and sentinel lymph node (SLN biopsy. SLN was evaluated histologically and tested positive for melanoma. A radical axillary lymphadenectomy was performed on the patient without evidence of metas-tasis in any other LN. In the 40th week of pregnancy, labor was induced and a healthy newborn was deli-vered via cesarean. Discussion: melanoma management in pregnancy is more complex and requires multidisciplinary coor-dination, as well as extensive discussion with the patient and her family. We present a case report description in which treatment recommendations are established according to no pregnancy experience.

  16. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  17. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  18. Human malignant melanomas in nude mice

    International Nuclear Information System (INIS)

    Atlas, S.W.; Braffman, B.H.; Lo Brutto, R.; Elder, D.E.; Herlyn, D.

    1988-01-01

    The purpose of this study was to correlate signal intensities and relaxation times on MR images in malignant melanomas with histopathologic features and electron paramagnetic resonance (EPR) spectra. Cell lines from human malignant melanomas in tissue culture were implanted subcutaneously into nude mice. MR imaging was performed in vivo at 1.9 T to assess 12 separate lesions in ten mice using spin-echo and inversion-recovery techniques. T1,T2, and N(H) were calculated in all cases. Histopathologic examination was performed on specimens resected immediately after imaging, using hematoxylin and eosin, Prussian blue, and Fontan stains to assess for tumor necrosis, iron, and melanin content. EPR spectra were also obtained on four resected specimens. The authors' results indicate that the relaxation behavior of nonhemorrhagic malignant melanomas cannot be explained solely by the presence of necrosis, water content, or iron content. The degree of melanin within these tumors did correlate with T1 relaxation enhancement. T2 relaxation times did not correlate with the sole presence of either iron, melanin, or necrosis. Although the unique relaxation behavior of nonhemorrhagic malignant melanoma seems to have many causes, their data suggest that, contrary to previous investigations, it is influenced by the presence of melanin rather than iron

  19. GPU Pro 5 advanced rendering techniques

    CERN Document Server

    Engel, Wolfgang

    2014-01-01

    In GPU Pro5: Advanced Rendering Techniques, section editors Wolfgang Engel, Christopher Oat, Carsten Dachsbacher, Michal Valient, Wessam Bahnassi, and Marius Bjorge have once again assembled a high-quality collection of cutting-edge techniques for advanced graphics processing unit (GPU) programming. Divided into six sections, the book covers rendering, lighting, effects in image space, mobile devices, 3D engine design, and compute. It explores rasterization of liquids, ray tracing of art assets that would otherwise be used in a rasterized engine, physically based area lights, volumetric light

  20. GPU Pro advanced rendering techniques

    CERN Document Server

    Engel, Wolfgang

    2010-01-01

    This book covers essential tools and techniques for programming the graphics processing unit. Brought to you by Wolfgang Engel and the same team of editors who made the ShaderX series a success, this volume covers advanced rendering techniques, engine design, GPGPU techniques, related mathematical techniques, and game postmortems. A special emphasis is placed on handheld programming to account for the increased importance of graphics on mobile devices, especially the iPhone and iPod touch.Example programs and source code can be downloaded from the book's CRC Press web page. 

  1. Detection and capture of single circulating melanoma cells using photoacoustic flowmetry

    Science.gov (United States)

    O'Brien, Christine; Mosley, Jeffrey; Goldschmidt, Benjamin S.; Viator, John A.

    2010-02-01

    Photoacoustic flowmetry has been used to detect single circulating melanoma cells in vitro. Circulating melanoma cells are those cells that travel in the blood and lymph systems to create secondary tumors and are the hallmark of metastasis. This technique involves taking blood samples from patients, separating the white blood and melanoma cells from whole blood and irradiating them with a pulsed laser in a flowmetry set up. Rapid, visible wavelength laser pulses on the order of 5 ns can induce photoacoustic waves in melanoma cells due to their melanin content, while surrounding white blood cells remain acoustically passive. We have developed a system that identifies rare melanoma cells and captures them in 50 microliter volumes using suction applied near the photoacoustic detection chamber. The 50 microliter sample is then diluted and the experiment is repeated using the new sample until only a melanoma cell remains. We have tested this system on dyed microspheres ranging in size from 300 to 500 microns. Capture of circulating melanoma cells may provide the opportunity to study metastatic cells for basic understanding of the spread of cancer and to optimize patient specific therapies.

  2. Fear of new or recurrent melanoma after treatment for localised melanoma.

    Science.gov (United States)

    Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

    2017-11-01

    To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma.

    Science.gov (United States)

    Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. © 2013 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.

  4. GPU Pro 4 advanced rendering techniques

    CERN Document Server

    Engel, Wolfgang

    2013-01-01

    GPU Pro4: Advanced Rendering Techniques presents ready-to-use ideas and procedures that can help solve many of your day-to-day graphics programming challenges. Focusing on interactive media and games, the book covers up-to-date methods producing real-time graphics. Section editors Wolfgang Engel, Christopher Oat, Carsten Dachsbacher, Michal Valient, Wessam Bahnassi, and Sebastien St-Laurent have once again assembled a high-quality collection of cutting-edge techniques for advanced graphics processing unit (GPU) programming. Divided into six sections, the book begins with discussions on the abi

  5. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  6. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  7. SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.

    Science.gov (United States)

    Santini, R; Pietrobono, S; Pandolfi, S; Montagnani, V; D'Amico, M; Penachioni, J Y; Vinci, M C; Borgognoni, L; Stecca, B

    2014-09-18

    Melanoma is one of the most aggressive types of human cancer, characterized by enhanced heterogeneity and resistance to conventional therapy at advanced stages. We and others have previously shown that HEDGEHOG-GLI (HH-GLI) signaling is required for melanoma growth and for survival and expansion of melanoma-initiating cells (MICs). Recent reports indicate that HH-GLI signaling regulates a set of genes typically expressed in embryonic stem cells, including SOX2 (sex-determining region Y (SRY)-Box2). Here we address the function of SOX2 in human melanomas and MICs and its interaction with HH-GLI signaling. We find that SOX2 is highly expressed in melanoma stem cells. Knockdown of SOX2 sharply decreases self-renewal in melanoma spheres and in putative melanoma stem cells with high aldehyde dehydrogenase activity (ALDH(high)). Conversely, ectopic expression of SOX2 in melanoma cells enhances their self-renewal in vitro. SOX2 silencing also inhibits cell growth and induces apoptosis in melanoma cells. In addition, depletion of SOX2 progressively abrogates tumor growth and leads to a significant decrease in tumor-initiating capability of ALDH(high) MICs upon xenotransplantation, suggesting that SOX2 is required for tumor initiation and for continuous tumor growth. We show that SOX2 is regulated by HH signaling and that the transcription factors GLI1 and GLI2, the downstream effectors of HH-GLI signaling, bind to the proximal promoter region of SOX2 in primary melanoma cells. In functional studies, we find that SOX2 function is required for HH-induced melanoma cell growth and MIC self-renewal in vitro. Thus SOX2 is a critical factor for self-renewal and tumorigenicity of MICs and an important mediator of HH-GLI signaling in melanoma. These findings could provide the basis for novel therapeutic strategies based on the inhibition of SOX2 for the treatment of a subset of human melanomas.

  8. [Descriptive study of the costs of diagnosis and treatment of cutaneous melanoma].

    Science.gov (United States)

    Almazán-Fernández, F M; Serrano-Ortega, S; Moreno-Villalonga, J J

    2009-11-01

    Every year, health expenditure in Spain increases and, with it, the resources dedicated to cancer treatment. Cutaneous melanoma is the skin cancer with the highest morbidity and mortality. We performed a descriptive study of the costs, based on a theoretical model, to determine the healthcare expenditure for patients with cutaneous melanoma; the objective was to define the overall costs (direct and indirect) of the diagnostic and treatment process of cutaneous melanoma, divided into different stages or diagnostic-therapeutic steps, and the possible variations in these costs. For this purpose, we used the Andalusian analytical accountancy program of hospitals and districts (COAN-hyd) and the total costs module of the COAN for 2007, applied to the protocol we use in the melanoma unit of our hospital. The most important conclusions were that the greatest health care expenditure was observed inpatients with more advanced melanomas, with a poor prognosis. Management of the diagnostic-therapeutic process by dermatologists, the appropriate use of complementary tests, and operations performed by dermatologists reduce costs.

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

    Science.gov (United States)

    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.

  10. Minimally invasive liver resection to obtain tumor-infiltrating lymphocytes for adoptive cell therapy in patients with metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Alvarez-Downing Melissa M

    2012-06-01

    Full Text Available Abstract Background Adoptive cell therapy (ACT with tumor-infiltrating lymphocytes (TIL in patients with metastatic melanoma has been reported to have a 56% overall response rate with 20% complete responders. To increase the availability of this promising therapy in patients with advanced melanoma, a minimally invasive approach to procure tumor for TIL generation is warranted. Methods A feasibility study was performed to determine the safety and efficacy of laparoscopic liver resection to generate TIL for ACT. Retrospective review of a prospectively maintained database identified 22 patients with advanced melanoma and visceral metastasis (AJCC Stage M1c who underwent laparoscopic liver resection between 1 October 2005 and 31 July 2011. The indication for resection in all patients was to receive postoperative ACT with TIL. Results Twenty patients (91% underwent resection utilizing a closed laparoscopic technique, one required hand-assistance and another required conversion to open resection. Median intraoperative blood loss was 100 mL with most cases performed without a Pringle maneuver. Median hospital stay was 3 days. Three (14% patients experienced a complication from resection with no mortality. TIL were generated from 18 of 22 (82% patients. Twelve of 15 (80% TIL tested were found to have in vitro tumor reactivity. Eleven patients (50% received the intended ACT. Two patients were rendered no evidence of disease after surgical resection, with one undergoing delayed ACT with generated TIL after relapse. Objective tumor response was seen in 5 of 11 patients (45% who received TIL, with one patient experiencing an ongoing complete response (32+ months. Conclusions Laparoscopic liver resection can be performed with minimal morbidity and serve as an effective means to procure tumor to generate therapeutic TIL for ACT to patients with metastatic melanoma.

  11. The burden of malignant melanoma--lessons to be learned from Austria.

    Science.gov (United States)

    Monshi, Babak; Vujic, Marin; Kivaranovic, Danijel; Sesti, Alma; Oberaigner, Willi; Vujic, Igor; Ortiz-Urda, Susana; Posch, Christian; Feichtinger, Hans; Hackl, Monika; Rappersberger, Klemens

    2016-03-01

    Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma Database: A Validation Study.

    Science.gov (United States)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri; Pottegård, Anton; Friis, Søren; Hölmich, Lisbet Rosenkrantz; Gaist, David

    2018-05-01

    The nationwide Danish Cancer Registry and the Danish Melanoma Database both record data on melanoma for purposes of monitoring, quality assurance, and research. However, the data quality of the Cancer Registry and the Melanoma Database has not been formally evaluated. We estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200) during 2004-2014, using the Danish Pathology Registry as "gold standard" reference. We further validated tumor characteristics in the Cancer Registry and the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in 2004-2014. The PPVs of melanoma in the Cancer Registry and the Melanoma Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and 93% and 100% in the Melanoma Database. The PPVs for anatomical localization were 83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database. The data quality in both the Cancer Registry and the Melanoma Database is high, supporting their use in epidemiologic studies.

  13. Plasma 25-Hydroxyvitamin D and Risk of Non-Melanoma and Melanoma Skin Cancer

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Nordestgaard, Børge G; Bojesen, Stig E

    2013-01-01

    Sun exposure is a major risk factor for skin cancer and is also an important source of vitamin D. We tested the hypothesis that elevated plasma 25-hydroxyvitamin D (25-OH-vitD) associates with increased risk of non-melanoma and melanoma skin cancer in the general population. We measured plasma 25......-OH-vitD in 10,060 white individuals from the Danish general population. During 28 years of follow-up, 590 individuals developed non-melanoma skin cancer and 78 developed melanoma skin cancer. Increasing 25-OH-vitD levels, by clinical categories or by seasonally adjusted tertiles, were associated...... with increasing cumulative incidence of non-melanoma skin cancer (trend P=2 × 10(-15) and P=3 × 10(-17)) and melanoma skin cancer (P=0.003 and P=0.001). Multivariable adjusted hazard ratios of non-melanoma skin cancer were 5.04 (95% confidence interval (CI): 2.78-9.16) for 25-OH-vitD 50 vs. 60 years, 25-OH...

  14. Disparities of Immunotherapy Utilization in Patients with Stage III Cutaneous Melanoma: A National Perspective.

    Science.gov (United States)

    Al-Qurayshi, Zaid; Crowther, Jason E; Hamner, John B; Ducoin, Christopher; Killackey, Mary T; Kandil, Emad

    2018-05-01

    Immunotherapy combined with surgery is associated with better survival than surgery alone in patients with advanced melanoma. This study examined the utilization of immunotherapy in relation to population characteristics and the associated survival benefit. This was a retrospective cohort study utilizing the US National Cancer Database. The study population included 6,165 adult patients (≥18 years) with stage III cutaneous melanoma (median follow-up=32 months). A total of 1,854 patients underwent immunotherapy in addition to surgery, which was associated with a survival benefit over surgery alone (hazard ratio(HR)=0.66, 95% confidence interval(CI)=0.56-0.77, pimmunotherapy utilization (all pimmunotherapy usage was found (p=0.07). Compared to other demographic factors, insurance status was associated with the greatest disparities in immunotherapy utilization and mortality for patients who underwent surgery for advanced melanoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  16. Detection of melanoma cells suspended in mononuclear cells and blood plasma using photoacoustic generation

    Science.gov (United States)

    Spradling, Emily M.; Viator, John A.

    2009-02-01

    Melanoma is the deadliest form of skin cancer. Although the initial malignant cells are removed, it is impossible to determine whether or not the cancer has metastasized until a secondary tumor forms that is large enough to detect with conventional imaging. Photoacoustic detection of circulating melanoma cells in the bloodstream has shown promise for early detection of metastasis that may aid in treatment of this aggressive cancer. When blood is irradiated with energy from an Nd:YAG laser at 532 nm, photoacoustic signals are created and melanoma cells can be differentiated from the surrounding cells based on waveforms produced by an oscilloscope. Before this can be used as a diagnostic technique, however, we needed to investigate several parameters. Specifically, the current technique involves the in vitro separation of blood through centrifugation to isolate and test only the white blood cell layer. Using this method, we have detected a single cultured melanoma cell among a suspension of white blood cells. However, the process could be made simpler if the plasma layer were used for detection instead of the white blood cell layer. This layer is easier to obtain after blood separation, the optical difference between plasma and melanoma cells is more pronounced in this layer than in the white blood cell layer, and the possibility that any stray red blood cells could distort the results is eliminated. Using the photoacoustic apparatus, we detected no melanoma cells within the plasma of whole blood samples spiked with cultured melanoma cells.

  17. Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab.

    Science.gov (United States)

    Hodi, F Stephen; Hwu, Wen-Jen; Kefford, Richard; Weber, Jeffrey S; Daud, Adil; Hamid, Omid; Patnaik, Amita; Ribas, Antoni; Robert, Caroline; Gangadhar, Tara C; Joshua, Anthony M; Hersey, Peter; Dronca, Roxana; Joseph, Richard; Hille, Darcy; Xue, Dahai; Li, Xiaoyun Nicole; Kang, S Peter; Ebbinghaus, Scot; Perrone, Andrea; Wolchok, Jedd D

    2016-05-01

    We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment. © 2016 by American Society of Clinical Oncology.

  18. Detecting BRAF Mutations in Formalin-Fixed Melanoma: Experiences with TwoState-of-the-Art Techniques

    Directory of Open Access Journals (Sweden)

    Nicola L. Schoenewolf

    2012-06-01

    Full Text Available Background: Melanoma is characterized by a high frequency of BRAF mutations. It is unknown if the BRAF mutation status has any predictive value for therapeutic approaches such as angiogenesis inhibition. Patients and Methods: We used 2 methods to analyze the BRAF mutation status in 52 of 62 melanoma patients. Method 1 (mutation-specific real-time PCR specifically detects the most frequent BRAF mutations, V600E and V600K. Method 2 (denaturing gel gradient electrophoresis and direct sequencing identifies any mutations affecting exons 11 and 15. Results: Eighteen BRAF mutations and 15 wild-type mutations were identified with both methods. One tumor had a double mutation (GAA in codon 600. Results of 3 samples were discrepant. Additional mutations (V600M, K601E were detected using method 2. Sixteen DNA samples were analyzable with either method 1 or method 2. There was a significant association between BRAF V600E mutation and survival. Conclusion: Standardized tissue fixation protocols are needed to optimize BRAF mutation analysis in melanoma. For melanoma treatment decisions, the availability of a fast and reliable BRAF V600E screening method may be sufficient. If other BRAF mutations in exons 11 and 15 are found to be of predictive value, a combination of the 2 methods would be useful.

  19. Malignant melanoma - a warning

    International Nuclear Information System (INIS)

    Volden, G.; Rajka, G.; Thune, P.; Falk, E.S.; Krogh, H.K.

    1990-01-01

    Incidence of malignant melonoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. The intension of the authors is to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education. 15 refs., 2 tabs

  20. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

  1. Profiling of plasma metabolites in canine oral melanoma using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Kawabe, Mifumi; Baba, Yuta; Tamai, Reo; Yamamoto, Ryohei; Komori, Masayuki; Mori, Takashi; Takenaka, Shigeo

    2015-08-01

    Malignant melanoma is one of the most common and aggressive tumors in the oral cavity of dog. The tumor has a poor prognosis, and methods for diagnosis and prediction of prognosis after treatment are required. Here, we examined metabolite profiling using gas chromatography-mass spectrometry (GC-MS) for development of a discriminant model for evaluation of prognosis. Metabolite profiles were evaluated in healthy and melanoma plasma samples using orthogonal projection to latent structure using discriminant analysis (OPLS-DA). Cases that were predicted to be healthy using the OPLS discriminant model had no advanced lesions after radiation therapy. These results indicate that metabolite profiling may be useful in diagnosis and prediction of prognosis of canine malignant melanoma.

  2. [Melanoma in organ transplant patients].

    Science.gov (United States)

    Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D

    2000-02-01

    The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean

  3. Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

    Energy Technology Data Exchange (ETDEWEB)

    Hartsell, William F., E-mail: whartsell@chicagocancer.org [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Kapur, Rashmi [Retina Consultants, Des Plaines, Illinois (United States); Hartsell, Siobhan O' Connor; Sweeney, Patrick [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Lopes, Caitlin [Rush Medical College, Chicago, Illinois (United States); Duggal, Amanda [Northwestern Medicine Chicago Proton Center, Warrenville, Illinois (United States); Cohen, Jack [Department of Ophthalmology, Rush University, Chicago, Illinois (United States); Chang, John [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Polasani, Rajeev S. [Northwestern Medicine Central DuPage Hospital, Winfield, Illinois (United States); Dunn, Megan [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States); Pankuch, Mark [Northwestern Medicine Chicago Proton Center, Proton Collaborative Group, Warrenville, Illinois (United States)

    2016-05-01

    Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

  4. Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

    International Nuclear Information System (INIS)

    Hartsell, William F.; Kapur, Rashmi; Hartsell, Siobhan O'Connor; Sweeney, Patrick; Lopes, Caitlin; Duggal, Amanda; Cohen, Jack; Chang, John; Polasani, Rajeev S.; Dunn, Megan; Pankuch, Mark

    2016-01-01

    Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typically treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships for

  5. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

    Directory of Open Access Journals (Sweden)

    Li-Te Lin

    2011-08-01

    Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

  6. Novel Approaches for Diagnosing Melanoma Skin Lesions Through Supervised and Deep Learning Algorithms.

    Science.gov (United States)

    Premaladha, J; Ravichandran, K S

    2016-04-01

    Dermoscopy is a technique used to capture the images of skin, and these images are useful to analyze the different types of skin diseases. Malignant melanoma is a kind of skin cancer whose severity even leads to death. Earlier detection of melanoma prevents death and the clinicians can treat the patients to increase the chances of survival. Only few machine learning algorithms are developed to detect the melanoma using its features. This paper proposes a Computer Aided Diagnosis (CAD) system which equips efficient algorithms to classify and predict the melanoma. Enhancement of the images are done using Contrast Limited Adaptive Histogram Equalization technique (CLAHE) and median filter. A new segmentation algorithm called Normalized Otsu's Segmentation (NOS) is implemented to segment the affected skin lesion from the normal skin, which overcomes the problem of variable illumination. Fifteen features are derived and extracted from the segmented images are fed into the proposed classification techniques like Deep Learning based Neural Networks and Hybrid Adaboost-Support Vector Machine (SVM) algorithms. The proposed system is tested and validated with nearly 992 images (malignant & benign lesions) and it provides a high classification accuracy of 93 %. The proposed CAD system can assist the dermatologists to confirm the decision of the diagnosis and to avoid excisional biopsies.

  7. Transplantable Melanomas in Hamsters and Gerbils as Models for Human Melanoma. Sensitization in Melanoma Radiotherapy—From Animal Models to Clinical Trials

    Directory of Open Access Journals (Sweden)

    Martyna Śniegocka

    2018-04-01

    Full Text Available The focus of the present review is to investigate the role of melanin in the radioprotection of melanoma and attempts to sensitize tumors to radiation by inhibiting melanogenesis. Early studies showed radical scavenging, oxygen consumption and adsorption as mechanisms of melanin radioprotection. Experimental models of melanoma in hamsters and in gerbils are described as well as their use in biochemical and radiobiological studies, including a spontaneously metastasizing ocular model. Some results from in vitro studies on the inhibition of melanogenesis are presented as well as radio-chelation therapy in experimental and clinical settings. In contrast to cutaneous melanoma, uveal melanoma is very successfully treated with radiation, both using photon and proton beams. We point out that the presence or lack of melanin pigmentation should be considered, when choosing therapeutic options, and that both the experimental and clinical data suggest that melanin could be a target for radiosensitizing melanoma cells to increase efficacy of radiotherapy against melanoma.

  8. Immunohistochemical detection of XIAP in melanoma.

    Science.gov (United States)

    Emanuel, Patrick O M; Phelps, Robert G; Mudgil, Adarsh; Shafir, Michail; Burstein, David E

    2008-03-01

    The X-linked inhibitor of apoptosis protein (XIAP) is the most potent of the inhibitor of apoptosis family of eight proteins. High levels of XIAP have been found in melanoma cell lines and are believed to play a role in therapeutic resistance in a number of malignancies. XIAP expression has not been investigated in clinically obtained melanoma tissue samples, nor have studies attempted to correlate XIAP expression with prognostic variables or clinical aggressiveness of melanomas. Sixty-seven patients with primary cutaneous malignant melanoma for whom clinical follow up was available were identified from the records of the Mount Sinai Hospital, comprising 37 thin melanomas (Breslow thickness 1.0 mm). Archival paraffin sections from primary lesions and corresponding metastases were stained with monoclonal anti-XIAP antibody using routine immunohistochemical methods. Six benign intradermal nevi and four in situ melanomas were XIAP negative. 9 of 37 thin melanomas (24%) were XIAP positive. In contrast, 21 of 30 (73%) thick melanomas were XIAP positive, including 3 of 4 ulcerated melanomas that were strongly positive. Over a follow-up period ranging from 6 months to 6 years, 23 melanomas metastasized (22 thick, 1 thin). In total, XIAP was immunohistochemically detected in 17 of 23 metastases (74%). Metastasis occurred in 1 of 9 XIAP-positive thin melanomas; 0 of 28 XIAP-negative thin melanomas; 17 of 22 XIAP-positive thick melanomas, and 5 of 8 XIAP-negative thick melanomas (63%). XIAP is immunohistochemically detectable nearly three times more frequently in thick compared with thin melanomas. These results suggest that XIAP elevation may be correlated with increasing melanoma thickness and tumor progression.

  9. A study of melanoma in Eastern European migrants in Italy.

    Science.gov (United States)

    Astrua, Chiara; Fava, Paolo; Brizio, Matteo; Savoia, Paola

    2017-04-01

    Cancer survival rates are lower in Eastern Europe. To describe, based on a single-centre database in northern Italy, clinical, histopathological, and prognostic features of melanoma in a migrant population from Eastern Europe. We retrospectively analysed data from 18,190 consecutive foreign patients who visited our institution, with 49 cases of melanoma from Eastern Europe. The control group was represented by 1,003 Italian melanoma patients diagnosed and followed at our centre during the same time period. Patients from Eastern Europe were mainly females with lower median age, without significant differences regarding primary melanoma site, relative to the control group. Diagnosis was made at the place of birth in 30.6% and in our centre for the remainder. Median Breslow thickness was greater (p = 0.0178), and aggressive histotypes (p = 0.0017) and ulcerated melanomas (p = 0.002) were significantly over-represented, particularly when diagnosed in the patients' native country. Disease was more advanced at diagnosis (p = 0.0001), regardless of the place of initial diagnosis (51% had a progressive disease within one year which rose to 80% if diagnosed before admission to our centre), and the percentage of patients who died within one year was significantly higher (p = 0.022), relative to the control group. Our study shows a poor prognosis for melanoma patients diagnosed in Eastern Europe. Moreover, for migrant populations moving from Eastern to Western European countries, financial difficulties, poor social integration, and language barriers, with consequent late access to healthcare facilities, may account for a worse prognosis.

  10. Advanced electron beam techniques

    International Nuclear Information System (INIS)

    Hirotsu, Yoshihiko; Yoshida, Yoichi

    2007-01-01

    After 100 years from the time of discovery of electron, we now have many applications of electron beam in science and technology. In this report, we review two important applications of electron beam: electron microscopy and pulsed-electron beam. Advanced electron microscopy techniques to investigate atomic and electronic structures, and pulsed-electron beam for investigating time-resolved structural change are described. (author)

  11. Genetics of familial melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Wadt, Karin A W; Pritchard, Antonia L

    2015-01-01

    Twenty years ago, the first familial melanoma susceptibility gene, CDKN2A, was identified. Two years later, another high-penetrance gene, CDK4, was found to be responsible for melanoma development in some families. Progress in identifying new familial melanoma genes was subsequently slow; however...

  12. Sunburn, suntan and the risk of cutaneous malignant melanoma--The Western Canada Melanoma Study.

    Science.gov (United States)

    Elwood, J. M.; Gallagher, R. P.; Davison, J.; Hill, G. B.

    1985-01-01

    A comparison of interview data on 595 patients with newly incident cutaneous melanoma, excluding lentigo maligna melanoma and acral lentiginous melanoma, with data from comparison subjects drawn from the general population, showed that melanoma risk increased in association with the frequency and severity of past episodes of sunburn, and also that melanoma risk was higher in subjects who usually had a relatively mild degree of suntan compared to those with moderate or deep suntan in both winter and summer. The associations with sunburn and with suntan were independent. Melanoma risk is also increased in association with a tendency to burn easily and tan poorly and with pigmentation characteristics of light hair and skin colour, and history freckles; the associations with sunburn and suntan are no longer significant when these other factors are taken into account. This shows that pigmentation characteristics, and the usual skin reaction to sun, are more closely associated with melanoma risk than are sunburn and suntan histories. PMID:3978032

  13. Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

    Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, much attention has been paid to the establishment of selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells. This paper presents 10 B chlorpromazine compounds and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA) as tumor-seeking 10 B compounds which themselves possess selective affinity for the specific metabolic activity of the target cancer cells. An overview of the following studies on the effects of 10 B 1 -BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10 B 1 -BPA; 2) in vivo studies on therapeutic effects of 10 B 1 -BPA using melanoma-bearing hamsters; and 3) preclinical therapeutic experiments using spontaneously occurring malignant melanoma in Duroc pig skin, including experiments in which melanoma was successfully cured. (Namekawa, K.)

  14. Naturally occurring melanomas in dogs as models for non-UV pathways of human melanomas.

    Science.gov (United States)

    Gillard, Marc; Cadieu, Edouard; De Brito, Clotilde; Abadie, Jérôme; Vergier, Béatrice; Devauchelle, Patrick; Degorce, Frédérique; Dréano, Stephane; Primot, Aline; Dorso, Laetitia; Lagadic, Marie; Galibert, Francis; Hédan, Benoit; Galibert, Marie-Dominique; André, Catherine

    2014-01-01

    Spontaneously occurring melanomas are frequent in dogs. They appear at the same localizations as in humans, i.e. skin, mucosal sites, nail matrix and eyes. They display variable behaviors: tumors at oral localizations are more frequent and aggressive than at other anatomical sites. Interestingly, dog melanomas are associated with strong breed predispositions and overrepresentation of black-coated dogs. Epidemiological analysis of 2350 affected dogs showed that poodles are at high risk of developing oral melanoma, while schnauzers or Beauce shepherds mostly developped cutaneous melanoma. Clinical and histopathological analyses were performed on a cohort of 153 cases with a 4-yr follow-up. Histopathological characterization showed that most canine tumors are intradermal and homologous to human rare morphological melanomas types - 'nevocytoid type' and 'animal type'-. Tumor cDNA sequencing data, obtained from 95 dogs for six genes, relevant to human melanoma classification, detected somatic mutations in oral melanoma, in NRAS and PTEN genes, at human hotspot sites, but not in BRAF. Altogether, these findings support the relevance of the dog model for comparative oncology of melanomas, especially for the elucidation of non-UV induced pathways. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

    International Nuclear Information System (INIS)

    Lesinski, Gregory B; Zimmerer, Jason M; Kreiner, Melanie; Trefry, John; Bill, Matthew A; Young, Gregory S; Becknell, Brian; Carson, William E III

    2010-01-01

    Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr 701 -phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr 701 -phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ

  16. Antitumor potential induction and free radicals production in melanoma cells by Boron Neutron Capture Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P.; Muniz, R.O.R.; Souza, G.S. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.com.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

    2011-12-15

    Antiproliferative and oxidative damage effects occurring in Boron Neutron Capture Therapy (BNCT) in normal fibroblasts and melanoma cell lines were analyzed. Melanoma cells and normal fibroblasts were treated with different concentrations of Boronophenylalanine and irradiated with thermal neutron flux. The cellular viability and the oxidative stress were determined. BNCT induced free radicals production and proliferative potential inhibition in melanoma cells. Therefore, this therapeutic technique could be considered efficient to inhibit growth of melanoma with minimal effects on normal tissues. - Highlights: Black-Right-Pointing-Pointer Boron Neutron Capture Therapy (BNCT) induces melanoma cell death. Black-Right-Pointing-Pointer BNCT stimulates free radicals production and proliferative inhibition in melanoma cells. Black-Right-Pointing-Pointer It produces tumor membrane degeneration and destruction with apoptotic bodies formation. Black-Right-Pointing-Pointer This therapy damages tumor cells selectively, with minimum effects on normal adjacent tissue.

  17. Comparing Melanoma Invasiveness in Dermatologist- versus Patient-Detected Lesions: A Retrospective Chart Review

    Directory of Open Access Journals (Sweden)

    Cindy L. Lamerson

    2012-01-01

    Full Text Available This study examined whether patient-identified melanomas were more advanced than dermatologist-identified tumors at routine clinic visits, and whether a personal or family history of skin cancer was associated with patterns of detection. A retrospective chart review was performed on melanoma patients (N=201 in a private dermatology clinic. Variables included age, gender, pattern of detection (i.e., patient or a board certified dermatologist, personal or family history of skin cancer, skin type, and previous sun exposure, as well as tumor location and severity. Dermatologist-diagnosed melanomas were less invasive (P<0.0005, and more likely present on the chest, back, and legs (P<0.01. Conversely, patient-identified lesions were more likely to occur on the face, neck and scalp, be associated with younger patients, and a family history of melanoma, but not other types of skin cancer (P<0.01. In a post-hoc analysis examining these factors as predictors of tumor invasiveness, only diagnostic source was significant. Specifically, dermatologist-identified tumors were significantly less invasive than patient-identified tumors. Although age, family history, and tumor location played roles in the early detection of melanomas, the most important factor was diagnostic source. Thus, board-certified dermatologists play a key role in the early detection of malignant melanoma.

  18. Circulating Tumour DNA for Monitoring Treatment Response to Anti-PD-1 Immunotherapy in Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Atsuko Ashida

    2017-08-01

    Full Text Available Anti-programmed cell death-1 (anti-PD-1 antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations. In 3 cases in which the anti-PD-1 antibody was effective, ctDNA levels decreased within 2–4 weeks after treatment initiation. In 2 cases in which the anti-PD-1 antibody was ineffective, ctDNA levels did not decrease after treatment initiation. ctDNA could be a useful biomarker to predict early response to treatment in patients with advanced melanoma treated with anti-PD-1 immunotherapy.

  19. Dendritic cell-based vaccine in advanced melanoma: update of clinical outcome.

    Science.gov (United States)

    Ridolfi, Laura; Petrini, Massimiliano; Fiammenghi, Laura; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Brolli, Claudia; Selva, Mirna; Scarpi, Emanuela; Valmorri, Linda; Nicoletti, Stefania Vittoria Luisa; Guidoboni, Massimo; Riccobon, Angela; Ridolfi, Ruggero

    2011-12-01

    Dendritic cells (DCs) are unique specialized antigen-presenting cells capable of priming naive T cells and inducing antigen-specific cytotoxic T lymphocytes. This study presents an update of clinical results from a DC-based phase I-II clinical vaccine trial in stage IV melanoma. From 2003 to 2010, 27 patients with metastatic melanoma were treated with mature DCs pulsed with autologous tumor lysate and keyhole limpet hemocyanin and with subcutaneous low-dose interleukin-2. Delayed-type hypersensitivity (DTH) tests for in-vivo immunomonitoring were performed at baseline and every four vaccinations thereafter. Two complete, two mixed and six partial responses, and five stable diseases were observed (overall response, 37.0%; clinical benefit, 55.5%). All 15 responders showed DTH positivity. A median overall survival of 22.9 months [95% confidence interval (CI): 13.4-61.3] for DTH-positive patients (19) and 4.8 months (95% CI: 3.9-11.9) for DTH-negative patients (8; log rank=7.26; P=0.007) was observed. The overall median overall survival was 16 months (95% CI: 9-33). Our results would seem to highlight a relationship between positive-DTH test and an improved survival.

  20. A comprehensive patient-derived xenograft collection representing the heterogeneity of melanoma

    OpenAIRE

    Krepler, Clemens; Sproesser, Katrin; Brafford, Patricia; Beqiri, Marilda; Garman, Bradley; Xiao, Min; Shannan, Batool; Watters, Andrea; Perego, Michela; Zhang, Gao; Vultur, Adina; Yin, Xiangfan; Liu, Qin; Anastopoulos, Ioannis N; Wubbenhorst, Bradley

    2017-01-01

    Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological he...

  1. Malignant Melanoma in an Albino | Efem | Sudan Journal of Medical ...

    African Journals Online (AJOL)

    Oculocutaneous albinism is a rare autosomal recessive disorder characterised by generalised depigmentation, photophobia, decreased visual acuity, and nystagmus. Malignant melanoma is rare in patients with albinism. We report a case of a large advanced fumigating tumour on the right forearm of a male Nigerian albino ...

  2. BRAF-mutant melanoma: treatment approaches, resistance mechanisms, and diagnostic strategies

    Directory of Open Access Journals (Sweden)

    Spagnolo F

    2015-01-01

    available today for patients affected by BRAF V600-mutated metastatic melanoma, as well as to summarize the mechanisms of resistance to BRAF inhibitors and discuss the possible strategies to overcome them. Moreover, since the molecular analysis of tumor specimens is now a pivotal and decisional factor in the treatment strategy of metastatic melanoma patients, the advances in the molecular detection techniques for the BRAF V600 mutation will be reported. Keywords: melanoma, BRAF, vemurafenib, dabrafenib, resistance, BRAF inhibitor

  3. The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?

    Science.gov (United States)

    Nissan, Moriah H; Solit, David B

    2011-12-01

    Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.

  4. Monitoring the systemic human memory B cell compartment of melanoma patients for anti-tumor IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Amy E Gilbert

    Full Text Available Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10 to primary and metastatic melanoma cells compared to healthy volunteers (n = 10 (P<0.0001. Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21 (P<0.0001. Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800 compared to 2% of cultures from healthy controls (n = 600 produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer.

  5. Monitoring the Systemic Human Memory B Cell Compartment of Melanoma Patients for Anti-Tumor IgG Antibodies

    Science.gov (United States)

    Gilbert, Amy E.; Karagiannis, Panagiotis; Dodev, Tihomir; Koers, Alexander; Lacy, Katie; Josephs, Debra H.; Takhar, Pooja; Geh, Jenny L. C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Rudman, Sarah M.; Beavil, Rebecca L.; Blower, Philip J.; Beavil, Andrew J.; Gould, Hannah J.; Spicer, James; Nestle, Frank O.; Karagiannis, Sophia N.

    2011-01-01

    Melanoma, a potentially lethal skin cancer, is widely thought to be immunogenic in nature. While there has been much focus on T cell-mediated immune responses, limited knowledge exists on the role of mature B cells. We describe an approach, including a cell-based ELISA, to evaluate mature IgG antibody responses to melanoma from human peripheral blood B cells. We observed a significant increase in antibody responses from melanoma patients (n = 10) to primary and metastatic melanoma cells compared to healthy volunteers (n = 10) (P<0.0001). Interestingly, we detected a significant reduction in antibody responses to melanoma with advancing disease stage in our patient cohort (n = 21) (P<0.0001). Overall, 28% of melanoma patient-derived B cell cultures (n = 1,800) compared to 2% of cultures from healthy controls (n = 600) produced antibodies that recognized melanoma cells. Lastly, a patient-derived melanoma-specific monoclonal antibody was selected for further study. This antibody effectively killed melanoma cells in vitro via antibody-mediated cellular cytotoxicity. These data demonstrate the presence of a mature systemic B cell response in melanoma patients, which is reduced with disease progression, adding to previous reports of tumor-reactive antibodies in patient sera, and suggesting the merit of future work to elucidate the clinical relevance of activating humoral immune responses to cancer. PMID:21559411

  6. Evaluation of variants of melanoma-associated antigen genes and mRNA transcripts in melanomas of dogs.

    Science.gov (United States)

    Stell, Anneliese J; Dobson, Jane M; Scase, Timothy J; Catchpole, Brian

    2009-12-01

    OBJECTIVE-To characterize variability in melanoma-associated antigen (MAA) genes and gene expression in melanomas of dogs. ANIMALS-18 dogs with malignant melanomas and 8 healthy control dogs. PROCEDURES-cDNA was prepared from malignant melanoma biopsy specimens and from pigmented oral mucocutaneous tissues of healthy control dogs. Genomic DNA was extracted from poorly pigmented melanomas. A PCR assay was performed by use of Melan-A, SILV, or tyrosinase-specific primers. RESULTS-Splice variants of Melan-A and SILV were identified in malignant melanomas and also in healthy pigmented tissues, whereas a tyrosinase splice variant was detected in melanoma tissues only. A short interspersed nuclear element (SINE) insertion mutation was identified in the SILV gene in 1 of 10 poorly pigmented melanomas. Six novel exonic single nucleotide polymorphisms (SNPs; 3 synonymous and 3 nonsynonymous) were detected in the tyrosinase gene, and 1 nonsynonymous exonic SNP was detected in the SILV gene. CONCLUSIONS AND CLINICAL RELEVANCE-Variants of MAA mRNA were detected in malignant melanoma tissues of dogs. The importance of MAA alternative transcripts expressed in melanomas and normal pigmented tissues was unclear, but they may have represented a means of regulating melanin synthesis. The tyrosinase splice variant was detected only in melanomas and could potentially be a tumor-specific target for immunotherapy. A SILV SINE insertion mutation was identified in a melanoma from a Great Dane, a breed known to carry this mutation (associated with merle coat color). The nonsynonymous SNPs detected in tyrosinase and SILV transcripts did not appear to affect tumor pigmentation.

  7. Thick melanoma in Tuscany.

    Science.gov (United States)

    Chiarugi, Alessandra; Nardini, Paolo; Borgognoni, Lorenzo; Brandani, Paola; Gerlini, Gianni; Rubegni, Pietro; Lamberti, Arianna; Salvini, Camilla; Lo Scocco, Giovanni; Cecchi, Roberto; Sirna, Riccardo; Lorenzi, Stefano; Gattai, Riccardo; Battistini, Silvio; Crocetti, Emanuele

    2017-03-14

    The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type life style, where there is a progressive increasing incidence and a low but not decreasing mor- tality, or somewhere an increase too, especially in the older age groups. Also in Tuscany there is a steady rise in incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case- case study, thin and thick melanoma cases, trying to find out those personal and tumour characteristics which may help to customize preventive interventions. RESULTS The results confirmed the age and the lower edu- cation level are associated with a later detection. The habit to perform skin self-examination is resulted protec- tive forward thick melanoma and also the diagnosis by a doctor. The elements emerging from the survey allow to hypothesize a group of subjects resulting at higher risk for a late diagnosis, aged over 50 and carrier of a fewer constitutional and environmental risk factors: few total and few atypical nevi, and lower sun exposure and burning. It is assumable that a part of people did not be reached from messages of prevention because does not recognize oneself in the categories of people at risk for skin cancers described in educational cam- paigns. If we want to obtain better results on diagnosis of skin melanoma we have to think a new strategy. At least to think over the educational messages discriminating people more at risk of incidence of melanoma from people more at risk to die from melanoma, and to renewed active involvement of the Gen- eral Practitioners .

  8. Immunotherapy in advanced melanoma: a network meta-analysis.

    Science.gov (United States)

    Pyo, Jung-Soo; Kang, Guhyun

    2017-05-01

    The aim of this study was to compare the effects of various immunotherapeutic agents and chemotherapy for unresected or metastatic melanomas. We performed a network meta-analysis using a Bayesian statistical model to compare objective response rate (ORR) of various immunotherapies from 12 randomized controlled studies. The estimated ORRs of immunotherapy and chemotherapy were 0.224 and 0.108, respectively. The ORRs of immunotherapy in untreated and pretreated patients were 0.279 and 0.176, respectively. In network meta-analysis, the odds ratios for ORR of nivolumab (1 mg/kg)/ipilmumab (3 mg/kg), pembrolizumab 10 mg/kg and nivolumab 3 mg/kg were 8.54, 5.39 and 4.35, respectively, compared with chemotherapy alone. Our data showed that various immunotherapies had higher ORRs rather than chemotherapy alone.

  9. Toxicity and Immunogenicity in Murine Melanoma following Exposure to Physical Plasma-Derived Oxidants

    Directory of Open Access Journals (Sweden)

    Sander Bekeschus

    2017-01-01

    Full Text Available Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capable of redox modulating cells and tissues without thermal damage. Cold plasma has been suggested for anticancer therapy. Here, melanoma cell toxicity, motility, and immunogenicity of murine metastatic melanoma cells were investigated following plasma exposure in vitro. Cells were oxidized by plasma, leading to decreased metabolic activity and cell death. Moreover, plasma decelerated melanoma cell growth, viability, and cell cycling. This was accompanied by increased cellular stiffness and upregulation of zonula occludens 1 protein in the cell membrane. Importantly, expression levels of immunogenic cell surface molecules such as major histocompatibility complex I, calreticulin, and melanocortin receptor 1 were significantly increased in response to plasma. Finally, plasma treatment significantly decreased the release of vascular endothelial growth factor, a molecule with importance in angiogenesis. Altogether, these results suggest beneficial toxicity of cold plasma in murine melanomas with a concomitant immunogenicity of potential interest in oncology.

  10. Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

    International Nuclear Information System (INIS)

    Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

    1989-01-01

    Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

  11. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  12. Advanced imaging techniques in pediatric body MRI

    Energy Technology Data Exchange (ETDEWEB)

    Courtier, Jesse [UCSF Benioff Children' s Hospital, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Rao, Anil G. [Medical University of South Carolina, Department of Radiology, Charleston, SC (United States); Anupindi, Sudha A. [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States)

    2017-05-15

    While there are many challenges specific to pediatric abdomino-pelvic MRI, many recent advances are addressing these challenges. It is therefore essential for radiologists to be familiar with the latest advances in MR imaging. Laudable efforts have also recently been implemented in many centers to improve the overall experience of pediatric patients, including the use of dedicated radiology child life specialists, MRI video goggles, and improved MR suite environments. These efforts have allowed a larger number of children to be scanned while awake, with fewer studies being done under sedation or anesthesia; this has resulted in additional challenges from patient motion and difficulties with breath-holding and tolerating longer scan times. In this review, we highlight common challenges faced in imaging the pediatric abdomen and pelvis and discuss the application of the newest techniques to address these challenges. Additionally, we highlight the newest advances in quantified imaging techniques, specifically in MR liver iron quantification. The techniques described in this review are all commercially available and can be readily implemented. (orig.)

  13. Animal type melanoma: a report of two cases

    Directory of Open Access Journals (Sweden)

    Mariângela Esther Alencar Marques

    2010-08-01

    Full Text Available Dificuldade potencial no diagnóstico histológico de melanomas é a dificuldade em reconhecer variantes pouco frequentes de melanoma. Entre elas, as mais desafiantes incluem exemplos de melanoma desmoplásico, melanoma nevoide, o chamado "melanoma de desvio mínimo", melanomas com proeminente síntese de pigmento ou "melanoma tipo animal" e o nevo azul maligno. Os autores descrevem dois casos de melanoma tipo animal e discute-se a importância do diagnóstico diferencial clinico-histopatológico nesses casos.A potential diagnostic pitfall in the histological assessment of melanomas is the difficulty in recognizing unusual melanoma variants. Among them, the most challenging examples comprise desmoplastic melanomas, nevoid melanomas, the so-called minimal-deviation melanoma, melanomas with prominent pigment synthesis or animal-type melanoma, and the malignant blue nevus. Two cases of animal type melanoma are reported and the importance of clinical-histopathological differential diagnosis is discussed.

  14. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

    2002-01-01

    of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented...... neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45...

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

    Energy Technology Data Exchange (ETDEWEB)

    Sustarsic, Elahu G. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Junnila, Riia K. [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Kopchick, John J., E-mail: kopchick@ohio.edu [Edison Biotechnology Institute, 1 Watertower Drive, Athens, OH (United States); Department of Biological Sciences, Ohio University, Athens, OH (United States); Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH (United States)

    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

  16. Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

    Science.gov (United States)

    Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

    2010-06-01

    Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

  17. Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

    Science.gov (United States)

    Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

    2010-12-01

    This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

  18. AKT1 as the PageRank hub gene is associated with melanoma and its functional annotation is highly related to the estrogen signaling pathway that may regulate the growth of melanoma.

    Science.gov (United States)

    Zhao, Jingjing; Zeng, Xue; Song, Ping; Wu, Xiaohong; Shi, Hongbo

    2016-10-01

    In order to detect the disease-associated genes and their gene interaction function and association with melanoma mechanisms, we identified a total of 1,310 differentially expressed genes (DEGs) from the Gene Expression Omnibus database GSE3189 with FDR 2 using the R package. After constructing the gene interaction network by STRING with the selected DEGs, we applied a statistical approach to identify the topological hub genes with PageRank score. Forty-four genes were identified in this network and AKT1 was selected as the most important hub gene. The AKT1 gene encodes a serine‑threonine protein kinase (AKT). High expression of AKT is involved in the resistance of cell apoptosis as well as adaptive resistance to treatment in melanoma. Our results indicated that AKT1 with a higher expression in melanoma showed enriched binding sites in the negative regulation of response to external stimulus, which enables cells to adapt to changes in external stimulation for survival. Another finding was that AKT regulated the lipid metabolic process and may be involved in melanoma progression and promotion of tumor growth through gene enrichment function analysis. Two highlighted pathways were detected in our study: i) the estrogen signaling pathway modulates the immune tolerance and resistance to cell apoptosis, which contributes to the growth of melanoma and ii) the RAP1 signaling pathway which regulates focal adhesion (FA) negative feedback to cell migration and invasion in melanoma. Our studies highlighted the top differentially expressed gene AKT1 and its correlation with the estrogen signaling and RAP1 signaling pathways to alter the proliferation and apoptosis of melanoma cells. Analysis of the enrichment functions of genes associated with melanoma will help us find the exact mechanism of melanoma and advance the full potential of newly targeted cancer therapy.

  19. Label-free, multi-contrast optical coherence tomography for study of skin melanoma mice in vivo

    Science.gov (United States)

    Lai, Pei-Yu; Lin, Tim-Han; Chou, Ya-Shuan; Chang, Chung-Hsing; Kuo, Wen-Chuan

    2018-02-01

    The lymphatic system plays an important role in inflammation and cancer such as melanoma. Due to the limitations of current developed imaging techniques, visualization of lymphatic vessels within the tissue in vivo has been challenging. Optical imaging of lymphatic vessel is gaining increased interests because it does not involve any radiation and can achieve very high resolution. Here, we developed a multi-contrast, label-free optical coherence tomography (OCT) imaging technology with an axial resolution of 5 μm and lateral resolution of 7 μm, which is capable of providing microstructural information and microcirculatory system including blood and lymphatic vessels simultaneously. Using this technique, we observed the melanoma mice in vivo. Mice were treated topically on the ear with (Z)-4- Hydroxytamoxifen(4-OHT) to elicit BRAFV600E and to silence Pten expression. Also, to observing the structural information, angiogenesis and lymphangiogenesis in the ear of the induced melanoma mouse can be done. The advantage of using OCT over other imaging modalities is its ability to assess label-free blood flow along with lymphatic vessels simultaneously for imaging the microcirculatory system within tissue beds without any exogenous agents. Because the metastasis of melanoma is highly related to the lymphatic vessels, our findings can be a powerful tool to help the diagnosis of the metastasis melanoma. In the future, this may become a helpful tool for better understanding pathologic mechanisms and treatment technique development in some diseases.

  20. The cost of unresectable stage III or stage IV melanoma in Italy

    Directory of Open Access Journals (Sweden)

    Maio Michele

    2012-11-01

    Full Text Available Abstract Background In recent decades, melanoma incidence has been increasing in European countries; in 2006, there were approximately 60,000 cases leading to 13,000 deaths. Within Europe there is some geographical variation in the incidence of melanoma, with the highest rates reported in Scandinavia (15 cases per 100,000 inhabitants per year and the lowest in the Mediterranean countries (5 to 7 cases per 100,000 inhabitants per year. Methods The present article is based on the information collected in the MELODY study (MELanoma treatment patterns and Outcomes among patients with unresectable stage III or stage IV Disease: a retrospective longitudinal survey. In that study, the medical charts of patients were reviewed to document current treatment patterns and to analyse information on patients, disease characteristics and healthcare resource utilization related to the treatment of advanced melanoma regarding patients who presented with a diagnosis of malignant melanoma (stage I to IV at participating sites between 01 July, 2005 and 30 June, 2006. Results Summarizing, though the length of the follow-up period varies among sample patients, an amount of the yearly cost per patient can be estimated, dividing the average per patient total cost (€ 5.040 by the average follow-up duration (17.5 months and reporting to one year; on these grounds, unresectable stage III or stage IV melanoma in Italy would cost € 3,456 per patient per year.

  1. Interpretation of Melanoma Risk Feedback in First-Degree Relatives of Melanoma Patients

    International Nuclear Information System (INIS)

    Hay, J. L.; Baguer, C.; Li, Y.; Orlow, I.; Berwick, M.

    2012-01-01

    Little is known about how individuals might interpret brief genetic risk feedback. We examined interpretation and behavioral intentions (sun protection, skin screening) in melanoma first-degree relatives (FDRs) after exposure to brief prototypic melanoma risk feedback. Using a 3 by 2 experimental pre-post design where feedback type (high-risk mutation, gene environment, and nongenetic) and risk level (positive versus negative findings) were systematically varied, 139 melanoma FDRs were randomized to receive one of the six scenarios. All scenarios included an explicit reminder that melanoma family history increased their risk regardless of their feedback. The findings indicate main effects by risk level but not feedback type; positive findings led to heightened anticipated melanoma risk perceptions and anticipated behavioral intentions. Yet those who received negative findings often discounted their family melanoma history. As such, 25%, 30%, and 32% of those who received negative mutation, gene-environment, and nongenetic feedback, respectively, reported that their risk was similar to the general population. Given the frequency with which those who pursue genetic testing may receive negative feedback, attention is needed to identify ideal strategies to present negative genetic findings in contexts such as direct to consumer channels where extensive genetic counseling is not required.

  2. Radiation biology of malignant melanoma

    International Nuclear Information System (INIS)

    Rofstad, E.K.; Norwegian Cancer Society, Oslo)

    1986-01-01

    The survival curves for melanoma cells exposed to single radiation doses in vitro and the specific growth delays for melanoma xenografts irradiated with single doses in vivo were found to differ considerably among individual cell lines and tumours. In fact, the differences could be almost as large as the largest differences observed among cell lines and xenografts from tumours of different histology with very different clinical radiocurability. Moreover, radiobiologic parameters that may have significant influence on tumour response to fractionated irradiation, e.g. growth rate, hypoxic fraction, reoxygenation ability, PLD-repair capacity and contact repair capacity, were found to differ greatly in magnitude among individual melanomas. This review therefore concludes that malignant melanoma is a tumour type that is very heterogeneous in radioresponsiveness, i.e. malignant melanomas should no longer be considered to be radiation resistant in general. The values of the α/β ratio derived from cell survival curves for melanoma cells irradiated in vitro and melanoma xenografts irradiated in vivo were found to cover a wide range relative to those for acutely and late responding normal tissues. Although these α/β ratios are no more than estimates of the effective α/β ratios in a clinical situation, they still indicated that hyperfractionation may be beneficial in the treatment of some melanomas, whereas others may be more efficiently treated by use of conventional fractionation regimes, either based on 2 Gy or higher doses per fraction. Consequently, optimum radiation therapy of malignant melanoma will probably require an individualized treatment strategy. In vitro assays for prediction of radiocurability and choice of treatment strategy for individual melanoma patients seem therefore highly warranted. (orig.)

  3. Predictors of responses to immune checkpoint blockade in advanced melanoma

    DEFF Research Database (Denmark)

    Jacquelot, N; Roberti, M P; Enot, D P

    2017-01-01

    Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs....... Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB. Based on this assay, we...

  4. Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma

    International Nuclear Information System (INIS)

    Kobayashi, Masato; Nishii, Ryuichi; Shikano, Naoto; Flores, Leo G.; Mizutani, Asuka; Ogai, Kazuhiro; Sugama, Jyunko; Nagamachi, Shigeki; Kawai, Keiichi

    2015-01-01

    significantly different from 125 I-L-PC. Conclusions: 125 I-PCA is a better substrate for tyrosinase and DNA polymerase and has higher uptake and longer retention in B16 melanoma cells when compared with 125 I-L-PC. Therefore, 123/131 I-PCA has good potential for diagnosis for malignant melanoma. Advance in Knowledge: 125 I-PCA will be a specific diagnosis tool for malignant melanoma. Implications for Patient Care: 123/131 I-PCA has good potential for the diagnosis of malignant melanoma when compared with other SPECT tracers, as well as anti-melanoma chemotherapeutic drugs

  5. Malignant Melanoma of Nose and Paranasal Sinuses: 2 Case Reports

    Directory of Open Access Journals (Sweden)

    Sanjeev Bhagat

    2010-04-01

    Full Text Available Malignant melanoma is one of the rare and highly aggressive diseases of the sinonasal cavity. High index of suspicion is required for diagnosis as the patient usually presents with non specific signs and symptoms. In the natural course of the disease, higher rate of loco regional recurrences and distant metastasis are seen making the overall prognosis of disease very poor. In reviewing the various treatment modalities used in the past, surgical resection of the tumour with postoperative radiotherapy is preferred one. Advances in surgery, radiotherapy and chemotherapy don’t have any impact on improved survival, which remains poor in this disease. We report two cases of malignant melanoma, which were treated at our institute.

  6. Prognosis of patients with transected melanomas.

    Science.gov (United States)

    Martires, Kathryn J; Nandi, Tina; Honda, Kord; Cooper, Kevin D; Bordeaux, Jeremy S

    2013-04-01

    The management of melanoma is directly related to Breslow's depth. Biopsying melanomas in a fashion that transects the deep margin precludes an accurate measurement of the true depth. To examine the prognosis of melanomas transected along the deep margins, as well as cases where no residual melanoma was seen on re-excision after transection. Records from a cohort of patients at one institution were examined from 1996 through 2007. Patients were considered to have "transected" melanomas if tumor cells were present on the deep margin of the biopsy. Overall survival was determined. Seven hundred fourteen patients were examined. 171 (24%) of all melanomas were transected. 101(59%) of those lacked tumor cells on re-excision. Patients with transected melanomas were older (OR = 1.03, p < .001), and had higher Breslow's depths (OR = 1.21, p < .001) than those without transected tumors. Those with no residual melanoma after transection were younger (OR = 0.98, p = .010) and more likely to have no lymph node involvement (OR = 2.23, p = .037). Neither transection (p = .760), nor lack of residual melanoma on re-excision after transection (p = .793) influenced survival. A high number of melanomas are transected at diagnosis, many of which lack visible tumor. The original Breslow's depth of transected melanomas without residual tumor on re-excision accurately predicts survival and prognosis. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

  7. Lifetime prevalence of non-melanoma and melanoma skin cancer in Australian recreational and competitive surfers.

    Science.gov (United States)

    Climstein, Mike; Furness, James; Hing, Wayne; Walsh, Joe

    2016-07-01

    Surfing is one of the most popular outdoor aquatic activities in Australia with an estimated 2.7 million recreational surfers; however, Australia has long been recognized as having the highest incidence of melanoma in the world, and it is the most common type of cancer in young Australians. The aim of this study was to investigate the lifetime prevalence of non-melanoma [basal cell carcinoma (BCC), squamous cell carcinoma (SCC)] and melanoma skin cancers in Australian recreational and competitive surfers. Australian surfers were invited to complete an online surveillance survey to determine the lifetime prevalence of non-melanoma and melanoma skin cancers. A total of 1348 surfers (56.9% recreational) participated in this study, of which 184 surfers reported a skin cancer (competitive n = 96, recreational n = 87). Of non-melanoma and melanoma cancers reported, BCC was the most common (6.8%), followed by melanoma (1.4%) and SCC (0.6%). The relative risk was higher (P well as significantly (P surf are advised to regularly utilize sun protection strategies (avoid peak ultraviolet radiation (10 am-3 pm), rashvest, hat and sunscreen) and primary care physicians are recommended to regularly screen their patients who surf. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Genetics of uveal melanoma and cutaneous melanoma: two of a kind?

    NARCIS (Netherlands)

    T. van den Bosch (Thomas); E. Kiliç (Emine); A.D.A. Paridaens (Dion); J.E.M.M. de Klein (Annelies)

    2010-01-01

    textabstractCutaneous melanoma and uveal melanoma both derive from melanocytes but show remarkable differences in tumorigenesis, mode of metastatic spread, genetic alterations, and therapeutic response. In this review we discuss the differences and similarities along with the genetic research

  9. Increasing Melanoma Screening Among Hispanic/Latino Americans: A Community-Based Educational Intervention.

    Science.gov (United States)

    Chung, Grace Y; Brown, Gina; Gibson, Desmond

    2015-10-01

    Melanoma incidence is increasing among Hispanics/Latinos in California. This community-based project reached out to a rural Hispanic/Latino community in North San Diego County to provide melanoma prevention and screening education. At a local community health fair, bilingual volunteer lay health workers led 10- to 15-minute-long information sessions on melanoma disease, risk factors, and skin self-examination techniques. Pearson chi-square analyses of participants' (N = 34) responses to pre- and postintervention evaluation surveys indicate significant increases in knowledge, risk awareness, and self-efficacy for self-screening. The results revealed that Hispanics/Latinos in a low socioeconomic stratum might be at moderate to high risk for developing melanoma. Their low annual income, low level of education, occupational sun-exposure, and lack of access to health care are likely factors that deter at-risk Hispanics/Latinos from seeking health care. © 2015 Society for Public Health Education.

  10. Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma.

    Science.gov (United States)

    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

    2015-07-15

    The human endogenous retrovirus (HERV-K) envelope (env) protein is a tumor-associated antigen (TAA) 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. Expression of HERV-K protein was analyzed in 220 melanoma samples (with various stages of disease) and 139 normal organ donor tissues using immunohistochemical (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. We detected HERV-K env protein on melanoma but not in normal tissues. After electroporation of T cells and selection on HERV-K(+) AaPC, more than 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 that can be recognized by HERV-K env-specific CAR(+) T cells, we observed a significant antitumor effect. 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. ©2015 American Association for Cancer Research.

  11. Metastatic melanoma masquerading as a furuncle

    Directory of Open Access Journals (Sweden)

    Imran Aslam

    2017-10-01

    Full Text Available Melanoma metastasizes to the skin in about 10-17% of patients. Although there are reports of metastatic melanoma masquerading as panniculitis and erysipelas, it is very uncommon for it to present as an inflammatory skin lesion. When malignant melanoma cells invade the superficial dermal lymphatic vessels it can result in erythema, edema and induration of the overlying skin. This presentation can be problematic for clinicians if they do not suspect melanoma and choose not to biopsy the lesion. We report a case of an elderly man with a history of invasive melanoma who presented with a furuncle-like lesion that was found to be in-transit metastatic melanoma.

  12. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

    Full Text Available Importance—Pediatric melanoma occurs, albeit rarely. Should patients be treated by today’s medical standards, or be subjected to medically unnecessary clinical studies? Observations—We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in www.clinicaltrials.gov and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale. Regulatory authorities define children by chronological age, not physiologically. Newborns’ organs are immature but they develop and mature rapidly. Separate proof of efficacy in underage patients is justified formally/regulatorily but lacks medical sense. Children—especially post-puberty—and adults vis-a-vis medications are physiologically very similar. Two adolescent melanoma studies were terminated in 2016 because of waning recruitment, while five studies in pediatric melanoma and other solid tumors, triggered by European Union pediatric investigation plans, continue recruiting worldwide. Conclusions and Relevance—Regulatory-demanded pediatric melanoma studies are medically superfluous. Melanoma patients of all ages should be treated with effective combination treatment. Babies need special attention. Children need dose-finding and pharmacokinetic studies but adolescents metabolize and respond to drugs similarly to adults. Institutional Review Boards/ethics committees should suspend ongoing questionable pediatric melanoma studies and reject newly submitted questionable studies.

  13. Test Concept for Advanced Oxidation Techniques

    DEFF Research Database (Denmark)

    Bennedsen, Lars Rønn; Søgaard, Erik Gydesen; Mortensen, Lars

    advanced on-site oxidation tests. The remediation techniques included are electrochemical oxidation, photochemical/photocatalytic oxidation, ozone, hydrogen peroxide, permanganate, and persulfate among others. A versatile construction of the mobile test unit makes it possible to combine different...

  14. Activation of the Canonical Wnt/β-Catenin Signalling Pathway is Rare in Canine Malignant Melanoma Tissue and Cell Lines

    Science.gov (United States)

    Chon, E.; Thompson, V.; Schmid, S.; Stein, T. J.

    2012-01-01

    Summary Canine malignant melanoma is a highly aggressive tumour associated with a poor overall survival rate due to both local disease recurrence and its highly metastatic nature. Similar to advanced melanoma in man, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumour and different from normal cells. The Wnt signalling pathway is known to contribute to melanocytic lineage development in vertebrates and perturbation of the Wnt/β-catenin pathway has been implicated in numerous cancer types. Alterations of the Wnt/β-catenin pathway are suggested to occur in a subset of human melanomas, although the precise role of the Wnt/β-catenin pathway in melanoma is yet to be defined. This study investigates the activation status of the canonical Wnt/β-catenin pathway in canine malignant melanoma and its potential as a therapeutic target for treating this disease. The data indicate canonical Wnt/β-catenin pathway activation is a rare event in canine oral malignant melanoma tissue and canine malignant melanoma cell lines. PMID:22901430

  15. Pediatric brain MRI. Pt. 2. Advanced techniques

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Mai-Lan; Campeau, Norbert G.; Welker, Kirk M. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Ngo, Thang D. [Nemours Children' s Hospital, Department of Radiology, Orlando, FL (United States); Udayasankar, Unni K. [University of Arizona, Department of Radiology, Tucson, AZ (United States)

    2017-05-15

    Pediatric neuroimaging is a complex and specialized field that uses magnetic resonance (MR) imaging as the workhorse for diagnosis. MR protocols should be tailored to the specific indication and reviewed by the supervising radiologist in real time. Targeted advanced imaging sequences can be added to provide information regarding tissue microstructure, perfusion, metabolism and function. In part 2 of this review, we highlight the utility of advanced imaging techniques for superior evaluation of pediatric neurologic disease. We focus on the following techniques, with clinical examples: phase-contrast imaging, perfusion-weighted imaging, vessel wall imaging, diffusion tensor imaging, task-based functional MRI and MR spectroscopy. (orig.)

  16. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.

  17. Pulse-mediated chemotherapy enhances local control and survival in a spontaneous canine model of primary mucosal melanoma.

    Science.gov (United States)

    Spugnini, Enrico P; Dragonetti, Emanuele; Vincenzi, Bruno; Onori, Nicoletta; Citro, Gennaro; Baldi, Alfonso

    2006-02-01

    Mucosal melanomas account for 1% of all malignant melanomas in humans. Treatment options include surgery, chemotherapy, immunotherapy and radiation therapy; however, local recurrence and distant dissemination are still frequent. We treated locally aggressive spontaneous canine oral melanomas that, because of their advanced stage, were not treatable with conventional strategies. A cohort of 10 dogs with oral melanoma was enrolled over a 4-year period. The dogs received two sessions of local bleomycin, followed by the application of trains of biphasic pulses. The treatment was well tolerated and resulted in an overall response rate of 80% with 50% long-term control. Of interest, only one of the dogs died of metastatic disease, and four of the long-term survivors showed a vitiligo-like discoloration at the site of treatment, potentially suggesting a recruitment of the immune system by the therapy. Further studies are needed to characterize this approach and to determine its suitability for head and neck mucosal melanoma.

  18. Nail apparatus melanoma: a diagnostic opportunity Melanoma do aparelho ungueal: uma oportunidade diagnóstica

    Directory of Open Access Journals (Sweden)

    Ana Maria Carreño

    2013-04-01

    Full Text Available Malignant Melanoma is a high mortality neoplasm. The involvement of the nail apparatus is rare, with only 2 out of 3 patients seeking medical attention as the result of recent nail melanocytic lesions. This results in late diagnosis and a prognosis worse than cutaneous melanoma. We report a female, presenting with ulcerative lesions with clinical and laboratory features compatible with leishmaniasis. On return after treatment initiation a longitudinal melanonychia was observed on her first right finger. Biopsy of the nail matrix was performed. Histopathology was compatible with melanoma in situ. Longitudinal melanonychia is not a specific sign for melanoma and it is important that the dermatologist should identify the suspect lesions correctly. The incidental diagnosis of nail melanoma in situ in our case significantly impacted the patient's survival.Melanoma Maligno é uma neoplasia de alta mortalidade, sendo raro o acometimento do aparelho ungueal. Apenas 2/3 dos pacientes procuram atendimento médico devido lesão melanocítica ungueal recente, tornando o diagnóstico tardio e com prognóstico pior que do melanoma cutâneo. Descreve-se um caso de paciente sexo feminino, apresentando lesões ulceradas com características clínico-laboratoriais compatíveis com leishmaniose tegumentar americana. No retorno após início do tratamento foi observada melanoníquia longitudinal no primeiro quirodáctilo direito. Realizada biópsia da matriz ungueal com histopatológico compatível com melanoma in situ. Melanoníquia longitudinal não é sinal específico de melanoma. A identificação das lesões suspeitas é importante tarefa dos dermatologistas. O diagnóstico incidental de melanoma ungueal in situ do caso relatado resultou em grande impacto na sobrevida da paciente.

  19. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    International Nuclear Information System (INIS)

    Barker, Christopher A.; Postow, Michael A.

    2014-01-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study

  20. Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: barkerc@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Postow, Michael A. [Department of Medicine, Melanoma and Sarcoma Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-04-01

    Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

  1. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma

    NARCIS (Netherlands)

    Cobben, DCP; Koopal, S; Tiebosch, ATMG; Jager, PL; Elsinga, PH; Wobbes, T; Hoekstra, HJ

    2002-01-01

    The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection. in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research,

  2. Melanoma stem cells in experimental melanoma are killed by radioimmunotherapy

    International Nuclear Information System (INIS)

    Jandl, Thomas; Revskaya, Ekaterina; Jiang, Zewei; Harris, Matthew; Dorokhova, Olena; Tsukrov, Dina; Casadevall, Arturo; Dadachova, Ekaterina

    2013-01-01

    Introduction: In spite of recently approved B-RAF inhibitors and immunomodulating antibodies, metastatic melanoma has poor prognosis and novel treatments are needed. Melanoma stem cells (MSC) have been implicated in the resistance of this tumor to chemotherapy. Recently we demonstrated in a Phase I clinical trial in patients with metastatic melanoma that radioimmunotherapy (RIT) with 188-Rhenium( 188 Re)-6D2 antibody to melanin was a safe and effective modality. Here we investigated the interaction of MSC with RIT as a possible mechanism for RIT efficacy. Methods: Mice bearing A2058 melanoma xenografts were treated with either 1.5 mCi 188 Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188 Re-labeled non-specific IgM. Results: On Day 28 post-treatment the tumor size in the RIT group was 4-times less than in controls (P < 0.001). The tumors were analyzed by immunohistochemistry and FACS for two MSC markers — chemoresistance mediator ABCB5 and H3K4 demethylase JARID1B. There were no significant differences between RIT and control groups in percentage of ABCB5 or JARID1B-positive cells in the tumor population. Our results demonstrate that unlike chemotherapy, which kills tumor cells but leaves behind MSC leading to recurrence, RIT kills MSC at the same rate as the rest of tumor cells. Conclusions: These results have two main implications for melanoma treatment and possibly other cancers. First, the susceptibility of ABCB5 + and JARID1B + cells to RIT in melanoma might be indicative of their susceptibility to antibody-targeted radiation in other cancers where they are present as well. Second, specifically targeting cancer stem cells with radiolabeled antibodies to ABCB5 or JARID1B might help to completely eradicate cancer stem cells in various cancers

  3. Ultrasonic characterisation of malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    John Sheila

    1998-01-01

    Full Text Available An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in order to differentiate histological subtypes of malignant melanoma. To obtain the backscattering coefficient for the tissues, we used a broadband focussed transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz. Experimental measurement of backscattering coefficient and attenuation coefficient at various frequencies was done by substitution techniques. The backscattering coefficient, scatterer size, and root mean square velocity fluctuation were derived by the numerical method, while the attenuation coefficient at 1 MHz was derived from attenuation coefficient at different frequencies. This study revealed that backscattering coefficient and attenuation coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle cell type compared to the mixed cell type of malignant melanoma. Particularly, the scatterer size was significantly higher in the spindle cell group (p = 0.013 in contrast to the mixed cell type. Spindle cells have uniform and compact histological pattern which contributes to an increase in scatterer size and root mean square velocity fluctuation. The ultrasonically obtained parameters have been shown to have a good correlation with the histology of malignant melanoma.

  4. Curcumin and treatment of melanoma: The potential role of microRNAs.

    Science.gov (United States)

    Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein

    2017-04-01

    Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma.

    Science.gov (United States)

    Eton, O; Kharkevitch, D D; Gianan, M A; Ross, M I; Itoh, K; Pride, M W; Donawho, C; Buzaid, A C; Mansfield, P F; Lee, J E; Legha, S S; Plager, C; Papadopoulos, N E; Bedikian, A Y; Benjamin, R S; Balch, C M

    1998-03-01

    Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.

  6. Membrane-type-3 matrix metalloproteinase (MT3-MMP functions as a matrix composition-dependent effector of melanoma cell invasion.

    Directory of Open Access Journals (Sweden)

    Olga Tatti

    Full Text Available In primary human melanoma, the membrane-type matrix metalloproteinase, MT3-MMP, is overexpressed in the most aggressive nodular-type tumors. Unlike MT1-MMP and MT2-MMP, which promote cell invasion through basement membranes and collagen type I-rich tissues, the function of MT3-MMP in tumor progression remains unclear. Here, we demonstrate that MT3-MMP inhibits MT1-MMP-driven melanoma cell invasion in three-dimensional collagen, while yielding an altered, yet MT1-MMP-dependent, form of expansive growth behavior that phenocopies the formation of nodular cell colonies. In melanoma cell lines originating from advanced primary or metastatic lesions, endogenous MT3-MMP expression was associated with limited collagen-invasive potential. In the cell lines with highest MT3-MMP expression relative to MT1-MMP, collagen-invasive activity was increased following stable MT3-MMP gene silencing. Consistently, MT3-MMP overexpression in cells derived from less advanced superficially spreading melanoma lesions, or in the MT3-MMP knockdown cells, reduced MT1-MMP-dependent collagen invasion. Rather than altering MT1-MMP transcription, MT3-MMP interacted with MT1-MMP in membrane complexes and reduced its cell surface expression. By contrast, as a potent fibrinolytic enzyme, MT3-MMP induced efficient invasion of the cells in fibrin, a provisional matrix component frequently found at tumor-host tissue interfaces and perivascular spaces of melanoma. Since MT3-MMP was significantly upregulated in biopsies of human melanoma metastases, these results identify MT3-MMP as a matrix-dependent modifier of the invasive tumor cell functions during melanoma progression.

  7. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  8. HLA-B8 association with late-stage melanoma – an immunological lesson?

    Directory of Open Access Journals (Sweden)

    Andersen Mads

    2006-03-01

    Full Text Available Abstract Background Differences in HLA allele frequencies between the diseased and healthy populations may signify efficient immune responses, a notion that has been successfully tested for infectious diseases or for association with genetic elements involved in a distinct type of immunity. This retrospective study is intended to detect differences in MHC class I carrier frequencies of advanced melanoma patients compared to healthy bone marrow donors. Methods The HLA-A and -B carrier frequencies of 748 stage IV melanoma patients retrieved from serotyping at 6 different centers in Germany were compared using a chi-square test to 13,386 fully HLA typed bone marrow donors registered in the German national bone marrow donor registry. Results The comparison of HLA carrier frequencies in advanced cancer patients with healthy bone marrow donors revealed a significant decrease in HLA-B8 carrier frequencies, which was also apparent in patients with advanced disease compared to patients with loco-regional disease. Conclusion The data suggest that protective immune responses restricted to distinct MHC class I molecules may be operational in a subset of melanoma patients, which is the prerequisite for a large scale screen for the corresponding epitopes. Alternatively, the known association of the ancestral haplotype HLA-A1, -B8 and -DR3 with genetic elements such as distinct TNF-α alleles might have a protective effect on disease progression. In any case, identification of the cause of protection within this patient subset might lead to a significant improvement in the efficacy of current immunotherapeutic approaches.

  9. [Ultrasound in the management of non-melanoma skin cancer].

    Science.gov (United States)

    Hernández Ibáñez, C; Aguilar Bernier, M; de Troya Martín, M

    2015-11-01

    Cutaneous ultrasound plays an important role in the study and management of non-melanoma skin cancer. Among other factors, this technique contributes to the diagnosis and differential diagnosis of these tumours, the establishment of their size and relation to neighbouring structures, the delimitation of surgical margins, and the detection of subclinical and recurrent lesions. The present article analyses the role of cutaneous ultrasound in the field of non-melanoma skin cancer (basal and squamous cell carcinomas, lymphomas and dermatofibrosarcoma) through a literature review. Copyright © 2015 Academia Española de Dermatología y Venereología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Cancer immunology and canine malignant melanoma: A comparative review.

    Science.gov (United States)

    Atherton, Matthew J; Morris, Joanna S; McDermott, Mark R; Lichty, Brian D

    2016-01-01

    Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Immunohistochemical Analysis of Collagen IV and Laminin Expression in Spontaneous Melanoma Regression in the Melanoma-Bearing Libechov Minipig

    International Nuclear Information System (INIS)

    Planska, Daniela; Burocziova, Monika; Strnadel, Jan; Horak, Vratislav

    2015-01-01

    Spontaneous regression (SR) of human melanoma is a rare, well-documented phenomenon that is not still fully understood. Its detailed study cannot be performed in patients due to ethical reasons. Using the Melanoma-bearing Libechov Minipig (MeLiM) animals of various ages (from 3 weeks to 8 months) we implemented a long-term monitoring of melanoma growth and SR. We focused on immunohistochemical detection of two important extracellular matrix proteins, collagen IV and laminin, which are associated with cancer. We showed that SR of melanoma is a highly dynamic process. The expression of collagen IV and laminin correlated with changes in population of melanoma cells. Tumours of 3-week-old animals consisted primarily of melanoma cells with a granular expression of collagen IV and laminin around them. Thereafter, melanoma cells were gradually destroyed and tumour tissue was rebuilt into the connective tissue. Collagen IV expression slightly increased in tumours of 10-week-old pigs showing extracellular fibrous appearance. In tumours of older animals, areas lacking melanoma cells demonstrated a low expression and areas still containing melanoma cells a high expression of both proteins. We considered the age of 10 weeks as a turning point in the transition between tumour growth and SR of the MeLiM melanoma

  12. Molecular Classification of Melanoma

    Science.gov (United States)

    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.

  13. Two unusual cases of brain metastases from lung primary malignant melanoma

    International Nuclear Information System (INIS)

    Rodríguez, A.; Mañana, G.; Panuncio, A.; Rodríguez, R.; Roldán, G.; Sosa, A.

    2004-01-01

    Start with two cases of brain metastases from lung melanoma are presented who were diagnosed in the Neuropathology Laboratory of the Department of Anatomy Pathology, Institute of Neurology, Hospital de Clinicas, Montevideo, emphasizing the pathological diagnostic criteria and their evolution clinic. Both patients presented at the time of the initial consultation injuries amelánica respectively pigmented single brain. In both cases ruled by the morphology and the use of complementary techniques metastasis carcinoma. The main differential diagnosis of these lesions is whether is a primitive brain tumor, pigmented or not, or of a secondary tumor melanin: metastatic malignant melanoma. In both cases the patients had been studied one being in an unresectable lung injury, and in the other showed a single pulmonary nodule was resected in its entirety. the pulmonary lesions were for malignant melanoma, one with ample pigment and the other for the most part amelánico, with few areas retained pigment. He studied dermatologist, discarded the presence of a cutaneous malignant melanoma primitive. Other locations were also excluded

  14. Randomized phase I pharmacokinetic study of ipilimumab with or without one of two different chemotherapy regimens in patients with untreated advanced melanoma.

    Science.gov (United States)

    Weber, Jeffrey; Hamid, Omid; Amin, Asim; O'Day, Steven; Masson, Eric; Goldberg, Stacie M; Williams, Daphne; Parker, Susan M; Chasalow, Scott D; Alaparthy, Suresh; Wolchok, Jedd D

    2013-01-01

    We describe a randomized three-arm phase I study of ipilimumab administered alone (I group) or in combination with dacarbazine (D group) or carboplatin/paclitaxel (CP group) in patients with previously untreated advanced melanoma. The primary objective was to estimate the effect of ipilimumab on the pharmacokinetics (PK) of dacarbazine and paclitaxel and, conversely, to estimate the effects of dacarbazine and carboplatin/paclitaxel on the PK of ipilimumab. Secondary objectives included evaluation of the safety and anti-tumor activity of ipilimumab when administered alone or with either dacarbazine or carboplatin/paclitaxel, and assessment of pharmacodynamic (PD) effects of ipilimumab on the immune system when administered alone or with either of the two chemotherapies. Ipilimumab was administered at a dose of 10 mg/kg intravenously (IV) every 3 weeks for up to 4 doses. Patients in the D group received dacarbazine 850 mg/m(2) IV every 3 weeks. Patients in the CP group received paclitaxel 175 mg/m(2) IV and carboplatin [AUC=6] IV every 3 weeks. Starting at week 24, patients without dose-limiting toxicities were eligible to receive maintenance ipilimumab at 10 mg/kg every 12 weeks until disease progressed or toxicity required discontinuation. Of 59 randomized patients, 18 (30.5%) discontinued treatment due to adverse events. Response rates by modified WHO criteria were 29.4% (I group), 27.8% (D group), and 11.1% (CP group). No major PK or PD interactions were observed when ipilimumab was administered with dacarbazine or with the carboplatin/paclitaxel combination. This study demonstrated that ipilimumab can be combined safely with two chemotherapy regimens commonly used in advanced melanoma.

  15. Advanced sensing techniques for cognitive radio

    CERN Document Server

    Zhao, Guodong; Li, Shaoqian

    2017-01-01

    This SpringerBrief investigates advanced sensing techniques to detect and estimate the primary receiver for cognitive radio systems. Along with a comprehensive overview of existing spectrum sensing techniques, this brief focuses on the design of new signal processing techniques, including the region-based sensing, jamming-based probing, and relay-based probing. The proposed sensing techniques aim to detect the nearby primary receiver and estimate the cross-channel gain between the cognitive transmitter and primary receiver. The performance of the proposed algorithms is evaluated by simulations in terms of several performance parameters, including detection probability, interference probability, and estimation error. The results show that the proposed sensing techniques can effectively sense the primary receiver and improve the cognitive transmission throughput. Researchers and postgraduate students in electrical engineering will find this an exceptional resource.

  16. Xeroderma Pigmentosum with Melanoma of Face and Its Prosthetic Management

    International Nuclear Information System (INIS)

    Sadaf, A.; Yazdanie, N.

    2013-01-01

    Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous, ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also its secondary characters. This case report is about maxillofacial prosthetic management of a 10 years old child presented with xeroderma pigmentosum. The nose of the patient was excised surgically due to melanoma. This case report elaborates the role of prosthodontist and the whole procedure of constructing the nasal prosthesis via conventional technique by using the patient's sibling nasal form as template. Regular follow up revealed marked improvement in esthetics, function and ultimately patient's quality of life. (author)

  17. Xeroderma pigmentosum with melanoma of face and its prosthetic management.

    Science.gov (United States)

    Sadaf, Ayesha; Yazdanie, Nazia

    2013-10-01

    Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous, ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also its secondary characters. This case report is about maxillofacial prosthetic management of a 10 years old child presented with xeroderma pigmentosum. The nose of the patient was excised surgically due to melanoma. This case report elaborates the role of prosthodontist and the whole procedure of constructing the nasal prosthesis via conventional technique by using the patient's sibling nasal form as template. Regular follow up revealed marked improvement in esthetics, function and ultimately patient's quality of life.

  18. Advanced structural equation modeling issues and techniques

    CERN Document Server

    Marcoulides, George A

    2013-01-01

    By focusing primarily on the application of structural equation modeling (SEM) techniques in example cases and situations, this book provides an understanding and working knowledge of advanced SEM techniques with a minimum of mathematical derivations. The book was written for a broad audience crossing many disciplines, assumes an understanding of graduate level multivariate statistics, including an introduction to SEM.

  19. Autoantibodies May Predict Immune-Related Toxicity: Results from a Phase I Study of Intralesional Bacillus Calmette–Guérin followed by Ipilimumab in Patients with Advanced Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Jessica Da Gama Duarte

    2018-03-01

    Full Text Available Immune checkpoint inhibitors (ICIs have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4; however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL bacillus Calmette–Guérin (BCG, a living attenuated strain of Mycobacterium bovis, was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection. We evaluated these two immune stimulants in combination with melanoma with the aim of developing a more effective immunotherapy and to assess toxicity. In this phase I study, patients with histologically confirmed stage III/IV metastatic melanoma received IL BCG injection followed by up to four cycles of intravenous ipilimumab (anti-CTLA-4 (ClinicalTrials.gov number NCT01838200. The trial was discontinued following treatment of the first five patients as the two patients receiving the escalation dose of BCG developed high-grade immune-related adverse events (irAEs typical of ipilimumab monotherapy. These irAEs were characterized in both patients by profound increases in the repertoire of autoantibodies directed against both self- and cancer antigens. Interestingly, the induced autoantibodies were detected at time points that preceded the development of symptomatic toxicity. There was no overlap in the antigen specificity between patients and no evidence of clinical responses. Efforts to increase response rates through the use of novel immunotherapeutic combinations may be associated with higher rates of irAEs, thus the imperative to identify biomarkers of toxicity remains strong. While the small patient numbers in this trial do not allow for any conclusive evidence of predictive biomarkers, the observed changes warrant further examination of autoantibody repertoires in larger patient cohorts at risk of developing irAEs during their

  20. Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling.

    Science.gov (United States)

    Syed, Deeba N; Chamcheu, Jean-Christopher; Khan, Mohammad Imran; Sechi, Mario; Lall, Rahul K; Adhami, Vaqar M; Mukhtar, Hasan

    2014-06-01

    The incidence of melanoma continues to rise. Inspite of treatment advances, the prognosis remains grim once the disease has metastasized, emphasizing the need to explore additional therapeutic strategies. One such approach is through the use of mechanism-based dietary intervention. We previously showed that the flavonoid fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we studied fisetin-mediated regulation of kinases involved in melanoma growth and progression. Time-course analysis in 3-D melanoma constructs that transitioned from radial to vertical growth showed that fisetin treatment resulted in significant decrease in melanocytic lesions in contrast to untreated controls that showed large tumor nests and invading disseminated cells. Further studies in melanoma cultures and mouse xenografts showed that fisetin-mediated growth inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K proteins. In silico modeling indicated direct interaction of fisetin with mTOR and p70S6K with favorable free energy values. These findings were validated by cell-free competition assays that established binding of fisetin to p70S6K and mTOR while little affinity was detected with AKT. Kinase activity studies reflected similar trend with % inhibition observed for p70S6K and mTOR at lower doses than AKT. Our studies characterized, for the first time, the differential interactions of any botanical agent with kinases involved in melanoma growth and demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated pathways. Published by Elsevier Inc.

  1. When narrative medicine helps in the diagnosis of conjunctival melanoma – an exceptional case report [

    Directory of Open Access Journals (Sweden)

    Nunes, Ana Teresa

    2012-07-01

    Full Text Available [english] Introduction: Conjunctival melanoma is a relatively rare ocular malignancy with substantial associated morbidity and mortality. It can arise in previously unblemished and unpigmented regions (approximately 10% of cases, from a preexisting nevus (approximately 20% of cases, or from the flat, spreading pigmentation of primary acquired melanosis with atypia (60–70% of cases, actually called conjunctival melanocytic intraepithelial neoplasia (C-MIN with atypia (histopathologically more accurately term. Purpose: The authors describe an extremely rare case of malignant conjunctival melanoma, with a long evolution, in a young black woman. Results: Until now the patient has not shown any sign of relapse of this melanoma, after local excision.Conclusion: Conjunctival melanoma is a condition of concern because of its rarity and lethal potential. Advances in the understanding and management of this neoplasm have markedly reduced the mortality and possibly the morbidity associated with this malignancy. We observe that there are some cases of conjunctival melanoma that might be cured with only a local excision with posterior cryotherapy without more aggressive methods. The practice of narrative medicine brings new possibilities in the diagnosis and collection of classical history.

  2. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives.

    Science.gov (United States)

    Durando, Xavier; Thivat, Emilie; D'Incan, Michel; Sinsard, Anne; Madelmont, Jean-Claude; Chollet, Philippe

    2005-11-15

    Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of approximately 6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency.

  3. Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

    Science.gov (United States)

    Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

    2017-02-01

    Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

  4. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: Cessation of CTL responses is associated with disease progression

    DEFF Research Database (Denmark)

    Andersen, M.H.; Keikavoussi, P.; Brocker, E.B.

    2001-01-01

    Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease...... by Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical...

  5. Analysis of Enzymatic Activity of Matrix Metalloproteinase (MMP) by Collagen Zymography in Melanoma.

    Science.gov (United States)

    Walia, Vijay; Samuels, Yardena

    2018-01-01

    Protein zymography is the most commonly used technique to study the enzymatic activity of matrix metalloproteinases (MMPs) and their inhibitors. MMPs are proteolytic enzymes that promote extracellular matrix degradation. MMPs are frequently mutated in malignant melanomas as well as other cancers and are linked to increasing incidence of tumor metastasis. Substrate zymography characterizes MMP activity by their ability to degrade preferred substrates. Here we describe the collagen zymography technique to measure the active or latent form of MMPs using MMP-8 as an example, which is a frequently mutated MMP family member in malignant melanomas. The same technique can be used with the modification of substrate to detect metalloproteinase activity of other MMPs. Both wild-type and mutated forms of MMPs can be analyzed using a single gel using this method.

  6. In vitro and in vivo studies in boron neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    Allen, B.J.

    1982-01-01

    A multidisciplinary research project in boron neutron capture therapy of malignant melanoma is under consideration by the Australian Atomic Energy Commission. This paper reviews the biochemistry of melanoma and the properties of some melanoma-affined radiopharmaceuticals and their boron analogues. Human cell lines are being used for in vitro tests of uptake and incorporation of some of these compounds, and selected lines will then be implanted in nude mice for in vivo distribution studies. The fidelity of human melanoma xenografts in nude mice has been well studied, and results are reviewed in this paper. Boron concentration will be measured directly by plasma arc emission spectroscopy or liquid scintillation counting with 14 C-labelled boron analogues. Track-etch techniques will be used for the microscopic determination of boron in tumor sections. Neutron irradiation and radiobiology experiments are outlined

  7. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

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

    1985-01-01

    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. Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma.

    Science.gov (United States)

    Syed, Deeba N; Lall, Rahul K; Chamcheu, Jean Christopher; Haidar, Omar; Mukhtar, Hasan

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

  9. Combined BRAF and HSP90 inhibition in patients with unresectable BRAF V600E mutant melanoma.

    Science.gov (United States)

    Eroglu, Zeynep; Chen, Yian Ann; Gibney, Geoffrey T; Weber, Jeffrey S; Kudchadkar, Ragini R; Khushalani, Nikhil I; Markowitz, Joseph; Brohl, Andrew S; Tetteh, Leticia F; Ramadan, Howida; Arnone, Gina; Li, Jiannong; Zhao, Xiuhua; Sharma, Ritin; Darville, Lancia N F; Fang, Bin; Smalley, Inna; Messina, Jane L; Koomen, John M; Sondak, Vernon K; Smalley, Keiran S M

    2018-04-19

    BRAF inhibitors are clinically active in patients with advanced BRAF V600 -mutant melanoma, although acquired resistance remains common. Preclinical studies demonstrated that resistance could be overcome using concurrent treatment with the HSP90 inhibitor XL888. Vemurafenib (960 mg PO BID) combined with escalating doses of XL888 (30, 45, 90 or 135 mg PO twice weekly) was investigated in 21 patients with advanced BRAF V600 -mutant melanoma. Primary endpoints were safety and determination of a maximum tolerated dose. Correlative proteomic studies were performed to confirm HSP inhibitor activity. Objective responses were observed in 15/20 evaluable patients (75%; 95% CI: 51-91%), with 3 complete and 12 partial responses. Median progression-free and overall survival were 9.2 months (95% CI: 3.8-not reached) and 34.6 months (6.2-not reached), respectively. The most common grade 3/4 toxicities were skin toxicities such as rash (n=4, 19%) and cutaneous squamous cell carcinomas (n=3, 14%), along with diarrhea (n=3, 14%). Pharmacodynamic analysis of patients' PBMCs showed increased day 8 HSP70 expression compared to baseline in the three cohorts with XL888 doses ≥45 mg. Diverse effects of vemurafenib-XL888 upon intratumoral HSP-client protein expression were noted, with the expression of multiple proteins (including ERBB3 and BAD) modulated on therapy. XL888 in combination with vemurafenib has clinical activity in patients with advanced BRAF V600 -mutant melanoma, with a tolerable side-effect profile. HSP90 inhibitors warrant further evaluation in combination with current standard-of-care BRAF plus MEK inhibitors in BRAF V600 -mutant melanoma. Copyright ©2018, American Association for Cancer Research.

  10. Metastatic melanoma after 23 years of primary ocular melanoma.

    LENUS (Irish Health Repository)

    Karde, Supriya Ramesh

    2016-11-23

    We describe a case of 52-year-old man who presented with an episode of tonic-clonic seizures. He had right ocular melanoma 23 years ago with subsequent enucleation which was the standard treatment at that time. CT scans of the brain and of the thorax-abdomen-pelvis revealed widespread metastatic lesions in the brain, lung and liver. Further investigations including bronchoscopy with cytopathology uncovered that the metastatic disease was a recurrence of ocular melanoma. He received palliative radiotherapy and died 6 months later. Ocular melanoma is often associated with fulminant metastatic disease after a period of dormancy. Thus, despite successful treatment of the localised disease at initial presentation, an effort is needed for optimal long-term follow-up plan in order to improve survival in case of recurrence.

  11. 67Gallium citrate scintigraphy to assess metastatic spread in a dog with an oral melanoma.

    Science.gov (United States)

    Liuti, T; de Vos, J; Bosman, T; van de Wiele, C; Grinwis, G C M; van Bree, H; Peremans, K

    2009-01-01

    Gallium scintigraphy was used to evaluate therapeutic response in a 10-year-old, male, Dutch sheepdog, suffering from an oral melanoma. Treatment was performed with a combination of carboplatin and hypofractionated radiation. Nineteen weeks after radiation therapy, the left submandibular lymph node was surgically removed because of metastatic disease. Thirty weeks after radiation therapy, 67Gallium scintigraphy was performed to assess for residual disease and metastasis. Increased uptake in the right submandibular lymph node area was noted and identified as a melanoma metastasis on cytology. Surgical excision was performed. Twenty-one weeks later, the dog was euthanased because of advanced pulmonary metastases. This report of a case of oral melanoma illustrates the advantages of 67Gallium scintigraphy in monitoring for the presence of metastatic disease and effectiveness of therapy.

  12. Identification of an Immunogenic Subset of Metastatic Uveal Melanoma.

    Science.gov (United States)

    Rothermel, Luke D; Sabesan, Arvind C; Stephens, Daniel J; Chandran, Smita S; Paria, Biman C; Srivastava, Abhishek K; Somerville, Robert; Wunderlich, John R; Lee, Chyi-Chia R; Xi, Liqiang; Pham, Trinh H; Raffeld, Mark; Jailwala, Parthav; Kasoji, Manjula; Kammula, Udai S

    2016-05-01

    Uveal melanoma is a rare melanoma variant with no effective therapies once metastases develop. Although durable cancer regression can be achieved in metastatic cutaneous melanoma with immunotherapies that augment naturally existing antitumor T-cell responses, the role of these treatments for metastatic uveal melanoma remains unclear. We sought to define the relative immunogenicity of these two melanoma variants and determine whether endogenous antitumor immune responses exist against uveal melanoma. We surgically procured liver metastases from uveal melanoma (n = 16) and cutaneous melanoma (n = 35) patients and compared the attributes of their respective tumor cell populations and their infiltrating T cells (TIL) using clinical radiology, histopathology, immune assays, and whole-exomic sequencing. Despite having common melanocytic lineage, uveal melanoma and cutaneous melanoma metastases differed in their melanin content, tumor differentiation antigen expression, and somatic mutational profile. Immunologic analysis of TIL cultures expanded from these divergent forms of melanoma revealed cutaneous melanoma TIL were predominantly composed of CD8(+) T cells, whereas uveal melanoma TIL were CD4(+) dominant. Reactivity against autologous tumor was significantly greater in cutaneous melanoma TIL compared with uveal melanoma TIL. However, we identified TIL from a subset of uveal melanoma patients which had robust antitumor reactivity comparable in magnitude with cutaneous melanoma TIL. Interestingly, the absence of melanin pigmentation in the parental tumor strongly correlated with the generation of highly reactive uveal melanoma TIL. The discovery of this immunogenic group of uveal melanoma metastases should prompt clinical efforts to determine whether patients who harbor these unique tumors can benefit from immunotherapies that exploit endogenous antitumor T-cell populations. Clin Cancer Res; 22(9); 2237-49. ©2015 AACR. ©2015 American Association for Cancer Research.

  13. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

    Directory of Open Access Journals (Sweden)

    Sinsard Anne

    2005-11-01

    Full Text Available Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU (60 or 90 mg/m2. Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

  14. Xeroderma pigmentosum genes and melanoma risk.

    Science.gov (United States)

    Paszkowska-Szczur, K; Scott, R J; Serrano-Fernandez, P; Mirecka, A; Gapska, P; Górski, B; Cybulski, C; Maleszka, R; Sulikowski, M; Nagay, L; Lubinski, J; Dębniak, T

    2013-09-01

    Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. Copyright © 2013 UICC.

  15. Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Bjørn, Jon; Lyngaa, Rikke Birgitte; Andersen, Rikke

    2017-01-01

    Introduction: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thus...

  16. Influence of ipilimumab on expanded tumour derived T cells from patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Bjørn, Jon; Lyngaa, Rikke Birgitte; Andersen, Rikke

    2017-01-01

    Introduction: Tumour infiltrating lymphocyte (TIL) based adoptive cell therapy (ACT) is a promising treatment for patients with advanced melanoma. Retrospective studies suggested an association between previous treatment with anti-CTLA-4 antibodies and long term survival after subsequent ACT. Thu...

  17. Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

    Full Text Available The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction—based assay (TRAP. High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastasess = 54.5, lymph node metastasess = 56.5. Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9. Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

  18. On the role of classical and novel forms of vitamin D in melanoma progression and management.

    Science.gov (United States)

    Slominski, Andrzej T; Brożyna, Anna A; Skobowiat, Cezary; Zmijewski, Michal A; Kim, Tae-Kang; Janjetovic, Zorica; Oak, Allen S; Jozwicki, Wojciech; Jetten, Anton M; Mason, Rebecca S; Elmets, Craig; Li, We; Hoffman, Robert M; Tuckey, Robert C

    2018-03-01

    Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH) 2 D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors, or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as

  19. One Step Melanoma Surgery for Patient with Thick Primary Melanomas: "To Break the Rules, You Must First Master Them!"

    Science.gov (United States)

    Tchernev, Georgi

    2018-02-15

    We present to the attention of the medical, dermatological and oncosurgical community data that serves to indicate the indispensability of optimisation of the algorithm and recommendations for diagnosis and surgical treatment of cutaneous melanoma. These recommendations could be referred to different subgroups of patients in different clinical stages as well as to patients with different initial characterisation (histological morphology) of the primary tumours. One step surgery is not a myth, even more, it could prove to be one of the best solutions for some patient collectives with advanced stages of melanoma. We present a case of a 74 - year old patient with a congenital medium sized melanocytic nevus, located directly above the lateral part of the elbow joint. In one month and a half, an achromatic nodular formation evolves with a diameter of 2.7 x 2.3 cm, prominent over the skin level, painful by palpation and spontaneously bleeding. By the anamnestic, clinical and dermoscopic findings the patient was diagnosed with nodular melanoma associated with a congenital medium sized melanocytic nevus. A primary excision with a field of safety 0.5 cm in all directions was performed. After confirmation of the primary diagnosis (tumour thickness 8 mm with no ultrasonographic detection of enlarged lymph nodes), seven days later are - excision was performed with an additional field of surgical safety of 1.5 cm in all directions. In this case remains unclear the following question: For what reason a preoperative high - frequent ultrasonography (HFUS) is not recommended to be used as it will allow only one surgical excision with the elimination of a tumour with a safety field of 2cm in all directions? The enigma about the obstacles preventing such a rational optimisation of the current diagnostic and therapeutic algorithm in patients with melanomas remains unresolved. One step surgery for cutaneous melanoma is widely used in many countries although it continues to be

  20. The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

    Science.gov (United States)

    Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

    1991-08-01

    We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

  1. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

    Shamim, M. S.; Ali, S.A.; Shirazi, B.; Shamim, M.

    2004-01-01

    A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively. (author)

  2. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

    2014-01-01

    SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant...... of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

  3. MelanomaDB: a Web Tool for Integrative Analysis of Melanoma Genomic Information to Identify Disease-Associated Molecular Pathways

    Directory of Open Access Journals (Sweden)

    Alexander Joseph Trevarton

    2013-07-01

    Full Text Available Despite on-going research, metastatic melanoma survival rates remain low and treatment options are limited. Researchers can now access a rapidly growing amount of molecular and clinical information about melanoma. This information is becoming difficult to assemble and interpret due to its dispersed nature, yet as it grows it becomes increasingly valuable for understanding melanoma. Integration of this information into a comprehensive resource to aid rational experimental design and patient stratification is needed. As an initial step in this direction, we have assembled a web-accessible melanoma database, MelanomaDB, which incorporates clinical and molecular data from publically available sources, which will be regularly updated as new information becomes available. This database allows complex links to be drawn between many different aspects of melanoma biology: genetic changes (e.g. mutations in individual melanomas revealed by DNA sequencing, associations between gene expression and patient survival, data concerning drug targets, biomarkers, druggability and clinical trials, as well as our own statistical analysis of relationships between molecular pathways and clinical parameters that have been produced using these data sets. The database is freely available at http://genesetdb.auckland.ac.nz/melanomadb/about.html . A subset of the information in the database can also be accessed through a freely available web application in the Illumina genomic cloud computing platform BaseSpace at http://www.biomatters.com/apps/melanoma-profiler-for-research . This illustrates dysregulation of specific signalling pathways, both across 310 exome-sequenced melanomas and in individual tumours and identifies novel features about the distribution of somatic variants in melanoma. We suggest that this database can provide a context in which to interpret the tumour molecular profiles of individual melanoma patients relative to biological information and available

  4. Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

    Centers for Disease Control (CDC) Podcasts

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.

  5. Generation of blood-derived dendritic cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Catchpole, B; Stell, A J; Dobson, J M

    2002-01-01

    Advances in treatment of human melanoma indicate that immunotherapy, particularly dendritic cell (DC) immunization, may prove useful. The aim of this study was to investigate whether blood-derived DCs could be generated from canine melanoma patients. Peripheral blood mononuclear cells were isolated from three such dogs and cultured with recombinant canine granulocyte-macrophage colony stimulating factor (GM-CSF), canine interleukin 4 and human Flt3-ligand for 7 days. The resulting cells demonstrated a typical dendritic morphology, and were enriched for cells expressing CD1a, CD11c and MHC II by flow cytometric analysis. Thus, canine blood-derived DCs can be generated in vitro and DC immunization should be feasible in dogs. Copyright Harcourt Publishers Ltd.

  6. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-12-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistry. Of interest, PMab-38 stained the lymphatic endothelial cells and cancer-associated fibroblasts in melanoma tissues, although it did not stain any lymphatic endothelial cells in normal tissues. PMab-38 could be useful for uncovering the function of PDPN in canine melanomas.

  7. Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

    Science.gov (United States)

    Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

    2017-01-01

    Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

  8. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  9. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study

    DEFF Research Database (Denmark)

    Hannibal, C.G.; Jensen, A.; Sharif, H.

    2008-01-01

    . A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. RESULTS: 112 malignant melanomas were identified......OBJECTIVE: The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. METHODS: A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established...... with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency). CONCLUSIONS: Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use...

  10. Electron Paramagnetic Resonance Spectrometry and Imaging in Melanomas: Comparison between Pigmented and Nonpigmented Human Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

    Full Text Available It has been known for a long time that the melanin pigments present in normal skin, hair, and most of malignant melanomas can be detected by electron paramagnetic resonance (EPR spectrometry. In this study, we used EPR imaging as a tool to map the concentration of melanin inside ex vivo human pigmented and nonpigmented melanomas and correlated this cartography with anatomopathology. We obtained accurate mappings of the melanin inside pigmented human melanoma samples. The signal intensity observed on the EPR images correlated with the concentration of melanin within the tumors, visible on the histologic sections. In contrast, no EPR signal coming from melanin was observed from nonpigmented melanomas, therefore demonstrating the absence of EPR-detectable pigments inside these particular cases of skin cancer and the importance of pigmentation for further EPR imaging studies on melanoma.

  11. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes

    DEFF Research Database (Denmark)

    Donia, Marco; Ellebaek, Eva; Andersen, Mads Hald

    2012-01-01

    . In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T cells was found among the cell products from patients with an advanced disease stage. Vδ1 T cells...

  12. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  13. CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.

    Science.gov (United States)

    Lupia, Antonella; Peppicelli, Silvia; Witort, Ewa; Bianchini, Francesca; Carloni, Vinicio; Pimpinelli, Nicola; Urso, Carmelo; Borgognoni, Lorenzo; Capaccioli, Sergio; Calorini, Lido; Lulli, Matteo

    2014-12-01

    The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

  14. Case report of a KIT-mutated melanoma patient with an excellent response to apatinib and temozolomide combination therapy

    Directory of Open Access Journals (Sweden)

    Luo C

    2017-09-01

    Full Text Available Cong Luo,1 Jiayu Shen,2 Jieer Ying,1 Xianhua Fang,3 Xiaohong Wang,1 Zhixuan Fu,4 Peng Liu5 1Department of Abdominal Oncology, Zhejiang Cancer Hospital, 2The Second Clinical Medical College, Zhejiang Chinese Medical University, 3Department of Pathology, 4Department of Colorectal Surgery, 5Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2 and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation. Keywords: advanced melanoma, KIT mutation, apatinib, temozolomide, combination therapy

  15. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  16. Teaching advanced wound closure techniques using cattle digits.

    Science.gov (United States)

    Khalil, Philipe N; Kanz, Karl-Georg; Siebeck, Matthias; Mutschler, Wolf

    2011-03-01

    To evaluate a model used to impart advanced wound closure skills because available models do not meet the necessary requirements to a substantial degree. Seventy-one residents were asked to evaluate a 75-minute-long skills course using cadaveric cattle digits to learn Z-plasty, V-Y-plasty, and oval-shaped rotational flaps. A short film and the course instructor demonstrated each technique first. A Likert rating scale ranging from 1 to 6 was used for questions in the survey given to the residents. There was strong agreement among residents (1.65 ± 1.17 years of experience) that advanced wound closure training courses are necessary (5.73 ± 0.73), which corresponded to the residents' low level of knowledge and self-assessment of practical skills and present experience (2.84 ± 1.01). The course was evaluated with high acceptance, even though it was found to be demanding for the trainees (5.84 ± 0.40). This might also be related to the high rating of the model itself, which was found to be a suitable method for teaching advanced wound closure techniques (5.50 ± 0.71) that was easily comprehensible (5.73 ± 0.53). Skills training courses for young trainees are warranted to impart advanced wound closure techniques. The curriculum using cattle digits presented here is recommended. The authors have indicated no significant interest with commercial supporters. © 2011 by the American Society for Dermatologic Surgery, Inc.

  17. In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages.

    Science.gov (United States)

    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

    2010-08-24

    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 bioconjugated with [Nle(4),D-Phe(7)]-alpha-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 bioconjugated AuNCs enhanced contrast approximately 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).

  18. Melanoma Surveillance in the US: The Economic Burden of Melanoma

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Dr. Gery Guy, from the CDC’s Division of Cancer Prevention and Control, discusses the economic burden of melanoma.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  19. Dabrafenib: a new opportunity for the treatment of BRAF V600-positive melanoma

    Directory of Open Access Journals (Sweden)

    Banzi M

    2016-05-01

    Full Text Available Maria Banzi,1 Simona De Blasio,2 Aimilios Lallas,3 Caterina Longo,2 Elvira Moscarella,2 Roberto Alfano,4 Giuseppe Argenziano5 1Department of Medical Oncology, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy; 2Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy; 3First Department of Dermatology, Aristotle University, Thessaloniki, Greece; 4Department of Anesthesiology, Surgery and Emergency, 5Dermatology Unit, Second University of Naples, Naples, Italy Abstract: Prior to 2011, the 1-year survival rates for patients suffering from advanced or metastatic melanoma was as low as 33%, with a median overall survival of about 9 months. Several chemotherapeutic regimens have been applied, either as monochemotherapy or as polychemotherapy, overall not resulting in an improvement of progression-free or overall survival. Novel insights into the epidemiology and biology of melanoma allowed the development of newer therapies. The discovery of mutations in BRAF, a part of the mitogen-activated protein kinase, allowed the development of two BRAF inhibitors, vemurafenib and dabrafenib, which significantly improved the outcome of metastatic melanoma treatment. This article reviews the mechanism of action, efficacy, and safety profile of dabrafenib. An in-depth knowledge of this medication will encourage clinicians to select the appropriate therapeutic strategy for each patient, as well as to prevent or adequately manage side effects, optimizing, thus, the drug’s applicability. Keywords: melanoma, BRAF, target therapy, dabrafenib, melanoma survival

  20. A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women.

    Science.gov (United States)

    Merkel, Emily A; Martini, Mary C; Amin, Sapna M; Yélamos, Oriol; Lee, Christina Y; Sholl, Lauren M; Rademaker, Alfred W; Guitart, Joan; Gerami, Pedram

    2016-01-01

    The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy-associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  1. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... commonly in larynx, tongue, and tonsil.2 Primary mel- anoma of the larynx and trachea are very rare among the group of non-cutaneous melanomas. In primary melanoma of the larynx, the least common site is the subglottic mucosa.3 Here we present a case of primary malignant melanoma of aryepiglottic ...

  2. Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.

    Science.gov (United States)

    Mar, Victoria J; Chamberlain, Alex J; Kelly, John W; Murray, William K; Thompson, John F

    2017-10-16

    A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

  3. Thin film characterisation by advanced X-ray diffraction techniques

    International Nuclear Information System (INIS)

    Cappuccio, G.; Terranova, M.L.

    1996-09-01

    The Fifth School on X-ray diffraction from polycrystalline materials was devoted to thin film characterization by advanced X-ray diffraction techniques. Twenty contributions are contained in this volume; all twenty are recorded in the INIS Database. X-ray diffraction is known to be a powerful analytical tool for characterizing materials and understanding their structural features. The aim of these articles is to illustrate the fundamental contribution of modern diffraction techniques (grazing incidence, surface analysis, standing waves, etc.) to the characterization of thin and ultra-thin films, which have become important in many advanced technologies

  4. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  5. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  6. Impact of sentinel lymphadenectomy on survival in a murine model of melanoma.

    Science.gov (United States)

    Rebhun, Robert B; Lazar, Alexander J F; Fidler, Isaiah J; Gershenwald, Jeffrey E

    2008-01-01

    Lymphatic mapping and sentinel lymph node biopsy-also termed sentinel lymphadenectomy (SL)-has become a standard of care for patients with primary invasive cutaneous melanoma. This technique has been shown to provide accurate information about the disease status of the regional lymph node basins at risk for metastasis, provide prognostic information, and provide durable regional lymph node control. The potential survival benefit afforded to patients undergoing SL is controversial. Central to this controversy is whether metastasis to regional lymph nodes occurs independent of or prior to widespread hematogenous dissemination. A related area of uncertainty is whether tumor cells residing within regional lymph nodes have increased metastatic potential. We have used a murine model of primary invasive cutaneous melanoma based on injection of B16-BL6 melanoma cells into the pinna to address two questions: (1) does SL plus wide excision of the primary tumor result in a survival advantage over wide excision alone; and (2) do melanoma cells growing within lymph nodes produce a higher incidence of hematogenous metastases than do cells growing at the primary tumor site? We found that SL significantly improved the survival of mice with small primary tumors. We found no difference in the incidence of lung metastases produced by B16-BL6 melanoma cells growing exclusively within regional lymph nodes and cells growing within the pinna.

  7. Laser radiation therapy of skin melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, R.I.; Kozlov, A.P.; Moskalik, K.G.

    1981-10-01

    Pulsed neodymium laser radiation was used for the treatment of 79 patients with cutaneous melanomas and 19 patients with melanoma metastases to the skin. The patients were followed up from 3 months up to 8 years. During this period local recurrences were detected in 2 cases. Out of 70 patients with cutaneous melanomas, who by the start of the treatment had no metastases in the regional lymph nodes or distant organs, metastases developed in 15 patients (21.4%). There are all reasons to consider pulsed laser radiation an effective means of treatment of some forms of skin melanoma.

  8. Melanoma

    Science.gov (United States)

    ... cancers in females aged 15 to 29 years old. Tanning-bed use contributes to this. Melanoma: Who ... Publications Connect With Us Contact Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal ...

  9. Fundamentals and advanced techniques in derivatives hedging

    CERN Document Server

    Bouchard, Bruno

    2016-01-01

    This book covers the theory of derivatives pricing and hedging as well as techniques used in mathematical finance. The authors use a top-down approach, starting with fundamentals before moving to applications, and present theoretical developments alongside various exercises, providing many examples of practical interest. A large spectrum of concepts and mathematical tools that are usually found in separate monographs are presented here. In addition to the no-arbitrage theory in full generality, this book also explores models and practical hedging and pricing issues. Fundamentals and Advanced Techniques in Derivatives Hedging further introduces advanced methods in probability and analysis, including Malliavin calculus and the theory of viscosity solutions, as well as the recent theory of stochastic targets and its use in risk management, making it the first textbook covering this topic. Graduate students in applied mathematics with an understanding of probability theory and stochastic calculus will find this b...

  10. Scalp Melanoma Diagnosed by Fine Needle Aspiration Cytology in a Tertiary Health Center

    Directory of Open Access Journals (Sweden)

    A. B. Zarami

    2015-01-01

    Full Text Available Melanoma is one of the most aggressive malignant skin neoplasms worldwide with more than 20% of world melanoma seen in black Africa and Asia. Late presentation due to ignorance, poverty, and lack of adequate health facility in Nigeria is always the norms. We present this case report because of precision in diagnosis, using fine needle aspiration cytology (FNAC to reemphasize that the technique is cheap, cost effective, and quick that can reduce the burden of incisional biopsy before definitive surgery and improve early detection of the disease especially in developing countries.

  11. Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kowichi Jimbow

    2013-01-01

    Full Text Available Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP, sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP upon exposure to alternating magnetic field (AMF. During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system.

  12. A texture based pattern recognition approach to distinguish melanoma from non-melanoma cells in histopathological tissue microarray sections.

    Directory of Open Access Journals (Sweden)

    Elton Rexhepaj

    Full Text Available AIMS: Immunohistochemistry is a routine practice in clinical cancer diagnostics and also an established technology for tissue-based research regarding biomarker discovery efforts. Tedious manual assessment of immunohistochemically stained tissue needs to be fully automated to take full advantage of the potential for high throughput analyses enabled by tissue microarrays and digital pathology. Such automated tools also need to be reproducible for different experimental conditions and biomarker targets. In this study we present a novel supervised melanoma specific pattern recognition approach that is fully automated and quantitative. METHODS AND RESULTS: Melanoma samples were immunostained for the melanocyte specific target, Melan-A. Images representing immunostained melanoma tissue were then digitally processed to segment regions of interest, highlighting Melan-A positive and negative areas. Color deconvolution was applied to each region of interest to separate the channel containing the immunohistochemistry signal from the hematoxylin counterstaining channel. A support vector machine melanoma classification model was learned from a discovery melanoma patient cohort (n = 264 and subsequently validated on an independent cohort of melanoma patient tissue sample images (n = 157. CONCLUSION: Here we propose a novel method that takes advantage of utilizing an immuhistochemical marker highlighting melanocytes to fully automate the learning of a general melanoma cell classification model. The presented method can be applied on any protein of interest and thus provides a tool for quantification of immunohistochemistry-based protein expression in melanoma.

  13. Melanoma of the skin in the Danish Cancer Registry and the Danish Melanoma Database

    DEFF Research Database (Denmark)

    Pedersen, Sidsel Arnspang; Schmidt, Sigrun Alba Johannesdottir; Klausen, Siri

    2018-01-01

    estimated the positive predictive value (PPV) of melanoma diagnosis for random samples of 200 patients from the Cancer Registry (n=200) and the Melanoma Database (n=200) during 2004-2014, using the Danish Pathology Registry as 'gold-standard' reference. We further validated tumor characteristics...

  14. [Telomerase activity in uveal melanomas].

    Science.gov (United States)

    Rohrbach, J M; Riedinger, C; Wild, M; Partsch, M

    2000-05-01

    The maximum number of cell divisions of a certain cell population is genetically fixed so that aging cells become non-dividing (senescent) at least. This replicative life span, also known as "Hayflick limit", is probably defined by a "critical" length of the telomeres. Telomeres are special DNA-sequences located at the four ends of the chromosomes which are shortened with each cell cycle. Cells of most, but not all malignant tumours have been shown to reactivate the enzyme telomerase so that telomeres can be reconstructed, "Hayflick limit" can be overcome, and unlimited cell division can be established. This study was undertaken to elucidate whether telomerase reactivation is used by uveal melanoma cells. Fresh tumour tissue was removed from 10 untreated uveal melanomas after enucleation. Telomerase activity was determined using a PCR ELISA according to the Telomeric Repeat Amplification Protocol (TRAP). Normal tissue of the skin and the conjunctiva served as control. Telomerase activity was detectable in 90% of the investigated uveal melanomas. All control specimens were telomerase negative. Uveal melanoma growth seems to depend on telomerase reactivation. Thus, telomerase inhibition could offer a new principle for uveal melanoma therapy in the future.

  15. Oral Amelanotic Melanoma | Adisa | Annals of Ibadan Postgraduate ...

    African Journals Online (AJOL)

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases ...

  16. Lack of GNAQ and GNA11 germ-line mutations in familial melanoma pedigrees with uveal melanoma or blue nevi

    Directory of Open Access Journals (Sweden)

    Jason Ezra Hawkes

    2013-06-01

    Full Text Available Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q subunit alpha (GNAQ, Guanine nucleotide-binding protein G(q subunit alpha-11 (GNA11 and BRCA1 associated protein-1 (BAP1. Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.

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

    Science.gov (United States)

    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

  18. Outcomes of dogs undergoing radiotherapy for treatment of oral malignant melanoma: 111 cases (2006-2012).

    Science.gov (United States)

    Kawabe, Mifumi; Mori, Takashi; Ito, Yusuke; Murakami, Mami; Sakai, Hiroki; Yanai, Tokuma; Maruo, Kohji

    2015-11-15

    To evaluate the characteristics and outcomes of dogs with stage I, II, III, or IV oral malignant melanoma treated by various types of radiotherapy. Retrospective case series. 111 dogs. Medical records of dogs with oral malignant melanoma treated by radiotherapy (with or without adjunctive treatments) at a veterinary medical center between July 2006 and December 2012 were reviewed. Information regarding signalment, tumor location, disease stage, treatment protocols, adverse effects, and survival time were obtained from medical records and by telephone follow-up. Associations between variables of interest and outcome were analyzed. Dogs received orthovoltage x-ray (n = 68), megavoltage x-ray (39), or electron beam (4) radiotherapy. Adjunctive treatments included debulking surgery (n = 18), chemotherapy (39), or both (27). Median survival times for dogs with stage I, II, III, and IV melanoma were 758 days (n = 19), 278 days (24), 163 days (37), and 80 days (31), respectively, and differed significantly between dogs with stage I disease and those with all other disease stages. Among dogs with stage III melanoma, risk of death was significantly higher in those that received orthovoltage x-ray treatment than in those that received megavoltage x-ray treatment. Severe (primary or secondary) adverse effects were identified in 9 dogs. Median survival time was significantly longer for dogs with stage I oral malignant melanoma than for dogs with more advanced disease at the time of staging. The staging system used may be a useful tool for prognosis prediction in dogs undergoing similar treatment protocols for oral malignant melanomas.

  19. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

    DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

    Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

  20. Immunosuppressive cytokines in the regional lymph node of a dog suffering from oral malignant melanoma.

    Science.gov (United States)

    Catchpole, B; Gould, S M; Kellett-Gregory, L M; Dobson, J M

    2002-10-01

    A 10-year-old male cross-breed dog was referred for investigation of oral malignant melanoma. Fine-needle aspirates were taken from the draining submandibular lymph node. The presence of metastatic melanoma cells was confirmed by cytological examination and reverse transcription polymerase chain reaction (RT-PCR) using primers for the melanoma-associated antigens: tyrosinase and mart-1/melan A. Cytokine expression in the lymph node was evaluated by multiplex RT-PCR, which demonstrated the presence of mRNA for IL-10 and TGF-beta1. However, IL-2, IL-4 and IFNgamma mRNA could not be detected, suggesting a lack of immune activation. Thoracic radiographs showed a lesion within the caudal lung fields suggestive of pulmonary metastasis. The dog developed signs of dyspnoea and collapse and was euthanased four days later. This case illustrates that molecular techniques can be used to aid clinical staging of canine oral malignant melanoma, and suggests that immunosuppressive cytokines could be involved in the pathogenesis of disease.

  1. Noscapine alters microtubule dynamics in living cells and inhibits the progression of melanoma.

    Science.gov (United States)

    Landen, Jaren W; Lang, Roland; McMahon, Steve J; Rusan, Nasser M; Yvon, Anne-Marie; Adams, Ashley W; Sorcinelli, Mia D; Campbell, Ross; Bonaccorsi, Paola; Ansel, John C; Archer, David R; Wadsworth, Patricia; Armstrong, Cheryl A; Joshi, Harish C

    2002-07-15

    Cellular microtubules, polymers of tubulin, alternate relentlessly between phases of growth and shortening. We now show that noscapine, a tubulin-binding agent, increases the time that cellular microtubules spend idle in a paused state. As a result, most mammalian cell types observed arrest in mitosis in the presence of noscapine. We demonstrate that noscapine-treated murine melanoma B16LS9 cells do not arrest in mitosis but rather become polyploid followed by cell death, whereas primary melanocytes reversibly arrest in mitosis and resume a normal cell cycle after noscapine removal. Furthermore, in a syngeneic murine model of established s.c. melanoma, noscapine treatment resulted in an 85% inhibition of tumor volume on day 17 when delivered by gavage compared with untreated animals (P melanoma progression by 83% on day 18 when delivered in drinking water (P melanoma cells through alterations in microtubule dynamics, with no detected toxicity to the host. Consequently, noscapine could be a valuable chemotherapeutic agent, alone or in combination, for the treatment of advanced melanoma.

  2. Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

    DEFF Research Database (Denmark)

    Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

    2017-01-01

    BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV mal...

  3. [Multiple conjunctival malignant melanomas (author's transl)].

    Science.gov (United States)

    Haddad, R

    1979-04-01

    5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.

  4. Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

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    Alfredo Addeo

    2013-05-01

    Full Text Available Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, as second-line treatment after progression with dacarbazine, for (wild-type BRAF metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

  5. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    2007-07-01

    Full Text Available Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease.In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the specific genes identified within each class

  6. Early detection of melanoma with the combined use of acoustic microscopy, infrared reflectance and Raman spectroscopy

    Science.gov (United States)

    Karagiannis, Georgios T.; Grivas, Ioannis; Tsingotjidou, Anastasia; Apostolidis, Georgios K.; Grigoriadou, Ifigeneia; Dori, I.; Poulatsidou, Kyriaki-Nefeli; Doumas, Argyrios; Wesarg, Stefan; Georgoulias, Panagiotis

    2015-03-01

    Malignant melanoma is a form of skin cancer, with increasing incidence worldwide. Early diagnosis is crucial for the prognosis and treatment of the disease. The objective of this study is to develop a novel animal model of melanoma and apply a combination of the non-invasive imaging techniques acoustic microscopy, infrared (IR) and Raman spectroscopies, for the detection of developing tumors. Acoustic microscopy provides information about the 3D structure of the tumor, whereas, both spectroscopic modalities give qualitative insight of biochemical changes during melanoma development. In order to efficiently set up the final devices, propagation of ultrasonic and electromagnetic waves in normal skin and melanoma simulated structures was performed. Synthetic and grape-extracted melanin (simulated tumors), endermally injected, were scanned and compared to normal skin. For both cases acoustic microscopy with central operating frequencies of 110MHz and 175MHz were used, resulting to the tomographic imaging of the simulated tumor, while with the spectroscopic modalities IR and Raman differences among spectra of normal and melanin- injected sites were identified in skin depth. Subsequently, growth of actual tumors in an animal melanoma model, with the use of human malignant melanoma cells was achieved. Acoustic microscopy and IR and Raman spectroscopies were also applied. The development of tumors at different time points was displayed using acoustic microscopy. Moreover, the changes of the IR and Raman spectra were studied between the melanoma tumors and adjacent healthy skin. The most significant changes between healthy skin and the melanoma area were observed in the range of 900-1800cm-1 and 350-2000cm-1, respectively.

  7. Metastatic breast disease from cutaneous malignant melanoma.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-01-01

    Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Sarcoidosis in Melanoma Patients: Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Beutler, Bryce D., E-mail: brycebeutler@hotmail.com [School of Allied Health Sciences, University of Nevada, Las Vegas, 1060 Wiegand Road, Encinitas, CA 92024 (United States); Cohen, Philip R., E-mail: brycebeutler@hotmail.com [Department of Dermatology, University of California San Diego, 10991 Twinleaf Court, San Diego, CA 92131 (United States)

    2015-06-15

    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.

  9. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

    2014-01-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456

  10. Clinical experience of stereotactic radiosurgery at a linear accelerator for intraocular melanoma.

    Science.gov (United States)

    Furdova, Alena; Sramka, Miron; Chorvath, Martin; Kralik, Gabriel; Furda, Robert; Gregus, Michal

    2017-10-01

    Long-term results with linear accelerator LINAC-based stereotactic radiosurgery for intraocular uveal malignant melanoma were assessed. A retrospective study was carried out of patients with uveal melanoma after a 1-day session stereotactic radiosurgery at LINAC in Slovakia. In the period 2001-2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume at baseline was 0.5 cm (with range from 0.2 to 1.6 cm). Tumors ranged in size from 2.4 to 20.8 mm in basal diameter and from 2.0 to 18.3 mm in thickness. The therapeutic dose was 35.0 Gy by 99% of dose volume histogram. Older age at treatment was correlated with the largest basal tumor diameter, tumor thickness, and TNM stage. The survival after stereotactic irradiation was 96% in 1 year, 93% in 2 years, 84% in 5 years, 80% in 7 years, and 53% in 11 years. In 20 (13.3%) patients, secondary enucleation was necessary because of complications (secondary glaucoma). Enucleation-free interval ranged from 1 to 6 years. The median age at death was lower (65.7 years) for patients who died from metastatic disease than for those who died from any other cause (75.0 years). Survival rates at 5-year intervals and the need for secondary enucleation because of complications after linear accelerator irradiation are comparable to other techniques.

  11. Automated melanoma detection with a novel multispectral imaging system: results of a prospective study

    International Nuclear Information System (INIS)

    Tomatis, Stefano; Carrara, Mauro; Bono, Aldo; Bartoli, Cesare; Lualdi, Manuela; Tragni, Gabrina; Colombo, Ambrogio; Marchesini, Renato

    2005-01-01

    The aim of this research was to evaluate the performance of a new spectroscopic system in the diagnosis of melanoma. This study involves a consecutive series of 1278 patients with 1391 cutaneous pigmented lesions including 184 melanomas. In an attempt to approach the 'real world' of lesion population, a further set of 1022 not excised clinically reassuring lesions was also considered for analysis. Each lesion was imaged in vivo by a multispectral imaging system. The system operates at wavelengths between 483 and 950 nm by acquiring 15 images at equally spaced wavelength intervals. From the images, different lesion descriptors were extracted related to the colour distribution and morphology of the lesions. Data reduction techniques were applied before setting up a neural network classifier designed to perform automated diagnosis. The data set was randomly divided into three sets: train (696 lesions, including 90 melanomas) and verify (348 lesions, including 53 melanomas) for the instruction of a proper neural network, and an independent test set (347 lesions, including 41 melanomas). The neural network was able to discriminate between melanomas and non-melanoma lesions with a sensitivity of 80.4% and a specificity of 75.6% in the 1391 histologized cases data set. No major variations were found in classification scores when train, verify and test subsets were separately evaluated. Following receiver operating characteristic (ROC) analysis, the resulting area under the curve was 0.85. No significant differences were found among areas under train, verify and test set curves, supporting the good network ability to generalize for new cases. In addition, specificity and area under ROC curve increased up to 90% and 0.90, respectively, when the additional set of 1022 lesions without histology was added to the test set. Our data show that performance of an automated system is greatly population dependent, suggesting caution in the comparison with results reported in the

  12. Expansion of CD16-Negative Natural Killer Cells in the Peripheral Blood of Patients with Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Shernan G. Holtan

    2011-01-01

    Full Text Available Altered natural killer (NK cell function is a component of the global immune dysregulation that occurs in advanced malignancies. Another condition associated with altered NK homeostasis is normal pregnancy, where robust infiltration with CD16− CD9+ NK cells can be identified in decidual tissues, along with a concomitant expansion of CD16− NK cells in the maternal peripheral blood. In metastatic melanoma, we identified a similar expansion of peripheral blood CD16− NK cells (median 7.4% in 41 patients with melanoma compared with 3.0% in 29 controls, P<.001. A subset of NK cells in melanoma patients also expresses CD9, which is characteristically expressed only on NK cells within the female reproductive tract. Expansion of CD16− NK cells was associated with elevated plasma transforming growth factor-beta (TGF-β levels (median 20 ng/ml, Spearman's ρ=0.81,P=.015. These findings suggest the possibility of exploring anti-TGF-β therapy to restore NK function in melanoma.

  13. GAB2 amplifications refine molecular classification of melanoma.

    Science.gov (United States)

    Chernoff, Karen A; Bordone, Lindsey; Horst, Basil; Simon, Katherine; Twadell, William; Lee, Keagan; Cohen, Jason A; Wang, Shuang; Silvers, David N; Brunner, Georg; Celebi, Julide Tok

    2009-07-01

    Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.

  14. Advanced neuroimaging techniques for the term newborn with encephalopathy.

    Science.gov (United States)

    Chau, Vann; Poskitt, Kenneth John; Miller, Steven Paul

    2009-03-01

    Neonatal encephalopathy is associated with a high risk of morbidity and mortality in the neonatal period and of long-term neurodevelopmental disability in survivors. Advanced magnetic resonance techniques now play a major role in the clinical care of newborns with encephalopathy and in research addressing this important condition. From conventional magnetic resonance imaging, typical patterns of injury have been defined in neonatal encephalopathy. When applied in contemporary cohorts of newborns with encephalopathy, the patterns of brain injury on magnetic resonance imaging distinguish risk factors, clinical presentation, and risk of abnormal outcome. Advanced magnetic resonance techniques such as magnetic resonance spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging provide novel perspectives on neonatal brain metabolism, microstructure, and connectivity. With the application of these imaging tools, it is increasingly apparent that brain injury commonly occurs at or near the time of birth and evolves over the first weeks of life. These observations have complemented findings from trials of emerging strategies of brain protection, such as hypothermia. Application of these advanced magnetic resonance techniques may enable the earliest possible identification of newborns at risk of neurodevelopmental impairment, thereby ensuring appropriate follow-up with rehabilitation and psychoeducational resources.

  15. Solitary Secondary Malignant Melanoma of Clavicle Two Years after Enuclation for Ocular Melanoma

    Directory of Open Access Journals (Sweden)

    Halil Tozum

    2013-01-01

    Full Text Available Solitary metastasis of uveal melanoma to bone is extremely rare and usually associated with other organ involvement. We present a rare case of an ocular melanoma patient presenting with solitary metastasis to the clavicle two years after enucleation, without any other organ involvement. In this report, we tried to present our treatment strategy for the solitary metastasis of bone.

  16. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    International Nuclear Information System (INIS)

    Ghislin, Stephanie; Obino, Dorian; Middendorp, Sandrine; Boggetto, Nicole; Alcaide-Loridan, Catherine; Deshayes, Frederique

    2012-01-01

    Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration

  17. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    Directory of Open Access Journals (Sweden)

    Ghislin Stephanie

    2012-10-01

    Full Text Available Abstract Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18 expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration.

  18. A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted Therapy in Advanced Melanoma

    Directory of Open Access Journals (Sweden)

    Lukas Krähenbühl

    2018-02-01

    Full Text Available A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT. We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT. Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression over time in contrast to TT. Standardized repeated assessments of multiple immune markers in repeated biopsies will generate detailed insights in melanoma's immune evolution and adaption during therapies and might be used to support treatment decisions.

  19. BAP1 has a survival role in cutaneous melanoma.

    Science.gov (United States)

    Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny C-N; Jönsson, Göran; Frederick, Dennie T; Tsao, Hensin

    2015-04-01

    Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous melanoma (CM)/ocular melanoma predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of CM is not fully understood. We thus set out to characterize BAP1 in CM and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared with nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony-forming capability, induced apoptosis, and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin, a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may have a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology, which is context and cell dependent.

  20. Alpha particles for treatment of disseminated melanoma

    International Nuclear Information System (INIS)

    Link, E.M.

    2010-01-01

    Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. 211 At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)

  1. Skin protection behaviour and sex differences in melanoma location in patients with multiple primary melanomas.

    Science.gov (United States)

    Warren, Matthew; McMeniman, Erin; Adams, Agnieszka; De'Ambrosis, Brian

    2017-02-01

    Previous studies have shown that sunscreen usage, sun-protection measures and self-examination rates in patients with single primary melanomas (SPM) are similar to that in the general population. This study hypothesises that these rates would be different in a population with multiple primary melanomas (MPM). We further hypothesise that there would be a sex difference in melanoma location in patients with MPM. The objectives of this study were to determine skin protection measures, self-examinations and melanoma location in a cohort of patients with MPM. A survey was conducted on 137 patients with MPM examining their sun-protection measures, skin self-examination rates and medical and phenotypic characteristics. These data were combined with a review of their medical records to examine the patients' skin cancer history. Patients with MPM had higher rates of skin self-evaluation (74% vs 22%), sunscreen usage (70% vs 45%) and other sun-protection measures (95% vs 46%) than has been published for patients with a history of a SPM. We have also shown that women have a higher risk of developing melanomas on their arms (p skin self-examination, sunscreen usage and other sun-protection methods in patients with MPM is higher than in studies of patients with SPM. It also highlighted sex differences in terms of melanoma location for patients with MPM. Further studies to examine the cause of the differences in these forms of protective behaviour could help improve the utilisation of these important preventative measures in all patients. © 2015 The Australasian College of Dermatologists.

  2. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  3. Nuclear techniques in the development of advanced ceramic technologies

    International Nuclear Information System (INIS)

    Axe, J.D.; Hewat, A.W.; Maier, J.; Margaca, F.M.A.; Rauch, H.

    1999-01-01

    The importance of research, development and application of advanced materials is well understood by all developed and most developing countries. Amongst advanced materials, ceramics play a prominent role due to their specific chemical and physical properties. According to performance and importance, advanced ceramics can be classified as structural ceramics (mechanical function) and the so-called functional ceramics. In the latter class of materials, special electrical, chemical, thermal, magnetic and optical properties are of interest. The most valuable materials are multifunctional, for example, when structural ceramics combine beneficial mechanical properties with thermal and chemical sensitivity. Multifunctionality is characteristic of many composite materials (organic/inorganic composite). Additionally, properties of material can be changed by reducing its dimension (thin films, nanocrystalline ceramics). Nuclear techniques, found important applications in research and development of advanced ceramics. The use of neutron techniques has increased dramatically in recent years due to the development of advanced neutron sources, instrumentation and improved data analysis. Typical neutron techniques are neutron diffraction, neutron radiography, small angle neutron scattering and very small angle neutron scattering. Neutrons can penetrate deeply into most materials thus sampling their bulk properties. In determination of the crystal structure of HTSC, YBa 2 Cu 2 O 7 , XRD located the heavy metal atoms, but failed in finding many of the oxygen atoms, while the neutron diffraction located all atoms equally well in the crystal structure. Neutron diffraction is also unique for the determination of the magnetic structure of materials since the neutrons themselves have a magnetic moment. Application of small angle neutron scattering for the determination of the size of hydrocarbon aggregates within the zeolite channels is illustrated. (author)

  4. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

    Science.gov (United States)

    Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

    2017-01-02

    There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

  5. Meningeal Melanomas Associated With Transforming Ota Nevus to Malignant Melanoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammad Fereshtehnejad

    2010-11-01

    Full Text Available Intracranial invasion of cellular blue nevus (CBN from the skin is extremely rare and such a condition with malignant transformation is even rarer.A case of meningeal melanoma with malignant transformation which was derived from an Ota   nevus is presented in this report.   A21-year-old man with a neurocutaneous syndrome since childhood was referred with headache and mild left hemiparesia. CT scan and MRI demonstrated intracranial lesions and conjunctival biopsy leads to the pathologic diagnosis of blue nevus.Thereafter his parietal lesion was operated by craniotomy with total gross excision.On histopathological examination, diagnosis of malignant melanoma was confirmed.Approximately 2 months after radiotherapy and chemotherapy, he afflicted to diplopia and blurred vision on the leftside due to enlargement of orbital and cavernous sinus lesion. Following one year follow-up,he was survived and thrived with diffuse leptomeningeal nodular enhancement in favor of melanoma dissemination.Primary intracranial melanomas are though rare, but it should be suspected especially in the presence of periorbital blue nevus or nevus of Ota. Moreover, although CBN is considered benign, scalp or periorbital CBN has the potential for intracranial invasion and malignant ransformation.

  6. Melanoma Surveillance in the US: Melanoma, Ultraviolet Radiation, and Socioeconomic Status

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

    This podcast accompanies the publication of a series of articles on melanoma surveillance in the United States, available in the November supplement edition of the Journal of the American Academy of Dermatology. Chris Johnson, from the Cancer Data Registry of Idaho, discusses analyses examining the relationship between melanoma and two variables at the county level, ultraviolet radiation and socioeconomic status.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  7. Integrative Genome Comparison of Primary and Metastatic Melanomas

    Science.gov (United States)

    Feng, Bin; Nazarian, Rosalynn M.; Bosenberg, Marcus; Wu, Min; Scott, Kenneth L.; Kwong, Lawrence N.; Xiao, Yonghong; Cordon-Cardo, Carlos; Granter, Scott R.; Ramaswamy, Sridhar; Golub, Todd; Duncan, Lyn M.; Wagner, Stephan N.; Brennan, Cameron; Chin, Lynda

    2010-01-01

    A cardinal feature of malignant melanoma is its metastatic propensity. An incomplete view of the genetic events driving metastatic progression has been a major barrier to rational development of effective therapeutics and prognostic diagnostics for melanoma patients. In this study, we conducted global genomic characterization of primary and metastatic melanomas to examine the genomic landscape associated with metastatic progression. In addition to uncovering three genomic subclasses of metastastic melanomas, we delineated 39 focal and recurrent regions of amplification and deletions, many of which encompassed resident genes that have not been implicated in cancer or metastasis. To identify progression-associated metastasis gene candidates, we applied a statistical approach, Integrative Genome Comparison (IGC), to define 32 genomic regions of interest that were significantly altered in metastatic relative to primary melanomas, encompassing 30 resident genes with statistically significant expression deregulation. Functional assays on a subset of these candidates, including MET, ASPM, AKAP9, IMP3, PRKCA, RPA3, and SCAP2, validated their pro-invasion activities in human melanoma cells. Validity of the IGC approach was further reinforced by tissue microarray analysis of Survivin showing significant increased protein expression in thick versus thin primary cutaneous melanomas, and a progression correlation with lymph node metastases. Together, these functional validation results and correlative analysis of human tissues support the thesis that integrated genomic and pathological analyses of staged melanomas provide a productive entry point for discovery of melanoma metastases genes. PMID:20520718

  8. Reflectance confocal microscopy features of thin versus thick melanomas.

    Science.gov (United States)

    Kardynal, Agnieszka; Olszewska, Małgorzata; de Carvalho, Nathalie; Walecka, Irena; Pellacani, Giovanni; Rudnicka, Lidia

    2018-01-24

    In vivo reflectance confocal microscopy (RCM) plays an increasingly important role in differential diagnosis of melanoma. The aim of the study was to assess typical confocal features of thin (≤1mm according to Breslow index) versus thick (>1mm) melanomas. 30 patients with histopathologically confirmed cutaneous melanoma were included in the study. Reflectance confocal microscopy was performed with Vivascope equipment prior to excision. Fifteen melanomas were thin (Breslow thickness ≤ 1mm) and 15 were thick melanomas (Breslow thickness >1mm). In the RCM examination, the following features were more frequently observed in thin compared to thick melanomas: edged papillae (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs 6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in melanoma are good prognostic factors. The group of thick melanomas compared to the group of thin melanomas in the RCM images presented with greater frequency of roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006), numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3% vs 66.7%, p=0.068). Non-invasive imaging methods helps in deepening of knowledge about the evolution and biology of melanoma. The most characteristic features for thin melanomas in confocal examination are: fragments of cobblestone or honeycomb pattern and edged papillae (as good prognostic factors). The features of thick melanomas in RCM examination are: roundish cells, non-edged papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal disarray.

  9. Melanoma cells treated with GGTI and IFN-gamma allow murine vaccination and enhance cytotoxic response against human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    Full Text Available BACKGROUND: Suboptimal activation of T lymphocytes by melanoma cells is often due to the defective expression of class I major histocompatibility antigens (MHC-I and costimulatory molecules. We have previously shown that geranylgeranyl transferase inhibition (done with GGTI-298 stimulates anti-melanoma immune response through MHC-I and costimulatory molecule expression in the B16F10 murine model [1]. METHODOLOGY/PRINCIPAL FINDINGS: In this study, it is shown that vaccination with mIFN-gand GGTI-298 pretreated B16F10 cells induces a protection against untreated tumor growth and pulmonary metastases implantation. Furthermore, using a human melanoma model (LB1319-MEL, we demonstrated that in vitro treatment with hIFN-gamma and GGTI-298 led to the up regulation of MHC-I and a costimulatory molecule CD86 and down regulation of an inhibitory molecule PD-1L. Co-culture experiments with peripheral blood mononuclear cells (PBMC revealed that modifications induced by hIFN-gamma and GGTI-298 on the selected melanoma cells, enables the stimulation of lymphocytes from HLA compatible healthy donors. Indeed, as compared with untreated melanoma cells, pretreatment with hIFN-gamma and GGTI-298 together rendered the melanoma cells more efficient at inducing the: i activation of CD8 T lymphocytes (CD8+/CD69+; ii proliferation of tumor-specific CD8 T cells (MelanA-MART1/TCR+; iii secretion of hIFN-gamma; and iv anti-melanoma specific cytotoxic cells. CONCLUSIONS/SIGNIFICANCE: These data indicate that pharmacological treatment of melanoma cell lines with IFN-gamma and GGTI-298 stimulates their immunogenicity and could be a novel approach to produce tumor cells suitable for vaccination and for stimulation of anti-melanoma effector cells.

  10. Ambulatory Melanoma Care Patterns in the United States

    International Nuclear Information System (INIS)

    Ji, A. L.; Davis, S. A.; Feldman, S. R.; Fleischer, A. B.; Baze, M. R.; Feldman, S. R.; Feldman, S. R.; Fleischer, A. B.

    2013-01-01

    To examine trends in melanoma visits in the ambulatory care setting. Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979 to 2010 were used to analyze melanoma visit characteristics including number of visits, age and gender of patients, and physician specialty. These data were compared to US Census population estimates during the same time period. Results. The overall rate of melanoma visits increased (ρ< 0.0001) at an apparently higher rate than the increase in population over this time. The age of patients with melanoma visits increased at approximately double the rate (0.47 year per interval year, ρ< 0.0001) of the population increase in age (0.23 year per interval year). There was a nonsignificant(ρ=0.19) decline in the proportion of female patients seen over the study interval. Lastly, ambulatory care has shifted towards dermatologists and other specialties managing melanoma patients and away from family/internal medicine physicians and general/plastic surgeons. Conclusions. The number and age of melanoma visits has increased over time with respect to the overall population, mirroring the increase in melanoma incidence over the past three decades. These trends highlight the need for further studies regarding melanoma management efficiency

  11. Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    M. McComiskey

    2015-01-01

    Full Text Available Introduction. Primary malignant melanoma of the urethra is a rare tumour (0.2% of all melanomas that most commonly affects the meatus and distal urethra and is three times more common in women than men. Case. A 76-year-old lady presented with vaginal pain and discharge. On examination, a 4 cm mass was noted in the vagina and biopsy confirmed melanoma of a balloon type. Preoperative CT showed no distant metastases and an MRI scan of the pelvis demonstrated no associated lymphadenopathy. She underwent anterior exenterative surgery and vaginectomy also. Histology confirmed a urethral nodular malignant melanoma. Discussion. First-line treatment of melanoma is often surgical. Adjuvant treatment including chemotherapy, radiotherapy, or immunotherapy has also been reported. Even with aggressive management, malignant melanoma of the urogenital tract generally has a poor prognosis. Recurrence rates are high and the mean period between diagnosis and recurrence is 12.5 months. A 5-year survival rate of less than 20% has been reported in balloon cell melanomas along with nearly 20% developing local recurrence. Conclusion. To the best of our knowledge, this case is the first report of balloon cell melanoma arising in the urethra. The presentation and surgical management has been described and a literature review provided.

  12. Shared care in the follow-up of early-stage melanoma: a qualitative study of Australian melanoma clinicians’ perspectives and models of care

    Directory of Open Access Journals (Sweden)

    Rychetnik Lucie

    2012-12-01

    Full Text Available Abstract Background Patients with early stage melanoma have high survival rates but require long-term follow-up to detect recurrences and/or new primary tumours. Shared care between melanoma specialists and general practitioners is an increasingly important approach to meeting the needs of a growing population of melanoma survivors. Methods In-depth qualitative study based on semi-structured interviews with 16 clinicians (surgical oncologists, dermatologists and melanoma unit GPs who conduct post-treatment follow-up at two of Australia’s largest specialist referral melanoma treatment and diagnosis units. Interviews were recorded, transcribed and analysed to identify approaches to shared care in follow-up, variations in practice, and explanations of these. Results Melanoma unit clinicians utilised shared care in the follow-up of patients with early stage melanoma. Schedules were determined by patients’ clinical risk profiles. Final arrangements for delivery of those schedules (by whom and where were influenced by additional psychosocial, professional and organizational considerations. Four models of shared care were described: (a surgical oncologist alternating with dermatologist (in-house or local to patient; (b melanoma unit dermatologist and other local doctor (e.g. family physician; (c surgical oncologist and local doctor; or (d melanoma physician and local doctor. Conclusions These models of shared care offer alternative solutions to managing the requirements for long-term follow-up of a growing number of patients with stage I/II melanoma, and warrant further comparative evaluation of outcomes in clinical trials, with detailed cost/benefit analyses.

  13. The anti-apoptotic BAG3 protein is involved in BRAF inhibitor resistance in melanoma cells.

    Science.gov (United States)

    Guerriero, Luana; Palmieri, Giuseppe; De Marco, Margot; Cossu, Antonio; Remondelli, Paolo; Capunzo, Mario; Turco, Maria Caterina; Rosati, Alessandra

    2017-10-06

    BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas. BRAFV600E is the most frequent mutation detected in malignant melanomas and is targeted by Vemurafenib, a specific inhibitor found to be effective in the treatment of advanced melanoma. However, patients with BRAF-mutated melanoma may result insensitive ab initio or, mostly, develop acquired resistance to the treatment with this molecule. Here we show that BAG3 down-modulation interferes with BRAF levels in melanoma cells and sensitizes them to Vemurafenib treatment. Furthermore, the down-modulation of BAG3 protein in an in vitro model of acquired resistance to Vemurafenib can induce sensitization to the BRAFV600E specific inhibition by interfering with BRAF pathway through reduction of ERK phosphorylation, but also on parallel survival pathways. Future studies on BAG3 molecular interactions with key proteins responsible of acquired BRAF inhibitor resistance may represent a promising field for novel multi-drugs treatment design.

  14. Differentiating regressed melanoma from regressed lichenoid keratosis.

    Science.gov (United States)

    Chan, Aegean H; Shulman, Kenneth J; Lee, Bonnie A

    2017-04-01

    Distinguishing regressed lichen planus-like keratosis (LPLK) from regressed melanoma can be difficult on histopathologic examination, potentially resulting in mismanagement of patients. We aimed to identify histopathologic features by which regressed melanoma can be differentiated from regressed LPLK. Twenty actively inflamed LPLK, 12 LPLK with regression and 15 melanomas with regression were compared and evaluated by hematoxylin and eosin staining as well as Melan-A, microphthalmia transcription factor (MiTF) and cytokeratin (AE1/AE3) immunostaining. (1) A total of 40% of regressed melanomas showed complete or near complete loss of melanocytes within the epidermis with Melan-A and MiTF immunostaining, while 8% of regressed LPLK exhibited this finding. (2) Necrotic keratinocytes were seen in the epidermis in 33% regressed melanomas as opposed to all of the regressed LPLK. (3) A dense infiltrate of melanophages in the papillary dermis was seen in 40% of regressed melanomas, a feature not seen in regressed LPLK. In summary, our findings suggest that a complete or near complete loss of melanocytes within the epidermis strongly favors a regressed melanoma over a regressed LPLK. In addition, necrotic epidermal keratinocytes and the presence of a dense band-like distribution of dermal melanophages can be helpful in differentiating these lesions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Cutaneous side-effects during therapy of melanoma by vemurafenib

    Directory of Open Access Journals (Sweden)

    Anna Ankudowicz

    2015-06-01

    Full Text Available Introduction. Vemurafenib is a selective inhibitor of serine-threonine kinase BRAF used in the treatment of advanced melanoma with BRAF mutation. Effectiveness of this drug was confirmed in a large clinical trial, which led to the increase of its usage. During treatment with vemurafenib, particular attention should be paid to the numerous side effects, including those concerning the skin. Vemurafenib is highly toxic to the skin. Skin lesions occurring during the treatment of melanoma with this medicament can be divided into: early (observed 3 to 6 weeks after beginning treatment, late (observed 6 weeks after beginning treatment and hypersensitivity reactions to vemurafenib. Objective. Presentation of vemurafenib toxic effects on the skin and side effects that can be caused by this drug. Case report. We present a 58-year-old woman with metastatic melanoma who was treated with vemurafenib. During the course of therapy, numerous adverse reactions, including inflammatory tumors, emergence of a number of melanocytic naevi, skin horns, alopecia, hyperkeratosis of the palms and soles, and palmar erythrodysesthesia were observed. She was treated with anti-inflammatory drugs, an antibiotic, circulation-improving preparations and local moisturizing and keratolytic treatment. The patient remains under the care of oncologists and dermatologists. Conclusions. The new generation anti-cancer drugs bring hope for a cure or prolongation of life, but can also significantly reduce the quality of life by inducing both general and local adverse side effects. Oncological patients should also be taken care of by dermatologists.

  16. primary malignant amelanotic melanoma arising from a vitiligo patch

    African Journals Online (AJOL)

    2014-05-05

    May 5, 2014 ... Malignant melanoma is a rare tumour in people of. African descent including those affected by albinism. (1). The incidence of malignant melanoma in Africans is estimated to ranging from 0.5 to 1.5 per 100,000 people (2). Acrolentiginous melanoma is the most common type of melanoma in this population.

  17. Parental Attitudes Toward Advanced Behavior Guidance Techniques Used in Pediatric Dentistry.

    Science.gov (United States)

    Patel, Monica; McTigue, Dennis J; Thikkurissy, Sarat; Fields, Henry W

    2016-01-01

    To re-examine parental attitudes toward advanced behavior management techniques in pediatric dentistry and determine whether cost, urgency, and amount of treatment influence parental preferences. Parents viewed previously validated videotaped clinical vignettes of four advanced behavior guidance techniques: (1) passive immobilization; (2) active immobilization; (3) general anesthesia; and (4) oral sedation. The study was conducted in a children's hospital dental clinic and a suburban private pediatric dentistry office. Parents rated overall acceptance of the techniques, and acceptance under specified conditions using an anchored visual analogue scale. One hundred five parents completed the survey; 55 from the children's hospital and 50 from private practice. Oral sedation was rated as the most acceptable technique, followed by general anesthesia, active immobilization, and passive immobilization. As urgency, convenience, and previous experience increased, parental acceptance of the technique increased. As cost of treatment increased, parental acceptance decreased. Ratings between the children's hospital group and private practice group differed, as did the demographic variables of insurance, income, and race. The hierarchy of parental acceptance of advanced behavior guidance techniques is changing with increasing approval of pharmacological management and decreasing approval of physical management. The health care delivery system, urgency, convenience, previous experience, and cost all influence parental acceptance.

  18. Assessment of Optical Coherence Tomography Imaging in the Diagnosis of Non-Melanoma Skin Cancer and Benign Lesions Versus Normal Skin:

    DEFF Research Database (Denmark)

    Mogensen, Mette; Jørgensen, Thomas Martini; Nürnberg, Birgit Meincke

    2009-01-01

    BACKGROUND Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess the diagn......BACKGROUND Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess...

  19. Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study.

    Science.gov (United States)

    Hannibal, Charlotte Gerd; Jensen, Allan; Sharif, Heidi; Kjaer, Susanne Krüger

    2008-09-01

    The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. 112 malignant melanomas were identified during follow-up through 2000. Use of clomiphene, gonadotrophins, hCG or GnRH did not affect risk of malignant melanoma significantly. When stratifying for parity, however, use of gonadotrophins (RR = 2.29; CI: 1.16-4.52) or GnRH (RR = 3.26; 95% CI: 1.50-7.09) among parous women was associated with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency). Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use of gonadotrophins or GnRH might increase risk in parous women. Longer follow-up is needed to confirm our findings.

  20. Advanced inspection and repair techniques for primary side components

    International Nuclear Information System (INIS)

    Elm, Ralph

    1998-01-01

    The availability of nuclear power plant mainly depends on the components of the Nuclear Steam Supply System (NSSS) such as reactor pressure vessel, core internals and steam generators. The last decade has been characterized by intensive inspection and repair work on PWR steam generators. In the future, it can be expected, that the inspection of the reactor pressure vessel and the inspection and repair of its internals, in both PWR and BWR will be one of the challenges for the nuclear community. Due to this challenge, new, advanced inspection and repair techniques for the vital primary side components have been developed and applied, taking into account such issues as: use of reliable and fast inspection methods, repair of affected components instead of costly replacement, reduction of outage time compared to conventional methods, minimized radiation exposure, acceptable costs. This paper reflects on advanced inspection and repair techniques such as: Baffle Former Bolt inspection and replacement, Barrel Former Bolt inspection and replacement, Mechanized UT and visual inspection of reactor pressure vessels, Steam Generator repair by advanced sleeving technology. The techniques described have been successfully applied in nuclear power plants and improved the operation performance of the components and the NPP. (author). 6 figs

  1. Computer-assisted diagnosis of melanoma.

    Science.gov (United States)

    Fuller, Collin; Cellura, A Paul; Hibler, Brian P; Burris, Katy

    2016-03-01

    The computer-assisted diagnosis of melanoma is an exciting area of research where imaging techniques are combined with diagnostic algorithms in an attempt to improve detection and outcomes for patients with skin lesions suspicious for malignancy. Once an image has been acquired, it undergoes a processing pathway which includes preprocessing, enhancement, segmentation, feature extraction, feature selection, change detection, and ultimately classification. Practicality for everyday clinical use remains a vital question. A successful model must obtain results that are on par or outperform experienced dermatologists, keep costs at a minimum, be user-friendly, and be time efficient with high sensitivity and specificity. ©2015 Frontline Medical Communications.

  2. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J

    2010-12-01

    The natural history of metastatic melanoma involving lymph nodes, in the absence of a known primary site (cutaneous, ocular or mucosal) has, to date, been poorly defined; and the optimal management of this rare subtype of disease is therefore unclear. Melanomas of unknown primary site (MUP) are estimated to comprise between 3.7 and 6% of all melanomas (Anbari et al. in Cancer 79:1861-1821, 1997).

  3. Subretinal lipid exudation associated with untreated choroidal melanoma

    Directory of Open Access Journals (Sweden)

    C K Minija

    2011-01-01

    Full Text Available Subretinal lipid exudation in an untreated choroidal melanoma is very rare. It is seen following plaque radiotherapy in choroidal melanoma. There is only one case report of untreated choroidal melanoma with massive lipid exudation in a patient with metastatic hypernephroma. We report here a rare case of untreated choroidal melanoma with lipid exudation. Subretinal exudation that is rarely seen following plaque brachytherapy was noted at the borders of this untreated tumor. Lipid exudation partially resolved following brachytherapy.

  4. The clinical role of immunoscintigraphy for the detection of ocular melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Schaling, D.F. [Leiden, Univ. Hospital (Netherlands). Dipt. of Ophtalmology. Dpt. of Diagnostic Radiology and Nuclear Medicine; Pauwels, E.K. [Leiden, Univ. Hospital (Netherlands). Dipt. of Diagnostic Radiology and Nuclear Medicine

    1996-12-01

    The value of immunoscintigraphy in the diagnostic of choroidal melanoma is discussed and compared with other diagnostic procedures with isotopes and diagnostic modalities like fluorescein angiography, standardized ultrasonography and magnetic resonance imaging. Consecutive studies with immunoscintigraphy in choroidal melanoma show a sensitivity of 41 to 49%, witch can be improved by use of single photon emission computerized tomography (SPECT). Another technique which has improved the results of radio-immunoscintigraphy is the use of a three-step labelling procedure with biotinylated anti-tumor antibodies and avidin. The specificity of the 225.288 antibody is discussed with regard to the expression of the chondroitin sulfate proteoglycan (CSPG) - to which the 225.288 antibody is directed - in normal tissue and in other malignant tumours.

  5. Satellite in transit metastases in rapidly fatal conjunctival melanoma: implications for angiotropism and extravascular migratory metastasis (description of a murine model for conjunctival melanoma).

    Science.gov (United States)

    Barnhill, Raymond L; Lemaitre, Stéphanie; Lévy-Gabrielle, Christine; Rodrigues, Manuel; Desjardins, Laurence; Dendale, Rémi; Vincent-Salomon, Anne; Roman-Roman, Sergio; Lugassy, Claire; Cassoux, Nathalie

    2016-02-01

    Little information is currently available concerning loco-regional metastases such as satellite and in transit metastases and their natural history in conjunctival melanoma as compared to cutaneous melanoma. Angiotropism, a marker of extravascular migration of melanoma cells along vascular channels, often appears responsible for microscopic satellite, satellite and in transit metastases development in cutaneous melanoma. In addition, diffuse tissue microscopic satellites are correlated with widespread melanoma dissemination and death. Herein we report rapid conjunctival melanoma progression and a fatal outcome in four of five patients following recurrence as satellite in transit metastases. Five patients aged 31, 60, 63, 56, and 67 years developed primary conjunctival melanoma, histologically characterised by tumour thicknesses of 4, 4, 1.1, 3, and 2 mm. Two or more conjunctival melanomas manifested ulceration, significant mitotic rates, necrosis, angiotropism, and intralesional transformation. The conjunctival melanoma recurred in a matter of months as one or more discrete satellite in transit lesions in the vicinity of the primary melanoma. Histological examination revealed well-defined micronodules containing atypical melanocytes in the subepithelial connective tissue stroma. All lesions were extravascular and most appeared angiotropic. Four of five patients subsequently developed parotid or other loco-regional nodal disease and rapidly ensuing widespread metastases and death. The time course from diagnosis to the demise of the patients averaged about 13 (range 7-20) months. Our findings suggest that satellite in transit metastases constitute an important new risk marker for possible rapid metastatic disease progression and death in patients with conjunctival melanoma. This finding appears to take on even greater significance if such lesions develop rapidly, i.e., in a matter of weeks or months following diagnosis of primary conjunctival melanoma, and if the

  6. Immunizing Patients With Metastatic Melanoma Using Recombinant Adenoviruses Encoding MART-1 or gp100 Melanoma Antigens

    Science.gov (United States)

    Rosenberg, Steven A.; Zhai, Yifan; Yang, James C.; Schwartzentruber, Douglas J.; Hwu, Patrick; Marincola, Francesco M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Seipp, Claudia A.; Einhorn, Jan H.; Roberts, Bruce; White, Donald E.

    2008-01-01

    Background: The characterization of the genes encoding melanoma-associated antigens MART-1 or gp100, recognized by T cells, has opened new possibilities for the development of immunization strategies for patients with metastatic melanoma. With the use of recombinant adenoviruses expressing either MART-1 or gp100 to immunize patients with metastatic melanoma, we evaluated the safety, immunologic, and potential therapeutic aspects of these immunizations. Methods: In phase I studies, 54 patients received escalating doses (between 107 and 1011 plaque-forming units) of recombinant adenovirus encoding either MART-1 or gp100 melanoma antigen administered either alone or followed by the administration of interleukin 2 (IL-2). The immunologic impact of these immunizations on the development of cellular and antibody reactivity was assayed. Results: Recombinant adenoviruses expressing MART-1 or gp100 were safely administered. One of 16 patients with metastatic melanoma receiving the recombinant adenovirus MART-1 alone experienced a complete response. Other patients achieved objective responses, but they had received IL-2 along with an adenovirus, and their responses could be attributed to the cytokine. Immunologic assays showed no consistent immunization to the MART-1 or gp100 transgenes expressed by the recombinant adenoviruses. High levels of neutralizing antibody were found in the pretreatment sera of the patients. Conclusions: High doses of recombinant adenoviruses could be safely administered to cancer patients. High levels of neutralizing antibody present in patients' sera prior to treatment may have impaired the ability of these viruses to immunize patients against melanoma antigens. PMID:9862627

  7. Melanoma costs: a dynamic model comparing estimated overall costs of various clinical stages.

    Science.gov (United States)

    Alexandrescu, Doru Traian

    2009-11-15

    adjuvant treatment with IFN-alpha ($75,955.18), palliative care ($14,500), and administration of chemotherapy ($1,967.10 for a triple combination of agents); there are even higher costs for biochemotherapy, the new tyrosine kinase and antiangiogenic drugs, and hospital treatment of neutropenic fever ($1,535.00 to $1,800.00/day). There is a significant cost decrement when melanoma is diagnosed at an earlier stage, with a T4b lesion being approximately 2200 percent more expensive to diagnose and treat than an early in situ melanoma and 1000 percent more expensive than a stage T1a tumor. Although a direct comparison with other cancers would require the use of the same dynamic model, it is apparent that the high costs of melanoma care places it at the top of the most expensive cancers to diagnose, follow, and treat. These high costs for advanced-stage melanoma warrant an increased emphasis on developing effective strategies for its early diagnosis and treatment.

  8. Relato de um caso de melanoma de conjuntiva Conjuntival melanoma: a case report

    Directory of Open Access Journals (Sweden)

    Carlos Gustavo Leite Vieira

    2000-10-01

    Full Text Available Objetivo: Relatar um caso raro de melanoma de conjuntiva de longa evolução em paciente melanodérmica. Método: Análise de caso. Resultado: Até a presente data a paciente encontra-se bem sem evidências de recorrência da patologia em questão após excisão local. Conclusão: Observamos que mesmo sem a realização de crioterapia adjuvante ou medidas mais agressivas, existem alguns casos como esse que acabamos de relatar para o qual a excisão simples pode garantir a cura. Um aspecto importante deste relato é a importância do exame histopatológico de peças e fragmentos cirúrgicos removidos.Purpose: The authors describe a rare case of malignant conjunctival melanoma with a long evolution. Methods: A case report. Results: Until this time the patient does not show any sign of relapse of this melanoma, after local excision. Conclusion: Without cryotherapy or more agressive methods we observe that there are some cases of conjunctival melanoma that might be cured with only a local excision. An important aspect of this case is the relevance of the histopathologic analysis of the removed surgical fragments.

  9. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi

    2013-01-01

    Full Text Available 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.

  10. Cartilaginous melanoma: case report and review of the literature Melanoma cartilagíneo: caso clínico e revisão da literatura

    Directory of Open Access Journals (Sweden)

    Parente Joana Devesa

    2013-06-01

    Full Text Available Malignant melanoma can present a variety of histopathological patterns. Cartilaginous change in the absence of osteogenic differentiation is extremely rare in malignant melanoma, being among the least frequent of the wide range of melanoma histologic patterns. We report a case of a 47-year-old woman with a subungual nodule on her right great toe for many years. Histopathological examination of the lesion led to a diagnosis of malignant melanoma with cartilaginous differentiation devoid of concomitant osseous areas. It would appear that this unusual form of melanoma has a predilection for acral location, particularly the subungual region. Malignant melanoma with chondroid stroma should therefore be considered in the differential diagnosis of cartilaginous lesions of the toes and fingers. Careful examination of the overlying epidermis and identification of an in situ component of melanoma may be necessary in order to establish the correct diagnosis.O melanoma maligno pode apresentar uma grande variedade de padrões histopatológicos. A presença de diferenciação cartilagínea, na ausência de diferenciação osteogénica, é extremamente rara no melanoma maligno. O melanoma cartilagíneo está entre os padrões histológicos menos frequentes. Relatamos um caso de uma doente do sexo feminino de 47 anos de idade com um nódulo subungueal no 1º dedo do pé direito com muitos anos de evolução. O exame histopatológico da lesão revelou melanoma cartilagíneo, sem áreas de diferenciação osteogénica. Esta variante de melanoma parece ter predileção pela extremidades, sobretudo pela região subungueal. Assim, o melanoma maligno com diferenciação condróide, deve ser tido em consideração no diagnóstico diferencial de lesões acrais cartilagíneas. A observação cuidadosa da epiderme e a identificação de um componente do melanoma in situ podem ser necessários para estabelecer um diagnóstico correto.

  11. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna

    2012-02-01

    INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

  12. Development of a multiple-marker polymerase chain reaction assay for detection of metastatic melanoma in lymph node aspirates of dogs.

    Science.gov (United States)

    Catchpole, Brian; Gould, Sara M; Kellett-Gregory, Lindsay M; Dobson, Jane M

    2003-05-01

    To develop a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect canine melanoma-associated antigens (MAAs) and to use this technique to screen aspirates of lymph nodes (LNs) for evidence of metastatic spread of oral malignant melanoma. 7 dogs with oral malignant melanoma and 4 dogs with multicentric lymphosarcoma. We prepared cDNA from melanoma tumor biopsies and fine-needle aspirates obtained from submandibular LNs of dogs with oral malignant melanoma or multicentric lymphosarcoma. The RT-PCR assay was performed by use of tyrosinase, Melan-A, gp100, tyrosinase-related protein 2 (TRP-2), or melanoma antigen-encoding gene B (MAGE-B)-specific primers. We detected MAGE-B mRNA in canine testicular tissue but not in melanoma biopsy specimens. Tyrosinase, Melan-A, gp100, and TRP-2 mRNAs were detected in tumor biopsy specimens and in 2 of 5 LN aspirates from dogs with melanoma, suggesting metastatic spread in those 2 dogs. We did not detect MAAs in LN aspirates obtained from dogs with multicentric lymphosarcoma. Sequencing of canine Melan-A and gp100 PCR products confirmed the specificity of the assay for these genes. Clinical staging of dogs with oral malignant melanoma is useful to assist in designing appropriate treatments. However, results of histologic examination of LN biopsy specimens can be inconclusive and, in humans, can underestimate the number of patients with metastatic disease. Molecular staging of melanomas in dogs can be achieved by screening LN aspirates for MAA mRNA, and this can be performed in combination with cytologic examination to aid in detection of metastatic disease.

  13. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600 to 800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800 to 400 to 400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  14. Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients.

    Science.gov (United States)

    Salvaggio, Christine; Han, Sung Won; Martires, Kathryn; Robinson, Eric; Madankumar, Reshmi; Gumaste, Priyanka; Polsky, David; Stein, Jennifer; Berman, Russell; Shapiro, Richard; Zhong, Judy; Osman, Iman

    2016-01-01

    The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the χ² test and multivariate logistic regression. We compared survival distributions using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard ratios. Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background. © 2016 S. Karger AG, Basel.

  15. Usefulness of V-Y Advancement Flap for Defects after Skin Tumor Excision

    Directory of Open Access Journals (Sweden)

    Ki Hyun Kwon

    2012-11-01

    Full Text Available BackgroundAfter skin tumor excision on the face, extremities, or trunk, the choice of treatment for a skin defect is highly variable. Many surgeons prefer to use a local flap rather than a skin graft or free flap for small- or moderately-sized circular defects. We have used unilateral or bilateral V-Y advancement flaps, especially on the face. Here we evaluated the functional and aesthetic results of this technique.MethodsAll of the patients were pathologically diagnosed with squamous cell carcinoma (SCC, basal cell carcinoma (BCC, or malignant melanoma or premalignant lesion (Bowen's disease. Thirty-two patients underwent V-Y advancement flap repair (11 unilateral and 21 bilateral from January 2007 to June 2011. We analyzed the patients' age and satisfaction, and location and size of defect. The patients were followed up for 6 months or more.ResultsThere were 22 women and 10 men. The ages ranged from 47 to 93 years with a mean age of 66 years. The causes were SCC in 15 cases, BCC in 13 cases, malignant melanoma in 1 case, Bowen's disease in 2 cases, and another cause in 1 case. The tumor locations were the face in 28 patients, and the scalp, upper limb, and flank each in one patient. All of the flaps survived and the aesthetic results were good. Postoperative recovery was usually rapid, and no complication or tumor recurrence was observed.ConclusionsThe V-Y advancement flap is often used not only for facial circular defects but also for defects of the trunk and extremities. Its advantages are less scarring and superior aesthetic results as compared with other local flap methods, because of less scarification of adjacent tissue and because it is an easy surgical technique.

  16. Melanoma or Pseudo melanoma Change in a pigmented lesion after application of topical 5-Fluorouracil

    Science.gov (United States)

    2017-10-26

    2. REPORT TYPE 3. DATES COVERED (From - To) 10/26/2017 Poster 10/26/2017-10/29/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Melanoma or Pseudo...melanoma? Change in a pigmented lesion after application of topical 5-Fluorouracil. 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d

  17. Immunohistochemical Expression of MCAM/CD146 in Canine Melanoma.

    Science.gov (United States)

    Abou Asa, S

    2017-07-01

    MCAM/CD146 (melanoma cell adhesion molecule/CD146) is a transmembrane immunoglobulin superfamily cell adhesion molecule involved in transendothelial migration and signal transduction. It is expressed in melanoma, squamous cell carcinoma, prostatic, ovarian, cervical and endometrial cancers and promotes tumour growth, angiogenesis and metastasis. Melanoma is the most common malignant oral tumour of dogs and also arises in the skin, nail bed and footpad. The aim of this study was to investigate the immunohistochemical expression of MCAM/CD146 in 51 canine melanomas, including oral, cutaneous and ocular tumours. Seventeen of the 51 (33.3%) cases were negative, eight (15.7%) were weakly positive, seven (13.7%) were moderately positive and 19 (37.3%) were strongly positive. MCAM/CD146 was expressed by both oral and cutaneous melanomas; however, the intensity and the extent of the immunoreactivity was higher in oral (P = 0.009) than in cutaneous tumours (P = 0.058). Most ocular melanomas did not express MCAM/CD146 (P = 0.256). Expression of MCAM/CD146 by canine melanomas may suggest the molecule as a target for treatment, especially in oral melanomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma

    International Nuclear Information System (INIS)

    Goppner, D.; Leverkus, M.

    2011-01-01

    Due to intensified research in recent years, the understanding of the molecular mechanisms involved in the development of melanoma has dramatically improved. The discovery of specific, causal mutations such as BRAF or KIT oncogenes not only renders a targeted and thus more effective therapeutic approach possible, but also gives rise to a new genetic-based classification. Targeting just a few out of several potential mutations, BRAF-Inhibitors such as PLX 4032 achieved already tremendous results in the therapy of metastatic melanoma. Up to now, the correlation of clinical, histomorphologic, and genetic features is, however, not understood. Even more, is it not well known precisely what kind of molecular changes predispose the primary melanoma for metastasis. The identification of morphological surrogates and prognostic parameters in tumors with such genetic alteration seems therefore crucial when differentiating and classifying this heterogeneous tumor entity in more detail and thus facilitates the stratification of prognosis as well as therapy. This review summarizes the current understanding of carcinogenesis and gives a detailed overview of known morphologic and potentially future genetic prognostic parameters in malignant melanoma.

  19. Killing of Human Melanoma Cells Induced by Activation of Class I Interferon–Regulated Signaling Pathways via MDA-7/IL-24

    Science.gov (United States)

    Ekmekcioglu, Suhendan; Mumm, John B.; Udtha, Malini; Chada, Sunil; Grimm, Elizabeth A.

    2008-01-01

    Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1–regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN alfa) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of Class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN beta induction followed by IRF regulation and TRAIL/FasL system activation. PMID:18511292

  20. In-depth characterization of microRNA transcriptome in melanoma.

    Directory of Open Access Journals (Sweden)

    James Kozubek

    Full Text Available The full repertoire of human microRNAs (miRNAs that could distinguish common (benign nevi from cutaneous (malignant melanomas remains to be established. In an effort to gain further insight into the role of miRNAs in melanoma, we applied Illumina next-generation sequencing (NGS platform to carry out an in-depth analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm and metastatic melanomas with matched normal skin in parallel to melanocytes and melanoma cell lines (both primary and metastatic (n=28. From this data representing 698 known miRNAs, we defined a set of top-40 list, which properly classified normal from cancer; also confirming 23 (58% previously discovered miRNAs while introducing an additional 17 (42% known and top-15 putative novel candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA signature distinguishing specimens of melanoma from nevus was significantly different than that of melanoma cell lines from melanocytes. Among the top list, miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b-5p were decreased in melanomas vs. nevi. In a validation cohort (n=101, we verified the NGS results by qRT-PCR and showed that receiver-operating characteristic curves for miR-211-5p expression accurately discriminated invasive melanoma (AUC=0.933, melanoma in situ (AUC=0.933 and dysplastic (atypical nevi (AUC=0.951 from common nevi. Target prediction analysis of co-transcribed miRNAs showed a cooperative regulation of key elements in the MAPK signaling pathway. Furthermore, we found extensive sequence variations (isomiRs and other non-coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing small RNAs directly from clinically defined specimens provides a robust strategy to improve melanoma diagnostics.

  1. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan

    2010-04-01

    Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

  2. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  3. Pathogenesis, diagnosis and management of primary melanoma of the colon

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    Full Text Available Abstract Background Melanomas within the alimentary tract are usually metastatic in origin. On the other hand, primary melanomas of the gastrointestinal tract are relatively uncommon. There are several published reports of melanomas occurring in the esophagus, stomach, small bowel, and anorectum. The occurrence of primary melanoma of the colon has, however, only been rarely reported. The optimum modus operandi for the management of primary colonic melanoma remains nebulous due to the limited number of reports in literature. Methods A comprehensive search of Medline, Cochrane and Highwire was performed using the following keywords: 'melanoma', 'malignant melanoma', 'primary melanoma', 'colon', 'gastrointestinal tract', 'alimentary tract', 'digestive tract', and 'large bowel'. All patients with primary melanoma localized to the colon were included in the review. Patients with metastatic melanomas to the gastrointestinal (GI tract and primary melanomas localized to the GI tract in anatomic locations other than colon were excluded. Results There have been only 12 reported cases of primary melanoma of the colon to date. The average age of patients on presentation was 60.4 years without any significant gender predilection. Right colon (33% and cecum (33% were the most common sites for the occurrence of primary colonic melanoma while abdominal pain (58% and weight loss (50% were the most common presenting complaints. Colonoscopy is the most reliable diagnostic investigation and offers the additional advantage of obtaining tissue for diagnosis. S-100 and HMB-45 are highly sensitive and specific for the diagnosis of this malignancy. For primary colonic melanomas that have not metastasized to any distant parts of the body, surgical resection with wide margins appears to be the treatment of choice. Although the management was individualized in every case, most of the authors preferred traditional hemicolectomy as the favored surgical approach

  4. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma...

  5. ARDENT to develop advanced dosimetric techniques

    CERN Document Server

    Antonella Del Rosso

    2012-01-01

    Earlier this week, the EU-supported Marie Curie training network ARDENT kicked off at a meeting held at CERN. The overall aim of the project is the development of advanced instrumentation for radiation dosimetry. The applications range from radiation measurements around particle accelerators, onboard commercial flights and in space, to the characterization of radioactive waste and medicine, where accurate dosimetry is of vital importance.   The ARDENT (Advanced Radiation Dosimetry European Network Training) project is both a research and a training programme, which aims at developing new dosimetric techniques while providing 15 Early-Stage Researchers (ESR) with state-of-the-art training. The project, coordinated by CERN, is funded by the European Union with a contribution of about 3.9 million euros over four years. The ARDENT initiative will focus on three main technologies: gas detectors, in particular Gas Electron Multipliers (GEM) and Tissue Equivalent Proportional Counters (TEPC); solid stat...

  6. Sunnier European countries have lower melanoma mortality.

    Science.gov (United States)

    Shipman, A R; Clark, A B; Levell, N J

    2011-07-01

    Doubt has been cast on sunlight as the major causative factor for malignant melanoma. We performed statistical analysis of the average annual sunlight hours in 36 European capital cities compared with the country's melanoma mortality rate. A significant inverse proportionality was identified in both men and women, indicating that sun exposure is unlikely to be the strongest factor affecting mortality from malignant melanoma. © The Author(s). CED © 2011 British Association of Dermatologists.

  7. Born to be Alive: A Role for the BCL-2 Family in Melanoma Tumor Cell Survival, Apoptosis, and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Anvekar, Rina A.; Asciolla, James J.; Missert, Derek J.; Chipuk, Jerry E., E-mail: jerry.chipuk@mssm.edu [Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY (United States); Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States); The Tisch Cancer Institute, Mount Sinai Medical Center, New York, NY (United States)

    2011-10-13

    The global incidence of melanoma has dramatically increased during the recent decades, yet the advancement of primary and adjuvant therapies has not kept a similar pace. The development of melanoma is often centered on cellular signaling that hyper-activates survival pathways, while inducing a concomitant blockade to cell death. Aberrations in cell death signaling not only promote tumor survival and enhanced metastatic potential, but also create resistance to anti-tumor strategies. Chemotherapeutic agents target melanoma tumor cells by inducing a form of cell death called apoptosis, which is governed by the BCL-2 family of proteins. The BCL-2 family is comprised of anti-apoptotic proteins (e.g., BCL-2, BCL-xL, and MCL-1) and pro-apoptotic proteins (e.g., BAK, BAX, and BIM), and their coordinated regulation and function are essential for optimal responses to chemotherapeutics. Here we will discuss what is currently known about the mechanisms of BCL-2 family function with a focus on the signaling pathways that maintain melanoma tumor cell survival. Importantly, we will critically evaluate the literature regarding how chemotherapeutic strategies directly impact on BCL-2 family function and offer several suggestions for future regimens to target melanoma and enhance patient survival.

  8. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    2014-01-01

    AND METHODS: A total of 84 perfusions were performed (53 women, 31 men, median age 63 years) from 1993 to 2010. 95% of the perfusions were administered to the lower limbs and 5% to the upper limbs. The inclusion criteria were recurrent and/or clinically apparent cutaneous/subcutaneous extremity in....... Time from ILP to recurrence was a median of seven months (range 1-37 months) for patients with CR or PR. Survival was longer for patients with CR or PR than for patients showing NC or progression. Several patients had mild or moderate local toxicity reactions, two patients developed severe local...... to improve local disease control in patients with multiple and/or recurrent melanoma confined to an extremity if surgical excision is not possible. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....

  9. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva

    2016-01-01

    melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. MAIN VARIABLES: The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor...... studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment...

  10. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.

    Science.gov (United States)

    Weber, Jeffrey S; D'Angelo, Sandra P; Minor, David; Hodi, F Stephen; Gutzmer, Ralf; Neyns, Bart; Hoeller, Christoph; Khushalani, Nikhil I; Miller, Wilson H; Lao, Christopher D; Linette, Gerald P; Thomas, Luc; Lorigan, Paul; Grossmann, Kenneth F; Hassel, Jessica C; Maio, Michele; Sznol, Mario; Ascierto, Paolo A; Mohr, Peter; Chmielowski, Bartosz; Bryce, Alan; Svane, Inge M; Grob, Jean-Jacques; Krackhardt, Angela M; Horak, Christine; Lambert, Alexandre; Yang, Arvin S; Larkin, James

    2015-04-01

    Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported

  11. IQGAP1 is an oncogenic target in canine melanoma.

    Directory of Open Access Journals (Sweden)

    Becky H Lee

    Full Text Available Canine oral mucosal melanoma is an aggressive malignant neoplasm and is characterized by local infiltration and a high metastatic potential. The disease progression is similar to that of human oral melanomas. Whereas human cutaneous melanoma is primarily driven by activating mutations in Braf (60% or Nras (20%, human mucosal melanoma harbors these mutations much less frequently. This makes therapeutic targeting and research modeling of the oral form potentially different from that of the cutaneous form in humans. Similarly, research has found only rare Nras mutations and no activating Braf mutations in canine oral melanomas, but they are still reliant on MAPK signaling. IQGAP1 is a signaling scaffold that regulates oncogenic ERK1/2 MAPK signaling in human Ras- and Raf- driven cancers, including melanomas. To investigate whether IQGAP1 is a potential target in canine melanoma, we examined the expression and localization of IQGAP1 in primary canine melanomas and canine oral melanoma cell lines obtained from the University of California-Davis. Using CRISPR/Cas9 knockout of IQGAP1, we examined effects on downstream ERK1/2 pathway activity and assayed proliferation of cell lines when treated with a peptide that blocks the interaction between IQGAP1 and ERK1/2. We observed that canine IQGAP1 is expressed and localizes to a similar extent in both human and canine melanoma by qPCR, Western blot, and immunofluorescence. Deletion of IQGAP1 reduces MAPK pathway activation in cell lines, similar to effects seen in human BrafV600E cell lines. Additionally, we demonstrated reduced proliferation when these cells are treated with a blocking peptide in vitro.

  12. Knowledge based systems advanced concepts, techniques and applications

    CERN Document Server

    1997-01-01

    The field of knowledge-based systems (KBS) has expanded enormously during the last years, and many important techniques and tools are currently available. Applications of KBS range from medicine to engineering and aerospace.This book provides a selected set of state-of-the-art contributions that present advanced techniques, tools and applications. These contributions have been prepared by a group of eminent researchers and professionals in the field.The theoretical topics covered include: knowledge acquisition, machine learning, genetic algorithms, knowledge management and processing under unc

  13. Precision Diagnosis Of Melanoma And Other Skin Lesions From Digital Images.

    Science.gov (United States)

    Bhattacharya, Abhishek; Young, Albert; Wong, Andrew; Stalling, Simone; Wei, Maria; Hadley, Dexter

    2017-01-01

    Melanoma will affect an estimated 73,000 new cases this year and result in 9,000 deaths, yet precise diagnosis remains a serious problem. Without early detection and preventative care, melanoma can quickly spread to become fatal (Stage IV 5-year survival rate is 20-10%) from a once localized skin lesion (Stage IA 5- year survival rate is 97%). There is no biomarker for melanoma in clinical use, and the current diagnostic criteria for skin lesions remains subjective and imprecise. Accurate diagnosis of melanoma relies on a histopathologic gold standard; thus, aggressive excision of melanocytic skin lesions has been the mainstay of treatment. It is estimated that 36 biopsies are performed for every melanoma confirmed by pathology among excised lesions. There is significant morbidity in misdiagnosing melanoma such as progression of the disease for a false negative prediction vs the risks of unnecessary surgery for a false positive prediction. Every year, poor diagnostic precision adds an estimated $673 million in overall cost to manage the disease. Currently, manual dermatoscopic imaging is the standard of care in selecting atypical skin lesions for biopsy, and at best it achieves 90% sensitivity but only 59% specificity when performed by an expert dermatologist. Many computer vision (CV) algorithms perform better than dermatologists in classifying skin lesions although not significantly so in clinical practice. Meanwhile, open source deep learning (DL) techniques in CV have been gaining dominance since 2012 for image classification, and today DL can outperform humans in classifying millions of digital images with less than 5% error rates. Moreover, DL algorithms are readily run on commoditized hardware and have a strong online community of developers supporting their rapid adoption. In this work, we performed a successful pilot study to show proof of concept to DL skin pathology from images. However, DL algorithms must be trained on very large labelled datasets of

  14. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2012-02-01

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  15. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C

    2011-04-17

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  16. Preferences of German melanoma patients for interferon (IFN) α-2b toxicities (the DeCOG "GERMELATOX survey") versus melanoma recurrence to quantify patients' relative values for adjuvant therapy.

    Science.gov (United States)

    Kaehler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Haalck, Thomas; Heinzerling, Lucie; Kornek, Thomas; Livingstone, Elisabeth; Loquai, Carmen; Maul, Lara Valeska; Lang, Berenice M; Schadendorf, Dirk; Stade, Barbara; Terheyden, Patrick; Utikal, Jochen; Wagner, Tobias; Hauschild, Axel; Garbe, Claus; Augustin, Matthias

    2016-11-01

    Currently interferon alfa-2b (IFNα-2b) is an approved adjuvant drug for high-risk melanoma patients that leads to an improvement in disease-free survival (DFS). However, it is unclear whether it also impacts overall survival. Widespread use of adjuvant high-dose IFNα has been tempered by its significant toxicity and its limited efficacy. Current therapeutic strategies like immune checkpoint blockade or targeted therapy may also be useful in the adjuvant setting. Therefore, it is important to weigh the trade-offs between possible side effects and therapeutic benefit.We assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a specific health state on a scale of 0 (death) to 1 (perfect health).Utilities were determined for health states associated with adjuvant IFN among 130 German low-risk melanoma patients using the standard gamble technique. Four IFNα-2b toxicity scenarios and the following 3 posttreatment outcomes were assessed: disease-free health and melanoma recurrence (with or without previous use of IFNα-2b) resulting in cancer death. Patients were asked to trade-off the improvement in 5-year DFS and the IFN-related side effects.Utilities for melanoma recurrence (mean 0.60) were significantly lower than for all IFNα-2b toxicity scenarios (mean 0.81-0.90). Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, respectively. Both utilities and threshold benefits were mostly independent from patient characteristics like gender, income, and social situation. Significant impact was only observed by age and previous personal experience with cancer.On average, German patients were willing to trade even severe IFNα-2b toxicity for reducing the rate of melanoma recurrence. This result points out the importance of a relapse-free survival for melanoma patients. The utilities measured in our study can be applied to decision-making processes in

  17. The role of spectrophotometry in the diagnosis of melanoma

    Science.gov (United States)

    2010-01-01

    Background Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. Methods During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy). Results Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. Conclusions Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions. PMID:20707921

  18. Sentinel lymphoscintigraphy in malignant melanoma and Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Dekova, M.; Kirov, V.; Donchev, M.; Slavova, M.; Tsarovska, T.

    2013-01-01

    Full text:Introduction: The concept of a biopsy of the sentinel lymph node (SLN) was developed by Mortan in 1992, using blue dye. In 1993. Alex and Krag identified SLN with radiocolloid and gamma probe in case of malignant melanoma. Today, both methods are applied separately or together with a success rate above 90% and false negative rate of 5 %. Materials and Methods: The study includes 10 patients, 9 of whom have been diagnosed with malignant melanoma and 1 – with Merkel cancer. All patients were of a higher risk of lymphatic metastases without distinct clinical symptoms. Lymphoscintigraphy was performed with double-headed SPECT gamma camera Toshiba CGA 7200 UI. The visualized lymph nodes were projected and marked on the skin by a point radioactive source under monitoring. The marked lymph nodes were verified during the operation by staining and patent Blau then removed and studies histopathologically. Results: In all patients the Lymphoscintigraphy visualized SLN, which were surgically found just below the skin markers and removed. In the SLN of one patient a diffuse metastasis was found. In the SLN of nine patients no evidence for metastatic process was found. Conclusion: The technique of marking the SLN with subsequent biopsy is a minimally invasive method for the detection of lymph node metastases in patients with malignant melanoma and Merkel carcinoma with a high degree of reliability of the results

  19. Recent advances on Charpy specimen reconstitution techniques

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J., E-mail: aandrade@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2017-07-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  20. Recent advances on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Andrade, Arnaldo H.P.; Lobo, Raquel M.; Miranda, Carlos Alexandre J.

    2017-01-01

    Charpy specimen reconstitution is widely used around the world as a tool to enhance or supplement surveillance programs of nuclear reactor pressure vessels. The reconstitution technique consists in the incorporation of a small piece from a previously tested specimen into a compound specimen, allowing to increase the number of tests. This is especially important if the available materials is restricted and fracture mechanics parameter have to be determined. The reconstitution technique must fulfill some demands, among them tests results like the original standard specimens and the loaded material of the insert must not be influenced by the welding and machining procedure. It is known that reconstitution of Charpy specimens may affect the impact energy in a consequence of the constraint of plastic deformation by the hardened weldment and HAZ. This paper reviews some recent advances of the reconstitution technique and its applications. (author)

  1. Metastatic malignant subungal melanoma: Importance of FNAC

    Directory of Open Access Journals (Sweden)

    Radhika Punshi Nandwani

    2014-01-01

    Full Text Available Subungual melanoma is a rare type of skin cancer. It is an uncommon form of acral lentiginous melanoma. Approximately 85% of cases are misdiagnosed initially, and it is generally associated with a poor prognosis. Herein, we describe a case of metastatic subungal melanoma to the axillary lymph node in a 45-year-old male. Diagnosis of metastasis was made based on cytology, where the clinicians were guided to search for primary. This case report highlights the role of fine-needle aspiration cytology (FNAC in the diagnosis of this entity to draw the attention of the reader to the possible underreporting of melanoma because of a variant that evades diagnosis and our reluctance to think about its existence.

  2. Cross-cultural development of a quality-of-life measure for patients with melanoma: phase 3 testing of an EORTC Melanoma Module.

    Science.gov (United States)

    Winstanley, Julie B; Young, Teresa E; Boyle, Frances M; Bergenmar, Mia; Bottomley, Andrew; Burmeister, Bryan; Campana, Luca G; Garioch, Jennifer J; King, Madeleine; Nikolic, Dejan V; van de Poll-Franse, Lonneke V; Saw, Robyn; Thompson, John F; White, Edward G

    2015-02-01

    Melanoma is an increasingly common skin cancer worldwide. Recent treatment advances have provided patients and healthcare professionals (HCPs) with choices where quality of life (QoL) and toxicity are important considerations. A melanoma-specific QoL questionnaire is being developed in a cross-cultural setting using a four phase process developed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group. In phase 1, a literature search identified a list of pertinent QoL issues; this was shown to HCPs and patients in eight countries and rated for importance and relevance. Questions were constructed for the highest-rated issues (phase 2) and piloted in another patient sample (phase 3). Using EORTC Quality of Life Group criteria and sequential use of factor and Rasch analysis, scales were hypothesized for field testing (phase 4). Seven QoL domains (disease symptoms, treatment issues, financial issues, access/quality of information, satisfaction with care, psychosocial issues and support), comprising 73 QoL issues, were rated by 46 HCPs and 78 patients. Fifty-six issues were rephrased as questions and piloted with 132 patients. A 38-item questionnaire (QLQ-MEL38) is available for field testing in conjunction with the EORTC QLQ-C30. This study has shown that melanoma patients have important QoL issues that have been incorporated into a new cross-culturally validated instrument. Future testing of this EORTC module is planned and will be an important step forward in providing reliable QoL data to aid future decision-making in the management and clinical trials of this complex group of patients.

  3. In vivo pump-probe microscopy of melanoma and pigmented lesions

    Science.gov (United States)

    Wilson, Jesse W.; Degan, Simone; Mitropoulos, Tanya; Selim, M. Angelica; Zhang, Jennifer Y.; Warren, Warren S.

    2012-03-01

    A growing number of dermatologists and pathologists are concerned that the rapidly rising incidence of melanoma reflects not a true 'epidemic' but an increasing tendency to overdiagnose pigmented lesions. Addressing this problem requires both a better understanding of early-stage melanoma and new diagnostic criteria based on more than just cellular morphology and architecture. Here we present a method for in-vivo optical microscopy that utilizes pump-probe spectroscopy to image the distribution of the two forms of melanin in skin: eumelanin and pheomelanin. Images are acquired in a scanning microscope with a sensitive modulation transfer technique by analyzing back-scattered probe light with a lock-in amplifier. Early-stage melanoma is studied in a human skin xenografted mouse model. Individual melanocytes have been observed, in addition to pigmented keratinocytes. Combining the pump-probe images simultaneously with other noninvasive laser microscopy methods (confocal reflectance, multiphoton autofluorescence, and second harmonic generation) allows visualization of the skin architecture, framing the functional pump-probe image in the context of the surrounding tissue morphology. It is found that pump-probe images of melanin can be acquired with low peak intensities, enabling wide field-of-view pigmentation surveys. Finally, we investigate the diagnostic potential of the additional chemical information available from pump-probe microscopy.

  4. Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

    Directory of Open Access Journals (Sweden)

    Tosti G

    2013-10-01

    Full Text Available Giulio Tosti, Emilia Cocorocchio, Elisabetta PennacchioliDivisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, ItalyAbstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4 antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under

  5. Incorporating Colour Information for Computer-Aided Diagnosis of Melanoma from Dermoscopy Images: A Retrospective Survey and Critical Analysis

    Directory of Open Access Journals (Sweden)

    Ali Madooei

    2016-01-01

    Full Text Available Cutaneous melanoma is the most life-threatening form of skin cancer. Although advanced melanoma is often considered as incurable, if detected and excised early, the prognosis is promising. Today, clinicians use computer vision in an increasing number of applications to aid early detection of melanoma through dermatological image analysis (dermoscopy images, in particular. Colour assessment is essential for the clinical diagnosis of skin cancers. Due to this diagnostic importance, many studies have either focused on or employed colour features as a constituent part of their skin lesion analysis systems. These studies range from using low-level colour features, such as simple statistical measures of colours occurring in the lesion, to availing themselves of high-level semantic features such as the presence of blue-white veil, globules, or colour variegation in the lesion. This paper provides a retrospective survey and critical analysis of contributions in this research direction.

  6. Poliosis circumscripta unmasking a scalp melanoma.

    Science.gov (United States)

    Yeo, L; Husain, E; Rajpara, S

    2015-12-01

    A 28-year-old man presented with a 1-year history of a localized patch of grey hair and an underlying darkly pigmented lesion on his right occipital area. Clinical appearance revealed poliosis overlying an asymmetrical plaque with variable degrees of brown pigmentation and white discolouration. Owing to the suspicious nature of the lesion, excision with a 2 mm margin was performed. Histology revealed an invasive melanoma with extensive regression and prominent involvement of multiple hair follicles. Scalp melanoma with associated poliosis is extremely rare, and has only been reported once in the literature to date. There have been two reports in the opthalmology literature regarding eyelash poliosis associated with orbital melanoma. The pathogenesis of poliosis still remains unclear. This is the second reported case of poliosis circmscripta unmasking a scalp melanoma, and highlights the importance of being vigilant when examining patients with poliosis of the scalp. © 2014 British Association of Dermatologists.

  7. Magnetic force microscopy: advanced technique for the observation of magnetic domains

    International Nuclear Information System (INIS)

    Asenjo, A.; Garcia, J. M.; Vazquez, M.

    2001-01-01

    An overview on the Magnetic Force Microscopy, MFM, as an advanced technique to observe magnetic domains and walls is displayed. Basic concepts are first introduced on the domain structure formation as well as on other techniques to observe magnetic domains. Afterwards, the MFM instrumentation is described making also an emphasis in micro magnetic consideration to interpret the images. Finally, a set of selected advanced magnetic materials with different domain structures is chosen to show the wide possibilities of this techniques to characterise the surface magnetic behaviour. The domain structure of materials as commercial magnetic recording media, thin films and multilayers, amorphous micro tubes, nanocrystalline ribbons, perovskites or magnetic nano wires is shown. (Author) 16 refs

  8. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

    Science.gov (United States)

    Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

    2012-01-01

    Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

  9. Immunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

    1990-01-01

    Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

  10. Advanced Packaging Materials and Techniques for High Power TR Module: Standard Flight vs. Advanced Packaging

    Science.gov (United States)

    Hoffman, James Patrick; Del Castillo, Linda; Miller, Jennifer; Jenabi, Masud; Hunter, Donald; Birur, Gajanana

    2011-01-01

    The higher output power densities required of modern radar architectures, such as the proposed DESDynI [Deformation, Ecosystem Structure, and Dynamics of Ice] SAR [Synthetic Aperture Radar] Instrument (or DSI) require increasingly dense high power electronics. To enable these higher power densities, while maintaining or even improving hardware reliability, requires advances in integrating advanced thermal packaging technologies into radar transmit/receive (TR) modules. New materials and techniques have been studied and compared to standard technologies.

  11. Combined endoscopic and laparoscopic approach for palliative resection of metastatic melanoma of the stomach

    Directory of Open Access Journals (Sweden)

    Pritchard SA

    2006-03-01

    Full Text Available Abstract Background Metastatic tumours of the stomach present a clinical dilemma for the surgeon. Palliative surgical resection can alleviate symptoms and prolong survival in selected patients. However, previous studies have used open methods of surgical resection with potentially high morbidity and mortality. We describe the use of laparoscopic wedge resection of the stomach for palliative resection of metastatic melanoma to highlight the benefits of this technique. Case presentation A 58 year old male was investigated for iron deficiency anaemia while under treatment for pulmonary metastatic malignant melanoma. An upper gastrointestinal endoscopy revealed a 5 cm diameter ulcer on the anterior wall of the stomach, biopsies from the ulcer confirmed metastatic melanoma. Laparoscopic wedge resection of the stomach lesion was performed without complication. Conclusion Laparoscopic approach has many benefits and is useful for the palliative resection of rare tumours of the stomach in order to preserve the quality of life. Its use should be considered in selected patients.

  12. Germline BAP1 inactivation is preferentially associated with metastatic ocular melanoma and cutaneous-ocular melanoma families.

    Directory of Open Access Journals (Sweden)

    Ching-Ni Jenny Njauw

    Full Text Available BAP1 has been shown to be a target of both somatic alteration in high-risk ocular melanomas (OM and germline inactivation in a few individuals from cancer-prone families. These findings suggest that constitutional BAP1 changes may predispose individuals to metastatic OM and that familial permeation of deleterious alleles could delineate a new cancer syndrome.To characterize BAP1's contribution to melanoma risk, we sequenced BAP1 in a set of 100 patients with OM, including 50 metastatic OM cases and 50 matched non-metastatic OM controls, and 200 individuals with cutaneous melanoma (CM including 7 CM patients from CM-OM families and 193 CM patients from CM-non-OM kindreds.Germline BAP1 mutations were detected in 4/50 patients with metastatic OM and 0/50 cases of non-metastatic OM (8% vs. 0%, p = 0.059. Since 2/4 of the BAP1 carriers reported a family history of CM, we analyzed 200 additional hereditary CM patients and found mutations in 2/7 CM probands from CM-OM families and 1/193 probands from CM-non-OM kindreds (29% vs. 0.52%, p = .003. Germline mutations co-segregated with both CM and OM phenotypes and were associated with the presence of unique nevoid melanomas and highly atypical nevoid melanoma-like melanocytic proliferations (NEMMPs. Interestingly, 7/14 germline variants identified to date reside in C-terminus suggesting that the BRCA1 binding domain is important in cancer predisposition.Germline BAP1 mutations are associated with a more aggressive OM phenotype and a recurrent phenotypic complex of cutaneous/ocular melanoma, atypical melanocytic proliferations and other internal neoplasms (ie. COMMON syndrome, which could be a useful clinical marker for constitutive BAP1 inactivation.

  13. Camtasia Studio 8 advanced editing and publishing techniques

    CERN Document Server

    Dixon, Claire Broadley

    2013-01-01

    A practical guide packed with examples that will show you how to implement the different features of Camtasia Studio 8 and create professional looking projects.If you are familiar with Camtasia Studio and you want to experiment with more advanced techniques, then this is the guide you have been looking for!

  14. New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment.

    LENUS (Irish Health Repository)

    Murphy, Kevin P

    2014-01-01

    Ipilimumab, a cytotoxic monoclonal antibody that inhibits cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), has been established as an effective therapy in the management of advanced melanoma. Immune-mediated adverse events are a common side effect.

  15. Assessment of PALB2 as a candidate melanoma susceptibility gene.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Partner and localizer of BRCA2 (PALB2 interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998 causing a premature truncation of the protein (p.Y1183X in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition.

  16. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-01-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW’s are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  17. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  18. Nevoid melanoma of the vagina: report of one case diagnosed on thin layer cytological preparations

    Directory of Open Access Journals (Sweden)

    Ascierto Paolo

    2007-01-01

    Full Text Available Abstract Background Primary melanoma of the vagina is an extremely rare neoplasm with approximately 250 reported cases in the world literature 1234. In its amelanotic variant this lesion may raise several differential diagnostic problems in cytological specimens 5. In this setting, the usage of thin layer cytopathological techniques (Liquid Based Preparations = LBP may enhance the diagnostic sensitivity by permitting immunocytochemical study without having to repeat the sampling procedure. The aim of this paper is to describe the cytomorphological presentation of primary vaginal melanoma on LBP since it has not previously been reported up to now, to our knowledge. Case presentation a 79-y-o female complaining of vulvar itching and yellowish vaginal discharge underwent a complete gynaecological evaluation during which a LBP cytological sample was taken from a suspicious whitish mass protruding into the vaginal lumen. A cytopathological diagnosis of amelanotic melanoma was rendered. The mass was radically excised and the patient was treated with α-Interferon. Conclusion amelanotic melanoma may be successfully diagnosed on LBP cytological preparations. Thin layer preparations may enhance the diagnostic cytomorphological clues to its diagnosis and may permit an adequate immunocytochemical characterization of the neoplasm.

  19. Nevoid melanoma of the vagina: report of one case diagnosed on thin layer cytological preparations.

    Science.gov (United States)

    Fulciniti, Franco; Ascierto, Paolo Antonio; Simeone, Ester; Bove, Patrizia; Losito, Simona; Russo, Serena; Gallo, Maria Stella; Greggi, Stefano

    2007-07-03

    Primary melanoma of the vagina is an extremely rare neoplasm with approximately 250 reported cases in the world literature 1234. In its amelanotic variant this lesion may raise several differential diagnostic problems in cytological specimens 5. In this setting, the usage of thin layer cytopathological techniques (Liquid Based Preparations = LBP) may enhance the diagnostic sensitivity by permitting immunocytochemical study without having to repeat the sampling procedure. The aim of this paper is to describe the cytomorphological presentation of primary vaginal melanoma on LBP since it has not previously been reported up to now, to our knowledge. a 79-y-o female complaining of vulvar itching and yellowish vaginal discharge underwent a complete gynaecological evaluation during which a LBP cytological sample was taken from a suspicious whitish mass protruding into the vaginal lumen. A cytopathological diagnosis of amelanotic melanoma was rendered. The mass was radically excised and the patient was treated with alpha-Interferon. amelanotic melanoma may be successfully diagnosed on LBP cytological preparations. Thin layer preparations may enhance the diagnostic cytomorphological clues to its diagnosis and may permit an adequate immunocytochemical characterization of the neoplasm.

  20. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    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....

  1. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  2. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

    International Nuclear Information System (INIS)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

    2016-01-01

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

  3. Gingival osteogenic melanoma in two dogs.

    Science.gov (United States)

    Ellis, Angela E; Harmon, Barry G; Miller, Debra L; Northrup, Nicole C; Latimer, Kenneth S; Uhl, Elizabeth W

    2010-01-01

    Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

  4. The combination of MLN2238 (ixazomib) with interferon-alpha results in enhanced cell death in melanoma.

    Science.gov (United States)

    Suarez-Kelly, Lorena P; Kemper, Gregory M; Duggan, Megan C; Stiff, Andrew; Noel, Tiffany C; Markowitz, Joseph; Luedke, Eric A; Yildiz, Vedat O; Yu, Lianbo; Jaime-Ramirez, Alena Cristina; Karpa, Volodymyr; Zhang, Xiaoli; Carson, William E

    2016-12-06

    The ubiquitin-proteasome signaling pathway is critical for cell cycle regulation and neoplastic growth. Proteasome inhibition can activate apoptotic pathways. Bortezomib, a selective proteasome inhibitor, has anti-melanoma activity. MLN2238 (ixazomib), an oral proteasome inhibitor, has improved pharmacotherapeutic parameters compared to bortezomib. Interferon-alpha (IFN-α), an immune boosting agent, is FDA-approved for treatment of melanoma. In this study in vitro and in vivo evaluation of the antitumor potential of ixazomib and combination treatments with ixazomib and IFN-α were performed. Apoptosis induced by ixazomib was first observed at 12 hours and was maximal at 48 hours with similar levels of cell death compared to bortezomib. IFN-α alone had little effect on cell viability in vitro. However, the combination of ixazomib with IFN-α significantly enhanced ixazomib's ability to induce apoptotic cell death in BRAF V600E mutant and BRAF wild-type human melanoma tumor cells. The combination of ixazomib and IFN-α also enhanced inhibition of cell proliferation in BRAF V600E mutant melanoma tumor cells; however, this was not seen in BRAF wild-type cells. Ixazomib-induced apoptosis was associated with processing of the pro-apoptotic proteins procaspase-3, -7, -8, and -9, and cleavage of poly-ADP-ribose polymerase (PARP). In an in vivo xenograft model of human melanoma, combination treatment with IFN-α-2b and ixazomib demonstrated a significant reduction in tumor volume when compared to vehicle (p = 0.005) and single therapy ixazomib (p = 0.017) and IFN-α-2b (p = 0.036). These pre-clinical results support further evaluation of combination treatment with ixazomib and IFN-α for the treatment of advanced BRAF V600E mutant melanoma.

  5. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  6. Melanoma NOS1 expression promotes dysfunctional IFN signaling.

    Science.gov (United States)

    Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Dai, Cuilian; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Zhang, Qianbing; Chouchane, Lotfi; Weiss, Geoffrey R; Slingluff, Craig L; Lee, Peter P; Rosenberg, Steven A; Alter, Harvey; Yao, Kaitai; Wang, Ena; Marincola, Francesco M

    2014-05-01

    In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

  7. Inhibition of human melanoma cell growth by dietary flavonoid fisetin is associated with disruption of Wnt/β-catenin signaling and decreased Mitf levels

    Science.gov (United States)

    Syed, Deeba N.; Afaq, Farrukh; Maddodi, Nityanand; Johnson, Jeremy J.; Sarfaraz, Sami; Ahmad, Adeel; Setaluri, Vijayasaradhi; Mukhtar, Hasan

    2011-01-01

    The prognosis of advanced melanoma remains poor in spite of treatment advances, emphasizing the importance of additional preventive measures. Flavonoids, natural components of our diet are being investigated for their chemopreventive/therapeutic properties. Microphthalmia-associated transcription factor (Mitf), downstream of Wnt/β-catenin pathway has become an important prognostic marker of melanoma. Here, we show that treatment of 451Lu melanoma cells with the dietary flavonoid fisetin resulted in decreased cell viability with G1-phase arrest and disruption of Wnt/β-catenin signaling. This was accompanied with a decrease in expression of Wnt protein and its co-receptors and a parallel increase in the expression of endogenous Wnt inhibitors. Fisetin-treated cells showed increased cytosolic levels of Axin and β-TrCP and decreased phosphorylation of GSK3-β assocaited with decreased β-catenin stabilization. Fisetin-mediated interference with the functional cooperation between β-catenin and LEF/TCF-2 resulted in downregulation of positively regulated TCF targets such as c-myc, Brn-2 and Mitf. Flowcytometric analysis of Mitf overexpressing cells showed that fisetin repressed Mitf-induced cell proliferation. Finally, administration of fisetin to 451Lu xenografted nude mice resulted in inhibition of tumor development and decreased Mitf expression. Our data suggest that fisetin can be developed as an effective agent against melanoma due to its potential inhibitory effect on β-catenin/Mitf signaling. PMID:21346776

  8. Addison's disease as a presentation of metastatic malignant melanoma.

    Science.gov (United States)

    Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V

    2016-01-01

    Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.

  9. Advanced techniques for actinide spectroscopy (ATAS 2012). Abstract book

    Energy Technology Data Exchange (ETDEWEB)

    Foerstendorf, Harald; Mueller, Katharina; Steudtner, Robin [eds.

    2012-07-01

    The abstract book of the International workshop on advanced techniques for actinide spectroscopy (ATAS 2012) include contributions concerning the following issues: environmental applications, NMR spectroscopy, vibrational spectroscopy, X-ray spectroscopy and theory, technical application: separation processes, emission spectroscopy.

  10. Advanced techniques for actinide spectroscopy (ATAS 2012). Abstract book

    International Nuclear Information System (INIS)

    Foerstendorf, Harald; Mueller, Katharina; Steudtner, Robin

    2012-01-01

    The abstract book of the International workshop on advanced techniques for actinide spectroscopy (ATAS 2012) include contributions concerning the following issues: environmental applications, NMR spectroscopy, vibrational spectroscopy, X-ray spectroscopy and theory, technical application: separation processes, emission spectroscopy.

  11. Advanced flow MRI: emerging techniques and applications

    International Nuclear Information System (INIS)

    Markl, M.; Schnell, S.; Wu, C.; Bollache, E.; Jarvis, K.; Barker, A.J.; Robinson, J.D.; Rigsby, C.K.

    2016-01-01

    Magnetic resonance imaging (MRI) techniques provide non-invasive and non-ionising methods for the highly accurate anatomical depiction of the heart and vessels throughout the cardiac cycle. In addition, the intrinsic sensitivity of MRI to motion offers the unique ability to acquire spatially registered blood flow simultaneously with the morphological data, within a single measurement. In clinical routine, flow MRI is typically accomplished using methods that resolve two spatial dimensions in individual planes and encode the time-resolved velocity in one principal direction, typically oriented perpendicular to the two-dimensional (2D) section. This review describes recently developed advanced MRI flow techniques, which allow for more comprehensive evaluation of blood flow characteristics, such as real-time flow imaging, 2D multiple-venc phase contrast MRI, four-dimensional (4D) flow MRI, quantification of complex haemodynamic properties, and highly accelerated flow imaging. Emerging techniques and novel applications are explored. In addition, applications of these new techniques for the improved evaluation of cardiovascular (aorta, pulmonary arteries, congenital heart disease, atrial fibrillation, coronary arteries) as well as cerebrovascular disease (intra-cranial arteries and veins) are presented.

  12. Vemurafenib for the treatment of melanoma.

    LENUS (Irish Health Repository)

    Jordan, Emmet John

    2012-12-01

    Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading \\'vemurafenib\\' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase\\/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

  13. Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

    Science.gov (United States)

    Gjorup, Caroline A; Groenvold, Mogens; Hendel, Helle W; Dahlstroem, Karin; Drzewiecki, Krzysztof T; Klausen, Tobias W; Hölmich, Lisbet R

    2017-11-01

    To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma

    Science.gov (United States)

    Frederick, Dennie Tompers; Piris, Adriano; Cogdill, Alexandria P.; Cooper, Zachary A.; Lezcano, Cecilia; Ferrone, Cristina R.; Mitra, Devarati; Boni, Andrea; Newton, Lindsay P.; Liu, Chengwen; Peng, Weiyi; Sullivan, Ryan J; Lawrence, Donald P.; Hodi, F. Stephen; Overwijk, Willem W.; Lizée, Gregory; Murphy, George F.; Hwu, Patrick; Flaherty, Keith T.; Fisher, David E.; Wargo, Jennifer A.

    2013-01-01

    Purpose To evaluate the effects BRAF inhibition on the tumor microenvironment in patients with metastatic melanoma. Experimental Design Thirty-five biopsies were collected from 16 patients with metastatic melanoma pretreatment (day 0) and at 10-14 days after initiation of treatment with either BRAF inhibitor alone (vemurafenib) or BRAF + MEK inhibition (dabrafenib + trametinib), and were also taken at time of progression. Biopsies were analyzed for melanoma antigens, T cell markers, and immunomodulatory cytokines. Results Treatment with either BRAF inhibitor alone or BRAF + MEK inhibitor was associated with an increased expression of melanoma antigens and an increase in CD8+ T cell infiltrate. This was also associated with a decrease in immunosuppressive cytokines (IL-6 & IL-8) and an increase in markers of T cell cytotoxicity. Interestingly, expression of exhaustion markers TIM-3 and PD1 and the immunosuppressive ligand PDL1 were increased on treatment. A decrease in melanoma antigen expression and CD8 T cell infiltrate was noted at time of progression on BRAF inhibitor alone, and was reversed with combined BRAF and MEK inhibition. Conclusions Together, this data suggests that treatment with BRAF inhibition enhances melanoma antigen expression and facilitates T cell cytotoxicity and a more favorable tumor microenvironment, providing support for potential synergy of BRAF-targeted therapy and immunotherapy. Interestingly, markers of T cell exhaustion and the immunosuppressive ligand PDL1 are also increased with BRAF inhibition, further implying that immune checkpoint blockade may be critical in augmenting responses to BRAF-targeted therapy in patients with melanoma. PMID:23307859

  15. [Advanced online search techniques and dedicated search engines for physicians].

    Science.gov (United States)

    Nahum, Yoav

    2008-02-01

    In recent years search engines have become an essential tool in the work of physicians. This article will review advanced search techniques from the world of information specialists, as well as some advanced search engine operators that may help physicians improve their online search capabilities, and maximize the yield of their searches. This article also reviews popular dedicated scientific and biomedical literature search engines.

  16. POC-scale testing of an advanced fine coal dewatering equipment/technique

    Energy Technology Data Exchange (ETDEWEB)

    Groppo, J.G.; Parekh, B.K. [Univ. of Kentucky, Lexington, KY (United States); Rawls, P. [Department of Energy, Pittsburgh, PA (United States)

    1995-11-01

    Froth flotation technique is an effective and efficient process for recovering of ultra-fine (minus 74 {mu}m) clean coal. Economical dewatering of an ultra-fine clean coal product to a 20 percent level moisture will be an important step in successful implementation of the advanced cleaning processes. This project is a step in the Department of Energy`s program to show that ultra-clean coal could be effectively dewatered to 20 percent or lower moisture using either conventional or advanced dewatering techniques. As the contract title suggests, the main focus of the program is on proof-of-concept testing of a dewatering technique for a fine clean coal product. The coal industry is reluctant to use the advanced fine coal recovery technology due to the non-availability of an economical dewatering process. in fact, in a recent survey conducted by U.S. DOE and Battelle, dewatering of fine clean coal was identified as the number one priority for the coal industry. This project will attempt to demonstrate an efficient and economic fine clean coal slurry dewatering process.

  17. Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma.

    Science.gov (United States)

    Puig, Susana; Potrony, Miriam; Cuellar, Francisco; Puig-Butille, Joan Anton; Carrera, Cristina; Aguilera, Paula; Nagore, Eduardo; Garcia-Casado, Zaida; Requena, Celia; Kumar, Rajiv; Landman, Gilles; Costa Soares de Sá, Bianca; Gargantini Rezze, Gisele; Facure, Luciana; de Avila, Alexandre Leon Ribeiro; Achatz, Maria Isabel; Carraro, Dirce Maria; Duprat Neto, João Pedreira; Grazziotin, Thais C; Bonamigo, Renan R; Rey, Maria Carolina W; Balestrini, Claudia; Morales, Enrique; Molgo, Montserrat; Bakos, Renato Marchiori; Ashton-Prolla, Patricia; Giugliani, Roberto; Larre Borges, Alejandra; Barquet, Virginia; Pérez, Javiera; Martínez, Miguel; Cabo, Horacio; Cohen Sabban, Emilia; Latorre, Clara; Carlos-Ortega, Blanca; Salas-Alanis, Julio C; Gonzalez, Roger; Olazaran, Zulema; Malvehy, Josep; Badenas, Celia

    2016-07-01

    CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736.

  18. Updates on the Management of Non-Melanoma Skin Cancer (NMSC

    Directory of Open Access Journals (Sweden)

    Artur Fahradyan

    2017-11-01

    Full Text Available Non-melanoma skin cancers (NMSCs are the most common malignancy worldwide, of which 99% are basal cell carcinomas (BCCs and squamous cell carcinomas (SCCs of skin. NMSCs are generally considered a curable diseases, yet they currently pose an increasing global healthcare problem due to rising incidence. This has led to a shift in emphasis on prevention of NMSCs with development of various skin cancer prevention programs worldwide. This article aims to summarize the most recent changes and advances made in NMSC management with a focus on prevention, screening, diagnosis, and staging.

  19. Clinical relevance of positron emission tomography for initial staging and follow-up of malignant melanoma

    International Nuclear Information System (INIS)

    Baum, R.P.; Rinne, D.; Kaufmann, R.

    2000-01-01

    The incidence of melanoma is rapidly increasing (at a rate of 5 percent per year) throughout the world. In Europe, the incidence is approximately 10-12 new cases of invasive melanoma per 100,000 inhabitants. The most important prognostic factor is the stage of disease (Clark Level and vertical tumor depth (TD) according to BRESLOW) at the time of presentation. Ten year survival is 90 percent with a TD of 1.5 mm; 5-year survival is 15-50 percent when there is regional lymph node involvement, and 5 percent when there is disseminated disease. Conventional diagnostic tests for staging include a chest X-ray, lymph node sonography and laboratory tests. Sentinel node biopsy is becoming an increasingly common procedure since melanoma usually metastasizes to regional lymph nodes before dissemination. CT scan of the thorax or abdomen, MRI of the brain and other tests are used only when signs or symptoms warrant. The results of a prospective study which we performed in 100 patients for staging of high risk melanoma (n=48) or for re-staging patients with suspected recurrence demonstrated that FDG whole-body PET is superior to conventional imaging techniques (X-ray, sonography, CT scan) except for the detection of brain metastases. The diagnostic accuracy of PET for the detection of metastases was 92.1% versus 55.7% for conventional imaging (p 1.5 mm); and 2) detection of occult metastases in patients with recurrent disease who are being considered for surgery. PET often changes the diagnostic evaluation and therapeutic management of patients with melanoma. PET has also shown to be cost effective in diagnosis and evaluation of patients with melanoma in the USA. (orig.) [de

  20. A modified COMS plaque for iris melanoma

    Directory of Open Access Journals (Sweden)

    Daniel J. Scanderbeg

    2011-09-01

    Full Text Available Melanoma of the iris is a rare condition compared to posterior ocular tumors and in this case report we presenta 51-year-old female patient with diffuse iris melanoma. Traditional COMS (Collaborative Ocular Melanoma Studyplaques are used at our institution for radiation therapy, so a novel modification of the traditional plaque was requiredto allow better conformance with placement on the cornea. The usual silastic insert was machined to dimensions incompliance with the cornea, placed without incident, and treatment delivered with excellent patient tolerance of themodified plaque.

  1. Dermatoscopic Findings of Seborrheic Keratosis in Melanoma.

    Science.gov (United States)

    Brandão, Maria Luiza; Oliveira Lima, Cíntia Maria; Moura, Heloísa Helena; Ishida, Cleide; Campos-do-Carmo, Gabriella; Cuzzi, Tullia; Ramos-E-Silva, Marcia

    2016-06-01

    Cutaneous melanoma may in some instances be confused with seborrheic keratosis, which is a very common neoplasia, more often mistaken for actinic keratosis and verruca vulgaris. Melanoma may clinically resemble seborrheic keratosis and should be considered as its possible clinical simulator. We report a case of melanoma with dermatoscopic characteristics of seborrheic keratosis and emphasize the importance of the dermatoscopy algorithm in differentiating between a melanocytic and a non-melanocytic lesion, of the excisional biopsy for the establishment of the diagnosis of cutaneous tumors, and of the histopathologic examination in all surgically removed samples.

  2. Podoplanin Expression in Canine Melanoma

    OpenAIRE

    Ogasawara, Satoshi; Honma, Ryusuke; Kaneko, Mika K.; Fujii, Yuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  3. Targeted alpha therapy for melanoma : from bench to bedside

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

    2001-01-01

    Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

  4. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

    International Nuclear Information System (INIS)

    Lindsey, S. F.; Byrnes, D. M.; Eller, M. S.; Rosa, A. M.; Dabas, N.; Escandon, J.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.

    2013-01-01

    Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis"could impact chromosomal instability in melanoma and other cancers.

  5. Mucosal melanoma of the head and neck. A treatment result of 25 cases

    International Nuclear Information System (INIS)

    Asakura, Kohji; Kataura, Akikatsu; Harabuchi, Yasuaki; Himi, Tetsuo; Hamamoto, Makoto; Hareyama, Masato; Sakata, Kouichi

    2001-01-01

    A retrospective review of 25 primary patients with head and neck mucosal melanoma, treated at Sapporo Medical University from 1970 to 1996, was performed. The disease-specific 5-year cumulative survival rate was 37.2% for all the cases, and 39.6% for cases with nasal cavity melanoma. The patients with tumors confined within one anatomical site showed a better prognosis than those with more advanced tumors. In relation to the treatment methods, the 5-year survival rate was 75% in the patients that received pre-operative radiotherapy, and 100% in those that received an adjuvant immunotherapy of daily intratumorous injections of OK432 during radiotherapy. The patients with poor prognoses tended to show a high incidence of residual tumors and earlier local recurrences than those with good prognoses. No recurrences have been noted in the long-term survivors that received adjuvant immunotherapy during radiotherapy. (author)

  6. Unilateral lichen planus pigmentosus mimicking acral lentiginous melanoma.

    Science.gov (United States)

    Bickle, Kelly; Smithberger, Erica; Lien, Mary H; Fenske, Neil Alan

    2010-07-01

    The authors report a case of a Latin American woman who developed progressive pigmentation primarily involving two digits of her right hand. She was scheduled for amputation based on a presumptive histologic diagnosis of melanoma with regression. Dermatology consultation with repeat biopsies disclosed a lichenoid tissue reaction with marked pigment incontinence and no evidence of melanoma. This report should prompt physicians to include lichen planus pigmentosus in the differential diagnosis of acral lentiginous melanoma.

  7. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma.

    Science.gov (United States)

    Byrum, Stephanie D; Larson, Signe K; Avaritt, Nathan L; Moreland, Linley E; Mackintosh, Samuel G; Cheung, Wang L; Tackett, Alan J

    2013-03-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression.

  8. Cost-effectiveness of treatment strategies for BRAF-mutated metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Patti Curl

    Full Text Available Genetically-targeted therapies are both promising and costly advances in the field of oncology. Several treatments for metastatic melanoma with a mutation in the BRAF gene have been approved. They extend life but are more expensive than the previous standard of care (dacarbazine. Vemurafenib, the first drug in this class, costs $13,000 per month ($207,000 for a patient with median survival. Patients failing vemurafenib are often given ipilimumab, an immunomodulator, at $150,000 per course. Assessment of cost-effectiveness is a valuable tool to help navigate the transition toward targeted cancer therapy.We performed a cost-utility analysis to compare three strategies for patients with BRAF+ metastatic melanoma using a deterministic expected-value decision tree model to calculate the present value of lifetime costs and quality-adjusted life years (QALYs for each strategy. We performed sensitivity analyses on all variables.In the base case, the incremental cost-effectiveness ratio (ICER for vemurafenib compared with dacarbazine was $353,993 per QALY gained (0.42 QALYs added, $156,831 added. The ICER for vemurafenib followed by ipilimumab compared with vemurafenib alone was $158,139. In sensitivity analysis, treatment cost had the largest influence on results: the ICER for vemurafenib versus dacarbazine dropped to $100,000 per QALY gained with a treatment cost of $3600 per month.The cost per QALY gained for treatment of BRAF+ metastatic melanoma with vemurafenib alone or in combination exceeds widely-cited thresholds for cost-effectiveness. These strategies may become cost-effective with lower drug prices or confirmation of a durable response without continued treatment.

  9. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  10. Advanced of X-ray fluorescence logging technique in China

    International Nuclear Information System (INIS)

    Zhou Sichun; Ge Liangquan; Lai Wanchang; Yang Qiang

    2010-01-01

    The paper discuses principle of X-ray fluorescence logging, and introduces advanced of X-ray fluorescence logging technique in China. By 2009, third generation XRF logging instrument has been developed in China, and good logging result has been obtained in Lala copper mine. (authors)

  11. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

    Directory of Open Access Journals (Sweden)

    Iván Márquez-Rodas

    Full Text Available Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.An observational study conducted by the Spanish Group of Melanoma (GEM analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.In all, 1047 patients were analyzed, and 69 (6.6% fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma. Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%. Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

  12. Selenium for the Prevention of Cutaneous Melanoma

    Science.gov (United States)

    Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

    2013-01-01

    The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

  13. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail: sbeebe@odu.edu; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)

    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. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    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

  15. Recent Advances in Techniques for Hyperspectral Image Processing

    Science.gov (United States)

    Plaza, Antonio; Benediktsson, Jon Atli; Boardman, Joseph W.; Brazile, Jason; Bruzzone, Lorenzo; Camps-Valls, Gustavo; Chanussot, Jocelyn; Fauvel, Mathieu; Gamba, Paolo; Gualtieri, Anthony; hide

    2009-01-01

    Imaging spectroscopy, also known as hyperspectral imaging, has been transformed in less than 30 years from being a sparse research tool into a commodity product available to a broad user community. Currently, there is a need for standardized data processing techniques able to take into account the special properties of hyperspectral data. In this paper, we provide a seminal view on recent advances in techniques for hyperspectral image processing. Our main focus is on the design of techniques able to deal with the highdimensional nature of the data, and to integrate the spatial and spectral information. Performance of the discussed techniques is evaluated in different analysis scenarios. To satisfy time-critical constraints in specific applications, we also develop efficient parallel implementations of some of the discussed algorithms. Combined, these parts provide an excellent snapshot of the state-of-the-art in those areas, and offer a thoughtful perspective on future potentials and emerging challenges in the design of robust hyperspectral imaging algorithms

  16. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  17. Oral Malignant Melanoma in a Ferret ( Mustela putorius furo).

    Science.gov (United States)

    d'Ovidio, Dario; Rossi, Giacomo; Meomartino, Leonardo

    2016-06-01

    Oral malignant melanomas are one of the most common oral malignant neoplasms in dogs but are rare in other domesticated species. This case report describes the clinical manifestations and histological appearance of oral melanoma in a ferret ( Mustela putorius furo). To the authors' knowledge, this is the first published description of a clinical case and histopathological findings of oral melanoma in this species.

  18. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  19. Advanced Morphological and Functional Magnetic Resonance Techniques in Glaucoma

    Directory of Open Access Journals (Sweden)

    Rodolfo Mastropasqua

    2015-01-01

    Full Text Available Glaucoma is a multifactorial disease that is the leading cause of irreversible blindness. Recent data documented that glaucoma is not limited to the retinal ganglion cells but that it also extends to the posterior visual pathway. The diagnosis is based on the presence of signs of glaucomatous optic neuropathy and consistent functional visual field alterations. Unfortunately these functional alterations often become evident when a significant amount of the nerve fibers that compose the optic nerve has been irreversibly lost. Advanced morphological and functional magnetic resonance (MR techniques (morphometry, diffusion tensor imaging, arterial spin labeling, and functional connectivity may provide a means for observing modifications induced by this fiber loss, within the optic nerve and the visual cortex, in an earlier stage. The aim of this systematic review was to determine if the use of these advanced MR techniques could offer the possibility of diagnosing glaucoma at an earlier stage than that currently possible.

  20. Recent Advances in Wireless Indoor Localization Techniques and System

    Directory of Open Access Journals (Sweden)

    Zahid Farid

    2013-01-01

    Full Text Available The advances in localization based technologies and the increasing importance of ubiquitous computing and context-dependent information have led to a growing business interest in location-based applications and services. Today, most application requirements are locating or real-time tracking of physical belongings inside buildings accurately; thus, the demand for indoor localization services has become a key prerequisite in some markets. Moreover, indoor localization technologies address the inadequacy of global positioning system inside a closed environment, like buildings. Based on this, though, this paper aims to provide the reader with a review of the recent advances in wireless indoor localization techniques and system to deliver a better understanding of state-of-the-art technologies and motivate new research efforts in this promising field. For this purpose, existing wireless localization position system and location estimation schemes are reviewed, as we also compare the related techniques and systems along with a conclusion and future trends.

  1. Inverse association between atopy and melanoma: A case-control study

    NARCIS (Netherlands)

    Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

    2017-01-01

    textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

  2. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

    NARCIS (Netherlands)

    Faries, M. B.; Thompson, J. F.; Cochran, A. J.; Andtbacka, R. H.; Mozzillo, N; Zager, Jonathan S.; Jahkola, T.; Bowles, T. L.; Testori, Alessandro; Beitsch, P. D.; Hoekstra, H. J.; Moncrieff, M.; Ingvar, C.; Wouters, M. W. J. M.; Sabel, M. S.; Levine, E. A.; Agnese, D.; Henderson, M.; Dummer, R; Rossi, C. R.; Neves, R. I.; Trocha, S. D.; Wright, Sara F.; Byrd, D. R.; Matter, M.; Hsueh, E.; MacKenzie-Ross, A.; Johnson, B. D.; Terheyden, P.; Berger, A. C.; Huston, T. L.; Wayne, J. D.; Smithers, B. Mark; Neuman, H. B.; Schneebaum, S.; Gershenwald, Jeffrey E.; Ariyan, C. E.; Desai, D. C.; Jacobs, L.; McMasters, K. M.; Gesierich, A.; Hersey, P.; Bines, S. D.; Kane, Michael J.; Barth, R. J.; McKinnon, J. G.; Farma, J. M.; Schultz, B. E.; Vidal-Sicart, S.; Hoefer, R. A.; Lewis, David J. M.; Scheri, R.; Kelley, M. C.; Nieweg, O. E.; Noyes, R. D.; Hoon, D. S. B.; Wang, H. -J.; Elashoff, D. A.; Elashoff, R. M.

    2017-01-01

    BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node

  3. Vitamin D and melanoma: state of the art and possible therapeutic uses.

    Science.gov (United States)

    Paolino, Giovanni; Moliterni, Elisa; Corsetti, Paola; Didona, Dario; Bottoni, Ugo; Calvieri, Stefano; Mattozzi, Carlo

    2017-12-15

    Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun- exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

  4. Anticancer potential of benzothiazolic derivative (E)-2-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol against melanoma cells.

    Science.gov (United States)

    Vasconcelos, Zanair Soares; Ralph, Ana Carolina Lima; Calcagno, Danielle Queiroz; Dos Santos Barbosa, Gleyce; do Nascimento Pedrosa, Tatiana; Antony, Lucas Pio; de Arruda Cardoso Smith, Marília; de Lucas Chazin, Eliza; Vasconcelos, Thatyana Rocha Alves; Montenegro, Raquel Carvalho; de Vasconcellos, Marne Carvalho

    2018-08-01

    Malignant melanoma is an important type of cancer worldwide due to its aggressiveness and poor survival rate. Significant efforts to understand the biology of melanoma and approaches to treat the advanced disease are focused on targeted gene inhibitors. Frequently mutated genes, such as NRAS, B-RAF and TP53, significantly exceed the frequency of mutations of other genes, emphasizing their importance for future targeted therapies. Considering the antitumor activity of benzothiazolic derivatives, this study aimed to demonstrate the action of benzothiazolic (E)-2-((2-(benzo[d]thiazol-2-yl)hydrazono)methyl)-4-nitrophenol (AFN01) against three established human melanoma cell lines that recapitulate the molecular landscape of the disease in terms of its genetic alterations and mutations, such as the TP53, NRAS and B-RAF genes. The results presented here indicate that AFN01, as a significant cytostatic and cytotoxic drug due to its induction of DNA fragmentation, causes single and double DNA strand breaks, consequently inhibiting cell proliferation, migration and invasion by promoting apoptosis. Our data suggest that AFN01 might be considered as a future therapeutic option for managing melanoma. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

    Science.gov (United States)

    Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B.; da Motta, Leonardo L.; Klamt, Fabio; Ibañez, Irene L.; Durán, Hebe

    2016-01-01

    Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy. PMID:27206672

  6. LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

    Science.gov (United States)

    Lian, Christine Guo; Xu, Yufei; Ceol, Craig; Wu, Feizhen; Larson, Allison; Dresser, Karen; Xu, Wenji; Tan, Li; Hu, Yeguang; Zhan, Qian; Lee, Chung-wei; Hu, Di; Lian, Bill Q.; Kleffel, Sonja; Yang, Yijun; Neiswender, James; Khorasani, Abraham J.; Fang, Rui; Lezcano, Cecilia; Duncan, Lyn M.; Scolyer, Richard A.; Thompson, John F.; Kakavand, Hojabr; Houvras, Yariv; Zon, Leonard; Mihm, Martin C.; Kaiser, Ursula B.; Schatton, Tobias; Woda, Bruce A.; Murphy, George F.; Shi, Yujiang G.

    2013-01-01

    SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that “loss of 5-hmC” is an epigenetic hallmark of melanoma with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of 5-hmC landscape in the melanoma epigenome. We show that down-regulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy. PMID:22980977

  7. Intussusception of the small intestine caused by a primary melanoma?

    Science.gov (United States)

    Schoneveld, M; De Vogelaere, K; Van De Winkel, N; Hoorens, A; Delvaux, G

    2012-01-01

    Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  8. Intussusception of the Small Intestine Caused by a Primary Melanoma

    Directory of Open Access Journals (Sweden)

    M. Schoneveld

    2012-01-01

    Full Text Available Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.

  9. Management of uveal tract melanoma: A comprehensive review

    International Nuclear Information System (INIS)

    Kapoor, A.; Kumar, H.S.; Beniwal, V.; Beniwal, S.; Mathur, H.

    2016-01-01

    Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient

  10. HTB140 melanoma cells under proton irradiation and/or alkylating agents

    Science.gov (United States)

    Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

    2007-09-01

    Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

  11. Ocular melanoma metastatic to skin: the value of HMB-45 staining.

    Science.gov (United States)

    Schwartz, Robert A; Kist, Joseph M; Thomas, Isabelle; Fernández, Geover; Cruz, Manuel A; Koziorynska, Ewa I; Lambert, W Clark

    2004-06-01

    Cutaneous metastatic disease is an important finding that may represent the first sign of systemic cancer, or, if already known, that may change tumor staging and thus dramatically altered therapeutic plans. Although cutaneous metastases are relatively frequent in patients with cutaneous melanoma, they are less so from ocular melanoma. To demonstrate the value of HMB-45, staining in the detection of ocular melanoma metastatic to skin. The immunohistochemical stain HMB-45 a monoclonal antibody directed against intact human melanoma cells, was employed on a skin biopsy specimen from a cutaneous tumor. HMB-45 staining was positive in the atypical hyperchromatic cells of the deep dermis. HMB-45 may be of value in the detection of ocular melanoma metastatic to skin. Cutaneous metastatic disease is a somewhat common and extremely important diagnosis. Although cutaneous metastases from cutaneous melanoma are relatively frequent, those from ocular melanomas are less so. Use of histochemical staining, especially the HMB-45 stain, allows confirmation of the diagnosis.

  12. Skin Cancer (Including Melanoma)—Patient Version

    Science.gov (United States)

    Skin cancer is the most common type of cancer. The main types of skin cancer are squamous cell carcinoma, basal cell carcinoma, and melanoma. Most deaths from skin cancer are caused by melanoma. Start here to find information on skin cancer treatment, causes and prevention, screening, research, and statistics.

  13. Uptake in melanoma cells of N-(2-diethylaminoethyl)-2-iodobenzamide (BZA2), an imaging agent for melanoma staging: relation to pigmentation

    International Nuclear Information System (INIS)

    Mansard, Sandrine; Papon, Janine; Moreau, Marie-France; Miot-Noirault, Elisabeth; Labarre, Pierre; Bayle, Martine; Veyre, Annie; Madelmont, Jean-Claude; Moins, Nicole

    2005-01-01

    N-(2-diethylaminoethyl)-2-iodobenzamide (BZA 2 ) has been singled out as the most efficacious melanoma scintigraphy imaging agent. Our work was designed to assess the mechanisms of the specific affinity of the radioiodinated iodobenzamide for melanoma tissue. We studied the cellular uptake and retention of [ 125 I]-BZA 2 on various cell lines. In vitro, cellular [ 125 I]-BZA 2 uptake was related to the pigmentation status of the cells: higher in pigmented melanoma cell lines (M4 Beu, IPC 227, B 16) than in a nonpigmented one (M3 Dau) and nonmelanoma cell lines (MCF 7 and L 929). Two mechanisms were assessed: binding of the tracer to melanin or to sigma receptors of melanoma cells. First, the uptake of [ 125 I]-BZA 2 after melanogenesis stimulation by α-melanocyte-stimulating hormone and L-tyrosine increased in the B 16 melanoma cell line both in vitro and in vivo according to melanin concentration. Moreover, the binding of [ 125 I]-BZA 2 to synthetic melanin was dependent on melanin concentration and could be saturated. Second, no competition was evidenced on M4 Beu cells between [ 125 I]-BZA 2 and haloperidol, a sigma ligand, at concentrations ≤10 -6 M. We show that the specificity and sensibility of BZA 2 as a melanoma scintigraphic imaging agent are mostly due to interactions with melanic pigments

  14. WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

    Science.gov (United States)

    Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

    2018-02-07

    Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

  15. Melanoma and tattoos: a case report and review of the literature.

    Science.gov (United States)

    Ricci, Francesco; Paradisi, Andrea; Maier, Stephanie Alissa; Kovacs, Maximilian; Podda, Maurizio; Peris, Ketty; Abeni, Damiano

    2018-02-01

    Malignant melanoma cases arising in tattoos have been increasingly described, however, there is no clear relationship between this practice and the development of cutaneous malignancies. We report a new case of melanoma in a dark-blue tattoo and we review all cases of melanoma reported in the medical literature from 1938 to date. Pubmed and Google Scholar were searched using the terms "melanoma tattoo", "tattoo skin tumour" and "ink melanoma". In most cases, the melanoma occurred on dark blue (10/30), black (8/30), or blue ink (3/30). The Breslow thickness at diagnosis was ≤1 mm in 13/30, 1-2 mm in 3/30, 2-4 mm in 2/30, >4 mm in 5/30, and Clark II in 2/30 (not available in 5/30). Both the incidence of melanoma and the number of tattoos have been increasing in recent years, but a possible carcinogenic effect of tattoos remains unproven. The spread of this decorative custom will make observation of melanoma in tattoos more frequent in dermatological practice, therefore these cases should be reported in national skin cancer registries.

  16. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  17. Acetylcholine receptor binding antibody-associated myasthenia gravis and rhabdomyolysis induced by nivolumab in a patient with melanoma.

    Science.gov (United States)

    Shirai, Takushi; Sano, Tasuku; Kamijo, Fuminao; Saito, Nana; Miyake, Tomomi; Kodaira, Minori; Katoh, Nagaaki; Nishie, Kenichi; Okuyama, Ryuhei; Uhara, Hisashi

    2016-01-01

    We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

    Science.gov (United States)

    Famenini, Shannon; Martires, Kathryn J; Zhou, Hui; Xavier, Marin F; Wu, Jashin J

    2015-01-01

    The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern California patients. The mortality of patients with melanoma was examined using Cox proportional hazards modeling. The age-adjusted incidence rate per 100,000 person-years for melanoma among patients with either CLL or NHL was 107 (95% confidence interval 84.4-129.6) versus 25.9 among the general population (95% confidence interval 84.4-129.6, P < .001). Patients with melanoma and a history of CLL or NHL had 2.46 greater odds of death compared with those without CLL or NHL (95% confidence interval 1.77-3.41). This study was retrospective in nature; the International Classification of Diseases, Ninth Revision codes used may contain diagnostic errors; and only overall survival was used in our analysis. Patients with a history of CLL or NHL have a higher incidence of melanoma. Patients with CLL or NHL who are subsequently given the diagnosis of melanoma have a higher mortality than patients with melanoma without a preceding diagnosis of CLL. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. Promoting early detection of melanoma during the mammography experience

    Directory of Open Access Journals (Sweden)

    A.K. Rzepecki, BS

    2017-12-01

    Full Text Available Background: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman’s risk of developing a melanoma. Objective: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE to a population of women who are already invested in preventive health. Methods: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women’s Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. Results: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560. Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. Conclusion: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women. Keywords: melanoma, skin self-examination, skin cancer screening

  20. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller

    2010-09-01

    Full Text Available 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.

  1. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 10 12 , γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10 B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

  2. Malignant melanoma in children: imaging spectrum

    International Nuclear Information System (INIS)

    Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

    1996-01-01

    Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

  3. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  4. Management of uveal tract melanoma: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2016-06-01

    Full Text Available Uveal tract melanoma is the most common primary intraocular malignancy in adults, accounting for about 5–10% of all the melanomas. Since there are no lymphatic vessels in the eye, uveal melanoma can only spread hematogenously leading to liver metastasis. A wide variety of treatment modalities are available for its management, leading to dilemma in selecting the appropriate therapy. This article reviews the diagnostic and therapeutic modalities available and thus, can help to individualize the treatment plan for each patient.

  5. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  6. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  7. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  8. Advanced Marketing Core Curriculum. Test Items and Assessment Techniques.

    Science.gov (United States)

    Smith, Clifton L.; And Others

    This document contains duties and tasks, multiple-choice test items, and other assessment techniques for Missouri's advanced marketing core curriculum. The core curriculum begins with a list of 13 suggested textbook resources. Next, nine duties with their associated tasks are given. Under each task appears one or more citations to appropriate…

  9. Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

    Science.gov (United States)

    Christianson, Dawn R; Dobroff, Andrey S; Proneth, Bettina; Zurita, Amado J; Salameh, Ahmad; Dondossola, Eleonora; Makino, Jun; Bologa, Cristian G; Smith, Tracey L; Yao, Virginia J; Calderone, Tiffany L; O'Connell, David J; Oprea, Tudor I; Kataoka, Kazunori; Cahill, Dolores J; Gershenwald, Jeffrey E; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2015-02-24

    Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

  10. Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

    Science.gov (United States)

    van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

    2018-01-19

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi. Multicenter, retrospective case series. Patients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment. Next-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples. Mutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis. In 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi. Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of

  11. Computer vision techniques for the diagnosis of skin cancer

    CERN Document Server

    Celebi, M

    2014-01-01

    The goal of this volume is to summarize the state-of-the-art in the utilization of computer vision techniques in the diagnosis of skin cancer. Malignant melanoma is one of the most rapidly increasing cancers in the world. Early diagnosis is particularly important since melanoma can be cured with a simple excision if detected early. In recent years, dermoscopy has proved valuable in visualizing the morphological structures in pigmented lesions. However, it has also been shown that dermoscopy is difficult to learn and subjective. Newer technologies such as infrared imaging, multispectral imaging, and confocal microscopy, have recently come to the forefront in providing greater diagnostic accuracy. These imaging technologies presented in this book can serve as an adjunct to physicians and  provide automated skin cancer screening. Although computerized techniques cannot as yet provide a definitive diagnosis, they can be used to improve biopsy decision-making as well as early melanoma detection, especially for pa...

  12. Advanced Inspection and Repair Welding Techniques for SCC Countermeasures

    International Nuclear Information System (INIS)

    Takagi, T.; Nishimoto, K.; Uchimoto, T.

    2012-01-01

    Feasibility studies of advanced inspection and repair welding techniques were conducted in the framework of the Nuclear and Industry Safety Agency of Japan (NISA) project on the enhancement of ageing management and maintenance of NPPs. In this paper, features of NDE methods investigated in the projects, main results of research activities and prospect of nickel based alloy weld inspection are discussed. We also make a review for the integrity and reliability evaluation techniques for repair welding of ageing plants which were intensively investigated in view of regulatory criteria, in NISA project. (author)

  13. Mutation analysis of genes that control the G1/S cell cycle in melanoma: TP53, CDKN1A, CDKN2A, and CDKN2B

    International Nuclear Information System (INIS)

    Soto, José Luis; Cabrera, Carmen M; Serrano, Salvio; López-Nevot, Miguel Ángel

    2005-01-01

    The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied

  14. Microculture-based chemosensitivity testing: a feasibility study comparing freshly explanted human melanoma cells with human melanoma cell lines.

    Science.gov (United States)

    Marshall, E S; Finlay, G J; Matthews, J H; Shaw, J H; Nixon, J; Baguley, B C

    1992-03-04

    The culture of cancer cells has many applications in chemosensitivity testing and new drug development. Our goal was to adapt simple semiautomated microculture methods for testing the chemosensitivity of melanoma cells freshly recovered from patients' tumors. Cells were cultured on a substrate of agarose and exposed continuously to cytotoxic drugs, the effects of which were measured by determining the uptake of [3H]thymidine 4-7 days later. Immunocytochemical staining of cells cultured with 5-bromo-2'-deoxyuridine demonstrated that tumor cells were responsible for the measured thymidine incorporation. The effects of cytotoxic drugs were calculated as logarithmic 50% inhibitory concentrations and expressed as divergences from the mean in a log-mean graph. The inhibitory effects of amsacrine, etoposide, doxorubicin, cisplatin, mitomycin C, and fluorouracil were tested. Tumors differed widely in their sensitivity to these drugs, although sensitivity to the three topoisomerase-II-directed agents was highly correlated. Cells from two non-neoplastic hematopoietic progenitor cell lines (FT and 32D) showed chemosensitivity patterns distinct from those in the melanoma cells, indicating tissue selectivity. Two established melanoma cell lines, MM-96 and FME, were tested under the same conditions and showed sensitivity typical of at least some fresh specimens. These results support the validity of melanoma cell lines as models of freshly resected melanoma cells. If successfully applied to other tumor types, such semiautomated approaches could find wide application in routine hospital laboratories for the chemosensitivity testing of patients' tumor cells.

  15. Preappointment testing for BRAF/KIT mutation in advanced melanoma: a model in molecular data delivery for individualized medicine.

    Science.gov (United States)

    Mounajjed, Taofic; Brown, Char L; Stern, Therese K; Bjorheim, Annette M; Bridgeman, Andrew J; Rumilla, Kandelaria M; McWilliams, Robert R; Flotte, Thomas J

    2014-11-01

    The emergence of individualized medicine is driven by developments in precision diagnostics, epitomized by molecular testing. Because treatment decisions are being made based on such molecular data, data management is gaining major importance. Among data management challenges, creating workflow solutions for timely delivery of molecular data has become pivotal. This study aims to design and implement a scalable process that permits preappointment BRAF/KIT mutation analysis in melanoma patients, allowing molecular results necessary for treatment plans to be available before the patient's appointment. Process implementation aims to provide a model for efficient molecular data delivery for individualized medicine. We examined the existing process of BRAF/KIT testing in melanoma patients visiting our institution for oncology consultation. We created 5 working groups, each designing a specific segment of an alternative process that would allow preappointment BRAF/KIT testing and delivery of results. Data were captured and analyzed to evaluate the success of the alternative process. For 1 year, 35 (59%) of 55 patients had prior BRAF/KIT testing. The remaining 20 patients went through the new process of preappointment testing; results were available at the time of appointment for 12 patients (overall preappointment results availability, 85.5%). The overall process averaged 13.4 ± 4.7 days. In conclusion, we describe the successful implementation of a scalable workflow solution that permits preappointment BRAF/KIT mutation analysis and result delivery in melanoma patients. This sets the stage for further applications of this model to other conditions, answering an increasing demand for robust delivery of molecular data for individualized medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

    Directory of Open Access Journals (Sweden)

    Archis Bagati

    2017-09-01

    Full Text Available Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas or repress (in melanoma transcription of the N-cadherin gene (CDH2. We demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and the β-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes.

  17. CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

    Science.gov (United States)

    Itty, Sujit; Richter, Elizabeth R; McCannel, Tara A

    2015-01-01

    To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. Clinical examination and multimodal imaging of the case. A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

  18. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P.; Cheng, Elaine; Davis, Matthew J.; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C.; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M.; Brash, Douglas E.; Stern, David F.; Materin, Miguel A.; Lo, Roger S.; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K.; Hayward, Nicholas K.; Lifton, Richard P.; Schlessinger, Joseph; Boggon, Titus J.; Halaban, Ruth (Yale-MED); (UCLA); (Queens)

    2012-10-11

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  19. Melanoma transition is frequently accompanied by a loss of cytoglobin expression in melanocytes: a novel expression site of cytoglobin.

    Directory of Open Access Journals (Sweden)

    Yoshihiko Fujita

    Full Text Available The tissue distribution and function of hemoglobin or myoglobin are well known; however, a newly found cytoglobin (CYGB, which also belongs to the globin family, remains to be characterized. To assess its expression in human malignancies, we sought to screen a number of cell lines originated from many tissues using northern blotting and real time PCR techniques. Unexpectedly, we found that several, but not all, melanoma cell lines expressed CYGB mRNA and protein at much higher levels than cells of other origins. Melanocytes, the primary origin of melanoma, also expressed CYGB at a high level. To verify these observations, immunostaining and immunoblotting using anti-CYGB antibody were also performed. Bisulfite-modified genomic sequencing re