Sample records for melanoma

  1. Melanoma (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  2. Melanoma (United States)

    ... from generations ago. Back in your parents' and grandparents' day, most people (including doctors) thought it was safe and even ... it again somewhere else) Although it's less likely, people can still get melanoma even if they're dark skinned, young, and have no family history. Even for them, ...

  3. Ocular Melanoma (United States)

    ... Español Eye Health / Eye Health A-Z Ocular Melanoma Sections What is Ocular Melanoma? Ocular Melanoma Causes ... Melanoma Diagnosis Ocular Melanoma Treatment What is Ocular Melanoma? Written by: Daniel Porter Reviewed by: Robert H ...

  4. Melanoma genetics

    DEFF Research Database (Denmark)

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


    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 heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated...... 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...

  5. Cutaneous melanoma. (United States)

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


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

  6. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera


    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  7. Melanoma immunotherapy. (United States)

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


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

  8. [Vulvar melanoma]. (United States)

    Chokoeva, A; Tchernev, G; Wollina, U


    Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist melanoma in females, as the ratio of its manifestation, compared with the cutaneous melanoma is 1:71. Higher risk of developing melanoma of the vulva is established in white women, as the peak of the incidence is between 60 and 70 years of age. Clinically, MM of the vulva manifests as asymptomatic pigmented, rarely a pigmented lesion, as the usual clinical form is superficial spreading MM and much less common nodular MM, which is associated with a poorer prognosis in. general. The diagnosis is confirmed by histological examination. Conduction of PCR and DNA analysis for detection of BRAF mutations, NRAS mutations and KIT amplification is also appropriate. Advanced age, black race, tumor size, tumor thickness, ulceration, presence of satellite lesions, involvement of adjacent organs (vagina, urethra), and the presence of regional or distant metastases are identified as the most important prognostic markers. Radical wide excision followed by bilateral lymphadenectomy id considered as the optimal therapeutic approach.

  9. What Does Melanoma Look Like? (United States)

    ... Skin Cancer Skin Cancer Screening Research What Does Melanoma Look Like? Melanoma is a type of cancer ... melanoma is itchy, tender, or painful. Photos of Melanoma A large, asymmetrical melanoma with an uneven color ...

  10. Nutrition and melanoma prevention. (United States)

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


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

  11. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma (United States)


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

  12. What Is Melanoma Skin Cancer? (United States)

    ... Skin Cancer About Melanoma Skin Cancer What Is Melanoma Skin Cancer? Cancer starts when cells in the ... pigment, causing the skin to tan or darken. Melanoma skin cancers Melanoma is a cancer that begins ...

  13. Pregnancy and melanoma. (United States)

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


    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.

  14. Drugs Approved for Melanoma (United States)

    ... Ask about Your Treatment Research Drugs Approved for Melanoma This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome ( ...

  15. Melanoma - neck (image) (United States)

    This melanoma on the neck is variously colored with a very darkly pigmented area found centrally. It has irregular ... be larger than 0.5 cm. Prognosis in melanoma is best defined by its depth on resection.

  16. Molecular Classification of Melanoma (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.

  17. Pedunculated malignant melanoma

    Directory of Open Access Journals (Sweden)

    Bhat Ramesha


    Full Text Available Pedunculated malignant melanoma is a rare occurrence. A 29 year old woman presented with a pedunculated malignant melanoma on a congenital melanocytic naevus with halo. Pedunculated malignant melanoma is known to have a high incidence of metastasis. The absence of metastasis and the presence of halo, in the case presented, suggests, that the body′s immunological process may have arrested the spread of the melanoma.

  18. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)


    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.

  19. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie


    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are lackin

  20. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert


    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review...

  1. Acid Ceramidase in Melanoma

    DEFF Research Database (Denmark)

    Realini, Natalia; Palese, Francesca; Pizzirani, Daniela


    -regulated sphingolipid signaling in melanoma. We found that AC expression is markedly elevated in normal human melanocytes and proliferative melanoma cell lines, compared with other skin cells (keratinocytes and fibroblasts) and non-melanoma cancer cells. High AC expression was also observed in biopsies from human...... subjects with Stage II melanoma. Immunofluorescence studies revealed that the subcellular localization of AC differs between melanocytes (where it is found in both cytosol and nucleus) and melanoma cells (where it is primarily localized to cytosol). In addition to having high AC levels, melanoma cells...... generate lower amounts of ceramides than normal melanocytes do. This down-regulation in ceramide production appears to result from suppression of the de novo biosynthesis pathway. To test whether AC might contribute to melanoma cell proliferation, we blocked AC activity using a new potent (IC50 = 12 n...

  2. Malignant Melanoma of the Foot (United States)

    ... page. Please enable Javascript in your browser. Malignant Melanoma of the Foot What Is Malignant Melanoma? Melanoma is a cancer that begins in the ... people of all age groups, even the young. Melanoma in the Foot Melanoma that occurs in the ...

  3. CDC Vital Signs: Preventing Melanoma (United States)

    ... Press Kit Read the MMWR Science Clips Preventing Melanoma Communities Play a Vital Role Language: English Español ( ... and use of indoor tanning by minors. Problem Melanoma is increasing. Melanoma skin cancer is common and ...

  4. Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma (United States)


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

  5. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)


    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  6. Decoding Melanoma Metastasis

    Directory of Open Access Journals (Sweden)

    Marcus Bosenberg


    Full Text Available Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  7. [Targeted therapies for melanoma]. (United States)

    Leiter, U; Meier, F; Garbe, C


    Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

  8. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva


    AIM OF DATABASE: The aim of the database is to monitor and improve the treatment and survival of melanoma patients. STUDY POPULATION: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD). In 2014, 2,525 patients with invasive...... 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...... quality register. The coverage is high, and the performance in the five Danish regions is quite similar due to strong adherence to guidelines provided by the Danish Melanoma Group. The list of monitored indicators is constantly expanding, and annual quality reports are issued. Several important scientific...

  9. Genetics of familial melanoma

    DEFF Research Database (Denmark)

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


    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......, with the advent of next-generation sequencing, a small number of new high-penetrance genes have recently been uncovered. This approach has identified the lineage-specific oncogene MITF as a susceptibility gene both in melanoma families and in the general population, as well as the discovery of telomere...... maintenance as a key pathway underlying melanoma predisposition. Given these rapid recent advances, this approach seems likely to continue to pay dividends. Here, we review the currently known familial melanoma genes, providing evidence that most additionally confer risk to other cancers, indicating...

  10. Primary leptomeningeal melanoma. (United States)

    Xie, Zhao-Yu; Hsieh, Kevin Li-Chun; Tsang, Yuk-Ming; Cheung, Wing-Keung; Hsieh, Chen-Hsi


    Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature.

  11. Bronchial malignant melanoma. (United States)

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E


    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  12. Translational research in melanoma. (United States)

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


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

  13. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik


    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6...... is deregulated in many types of cancers, and increased serum concentration of IL-6 has been correlated with a worse prognosis in patients with different cancers, including melanoma. Several serum cytokines including IL-6 play an important role in the development and progression of melanoma; however, the specific...... biological functions of IL-6 in progression of melanoma are unknown. In this review, we present studies on cell cultures and mouse models and summarize published clinical studies on IL-6 and melanoma....

  14. Melanoma during pregnancy

    DEFF Research Database (Denmark)

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


    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...

  15. Synchronous anorectal melanoma

    Institute of Scientific and Technical Information of China (English)

    Drinko Balicevic; Karla Tomic; Miroslav Bekavac-Beslin; Igor Kovacevic; August Mijic; Mladen Belicza; Bozo Kruslin


    Anorectal melanoma is a very rare tumor with poor prognosis. Rectal bleeding is the most frequent symptom and surgical treatment ranges from local excision to radical abdominoperineal resection. We report a case of a 75-years-old male patient who presented with a history of recurrent rectal bleeding, and whose histopathological diagnosis was melanoma. Macroscopically, we found two distinct tumors in anorectal region, 0.5 cm and 1.5 cm from dentate line. The first one was pedunculated, on a thin stalk, measuring 1 cm in greatest diameter, and the second one was sessile and nodular measuring up to 2.8 cm in largest diameter. Microscopic examination and immunohistochemical analysis of both tumors confirmed the diagnosis of melanoma. This case represents multiple synchronous primary melanoma of the anorectal region, with a possibility that one of the lesions is primary melanoma and the second one is a satellite lesion.

  16. Familial malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.


    Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

  17. Neurotropic melanoma with prominent melanization. (United States)

    Barnhill, R L; Bolognia, J L


    Neurotropic melanoma has generally been described in the context of desmoplastic melanoma. The vast majority of melanomas displaying neurotropism contain relatively little or no melanin. Herein, we report an unusual case of neurotropic melanoma with prominent melanin content. The patient developed a tumor notable for pagetoid (superficial spreading) melanoma with partial regression and a deep component characterized by perineurial aggregates of melanophages and intraneural infiltration by melanoma cells. This case serves to alert dermatopathologists to the fact that the spectrum of neurotropic melanoma includes tumors with perineurial aggregates of pigment-containing cells.

  18. How Is Melanoma Skin Cancer Diagnosed? (United States)

    ... Cancer Early Detection, Diagnosis, and Staging Tests for Melanoma Skin Cancer Most melanomas are brought to a ... New in Melanoma Skin Cancer Research? Biopsies of melanoma that may have spread Biopsies of areas other ...

  19. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.


    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  20. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma


    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.

  1. General Information about Melanoma (United States)

    ... or cauterized (destroyed with a hot instrument, an electric current, or a caustic substance) because cancer cells ... or being studied in the treatment of melanoma: Signal transduction inhibitor therapy: Signal transduction inhibitors block signals ...

  2. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot


    Full Text Available Genomic variation is a trend observed in various human diseases including cancer. Genetic studies have set out to understand how and why these variations result in cancer, why some populations are predisposed to the disease, and also how genetics affect drug responses. The melanoma incidence has been increasing at an alarming rate worldwide. The burden posed by melanoma has made it a necessity to understand the fundamental signaling pathways involved in this deadly disease. Signaling cascades such as MAPK and PI3K/AKT have been shown to be crucial in the regulation of processes that are commonly dysregulated during cancer development such as aberrant proliferation, loss of cell cycle control, impaired apoptosis and altered drug metabolism. Understanding how these and other oncogenic pathways are regulated has been integral in our challenge to develop potent anti-melanoma drugs. With advances in technology and especially in next generation sequencing, we have been able to explore melanoma genomes and exomes leading to the identification of previously unknown genes with functions in melanomagenesis such as GRIN2A and PREX2. The therapeutic potential of these novel candidate genes is actively being pursued with some presenting as druggable targets while others serve as indicators of therapeutic responses. In addition, the analysis of the mutational signatures of melanoma tumors continues to cement the causative role of UV exposure in melanoma pathogenesis. It has become distinctly clear that melanomas from sun exposed skin areas have distinct mutational signatures including C to T transitions indicative of UV-induced damage. It is thus necessary to continue spreading awareness on how to decrease the risk factors of developing the disease while at the same time working for a cure. Given the large amount of information gained from these sequencing studies, it is likely that in the future, treatment of melanoma will follow a highly personalized route

  3. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery (United States)


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

  4. 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


    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.

  5. Targeted therapy in melanoma. (United States)

    Kudchadkar, Ragini R; Smalley, Keiran S M; Glass, L Frank; Trimble, James S; Sondak, Vernon K


    Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.

  6. The Danish Melanoma Database

    Directory of Open Access Journals (Sweden)

    Hölmich Lr


    Full Text Available Lisbet Rosenkrantz Hölmich,1 Siri Klausen,2 Eva Spaun,3 Grethe Schmidt,4 Dorte Gad,5 Inge Marie Svane,6,7 Henrik Schmidt,8 Henrik Frank Lorentzen,9 Else Helene Ibfelt10 1Department of Plastic Surgery, 2Department of Pathology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 3Institute of Pathology, Aarhus University Hospital, Aarhus, 4Department of Plastic and Reconstructive Surgery, Breast Surgery and Burns, Rigshospitalet – Glostrup, University of Copenhagen, Copenhagen, 5Department of Plastic Surgery, Odense University Hospital, Odense, 6Center for Cancer Immune Therapy, Department of Hematology, 7Department of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, 8Department of Oncology, 9Department of Dermatology, Aarhus University Hospital, Aarhus, 10Registry Support Centre (East – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Glostrup – Rigshospitalet, University of Copenhagen, Glostrup, Denmark Aim of database: The aim of the database is to monitor and improve the treatment and survival of melanoma patients.Study population: All Danish patients with cutaneous melanoma and in situ melanomas must be registered in the Danish Melanoma Database (DMD. In 2014, 2,525 patients with invasive 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–node–metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a, results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence, nature, and treatment hereof is registered. In case of death, the cause and date

  7. Treatment Options by Stage (Melanoma) (United States)

    ... of Skin Cancer Skin Cancer Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment ...

  8. Um Melanoma “mascarado” Melanoma disfrazado A disguised Melanoma

    Directory of Open Access Journals (Sweden)

    Elias Ribeiro


    Full Text Available O melanoma é um tumor que se desenvolve como resultado da transformação maligna dos melanócitos, estimando-se a sua incidência global em 132.000 casos/ano. Este relato de caso reporta-se a um doente do sexo masculino com 70 anos, história de Diabetes Mellitus tipo 2 há dez anos e psoríase vulgar extensa há seis anos. Em aproximadamente um ano, este desenvolveu lesão ulcerada da região plantar do pé direito, que ao exame histológico revelou melanoma maligno, ulcerado, nível V de Clark, com 5,6 mm de espessura (Breslow. Foi submetido à exérese cirúrgica da lesão e biópsia de gânglio sentinela que foi negativa. O estadiamento inicial revelou evolução avançada do tumor primário (TNM IIC. Exames imagiológicos detetaram metastização gástrica, reclassificando a doença num estádio TNM IV. O melanoma maligno pode ser de difícil diagnóstico como se pode constatar neste caso em que uma ulceração plantar foi avaliada tardiamente, atrasando o diagnóstico de uma neoplasia grave e com elevada taxa de mortalidade. El melanoma es un tumor que se desarrolla como resultado de la transformación maligna de los melanocitos, estimándose su incidencia global en 132,000 casos/año. Este informe presenta a un paciente de sexo masculino de 70 años, con antecedentes de Diabetes Mellitus tipo 2 desde hace diez años y psoriasis vulgar extensa desde hace seis años. En aproximadamente un año el paciente desarrolló una lesión ulcerada en la región plantar del pie derecho, el examen histológico reveló un melanoma maligno, ulcerado, nivel V de Clark, de 5.6 mm de espesor (Breslow. Después de una escisión quirúrgica de la lesión, se realizó una biopsia de ganglio centinela que fue negativa. Las conclusiones iniciales revelaron una evolución avanzada del tumor primario (TNM IIC. Exámenes radiológicos detectaron una metástasis gástrica, reclasificando la enfermedad en una etapa TNM IV. El melanoma maligno puede ser de

  9. Genotyping of cutaneous melanoma. (United States)

    Glitza, Isabella C; Davies, Michael A


    Until recently, treatment options for patients with metastatic melanoma were very limited. This landscape has evolved dramatically since the discovery of activating mutations in the BRAF gene in ~45% of cutaneous melanomas. Vemurafenib, dabrafenib, and trametinib have all received regulatory approval for the treatment of metastatic melanoma patients with a BRAF(V600) mutation. Based on the necessity to document the presence of a BRAF(V600) mutation to prescribe these agents, molecular testing is now the standard of care in this disease. However, the options and rationale for testing are evolving rapidly due to an improved understanding of the molecular drivers and heterogeneity of melanoma. Such testing may identify rational combinatorial approaches to prevent or overcome resistance for the approved BRAF inhibitors. In addition, new clinical strategies have been identified for a number of other molecular changes that are detected in this disease, including somatic changes in NRAS, PTEN, CDKN2A, and c-KIT, among others. This review summarizes the current understanding of the genetic landscape of mutations in melanoma, their associations with clinicopathological features, and their implications for clinical testing and treatment.

  10. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  11. Targeted therapies for cutaneous melanoma. (United States)

    Kee, Damien; McArthur, Grant


    Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.

  12. Melanoma Risk Prediction Models (United States)

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

  13. Congenital uveal melanoma? (United States)

    Singh, Arun D; Schoenfield, Lynn A; Bastian, Boris C; Aziz, Hassan A; Marino, Meghan J; Biscotti, Charles V


    A 3-month-old infant with a white mother and Asian father presented with discoloration and prominence of the left eye since birth. Examination revealed a normal right eye. The left eye had hyperchromic heterochromia and an enlarged cornea (diameter, 13.0 mm) with intraocular pressure of 26 mm Hg. There were multiple areas of subconjunctival nodular pigmentation that extended posteriorly into the superior fornix. Fundus examination showed a large ciliochoroidal pigmented mass extending from 10:30 to 3:00 o'clock position involving the superior half of the choroid and adjacent ciliary body. The eye was enucleated, confirming the diagnosis of diffuse uveal melanoma with extraocular extension. Systemic surveillance (hepatic panel and ultrasonography of the liver) performed every 6 months for 5 years was has been negative for metastases. The tumor was investigated intensively for the panel of genes (BAP1, BRAF, NRAS12, NRAS61, GNAQ, Kit 9,11,13,17,18) implicated in pathogenesis of blue nevus, cutaneous melanoma, and mucosal melanomas with negative results. Moreover, germline BAP1 mutation could not be identified. This case possibly represents as yet unidentified uveal melanocytic proliferation rather than a true variant of uveal melanoma.

  14. Chemotherapy for Melanoma. (United States)

    Wilson, Melissa A; Schuchter, Lynn M


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

  15. Melanoma maligno conjuntival

    Directory of Open Access Journals (Sweden)

    Gustavo Amorim Novais


    Full Text Available INTRODUÇÃO: Os tumores melanocíticos conjuntivais compreendem lesões que podem variar desde lesões benignas como os nevos conjuntivais, lesões pré-cancerosas como melanose adquirida primária com atipia até o melanoma maligno conjuntival. O reconhecimento das características clinicas destas lesões e seu diagnóstico preciso permitem o tratamento adequado, contribuindo para a redução da morbidade e mortalidade associados ao melanoma de conjuntiva. OBJETIVO: Revisão das características clinicas, diagnóstico e modalidades de tratamento clínico e cirúrgico das lesões precursoras (Nevos e melanose adquirida primária e do maligno conjuntival. MÉTODOS: Revisão de literatura através de pesquisa no banco de dados MEDLINE, PUBMED, LILACS e SciELO no período de 1980 a 2011. As palavras-chave utilizadas, individualmente ou em conjunto, foram: "conjunctival melanoma", "primary acquired melanosis", "nevi", "treatment", "chemotherapy", "recurrence", "metastasis" e "mortality". RESULTADO: Características clínicas que permitem o diagnóstico do melanoma conjuntival e sua diferenciação de outras lesões pigmentadas conjuntivais foram consideradas. O estadiamento clínico e patológico, assim como modalidades de tratamento para o melanoma maligno foram revisadas. CONCLUSÕES: Pacientes portadores de lesões pigmentadas conjuntivais devem ser avaliados por um oftalmologista especialista. A história oftalmológica, a história familiar de melanoma, e características clínicas da lesão necessitam de cuidadosa avaliação, incluindo-se a determinação do risco de malignidade. A documentação fotográfica deve ser realizada. O tratamento clínico e planejamento cirúrgico devem ser baseados na suspeita clinica. A análise histopatológica por patologista experiente é fundamental para orientação do tratamento e para identificação de fatores prognósticos, principalmente em casos de doença maligna.

  16. Oncogenes in melanoma: an update. (United States)

    Kunz, Manfred


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

  17. Malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    Manohar S


    Full Text Available Four cases of malignant melanoma of the choroid are reported due to rarity of the condition in India. One of the cases presented with Naevus of Ota. All the cases had typical clinical and investigative features. All cases were enucleated. Histopathologically three of them were of mixed type and one was of the epithelioid type. Two of the cases were seen in patients below 40 years of age.

  18. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar


    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  19. Beyond BRAF in melanoma. (United States)

    Daud, Adil; Bastian, Boris C


    Recent progress in the analysis of genetic alterations in melanoma has identified recurrent mutations that result in the activation of critical signaling pathways promoting growth and survival of tumors cells. Alterations in the RAS-RAF-MAP kinase and PI3-kinase signaling pathways are commonly altered in melanoma. Mutations in BRAF, NRAS, KIT, and GNAQ occur in a mutually exclusive pattern and lead to MAP-kinase activation. Loss of PTEN function, primarily by deletion, is the most common known genetic alteration in the PI3-kinase cascade, and is commonly associated with BRAF mutations (Curtin et al., N Engl J Med 353:2135-2147, 2005; Tsao et al., Cancer Res 60:1800-1804, 2000, J Investig Dermatol 122:337-341, 2004). The growth advantage conveyed by the constitutive activation of these pathways leads to positive selection of cells that have acquired the mutations and in many instances leads to critical dependency of the cancer cells on their activation. This creates opportunities for therapeutic interventions targeted at signaling components within these pathways that are amenable for pharmacological inhibition. This concept follows the paradigm established by the landmark discovery that inhibition of the fusion kinase BCR-ABL can be used to treat chronic myelogenous leukemia (Druker et al., N Engl J Med 344:1031-037, 2001). The review will focus primarily on kinases involved in signaling that are currently being evaluated for therapeutic intervention in melanoma.

  20. A disguised Melanoma

    Directory of Open Access Journals (Sweden)

    Cláudia Sofia Rego


    Full Text Available Melanoma is a tumor that develops as a result of the malignant transformation of the melanocytes. There is a worldwide estimate of 132,000 new cases per year. This case study presents a 70-year-old male person with history of Diabetes Mellitus type 2 for 10 years and extensive psoriasis vulgaris for 6 years. The patient developed an ulcerated lesion in the plantar region of the right foot in one-year time period. The histological examination revealed an ulcerated malignant melanoma, Clark level V, 5.6 mm thick (Breslow. The lesion was surgically removed and the sentinel lymph node biopsy was negative. Initial conclusions revealed an advanced state of evolution of the primary tumor (TNM IIC. CAT scan detected gastric metastasis, reclassifying the illness as a TNM IV stage. Malignant melanoma may be difficult to diagnose, as it was possible to observe in this case study, where a foot ulcer was late diagnosed, delaying the diagnosis of a severe neoplasia with high mortality rate.

  1. 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: [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)


    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.


    NARCIS (Netherlands)



    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 dis

  3. Angiogenic profile of uveal melanoma.

    NARCIS (Netherlands)

    Notting, I.C.; Missotten, G.S.; Sijmons, B.; Boonman, Z.F.; Keunen, J.E.E.; Pluijm, G. van der


    Uveal melanoma develops in one of the most capillary-rich tissues of the body and is disseminated hematogenously. Knowledge of the nature and the spatiotemporal expression of angiogenic factors in uveal melanoma is essential to the development of new treatment strategies, especially with regard to i

  4. Comparative Aspects of Canine Melanoma

    Directory of Open Access Journals (Sweden)

    Adriana Tomoko Nishiya


    Full Text Available Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas.

  5. Clinical characteristics and management of melanoma families

    NARCIS (Netherlands)

    Rhee, Jasper Immanuel van der


    Being a member of a melanoma family is a major risk factor for cutaneous malignant melanoma. In this thesis clinical characteristics and management of melanoma families are discussed. In the first part of the thesis clinical and histological characteristics of melanoma (patients) from families with

  6. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts


    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  7. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma (United States)


    Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

  8. Targeted Radionuclide Therapy of Melanoma. (United States)

    Norain, Abdullah; Dadachova, Ekaterina


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

  9. Melanoma Lentiginoso Acral

    Directory of Open Access Journals (Sweden)

    Gloria Andrea Vargas Suaza


    Full Text Available El melanoma lentiginoso acral (MLA es una variante rápidamente progresiva del melanoma maligno (MM. Constituye el 5-10% de todos los tipos de MM y se presenta con mayor frecuencia en pacientes de raza negra, asiáticos y latinoamericanos. En Colombia el MM se encuentra en aumento, con una incidencia de 3.5/100.000, siendo el MLA una de las variantes más comunes. La edad promedio de presentación es de 58 años, con una tasa de sobrevida menor para las personas de raza negra, asociado a un diagnóstico tardío. EL MLA se localiza en plantas, palmas y región subungueal y en su etiopatología se ha descrito la presencia de mutaciones en genes: 9p21 (p16: 67%, 11q13 (CCND1 (47%, 22q11-q13 (40% y 5p15 (20%. El diagnóstico de MLA, se ha fundamentado clásicamente en la histopatología. Herramientas de diagnóstico como la dermatoscopia, la evaluación del ganglio centinela y la determinación de alteraciones en las proteínas del ciclo celular contribuyen a la detección precoz del MLA y el MM en general.

  10. Morphogenesis of early stage melanoma (United States)

    Chatelain, Clément; Amar, Martine Ben


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

  11. 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.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  12. 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


    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...

  13. Podoplanin Expression in Canine Melanoma. (United States)

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


    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.

  14. [Ocular metastasis of cutaneous melanoma]. (United States)

    Galland, F; Balansard, B; Conrath, J; Forzano, O; Ridings, B


    We report a case of vitreal metastases from cutaneous melanoma. We describe the clinical findings and the histological aspects of the lesions, which allows us to discuss the diagnosis of masquerade syndrome and highlight the diagnostic importance of vitreous biopsy.

  15. BRAF mutations in conjunctival melanoma

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine; Dahl, Christina; Dahmcke, Christina M.


    Purpose: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection. Methods: Data from 139 patients...... with conjunctival melanoma (1960–2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings....... Results: The overall incidence of conjunctival melanoma (0.5 cases/1 000 000/year) increased during the study period with 0.13 cases/1 000 000/10 years. The increase comprised a higher proportion of patients aged >65 years, epibulbar tumours and tumours developed from a primary acquired melanosis...

  16. Management of melanoma during pregnancy. (United States)

    Leachman, Sancy A; Jackson, Ryan; Eliason, Mark J; Larson, April A; Bolognia, Jean L


    There is no conclusive evidence that pregnancy adversely affects overall survival in patients with melanoma. Clinicians caring for pregnant patients should be as suspicious of changes in melanocytic nevi in these patients as they are for nonpregnant patients. Treatment of early-stage melanoma is the same irrespective of whether or not the patient is pregnant. Chemotherapeutic regimens for metastatic disease administered during pregnancy have not demonstrated significant efficacy.

  17. [Choroidal melanoma - evolution and prognosis]. (United States)

    Chiruţa, Daria; Stan, Cristina


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

  18. Fulminant metastatic malignant melanoma

    Directory of Open Access Journals (Sweden)

    N.M.K. Faheem,


    Full Text Available A 50-year-old lady presented with complaints of chest pain and cough for the past one month. Right supraclavicular lymphadenopathy, bilateral pleural effusion were present. Fine needle aspiration cytology (FNAC from the lymph node showed brownish-black pigment laden tumour cells. Review of history subsequently revealed that she had undergone a surgical procedure over the sole of her left foot three years ago of which no records were available. Reexamination of sole of left foot showed a pigmented infiltraling lesion. Pleural biopsy revealed pigmented tumour deposits. The patient was diagnosed to have fulminant metastatic malignant melanoma of left foot with metastasis to cervical lymph nodes and pleura. This case report re-emphasizes the importance of combined approach to ascertain diagnosis early.

  19. The Danish Melanoma Database

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Klausen, Siri; Spaun, Eva;


    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-node......-metastasis stage. Information about the date of diagnosis, treatment, type of surgery, including safety margins, results of lymphoscintigraphy in patients for whom this was indicated (tumors > T1a), results of sentinel node biopsy, pathological evaluation hereof, and follow-up information, including recurrence......, nature, and treatment hereof is registered. In case of death, the cause and date are included. Currently, all data are entered manually; however, data catchment from the existing registries is planned to be included shortly. DESCRIPTIVE DATA: The DMD is an old research database, but new as a clinical...

  20. Melanoma therapy: Check the checkpoints. (United States)

    Furue, Masutaka; Kadono, Takafumi


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

  1. Reproducibility of self-reported melanoma risk factors in melanoma patients

    NARCIS (Netherlands)

    Waal, A.C. de; Rossum, M.M. van; Kiemeney, L.A.L.M.; Aben, K.K.H.


    As melanoma researchers continue to investigate environmental and lifestyle-related risk factors, questionnaire data remain important. The reproducibility of a questionnaire on melanoma risk factors was investigated using a test-retest approach in 389 Dutch melanoma patients. In 2011, 389 melanoma p

  2. Tool to Distinguish Moles from Melanoma (United States)

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

  3. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Datta, P; Heydenreich, J


    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis...

  4. Modeling Melanoma In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Kimberley A. Beaumont


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

  5. Donor Transmission of Melanoma Following Renal Transplant

    Directory of Open Access Journals (Sweden)

    Kathryn T. Chen


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

  6. Donor transmission of melanoma following renal transplant. (United States)

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


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

  7. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul


    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.......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....

  8. Functional Erythropoietin Autocrine Loop in Melanoma


    Kumar, Suresh M; Acs, Geza; Fang, Dong; Herlyn, Meenhard; Elder, David E.; Xu, Xiaowei


    Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and t...

  9. Malignant melanoma of the foot and ankle. (United States)

    John, K J; Hayes, D W; Green, D R; Dickerson, J


    Malignant melanoma is a serious and devastating skin disease that podiatrists may be called upon to treat. It is pertinent that delays in diagnosis and treatment of malignant melanoma be avoided. Some of the topics discussed in this article are causes, clinical features, classification, and treatment of malignant melanoma, focusing on the foot and ankle.

  10. Pregnancy and early-stage melanoma

    NARCIS (Netherlands)

    Daryanani, D; Plukker, JT; De Hullu, JA; Kuiper, H; Nap, RE; Hoekstra, HJ


    BACKGROUND. Cutaneous melanomas are aggressive tumors with an unpredictable biologic behavior. It has been suggested that women who present with melanoma during pregnancy have a worse prognosis due to more aggressive behavior of the melanoma. The objective of the current study was to evaluate the lo

  11. Surgical management of primary and recurrent melanoma. (United States)

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


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

  12. Coffee, tea and melanoma risk

    DEFF Research Database (Denmark)

    Caini, Saverio; Masala, Giovanna; Saieva, Calogero


    In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumpt......In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea...... consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a multicentre prospective study that enrolled over 500,000 participants aged 25-70 years from ten European countries in 1992-2000. Information on coffee and tea drinking was collected...... at baseline using validated country-specific dietary questionnaires. We used adjusted Cox proportional hazards regression models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between coffee and tea consumption and melanoma risk. Overall, 2,712 melanoma cases were...

  13. Melanoma: Last call for radiotherapy. (United States)

    Espenel, Sophie; Vallard, Alexis; Rancoule, Chloé; Garcia, Max-Adrien; Guy, Jean-Baptiste; Chargari, Cyrus; Deutsch, Eric; Magné, Nicolas


    Melanoma is traditionally considered to be a radioresistant tumor. However, radiotherapy and immunotherapy latest developments might upset this radiobiological dogma. Stereotactic radiotherapy allows high dose per fraction delivery, with high dose rate. More DNA lethal damages, less sublethal damages reparation, endothelial cell apoptosis, and finally clonogenic cell dysfunction are produced, resulting in improved local control. Radiotherapy can also enhance immune responses, inducing neoantigens formation, tumor antigen presentation, and cytokines release. A synergic effect of radiotherapy with immunotherapy is expected, and might lead to abscopal effects. If hadrontherapy biological properties seem able to suppress hypoxia-induced radioresistance and increase biological efficacy, ballistic advantages over photon radiations might also improve radiotherapy outcomes on usually poor prognosis locations. The present review addresses biological and clinical effects of high fraction dose, bystander effect, abscopal effect, and hadrontherapy features in melanoma. Clinical trials results are warranted to establish indications of innovative radiotherapy in melanoma.

  14. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J


    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...... stratification of ulcerated lesions. METHODS: From H&E-stained sections, the status (presence vs absence), extent (percentage of the total tumor length), and type (infiltrative vs attenuative) of ulceration and epidermal involvement were evaluated from 385 patients with cutaneous melanoma. RESULTS: The presence...... of ulceration (hazard ratio [HR], 1.83), an attenuative type of ulceration (HR, 3.02), and excessive ulceration (HR, 3.57) were independent predictors of poor melanoma-specific survival. Further subdivision of minimal/moderate ulceration showed independent prognostic value only for lesions with epidermal...

  15. Familial skin cancer syndromes: Increased melanoma risk. (United States)

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


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

  16. Melanoma: oncogenic drivers and the immune system (United States)

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


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

  17. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko


    Full Text Available Melanoma remains the most deadly form of malignant skin disease with high risk of metastases. Metastatic melanoma is prognostic highly unfavorable and resistant to traditional chemotherapy and biologic treatment. There is a great progress in understanding of the molecular mechanisms underlying melanoma initiation and progression. The external (ultraviolet irradiation and internal (genetic factors are involved in melanoma genesis. 5–14 % of melanoma cases occur in familial context due to genetic predisposition risk factors. Among them rare germinal mutations in the cell cycle genes regulators CDKN2A and CDK4 and in the master gene of melanocyte homeostasis MITF, as well as single nucleotide polymorphisms of several low-penetrated genes, namely MC1R, have been identified. The main cell signaling pathways and oncogene driver mutations are involved in melanoma pathogenesis. RAS / RAF / MEK / ERK cascade is hyperactivated in 75 % of cutaneous melanoma cases. Activation of PI3K / AKT / mTOR signaling pathway is important for melanoma progression. Recent studies revealed that melanomas are genetically and phenotypically heterogeneous tumors. Spectrum of chromosomal alterations and activating mutations corresponding to tumor molecular portraits varies in melanomas of different location. Most of cutaneous melanomas contain BRAF (50 % or NRAS (20 % mutations, and NRAS mutations occur on chronically sun-exposed skin. Activating KIT mutations have been reported in approximately 20–30 % of certain subtypes of melanoma, including acral and mucosal, and melanoma that develop on photodamaged skin. Cutaneous metastatic melanoma derive from preexisting nevi in 25 % of cases, molecular mechanisms of nevi malignization are discussed. Deepsequencing approaches of melanoma samples of different melanoma types highlighted new melanoma driver genes, that are damaged due to tumorigenic effects of ultraviolet: PPP6C, RAC1, SNX31, TACC1 and STK19. The

  18. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse


    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be in......A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains...

  19. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian


    melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins......Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral...... 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...

  20. Melanoma early detection and awareness

    DEFF Research Database (Denmark)

    Wainstein, Alberto; Algarra, Salvador Martin; Bastholt, Lars


    Risk factors for melanoma are well known and have guided plans for primary and secondary prevention. The presentation of the disease, however, varies widely depending on the geographic area, ethnicity, and socioeconomic status. For this reason, many countries have developed specific strategies...

  1. The genomic landscape of cutaneous melanoma. (United States)

    Zhang, Tongwu; Dutton-Regester, Ken; Brown, Kevin M; Hayward, Nicholas K


    Somatic mutation analysis of melanoma has been performed at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last 5 yr, next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multigene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer.

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


    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.

  3. Pediatric melanoma, moles, and sun safety. (United States)

    Hawryluk, Elena B; Liang, Marilyn G


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

  4. Massive nodular melanoma scalp: a case report

    Directory of Open Access Journals (Sweden)

    A. Bhagya Lakshmi


    Full Text Available Melanoma is responsible for 1% to 2% of all cancer deaths around the world. Nodular melanoma often carries a poor prognosis because of no prodromal radial growth phase, early distant metastasis and significant tumour volume. We present a case of nodular melanoma measuring 20x10x8 cm in 28 year old tribal women. [Int J Res Med Sci 2015; 3(4.000: 1002-1005

  5. Melanoma of unknown origin: a case series.

    LENUS (Irish Health Repository)

    Kelly, J


    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).

  6. Melanoma biomolecules: independently identified but functionally intertwined. (United States)

    Dye, Danielle E; Medic, Sandra; Ziman, Mel; Coombe, Deirdre R


    The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (CSPG4), and paired box 3 (PAX3). The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology.

  7. Novel Targeted Therapies for Metastatic Melanoma. (United States)

    Iams, Wade T; Sosman, Jeffrey A; Chandra, Sunandana

    Oncogene-targeted therapy is a major component of precision oncology, and although patients with metastatic melanoma have experienced improved outcomes with this strategy, there are a number of potential therapeutic targets currently under study that may further increase the drug armamentarium for this patient population. In this review, we discuss the landscape of targeted therapies for patients with advanced melanoma, focusing on oncogene mutation-specific targets. In patients with typical BRAF V600-mutant melanoma, combination BRAF and MEK inhibition has surpassed outcomes compared with monotherapy with BRAF or MEK inhibition alone, and current strategies seek to address inevitable resistance mechanisms. For patients with NRAS-mutant melanoma, MEK inhibitor monotherapy and combined MEK and CDK4/6 inhibition are burgeoning strategies; for patients with KIT-mutant melanoma, tyrosine kinase inhibition is being leveraged, and for NF-1-mutant melanoma, mTOR and MEK inhibition is being actively evaluated. In patients with atypical, non-V600 BRAF-mutant melanoma, MEK inhibitor monotherapy is the potential novel targeted approach on the horizon. For advanced uveal melanoma, novel targets such as IMCgp100 and glembatumumab have shown activity in early studies. We review additional strategies that remain in the preclinical and early clinical pipeline, so there is much hope for the future of targeted agents for distinct molecular cohorts of patients with advanced melanoma.

  8. Histone variants and melanoma: facts and hypotheses. (United States)

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


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

  9. [Orbital metastasis in malignant melanoma]. (United States)

    Pedroli, G L; Hamedani, M; Barraco, P; Oubaaz, A; Morax, S


    We report the case of a 60-year-old man presenting bilateral progressive proptosis with diplopia, weight loss, tachycardia, nervosity, and stomach pain. These signs seemed at first to favor a diagnosis of Graves'ophthalmopathy. Thyroid tests were negative and the initial orbital CT scan was considered normal. A new radiological investigation 4 months later in our hospital revealed typical hypertrophy of the extraocular muscles compatible with orbital metastasis. The systemic investigations demonstrated a pulmonary tumor, multiple hepatic lesions, and several pigmented nodules of gastric mucosa. The pathology of pulmonary and gastric specimens confirmed the diagnosis of malignant melanoma. The primary lesion remains unknown. The authors discuss the differential diagnoses of orbital metastasis and the radiological characteristics of orbital metastasis in malignant melanoma.

  10. Melanoma immunotherapy: dendritic cell vaccines


    Lozada-Requena, Ivan; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Núñez, César; Empresa de Investigación y Desarrollo en Cáncer (EMINDES) SAC. Lima, Perú.; Aguilar, José Luis; Laboratorios de Inmunología #108, Laboratorio de investigación y Desarrollo, Facultad de Ciencieas y Filosofía, Universidad Cayetano Heredia. Lima, Perú.


    This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy.Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion oftumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diversetypes of cancer in humans and animal models. However, given the low efficiency they have shown, we must implementstrateg...

  11. Malignant rectal melanoma. Case report. (United States)

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


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

  12. Choroidal Metastases From Cutaneous Melanoma. (United States)

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


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

  13. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian


    Full Text Available Spontaneous rupture of spleen due to malignant melanoma is a rare situation, with only a few case reports in the literature. This study reports a previously healthy, 30-year-old man who came with chief complaint of acute abdominal pain to emergency room. On physical examination, abdominal tenderness and guarding were detected to be coincident with hypotension. Ultrasonography revealed mild splenomegaly with moderate free fluid in abdominopelvic cavity. Considering acute abdominal pain and hemodynamic instability, he underwent splenectomy with splenic rupture as the source of bleeding. Histologic examination showed diffuse infiltration by tumor. Immunohistochemical study (positive for S100, HMB45, and vimentin and negative for CK, CD10, CK20, CK7, CD30, LCA, EMA, and chromogranin confirmed metastatic malignant melanoma. On further questioning, there was a past history of a nasal dark skin lesion which was removed two years ago with no pathologic examination. Spontaneous (nontraumatic rupture of spleen is an uncommon situation and it happens very rarely due to neoplastic metastasis. Metastasis of malignant melanoma is one of the rare causes of the spontaneous rupture of spleen.

  14. Melanoma of the female urethra

    Directory of Open Access Journals (Sweden)

    Juan A Ramos


    Full Text Available Melanoma is a malignant tumor that can affect any area of the anatomical economy. Its appearance in the female urethra is extremely rare, with approximately 121 cases in indexed literature since 1966. The subject to be described is an 86-year-old woman who seeks assessment for intermittent macroscopic hematuria with blood clots of 3 months progression. On physical examination, there are no suspicious lesions detected on the surface of the skin. On external genital examination, it is observed a friable lesion at the level of the urethral meatus, with heterogeneous digitations, dark brown to black, and irregular polycyclic borders. No inguinal adenomegalies were palpated. Cystourethroscopy and biopsy of the lesion confirm the diagnosis. Melanoma of the female urethra is an extremely infrequent pathology. Due to lack of published case reports and the absence of prospective randomized trials on treatment outcomes, treatment must be directed using the same anatomical and surgical criteria for female urethral tumors, adding also the concepts of treatment of mucosal melanoma, even though its prognosis is different from the before mentioned.

  15. Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey. (United States)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen


    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral 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 and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma).

  16. Esophageal melanomas harbor frequent NRAS mutations unlike melanomas of other mucosal sites. (United States)

    Sekine, Shigeki; Nakanishi, Yukihiro; Ogawa, Reiko; Kouda, Satoko; Kanai, Yae


    Mucosal melanomas have genetic alterations distinct from those in cutaneous melanomas. For example, NRAS- and BRAF-activating mutations occur frequently in cutaneous melanomas, but not in mucosal melanomas. We examined 16 esophageal melanomas for genetic alterations in NRAS, BRAF, and KIT to determine whether they exhibit genetic features common to melanomas arising from other mucosal sites. A sequencing analysis identified NRAS mutations in six cases; notably, four of these mutations were located in exon 1, an uncommon mutation site in cutaneous and other mucosal melanomas. BRAF and KIT mutations were found in one case each. Immunohistochemistry showed KIT expression in four cases, including the tumor with a KIT mutation and two other intramucosal tumors. The low frequency of BRAF mutations and the presence of a KIT mutation-positive case are findings similar to those of mucosal melanomas of other sites, but the prevalence of NRAS mutations was even higher than that of cutaneous melanomas. The present study implies that esophageal melanomas have genetic alterations unique from those observed in other mucosal melanomas.

  17. Genetic progression of malignant melanoma. (United States)

    Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E


    Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

  18. The worth of radiotherapy in malignant melanomas. (United States)

    Proppe, A H


    A new approach for the evaluation of the effectiveness of various forms of treatment of malignant melanomas is presented. Factors influencing the survival time from initiation of therapy until death were statistically analyzed in 548 patients who died from malignant melanoma. In slowly developing malignancies X-ray therapy was found to be superior to therapeutic methods.

  19. Update on the targeted therapy of melanoma. (United States)

    Johnson, Douglas B; Sosman, Jeffrey A


    Melanoma is the most aggressive of the cutaneous malignancies, causing more than 9,000 deaths in the past year in the United States. Historically, systemic therapies have been largely ineffective, because melanoma is usually resistant to cytotoxic chemotherapy. However, during the past few years, several targeted therapies have proved effective in this challenging disease. These recent advances have been facilitated by an improved understanding of the driving genetic aberrations of melanoma, particularly mutations in the mitogen-activated protein kinase (MAPK) pathway. Vemurafenib, a BRAF inhibitor, demonstrated an overall survival advantage in phase III trials and is an appropriate option for first-line therapy in metastatic BRAF mutant melanoma. Dabrafenib, another BRAF inhibitor, and trametinib, a MEK inhibitor, also have been shown to be effective in phase III trials for BRAF mutant melanoma and may be additional treatment options as monotherapy or in combination pending regulatory approval. Additionally, imatinib is a promising targeted therapy for patients whose tumors harbor a KIT mutation in exons 11 and 13. Although these targeted agents cause objective responses and clinical benefit in patients with metastatic melanoma, resistance invariably develops. New targets and strategies to overcome acquired resistance are urgently needed. Furthermore, no effective targeted therapy has been developed for NRAS mutant tumors or in melanomas with as yet unknown driver mutations. In this review, we discuss current molecular targeted treatment options and promising ongoing research to develop new strategies to treat melanoma.

  20. Mistletoe in the treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Esin Sakallı Çetin


    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

  1. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...

  2. Angiogenic and Metastatic Determinants of Malignant Melanoma

    NARCIS (Netherlands)

    A. Mooppilmadham Das (Asha)


    markdownabstractCutaneous melanoma or malignant melanoma of the skin is a highly metastatic disease, with an increasing rate of incidence, poor prognosis and high resistance to therapeutic intervention. Although early diagnosis and surgical resection of the primary lesion could significantly improve

  3. Malignant melanoma at a scientific laboratory

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  4. Novel approaches in melanoma prevention and therapy. (United States)

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


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

  5. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London Univ. (United Kingdom)


    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. {sup 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. (author)

  6. Alpha particles for treatment of disseminated melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Link, E.M. [London University (United Kingdom)


    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. {sup 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)

  7. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik


    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion...... in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve......; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large...

  8. Diagnostic and Prognostic Biomarkers in Melanoma (United States)

    Leininger, Jennifer; Hamby, Carl; Safai, Bijan


    Melanoma is a lethal melanocytic neoplasm. Unfortunately, the histological diagnosis can be difficult at times. Distinguishing ambiguous melanocytic neoplasms that are benign nevi from those that represent true melanoma is important both for treatment and prognosis. Diagnostic biomarkers currently used to assist in the diagnosis of melanoma are usually specific only for melanocytic neoplasms and not necessarily for their ability to metastasize. Traditional prognostic biomarkers include depth of invasion and mitotic count. Newer diagnostic and prognostic biomarkers utilize immunohistochemical staining as well as ribonucleic acid, micro-ribonucleic acid, and deoxyribonucleic acid assays and fluorescence in situ hybridization. Improved diagnostic and prognostic biomarkers are of increasing importance in the treatment of melanoma with the development of newer and more targeted therapies. Herein, the authors review many of the common as well as newer diagnostic and prognostic biomarkers used in melanoma. PMID:25013535

  9. Primary gastric melanoma: A case report

    Institute of Scientific and Technical Information of China (English)

    Emmanuel Eustathios Lagoudianakis; Michael Genetzakis; Dimitrios Konstantinos Tsekouras; Artemisia Papadima; Georgia Kafiri; Konstantinos Toutouzas; Vaggelogiannis Katergiannakis; Andreas Manouras


    Melanoma accounts for 1-3 per cent of all malignant tumors. Except cutaneous, other less common melanomas include, among others, those in the GI tract.However, their primary or secondary nature is often difficult to establish. Referring to the stomach, scattered cases of primary melanomas have been reported in the literature.We report a case of a man with an ulcerated submucosal mass at the antrum of the stomach, manifested with dull upper abdominal pain, nausea, vomiting,fatigue and anemia. This lesion was histologically proved to be melanoma. A detailed clinical and laboratory investigation revealed no primary site elsewhere.To our knowledge, very few cases of primary gastric melanoma have been reported. Our case is the fourth ever published and the first located at the antrum of the stomach. The debate upon the primitive nature of such lesions still persists. Thus, specific diagnostic criteria have been proposed.

  10. Melanoma Surveillance in the US: Collecting Melanoma Data

    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. Suephy Chen, a dermatologist from Emory University, discusses why the articles are important, as well as the need to increase dermatologists’ awareness of cancer registries and reporting requirements.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  11. Clinical and morphological characteristics of cutaneous melanoma. (United States)

    Balaban, Jagoda; Ninković Baroš, Djuka; Grujić, Dragana; Starović, Dragana; Ćelić, Milanka


    The incidence of cutaneous melanoma has increased significantly worldwide over the last several decades. The aim of this study is to determine clinical and morphology characteristics of primary melanoma, since some of them are important prognostic factors. This retrospective study included 172 patients. The data were collected by the Consulting team for malignant skin tumors in the Banja Luka Clinical Centre from 2009 to 2011. We did not use dermoscopy as a diagnostic tool in our investigation. We determined that melanoma occurs equally commonly in both sexes, in women in the sixth decade and the seventh in men. The most common sub-type was nodular melanoma (59.5%, P<0.05), followed by superficial spreading (27.8%) and acral lentiginous melanoma (11.4%). The most common localization was on the back in men (34.3%) and on the legs in women (P<0.05). More than half of our patients (55.8%) had melanoma thickness from 1.0 to 4.0 mm, and 38% had a melanoma thicker than 4.0 mm. The average Breslow thickness is 4.6 mm. More women than men had melanoma thicker than 4 mm (P<0.05). Spread of the primary tumor localization was found in 31.4% of patients, more frequently in men than in women (P<0.05). In most cases it was abstraction of lymph nodes (P<0.05). The average thickness of the melanoma in our patients is much higher than the average in the world and the countries of Europe. The results of this study indicate a need for better unique regional registry in this part of Bosnia and Herzegovina and improvement of preventive measures in the early diagnosis of melanoma.

  12. Adoptive immunotherapy of advanced melanoma. (United States)

    Shapira-Frommer, Ronnie; Schachter, Jacob


    Adoptive cell therapy (ACT) has emerged as an effective therapy for patients with metastatic melanoma. Since the first introduction of the protocol in 1988 [1], major improvements have been achieved with response rates of 40%-72% among patients who were resistant to previous treatment lines. Both cell product and conditioning regimen are major determinants of treatment efficacy; therefore, developing ACT protocols explore diverse ways to establish autologous intra-tumoral lymphocyte cultures or peripheral effector cells as well as different lymphodepleting regimens. While a proof of feasibility and a proof of concept had been established with previous published results, ACT will need to move beyond single-center experiences, to confirmatory, multi-center studies. If ACT is to move into widespread practice, it will be necessary to develop reproducible high quality cell production methods and accepted lymphodepleting regimen. Two new drugs, ipilimumab (Yervoy, Bristol-Myers Squibb) and vemurafenib (Zelboraf, Roche), were approved in 2011 for the treatment of metastatic melanoma based on positive phase III trials. Both drugs show a clear overall survival benefit, so the timing of when to use ACT will need to be carefully thought out. In contrast to these 2 new, commercially available outpatient treatments, ACT is a personally-specified product and labor-intensive therapy that demands both acquisition of high standard laboratory procedures and close clinical inpatient monitoring during treatment. It is unique among other anti-melanoma treatments, providing the potential for a durable response following a single, self-limited treatment. This perspective drives the efforts to make this protocol accessible for more patients and to explore modifications that may optimize treatment results.

  13. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung


    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.

  14. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine. (United States)

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


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

  15. Dermoscopy on subungual melanoma 

    Directory of Open Access Journals (Sweden)

    Grażyna Kamińska-Winciorek


    Full Text Available Subungual melanoma is a rare, but one of the diagnostically most difficult variants of melanoma. Unfortunately, due to its late detection, lack of an early reaction from the patient and diagnosis in advanced stages, subungual melanoma is deemed as a prognostically unfavorable variant of this malignancy. Diagnosis of subungual melanoma is very difficult to establish merely on the basis of clinical examination due to the resemblance of subungual hematoma to melanocytic nevus, fungal or bacterial infections. Dermoscopy seems to be the ideal diagnostic tool in the differential diagnosis of this life-threatening disease. Aims. To describe the basic aspects of dermoscopy of subungual melanoma and other conditions involving the nails. Methods. Review of medical database PubMed for the literature of the last 10 years on the dermoscopic patterns of subungual melanoma and other subungual diseases. Results. We collate the fundamental rules of performing dermoscopy in subungual melanoma, as well as basic dermoscopic features and diagnostic algorithms of selected subungual lesions requiring differentiation from melanoma. Conclusions. Dermoscopy is a safe, easily repeatable diagnostic method, and the knowledge of basic dermoscopic patterns of developing melanoma in subungual localization, along with the differential diagnosis of other diseases within the nail plate, will help not only dermatologists, but also the professionals of other specialties, such as surgeons, oncologists, orthopedists, and also general practitioners.

  16. Primary retroperitoneal melanoma presented in a rare extracutaneous site for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Mohamed Alsharedi


    Full Text Available Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature.


    Directory of Open Access Journals (Sweden)

    Vishnu Prasad


    Full Text Available Oral malignant melanoma is a rare aggressive neoplasm commonly affects males and is more frequently seen at the level of the hard palate and gingiva. In many cases, melanoma has evolved from the pre-existing pigmented lesions. These neoplasms are biologically aggressive, but they often go unnoticed since they usually present merely as a hyperpigmented patch on the gingival surface. Performing biopsies of doubtful pigmented lesions helps in early treatment and better prognosis. The surgical excision combined with the chemotherapy is the treatment of choice. Here, we report a rare case of an elderly male patient with oral malignant melanoma with metastasis to vertebral column.

  18. Tea tree oil might combat melanoma. (United States)

    Bozzuto, Giuseppina; Colone, Marisa; Toccacieli, Laura; Stringaro, Annarita; Molinari, Agnese


    In this study we present new data from experiments focused on the antitumor activity of tea tree oil (TTO), an essential oil distilled from Melaleuca alternifolia. TTO proved to be capable of inhibiting the growth of melanoma cells and of overcoming multidrug resistance (MDR), as we reported in our previous study. Moreover, the survival role of the MDR-marker P-glycoprotein appears to be involved in the mechanism of invasion of melanoma cells. The results reported herein indicate that TTO and its main active component, terpinen-4-ol, can also interfere with the migration and invasion processes of drug-sensitive and drug-resistant melanoma cells.

  19. Targeting Brain Metastases in Patients with Melanoma

    Directory of Open Access Journals (Sweden)

    Dionysis Papadatos-Pastos


    Full Text Available Patients with brain metastases from malignant melanoma historically have a very poor outcome. Surgery and radiotherapy can be used, but for the majority of patients the disease will progress quickly. In the recent past, patients with brain metastases derived only minimal benefit from cytotoxic chemotherapy. Novel therapies that have been shown to be superior to chemotherapy in metastatic melanoma have made their way in clinic and data regarding their use in patients with treated or untreated brain metastases are encouraging. In this paper we describe the use of vemurafenib, dabrafenib, and ipilimumab in patients with melanoma disseminated to the brain in addition to other treatments currently in development.

  20. Dermoscopic patterns of cutaneous melanoma metastases. (United States)

    Rubegni, Pietro; Lamberti, Arianna; Mandato, Filomena; Perotti, Roberto; Fimiani, Michele


    In 2-8% of patients with melanoma, the first clinical manifestation of the disease may be skin metastasis. In these cases, differential diagnosis with the primary melanoma, benign melanocytic lesions, and other malignant and benign skin growths is particularly challenging. For this reason, the dermatologist's approach to cutaneous metastases of malignant melanoma calls for knowledge of the great morphological variety of these lesions. Dermoscopic characteristics associated with CMMMs have not yet been codified. The aim of the present review is to provide additional information about dermoscopic aspects of these skin lesions.

  1. Nivolumab-Based Treatments for Advanced Melanoma (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.

  2. Pembrolizumab for Ipilimumab-Resistant Melanoma (United States)

    KEYNOTE-002 was designed to test the safety and efficacy of two doses of pembrolizumab compared with chemotherapy in patients with ipilimumab-resistant melanoma; interim results show that pembrolizumab improves progression-free survival for these patients

  3. Pembrolizumab superior to ipilimumab in melanoma. (United States)


    In the first randomized trial to compare FDA-approved immune checkpoint inhibitors as first-line therapy for patients with advanced melanoma, pembrolizumab yielded significantly better treatment outcomes than ipilimumab.

  4. Updates in Therapy for Advanced Melanoma. (United States)

    Singh, Bhavana P; Salama, April K S


    Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5-10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

  5. The State of Melanoma: Challenges and Opportunities (United States)

    Merlino, Glenn; Herlyn, Meenhard; Fisher, David E.; Bastian, Boris C.; Flaherty, Keith T.; Davies, Michael A.; Wargo, Jennifer A.; Curiel-Lewandrowski, Clara; Weber, Michael J.; Leachman, Sancy A.; Soengas, Maria S.; McMahon, Martin; Harbour, J. William; Swetter, Susan M.; Aplin, Andrew E.; Atkins, Michael B.; Bosenberg, Marcus W.; Dummer, Reinhard; Gershenwald, Jeff; Halpern, Allan C.; Herlyn, Dorothee; Karakousis, Giorgos C.; Kirkwood, John M.; Krauthammer, Michael; Lo, Roger S.; Long, Georgina V.; McArthur, Grant; Ribas, Antoni; Schuchter, Lynn; Sosman, Jeffrey A.; Smalley, Keiran S.; Steeg, Patricia; Thomas, Nancy E.; Tsao, Hensin; Tueting, Thomas; Weeraratna, Ashani; Xu, George; Lomax, Randy; Martin, Alison; Silverstein, Steve; Turnham, Tim; Ronai, Ze’ev A.


    The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas—diagnosis/early detection, prevention, tumor cell dormancy (including metastasis) and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts per the current status, challenges and opportunities in the four respective areas. The current state and immediate and long-term needs of the melanoma field, from basic research to clinical management, are presented in the following report. PMID:27087480

  6. [Molecular alterations in melanoma and targeted therapies]. (United States)

    Mourah, Samia; Lebbé, Céleste


    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology.

  7. TERT promoter mutations in melanoma survival. (United States)

    Nagore, Eduardo; Heidenreich, Barbara; Rachakonda, Sívaramakrishna; Garcia-Casado, Zaida; Requena, Celia; Soriano, Virtudes; Frank, Christoph; Traves, Victor; Quecedo, Esther; Sanjuan-Gimenez, Josefa; Hemminki, Kari; Landi, Maria Teresa; Kumar, Rajiv


    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter.

  8. Synchronous melanomas arising within nevus spilus* (United States)

    de Brito, Maria Helena Toda Sanches; Dionísio, Cecília Silva Nunes de Moura; Fernandes, Cândida Margarida Branco Martins; Ferreira, Joana Cintia Monteiro; Rosa, Maria Joaninha Madalena de Palma Mendonça da Costa; Garcia, Maria Manuela Antunes Pecegueiro da Silva


    Nevus spilus is a melanocytic cutaneous lesion consisting of a light brown background macule with numerous superimposed darker maculopapular speckles. Melanoma arising from a nevus spilus is rare, with less than 40 cases reported to date. The absolute risk for malignant transformation is not well defined, lacking a standardized management approach. We report a new case of melanoma arising from nevus spilus, with the additional peculiarity of multifocality. We offer our recommendations for the management of the condition. PMID:28225967

  9. A Case of Melanoma Associated Leukoderma

    Directory of Open Access Journals (Sweden)

    Özer Arıcan


    Full Text Available Melanoma associated leukoderma is a rare disease characterized by hypopigmented or depigmented macules, which are usualy localized at distant sites from the primary malignant melonoma. Immunologic response to abnormal melanocytes is thought to be responsible for the physiopathology of the disease. A 34-year- old male patient with a facially localized melanoma associated leukoderma is presented and the clinical features, pathogenesis, differential diagnosis, treatment and follow-up of the disease are discussed with the recent literature.

  10. Ipilimumab til behandling af metastaserende melanoma

    DEFF Research Database (Denmark)

    Ghasemi, Habib; Schmidt, Henrik; Stolle, Lars Bjørn


    Until recently metastatic melanoma was a disease with limited treatment options and a poor prognosis. However, new promising products have been developed. Ipilimumab, a full human anti-cytotoxic T-lymphocyte antigen-4 antibody, has shown improved survival in several clinical trials and is now...... a part of the standard treatment options for this disease in Denmark. In this case report we present a 78-year-old man with metastatic melanoma who had complete remission after treatment with ipilimumab....

  11. Novel anti-melanoma treatment:focus on immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Meng-Ze Hao; Wen-Ya Zhou; Xiao-Ling Du; Ke-Xin Chen; Guo-Wen Wang; Yun Yang; Ji-Long Yang


    Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

  12. Spitzoid Melanoma: A Ten Year-Old Boy

    Directory of Open Access Journals (Sweden)

    Işıl Kılınç Karaarslan


    Full Text Available Spitzoid melanoma is a rare variant of melanoma, in which the clinical and histopathologic diagnoses are difficult. Data on the features of Spitzoid melanoma in children is limited in the literature, since melanoma is rarely seen in childhood. Here, we report a 10 year-old child with a Spitzoid melanoma. By the means of this case, it has been emphasized that melanoma should be considered in the differential diagnosis of vascular lesions even seen in childhood, unless the clinical and dermoscopic features are characteristic for an entity. (Journal of Current Pediatrics 2008; 6: 127-9

  13. Thigmotropism of Malignant Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Pascale Quatresooz


    Full Text Available During malignant melanoma (MM progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape. These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called “accretive” growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread.

  14. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna


    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.

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


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

  16. Melanoma (United States)

    ... a type of cancer that begins in the melanocytes. Melanocytes are skin cells that produce melanin, the pigment that gives skin its color. Melanocytes commonly cluster together to form skin growths called ...

  17. Melanoma (United States)

    ... partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

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


    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.

  19. Current guidelines in melanoma treatment. Melanoma Working Group of Gent and Bordet. (United States)

    Brochez, L; Verhaeghe, E; Sales, F; Del Marmol, V; Deraemaecker, R; Vossaert, K; Naeyaert, J M


    This article focuses on the actual management of cutaneous melanoma, dealing both with established, internationally well-accepted standard procedures and interventions which are still being investigated. It wants to offer a global picture to the dermatologist of what is currently available in the therapeutic arsenal against melanoma.

  20. Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome. (United States)

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


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

  1. [ Spectrum of oncogene mutations is different in melanoma subtypes]. (United States)

    Mazurenko, N N; Tsyganova, I V; Lushnikova, A A; Ponkratova, D A; Anurova, O A; Cheremushkin, E A; Mikhailova, I N; Demidov, L V


    Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.

  2. AC-93253 triggers the downregulation of melanoma progression markers and the inhibition of melanoma cell proliferation. (United States)

    Karwaciak, Iwona; Gorzkiewicz, Michal; Ryba, Katarzyna; Dastych, Jaroslaw; Pulaski, Lukasz; Ratajewski, Marcin


    A major challenge in anti-melanoma therapy is to develop treatments that are effective for advanced melanoma patients. Unfortunately, the currently used regimens are not efficient and have unsatisfactory effects on disease progression, thus increasing the pressure to develop new, profitable drugs and to identify new molecular targets. Here, we show for the first time that AC-93253, a SIRT2 inhibitor, exerts a negative effect on the expression of a set of genes involved in the progression and chemoresistance (e.g., oncogenes, apoptosis-related genes, ABC transporter genes, and cell cycle control genes) of melanoma cells. Furthermore, melanoma cells exposed to AC-93253 and doxorubicin displayed altered biological responses, including apoptosis and proliferation, compared to cells exposed to single treatments. Taken together, we conclude that the usage of AC-93253 in combined therapy could be a promising strategy for melanoma patients.

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

    Directory of Open Access Journals (Sweden)

    Goldenberg A


    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

  4. Genome-Wide Scan Reveals Mutation Associated with Melanoma (United States)

    ... historical) Genome-Wide Scan Reveals Mutation Associated with Melanoma A team of international researchers supported by the ... when they divide and grow uncontrollably, develop into melanoma. Also, MITF activity is known to be amplified ...

  5. Common Moles, Atypical Moles (Dysplastic Nevi), and Risk of Melanoma (United States)

    ... Research Common Moles, Dysplastic Nevi, and Risk of Melanoma On This Page What is a common mole? ... slightly scaly, or rough, irregular, and pebbly appearance. Melanoma Is it cancer? Yes. How many people have ...

  6. Some Melanoma Survivors Still Seek Out the Sun (United States)

    ... Some Melanoma Survivors Still Seek Out the Sun 1 in ... Even after surviving the potentially deadly skin cancer melanoma, some people continue to go out in the ...

  7. What's New in Research and Treatment of Melanoma Skin Cancer? (United States)

    ... starts them on a path to becoming melanoma cells many years later. Some doctors think this might help explain why melanomas often occur on the thighs (in women) and trunk (in men), areas that generally aren’t exposed ...

  8. Functional Implication of Netrin Expression in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Simone Kaufmann


    Full Text Available Background: Malignant melanoma cells are known to have altered expression of genes supporting proliferation and invasion, however, the expression of molecules of the Netrin family of repellent factors has not been analyzed in melanomas until now.

  9. Melanoma Rates Rise in Some States, Fall in Others (United States)

    ... page: Melanoma Rates Rise in Some States, Fall in Others ... THURSDAY, Dec. 29, 2016 (HealthDay News) -- Rates of melanoma cases and deaths are either rising or falling, ...

  10. U.S. Melanoma Rate Is Rising, Study Finds (United States)

    ... U.S. Melanoma Rate Is Rising, Study Finds 1 in every ... developing the potentially deadly skin cancer known as melanoma than in the past, new research shows. In ...

  11. Screening for metastatic malignant melanoma of the uvea revisited

    DEFF Research Database (Denmark)

    Eskelin, Sebastian; Pyrhönen, Seppo; Summanen, Paula


    ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases......ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases...

  12. Subretinal lipid exudation associated with untreated choroidal melanoma

    Directory of Open Access Journals (Sweden)

    C K Minija


    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.

  13. Metastatic Malignant Melanoma Presenting as an Appendiceal Mucocele

    Directory of Open Access Journals (Sweden)

    A. A. Alduaij


    Full Text Available Melanoma metastatic to the appendix is extremely rare. Here we describe a case of a 31-year-old female from Bolivia with a remote history of metastatic malignant melanoma first diagnosed as a cutaneous malignant melanoma ten years prior to this presentation. The patient was being followed for a mucocele which on resection was found to be metastatic melanoma. “Mucocele” is a generic diagnosis that warrants further characterization and treatment.

  14. Hormonal exposures and the risk of uveal melanoma

    DEFF Research Database (Denmark)

    Behrens, Thomas Flensted; Kaerlev, Linda; Cree, Ian


    Several studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma. Therefore, the association between the risk of uveal melanoma and exposure to hormonal exposures was investigated in a case-control study from nine European countries.......Several studies suggest that hormonal mechanisms may be associated with the development of uveal melanoma. Therefore, the association between the risk of uveal melanoma and exposure to hormonal exposures was investigated in a case-control study from nine European countries....


    Directory of Open Access Journals (Sweden)



    Full Text Available Primary mucosal malignant melanomas of sinonasal tract are uncommon tumors comprising 0.3-2% of all malignant melanomas and 4% of all head and Neck melanomas. We are reporting a rare case of mucosal malignant melanoma in a 45 year old female arising from nasopharynx which was excised completely by trans palatal approach followed by irradiation. This case is being reported because of its isolated involvement of nasopharynx, and early age of presentation.

  16. Jejuno-jejunal invagination due to intestinal melanoma

    Institute of Scientific and Technical Information of China (English)

    Giuseppe Resta; Gianfranco Azzena; Savino Occhionorelli; Gabriele Anania; Federico Messina; Damiano de Tullio; Gloria Ferrocci; Federico Zanzi; Davide Pellegrini; Rocco Stano; Giorgio Cavallesco


    Cutaneous melanoma is one of the most studied neoplastic lesions in biology and clinical oncology. It has been well documented that this type of neoplasm presents a high metastatic rate, and is able to involve nearly every tissue. Non-cutaneous melanoma represents an unusual pattern of melanoma, and the small intestine is an uncommon anatomic localization. Herein we report an extremely rare clinical case of a young woman affected by a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination.

  17. Dermoscopy of Scalp Melanoma: Report of Three Cases

    Directory of Open Access Journals (Sweden)

    Antonella Tosti


    Full Text Available Scalp melanoma is rare and often late-discovered because of its unusual position. As a consequence, its prognosis is poorer than melanoma on other body sites and only few clinical reports about its dermoscopic pattern have been published. In this paper, we report three clinical cases of scalp melanoma with photographic documentation and dermoscopic images, in order to improve the early detection of scalp melanoma.

  18. Cytotoxic T lymphocyte responses against melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Schwartz Erich J


    Full Text Available Abstract Background Vitiligo is a common toxicity associated with immunotherapy for melanoma. Cytotoxic T lymphocytes (CTLs against melanoma commonly target melanoma-associated antigens (MAAs which are also expressed by melanocytes. To uncouple vitiligo from melanoma destruction, it is important to understand if CTLs can respond against melanoma and melanocytes at different levels. Methods To understand the dichotomous role of MAA-specific CTL, we characterized the functional reactivities of established CTL clones directed to MAAs against melanoma and melanocyte cell lines. Results CTL clones generated from melanoma patients were capable of eliciting MHC-restricted, MAA-specific lysis against melanocyte cell lines as well as melanoma cells. Among the tested HLA-A*0201-restricted CTL clones, melanocytes evoked equal to slightly higher degranulation and cytolytic responses as compared to melanoma cells. Moreover, MAA-specific T cells from vaccinated patients responded directly ex vivo to melanoma and melanocytes. Melanoma cells express slightly higher levels of MART-1 and gp100 than melanocytes as measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR and immunohistochemistry. Conclusions Our data suggest that CTLs respond to melanoma and melanocytes equally in vitro and directly ex vivo.

  19. Multiple primary melanoma in a Thai male: a case report. (United States)

    Payapvipapong, Kittisak; Kanechorn-Na-Ayuthaya, Pinyapat


    Melanoma is a malignant tumor of melanocytes and the most threatening skin cancer documenting one of the highest in mortality rates in comparison to other non-skin cancers due to its potential to metastasize. Although the global incidence of melanoma has increased, the melanoma-related deaths decreased owing to the fact that melanoma is curable under the condition that early diagnosis is made and treatment is undertaken as soon as possible. Patients with primary melanoma developing a second primary melanoma are less common compared to the generalpopulation developing the first. Not only is melanoma less commonly found in Thaipatients but multiple primary melanomas (MPM) are rarely reported. The present report of a 48-year-old Thai male who presented with asymptomatic black patch on the right big toe nail and an atypical mole on the back, both ofwhich were histologically confirmed melanomas. Treatment included amputation of the right big toe and wide excision of melanoma on the back, which cleared the malignancy without recurrence until present. Although MPM are rare in Thais, the authors should be alert in cases displaying multiple moles for the possibility of melanomas. The total body examination, early diagnosis and regular follow-up are important to decrease the mortality rate in melanoma patient.

  20. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Biggs, M.W.; Eiselein, J.E.


    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.

  1. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Douglas Grossman


    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.

  2. [Molecular and immunohistochemical diagnostics in melanoma]. (United States)

    Schilling, B; Griewank, K G


    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. (Neo)adjuvant systemic therapy for melanoma. (United States)

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M


    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  4. Melanocyte and Melanoma Cell Activation by Calprotectin

    Directory of Open Access Journals (Sweden)

    Stephanie H. Shirley


    Full Text Available Calprotectin, a heterodimer of S100A8 and S100A9, is a proinflammatory cytokine released from ultraviolet radiation-exposed keratinocytes. Calprotectin binds to Toll-like receptor 4, the receptor for advanced glycation end-products, and extracellular matrix metalloproteinase inducer on target cells to stimulate migration. Melanocytes and melanoma cells produce little if any calprotectin, but they do express receptors for the cytokine. Thus, keratinocyte-derived calprotectin has the potential to activate melanocytes and melanoma cells within the epidermis in a paracrine manner. We examined the ability of calprotectin to stimulate proliferation and migration in normal human melanocytes and melanoma cells in vitro. We first showed, by immunofluorescence and quantitative RT-PCR, that the melanocytic cells employed expressed a calprotectin receptor, the receptor for advanced end-products. We then demonstrated that calprotectin significantly enhanced proliferation, migration, and Matrigel invasion in both normal human melanocytes and melanoma cells. Thus, calprotectin is one of the numerous paracrine factors released by ultraviolet radiation-exposed keratinocytes that may promote melanomagenesis and is a potential target for melanoma prevention or therapy.

  5. Autophagy- An emerging target for melanoma therapy (United States)

    Ndoye, Abibatou; Weeraratna, Ashani T.


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

  6. Ras, Raf, and MAP kinase in melanoma. (United States)

    Solus, Jason F; Kraft, Stefan


    A growing understanding of the biology and molecular mechanisms of melanoma has led to the identification of a number of driver mutations for this aggressive tumor. The most common mutations affect signaling of the Ras/Raf/MAPK (mitogen-activated protein kinase) pathway. This review will focus on mutations in genes encoding proteins that play a role in the MAPK pathway and that have been implicated in melanoma biology, such as BRAF, NRAS, and MEK (MAPK kinase), and detail the current understanding of their role in melanoma progression from a molecular biology perspective. Furthermore, this review will also consider some additional mutations in genes such as KIT, GNAQ, and GNA11, which can be seen in certain subtypes of melanoma and whose gene products interact with the MAPK pathway. In addition, the association of these molecular changes with clinical and classical histopathologic characteristics of melanoma will be outlined and their role in diagnosis of melanocytic lesions discussed. Finally, a basic overview of the current targeted therapy landscape, as far as relevant to the pathologist, will be provided.

  7. Vemurafenib for the treatment of melanoma.

    LENUS (Irish Health Repository)

    Jordan, Emmet John


    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.

  8. Frequent MAGE mutations in human melanoma.

    Directory of Open Access Journals (Sweden)

    Otavia L Caballero

    Full Text Available BACKGROUND: Cancer/testis (CT genes are expressed only in the germ line and certain tumors and are most frequently located on the X-chromosome (the CT-X genes. Amongst the best studied CT-X genes are those encoding several MAGE protein families. The function of MAGE proteins is not well understood, but several have been shown to potentially influence the tumorigenic phenotype. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a mutational analysis of coding regions of four CT-X MAGE genes, MAGEA1, MAGEA4, MAGEC1, MAGEC2 and the ubiquitously expressed MAGEE1 in human melanoma samples. We first examined cell lines established from tumors and matching blood samples from 27 melanoma patients. We found that melanoma cell lines from 37% of patients contained at least one mutated MAGE gene. The frequency of mutations in the coding regions of individual MAGE genes varied from 3.7% for MAGEA1 and MAGEA4 to 14.8% for MAGEC2. We also examined 111 fresh melanoma samples collected from 86 patients. In this case, samples from 32% of the patients exhibited mutations in one or more MAGE genes with the frequency of mutations in individual MAGE genes ranging from 6% in MAGEA1 to 16% in MAGEC1. SIGNIFICANCE: These results demonstrate for the first time that the MAGE gene family is frequently mutated in melanoma.

  9. 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


    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...

  10. Report from the Melanoma Independent Board First Melanoma MIB Conference, 21-22 October 2013. (United States)

    Testori, A; Ascierto, P; Chiarion Sileni, V; De Lorenzo, F; Pelicci, Pg; Rossi, Cr


    The Melanoma Independent Board (MIB) held its first conference from 21 to 22 October, 2013, in Rome, Italy. Like the MIB itself, the conference brought together specialists from all aspects of cancer care: doctors, patient associations, journalists, and representatives from local government, hospitals, and pharma to encourage an interdisciplinary discussion on the future of melanoma. It was hoped that the conference would be an opportunity for all participants to see and understand each other's points of view. In memoriam of melanoma pioneer Natalie Cascinelli, the conference focussed on innovation and sustainability as well as the latest drug developments.

  11. Role of nuclear medicine in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands)


    Melanoma is a malignant tumour of the melanocytes presenting characteristic metabolic and biological features, which remains a difficult and important issue in oncology. As a functional modality, nuclear medicine offers a variety of possibilities to assist in the clinical management of this disease. A brief survey of currently available techniques is presented for the diagnosis, staging and follow up, either by organ imaging or by using a great spectrum of tumour-seeking radiopharmaceuticals. The role of lymphoscintigraphy in melanoma is emphasized, as well as the supportive role of nuclear medicine in the surgical theater, enabling selective lymph node dissection by the sentinel node procedure and high dose regional chemotherapy by isolated limb perfusion. Although hardly used for metastatic melanoma so far, with all its tumour-seeking approaches nuclear medicine holds a therapeutic potential for this disease as well. (orig.) With 4 figs., 2 tabs., 47 refs.

  12. Pembrolizumab for the treatment of melanoma. (United States)

    Kumar, Sanjeev Srinivas; McNeil, Catriona Mairi


    The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. In particular, blockade of programmed cell death protein 1 (PD-1) in advanced melanoma has proven to be a most promising new anticancer strategy. Pembrolizumab is a humanized IgG4 anti-PD-1 antibody that exerts its anti-tumor effect through blocking the interaction of the immune inhibitory molecule PD-1 with its ligands. Its effect has been most convincingly demonstrated in the setting of advanced melanoma, with growing evidence of clinical responses across a broad spectrum of other solid and hematological malignancies.

  13. Orbital melanoma with calcification: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Sukhdeep Bains


    Full Text Available Primary orbital melanoma is rare and has varied initial presentation. A 28-year-old female presented with proptosis and decreased vision in the left eye. Computed tomography scan showed an orbital mass with contrast enhancement and calcification around the optic nerve leading to a diagnosis of meningioma. The patient chose to be on observation. Loss of vision with an increase in proptosis was seen at 6 months follow-up. On surgical exploration, a well-defined pigmented mass was seen encasing the optic nerve. Histopathological analysis revealed a malignant melanoma. Metastatic workup was negative. Left eye lid sparing exenteration was done. A high index of suspicion is necessary in a rapidly growing suspected optic nerve sheath meningioma and a differential diagnosis including orbital melanoma be considered.

  14. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller


    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.

  15. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Beebe, Stephen J., E-mail:; Schoenbach, Karl H.; Heller, Richard [Frank Reidy Research Center for Bioelectrics/Old Dominion University 4211 Monarch Way, Suite 300, Norfolk, Virginia 23508 (United States)


    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.

  16. Melanoma metastasis to the spleen: Laparoscopic approach

    Directory of Open Access Journals (Sweden)

    Trindade Manoel Roberto


    Full Text Available We report a case of minimally invasive surgery in the management of metastasis to the spleen. A 67-year-old male patient with possible splenic soft tissue melanoma metastasis was referred to our hospital. He had a history of an excised soft tissue melanoma from his back eight months earlier, and the control abdominal computer tomography (CT scan revealed a hypodense spleen lesion. The patient underwent laparoscopic surgery to diagnose and treat the splenic lesion. The splenectomy was performed and the histological examination revealed a melanoma. The patient had a good postoperative course and was discharged on the second postoperative day. On his 12-month follow-up there was no sign of recurrence. The laparoscopic approach is a safe and effective alternative for treatment of splenic metastases.

  17. Melanoma metastasis to the spleen: Laparoscopic approach (United States)

    Trindade, Manoel Roberto Maciel; Blaya, Rodrigo; Trindade, Eduardo Neubarth


    We report a case of minimally invasive surgery in the management of metastasis to the spleen. A 67-year-old male patient with possible splenic soft tissue melanoma metastasis was referred to our hospital. He had a history of an excised soft tissue melanoma from his back eight months earlier, and the control abdominal computer tomography (CT) scan revealed a hypodense spleen lesion. The patient underwent laparoscopic surgery to diagnose and treat the splenic lesion. The splenectomy was performed and the histological examination revealed a melanoma. The patient had a good postoperative course and was discharged on the second postoperative day. On his 12-month follow-up there was no sign of recurrence. The laparoscopic approach is a safe and effective alternative for treatment of splenic metastases. PMID:19547681

  18. Genetic Testing in the Multidisciplinary Management of Melanoma. (United States)

    Rashid, Omar M; Zager, Jonathan S


    Melanoma is increasing in incidence and represents an aggressive type of cancer. Efforts have focused on identifying genetic factors in melanoma carcinogenesis to guide prevention, screening, early detection, and targeted therapy. This article reviews the hereditary risk factors associated with melanoma and the known molecular pathways and genetic mutations associated with this disease. This article also explores the controversies associated with genetic testing and the latest advances in identifying genetic targets in melanoma, which offer promise for future application in the multidisciplinary management of melanoma.

  19. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan


    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.

  20. Braf V600E mutation in melanoma: translational current scenario. (United States)

    Guadarrama-Orozco, J A; Ortega-Gómez, A; Ruiz-García, E B; Astudillo-de la Vega, H; Meneses-García, A; Lopez-Camarillo, C


    Melanoma was one of the translational cancer examples in clinic, including target therapy related to specific biomarkers impacting in the outcome of melanoma patients. Melanomagenesis involved a wide variety of mutations during his evolution; many of these mutated proteins have a kinase activity. One of the most cited proteins in melanoma is BRAF (about 50-60 % of melanomas harbors activating BRAF mutations), for these the most common is a substitution of valine to glutamic acid at codon 600 (p.V600E). Therefore, the precise identification of this underlying somatic mutation is essential; knowing the translational implications has opened a wide view of melanoma biology and therapy.

  1. Melanoma biomolecules: independently identified but functionally intertwined

    Directory of Open Access Journals (Sweden)

    Danielle Erin Dye


    Full Text Available The majority of patients diagnosed with melanoma present with thin lesions and generally these patients have a good prognosis. However, 5% of patients with early melanoma (< 1mm thick will have recurrence and die within 10 years, despite no evidence of local or metastatic spread at the time of diagnosis. Thus, there is a need for additional prognostic markers to help identify those patients that may be at risk of recurrent disease. Many studies and several meta-analyses have compared gene and protein expression in melanocytes, naevi, primary and metastatic melanoma in an attempt to find informative prognostic markers for these patients. However, although a large number of putative biomarkers have been described, few of these molecules are informative when used in isolation. The best approach is likely to involve a combination of molecules. We believe one approach could be to analyze the expression of a group of interacting proteins that regulate different aspects of the metastatic pathway. This is because a primary lesion expressing proteins involved in multiple stages of metastasis may be more likely to lead to secondary disease than one that does not. This review focuses on five putative biomarkers - melanoma cell adhesion molecule (MCAM, galectin-3 (gal-3, matrix metalloproteinase 2 (MMP-2, chondroitin sulfate proteoglycan 4 (CSPG4 and paired box 3 (PAX3. The goal is to provide context around what is known about the contribution of these biomarkers to melanoma biology and metastasis. Although each of these molecules have been independently identified as likely biomarkers, it is clear from our analyses that each are closely linked with each other, with intertwined roles in melanoma biology.

  2. Metastatic melanoma and vemurafenib: novel approaches

    Directory of Open Access Journals (Sweden)

    Ramon Andrade De Mello


    Full Text Available Metastatic melanoma (MM presents a treatment challenge to oncologists worldwide. Dacarbazine is the first line chemotherapy treatment for MM, though the overall response rates are very poor. Recently, the v-raf murine sarcoma viral oncogene homolog B1 (BRAF V600 mutation was found to play a main role in MM. This mutation is present in 40-60% of melanoma patients. Vemurafenib is a BRAF kinase inhibitor that showed impressive results in phase I-III trials and was thus recently approved for the treatment of MM. This paper will briefly focus on vemurafenib in the treatment of MM and highlight concerns.

  3. [Diagnostic Approaches to Suspected Choroidal Melanoma]. (United States)

    Girbardt, C; Rehak, M; Wiedemann, P


    Whenever funduscopy reveals possible choroidal melanoma, all available information must be gathered to either confirm or exclude the diagnosis. Well-defined funduscopic criteria are available, which can already lead to a high degree of diagnostic certainty. Additional technical examinations can be used to exclude possible differential diagnoses. In cases where no clear diagnosis can be established, it is possible to take a biopsy or to watch and wait in order to observe possible growth. Whenever the diagnosis of a choroidal melanoma is established, cancer staging has to be performed in order to search for possible metastases.

  4. Anorectal melanoma: report of two cases. (United States)

    Remigio, P A; Der, B K; Forsberg, R T


    We have described the clinicopathologic findings in two cases of anorectal melanoma, and extracted the salient features from the medical literature. The disease is rare. Melanoma arises from the anal squamous membrane and very often spreads upward through submucosal planes, producing secondary satelites in the rectum. Trauma from defecation, vast lymphatic and venous systems in the anorectal region, and high invasiveness of the tumor cells eviden;ly account for early distant metastases. Histologically, the neoplastic cells often mimic other cancers. Treatment is surgical, with dismal end results.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Bhavana Doshi


    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.

  7. Isolation and Molecular Characterization of Circulating Melanoma Cells

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    Xi Luo


    Full Text Available Melanoma is an invasive malignancy with a high frequency of blood-borne metastases, but circulating tumor cells (CTCs have not been readily isolated. We adapted microfluidic CTC capture to a tamoxifen-driven B-RAF/PTEN mouse melanoma model. CTCs were detected in all tumor-bearing mice and rapidly declined after B-RAF inhibitor treatment. CTCs were shed early from localized tumors, and a short course of B-RAF inhibition following surgical resection was sufficient to dramatically suppress distant metastases. The large number of CTCs in melanoma-bearing mice enabled a comparison of RNA-sequencing profiles with matched primary tumors. A mouse melanoma CTC-derived signature correlated with invasiveness and cellular motility in human melanoma. CTCs were detected in smaller numbers in patients with metastatic melanoma and declined with successful B-RAF-targeted therapy. Together, the capture and molecular characterization of CTCs provide insight into the hematogenous spread of melanoma.

  8. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

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


    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...... melanoma is a potentially fatal disease. Surgical excision is the primary treatment of choice for malignant melanoma. Clinicians need to be aware of the possible malignant transformation in children with congenital melanocytic nevus because early diagnosis and treatment improves prognosis. The suspicion...... 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...

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

    DEFF Research Database (Denmark)

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


    . CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity...

  10. Melanomas of unknown primary have a mutation profile consistent with cutaneous sun-exposed melanoma. (United States)

    Dutton-Regester, Ken; Kakavand, Hojabr; Aoude, Lauren G; Stark, Mitchell S; Gartside, Michael G; Johansson, Peter; O'Connor, Linda; Lanagan, Cathy; Tembe, Varsha; Pupo, Gulietta M; Haydu, Lauren E; Schmidt, Christopher W; Mann, Graham J; Thompson, John F; Scolyer, Richard A; Hayward, Nicholas K


    Melanoma of unknown primary (MUP) is an uncommon phenomenon whereby patients present with metastatic disease without an evident primary site. To determine their likely site of origin, we combined exome sequencing from 33 MUPs to assess the total rate of somatic mutations and degree of UV mutagenesis. An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11. Results showed that the majority of MUPs exhibited high somatic mutation rates, high ratios of C>T/G>A transitions, and a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas. These data suggest that a significant proportion of MUPs arise from regressed or unrecognized primary cutaneous melanomas or arise de novo in lymph nodes from nevus cells that have migrated from the skin.

  11. Pathogenesis, diagnosis and management of primary melanoma of the colon

    Directory of Open Access Journals (Sweden)

    Imam Ayesha


    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

  12. Amuvatinib has cytotoxic effects against NRAS-mutant melanoma but not BRAF-mutant melanoma. (United States)

    Fedorenko, Inna V; Fang, Bin; Koomen, John M; Gibney, Geoffrey T; Smalley, Keiran S M


    Effective targeted therapy strategies are still lacking for the 15-20% of melanoma patients whose melanomas are driven by oncogenic NRAS. Here, we report on the NRAS-specific behavior of amuvatinib, a kinase inhibitor with activity against c-KIT, Axl, PDGFRα, and Rad51. An analysis of BRAF-mutant and NRAS-mutant melanoma cell lines showed the NRAS-mutant cohort to be enriched for targets of amuvatinib, including Axl, c-KIT, and the Axl ligand Gas6. Increasing concentrations of amuvatinib selectively inhibited the growth of NRAS-mutant, but not BRAF-mutant melanoma cell lines, an effect associated with induction of S-phase and G2/M-phase cell cycle arrest and induction of apoptosis. Mechanistically, amuvatinib was noted to either inhibit Axl, AKT, and MAPK signaling or Axl and AKT signaling and to induce a DNA damage response. In three-dimensional cell culture experiments, amuvatinib was cytotoxic against NRAS-mutant melanoma cell lines. Thus, we show for the first time that amuvatinib has proapoptotic activity against melanoma cell lines, with selectivity observed for those harboring oncogenic NRAS.

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

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hay


    Full Text Available 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.

  14. Melanoma cutáneo asociado a nevo previo Cutaneous melanoma associated with previous nevus

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    María P. Gutiérrez


    Full Text Available El melanoma maligno es una neoplasia originada en los melanocitos de la piel y otras localizaciones. No existe información en nuestro país acerca de su incidencia y prevalecencia, sí se sabe cuáles son los factores de riesgo más importantes. El melanoma puede originarse de novo o a partir de lesiones melanocíticas previas. La noción de que un nevo melanocítico pueda servir como lesión precursora es sustentada por evidencias clínicas e histológicas. Realizamos en el Hospital Privado de Córdoba un estudio observacional, retrospectivo y analítico. El objetivo de este trabajo fue conocer cuál es la frecuencia de asociación de melanomas malignos que se desarrollan sobre nevos previos. Fueron analizados un total de 134 melanomas. En 32 pacientes (24%, los melanomas estuvieron histológicamente asociados con nevos, con espesores de Breslow mayores de 1 mm el porcentaje de asociación fue de 16.3%, y con Breslow menores de 1 mm, 38.1%. Al evaluar los melanomas en relación a la clasificación de Breslow y Clark, se objetivó que el grupo de melanomas asociados a nevos presentó un espesor de Breslow y niveles de Clark bajos y en el análisis estadístico fueron predictores significativos en la probabilidad de hallar esta asociación (p The malignant melanoma is a neoplasia originated from the melanocytes located in the skin and other locations. Even though there is not information regarding its incidence and prevalence in our country, its most important risk factors are known. The melanoma can originate de novo or from previous melanocytic lesions. The concept that a melanocytic nevus can serve as a precursor lesion is supported by clinical and histological evidence. An observational, retrospective and analytical study was carried out in the Hospital Privado de Córdoba. The objective was to determine which is the frequency of association of malignant melanomas that develop on previous nevus. A total of 134 melanomas were analyzed. In 32

  15. Malignant melanoma revealed by testicular metastasi.

    Directory of Open Access Journals (Sweden)

    Marie Dusaud


    Due to rapid disease progression and high mortality rate within a short interval, a complete staging looking for other secondary locations must be done and a multidisciplinary care and palliative involvement must also be initiated in the context of metastatic melanoma.

  16. Dabrafenib Plus Trametinib for Advanced Melanoma (United States)

    A summary of results from two phase III trials show that patients with metastatic melanoma whose tumors have specific mutations in the BRAF gene lived longer following treatment with dabrafenib (Tafinlar®), a BRAF inhibitor, plus trametinib (Mekinist®), a

  17. Testing Adjuvant Ipilimumab in Advanced Melanoma (United States)

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

  18. Choroidal melanoma clinically simulating a retinal angioma

    Energy Technology Data Exchange (ETDEWEB)

    Shields, J.A.; Joffe, L.; Guibor, P.


    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  19. Choroidal melanoma clinically simulating a retinal angioma. (United States)

    Shields, J A; Joffe, L; Guibor, P


    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  20. The biology of melanoma prognostic factors.

    NARCIS (Netherlands)

    Spatz, A.; Stock, N.; Batist, G.; Kempen, L.C.L.T. van


    Cutaneous melanoma still represents a paradox among all solid tumors. It is the cancer for which the best prognostic markers ever identified in solid tumors are available, yet there is very little understanding of their biological significance. This review focuses on recent biological data that shed

  1. Giant melanoma of the left thumb

    NARCIS (Netherlands)

    Zeebregts, CJAM; Schraffordt Koops, H.


    A 74-year-old female patient is described with a giant melanoma of the left thenar and concomitant bilateral pulmonary metastases. Palliative treatment consisted of a two-staged procedure in order to save the limb from amputation. Firstly, perfusion with gamma-interferon, tumour necrosis factor-alph

  2. Immunotherapy of melanoma : toward clinical application

    NARCIS (Netherlands)

    Jorritsma-Smit, Annelies


    This thesis describes different immunotherapeutic strategies that can be used for the treatment of cancer in general, and of melanoma in particular. Tumor-specific T cell responses can be induced via either active or passive immunization. Active immunization can be used to target tumors for which hi

  3. Gender Differences in Melanoma Progression and Survival

    NARCIS (Netherlands)

    A. Joosse (Arjen)


    markdownabstract__Abstract__ Cutaneous melanoma is developing into a major public health problem worldwide. Incidence differs greatly across the world with high incidence rates in the Unites states, Europe and especially in Australia and New Zealand, but relatively low incidence rates in Central an


    Directory of Open Access Journals (Sweden)

    Detanac Dženana A


    Full Text Available There has been significant progress made in the diagnosis and treatment of the primary uveal melanoma during the past decades and despite that, survival rate of uveal melanoma patients is still stable. Treatment options for uveal melanoma include phototherapy, brachytherapy, proton beam therapy, stereotactic radiotherapy, local resection, anti-angiogenic therapy, immunotherapy, and enucleation. Genetic analysis of tumors provides us with valuable prognostic information although effective therapies are lacking at this moment. It is not established yet whether prolonged survival is the result of treatment or whether it merely reflects earlier detection of metastases. Also, there are indications that survival after treatment of uveal melanoma probably does not depend on the method of treatment but rather on many clinical, histological and genetic risk factors. New studies are needed to provide a better understanding of of ocular treatment impact on survival in patients whose prognosis can be estimated according to the clinical stage, histological grade and genetic type. Therefore, the patients should be treated in experienced multi-disciplinary teams that must include these patients in clinical trial.

  5. [Cutaneous malignant melanoma and the new drugs]. (United States)

    Nieweg, Omgo E; Gallegos-Hernández, José Francisco


    The treatment of cutaneous melanoma has historically been essentially surgical. Much progress has been made in this area, and the resection margins have been established based on tumour depth. Candidates are also identified for lymphadenectomy, avoiding the morbidity of the procedure in patients who do not require it. But little progress has been made in systemic treatment, since the 70's when the use of dacarbazine was introduced for the treatment of patients with tumour progression or distant metastasis, with disappointing results. Despite this, Dacarbazine has been the most used drug to the present. Three years ago, two new drugs were introduced, one of them based on the target therapy and other one in the immunotherapy, offering, with the obtained results, an alternative in the treatment of cutaneous melanoma The objectives of this article are to show the pathways of these drugs, to describe the current role of surgery in cutaneous melanoma, with the arrival of these drugs, as well as to know the therapeutic alternatives that are emerging for the cutaneous melanoma based on scientific evidence.

  6. Molecular Bases of Cutaneous and Uveal Melanomas

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    Sudeep Gaudi


    Full Text Available Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.

  7. Blue light inhibits proliferation of melanoma cells (United States)

    Becker, Anja; Distler, Elisabeth; Klapczynski, Anna; Arpino, Fabiola; Kuch, Natalia; Simon-Keller, Katja; Sticht, Carsten; van Abeelen, Frank A.; Gretz, Norbert; Oversluizen, Gerrit


    Photobiomodulation with blue light is used for several treatment paradigms such as neonatal jaundice, psoriasis and back pain. However, little is known about possible side effects concerning melanoma cells in the skin. The aim of this study was to assess the safety of blue LED irradiation with respect to proliferation of melanoma cells. For that purpose we used the human malignant melanoma cell line SK-MEL28. Cell proliferation was decreased in blue light irradiated cells where the effect size depended on light irradiation dosage. Furthermore, with a repeated irradiation of the melanoma cells on two consecutive days the effect could be intensified. Fluorescence-activated cell sorting with Annexin V and Propidium iodide labeling did not show a higher number of dead cells after blue light irradiation compared to non-irradiated cells. Gene expression analysis revealed down-regulated genes in pathways connected to anti-inflammatory response, like B cell signaling and phagosome. Most prominent pathways with up-regulation of genes were cytochrome P450, steroid hormone biosynthesis. Furthermore, even though cells showed a decrease in proliferation, genes connected to the cell cycle were up-regulated after 24h. This result is concordant with XTT test 48h after irradiation, where irradiated cells showed the same proliferation as the no light negative control. In summary, proliferation of melanoma cells can be decreased using blue light irradiation. Nevertheless, the gene expression analysis has to be further evaluated and more studies, such as in-vivo experiments, are warranted to further assess the safety of blue light treatment.

  8. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan


    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.

  9. Comparative Metabolic Flux Profiling of Melanoma Cell Lines (United States)

    Scott, David A.; Richardson, Adam D.; Filipp, Fabian V.; Knutzen, Christine A.; Chiang, Gary G.; Ronai, Ze'ev A.; Osterman, Andrei L.; Smith, Jeffrey W.


    Metabolic rewiring is an established hallmark of cancer, but the details of this rewiring at a systems level are not well characterized. Here we acquire this insight in a melanoma cell line panel by tracking metabolic flux using isotopically labeled nutrients. Metabolic profiling and flux balance analysis were used to compare normal melanocytes to melanoma cell lines in both normoxic and hypoxic conditions. All melanoma cells exhibited the Warburg phenomenon; they used more glucose and produced more lactate than melanocytes. Other changes were observed in melanoma cells that are not described by the Warburg phenomenon. Hypoxic conditions increased fermentation of glucose to lactate in both melanocytes and melanoma cells (the Pasteur effect). However, metabolism was not strictly glycolytic, as the tricarboxylic acid (TCA) cycle was functional in all melanoma lines, even under hypoxia. Furthermore, glutamine was also a key nutrient providing a substantial anaplerotic contribution to the TCA cycle. In the WM35 melanoma line glutamine was metabolized in the “reverse” (reductive) direction in the TCA cycle, particularly under hypoxia. This reverse flux allowed the melanoma cells to synthesize fatty acids from glutamine while glucose was primarily converted to lactate. Altogether, this study, which is the first comprehensive comparative analysis of metabolism in melanoma cells, provides a foundation for targeting metabolism for therapeutic benefit in melanoma. PMID:21998308

  10. Tumoral Melanosis Associated with Pembrolizumab-Treated Metastatic Melanoma (United States)

    Cohen, Philip R


    Tumoral melanosis is a form of completely regressed melanoma that usually presents as darkly pigmented lesions suspicious for malignant melanoma. Histology reveals dense dermal and subcutaneous infiltration of melanophages. Pembrolizumab is an antibody directed against programmed death receptor-1 (PD1) and is frontline treatment for advanced melanoma. An 81-year-old man with metastatic melanoma treated with pembrolizumab who developed tumoral melanosis at previous sites of metastases is described. The PubMed database was searched with the key words: antibody, immunotherapy, melanoma, melanosis, metastasis, pembrolizumab, and tumoral. The papers generated by the search and their references were reviewed. The patient was initially diagnosed with lentigo maligna melanoma on the left cheek three years earlier, and he was treated with wide local excision. The patient was subsequently diagnosed with epidermotropic metastatic malignant melanoma on the left parietal scalp 14 months later and was treated with wide local excision. Three months later, the patient was found to have metastatic melanoma in the same area of the scalp and was started on pembrolizumab immunotherapy. The patient was diagnosed with tumoral melanosis in the site of previous metastases nine months later. The patient remained free of disease 13 months after starting pembrolizumab. Tumoral melanosis may mimic malignant melanoma; hence a workup, including skin biopsy, should be undertaken. Extensive tumoral melanosis has been reported with ipilimumab, and we add a case following treatment with pembrolizumab. Additional cases of tumoral melanosis may present since immunotherapy has become frontline therapy for advanced melanoma.  PMID:28348944

  11. Melanin content in melanoma metastases affects the outcome of radiotherapy. (United States)

    Brożyna, Anna A; Jóźwicki, Wojciech; Roszkowski, Krzysztof; Filipiak, Jan; Slominski, Andrzej T


    Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma.

  12. Melanoma and obesity: Should antioxidant vitamins be addressed? (United States)

    Oliveira, Sofia; Coelho, Pedro; Prudêncio, Cristina; Vieira, Mónica; Soares, Raquel; Guerreiro, Susana G; Fernandes, Rúben


    Melanoma is an aggressive form of skin cancer refractory to conventional therapies. Obesity has reached epidemic dimensions acting as a risk factor for several cancer types, such as melanoma. Several reactive species of oxygen are also involved in melanoma initiation and progression. Low levels of antioxidant content and/or activity in lightly pigmented cells could expose them to an extremely oxidative environment and rise the susceptibility to oxidative damage and consequently loss of cell homeostasis. Despite the knowledge about melanoma biology, pathogenesis and developed therapies, is extremely important to understand the antioxidant modulation of melanoma under an environment of obesity, especially the effect of some natural compounds of the diet, such as antioxidant vitamins A, C and E and selenium in order to establish alternatives to conventional therapies, which are known to be ineffective against melanoma.

  13. The NF1 gene in tumor syndromes and melanoma. (United States)

    Kiuru, Maija; Busam, Klaus J


    Activation of the RAS/MAPK pathway is critical in melanoma. Melanoma can be grouped into four molecular subtypes based on their main genetic driver: BRAF-mutant, NRAS-mutant, NF1-mutant, and triple wild-type tumors. The NF1 protein, neurofibromin 1, negatively regulates RAS proteins through GTPase activity. Germline mutations in NF1 cause neurofibromatosis type I, a common genetic tumor syndrome caused by dysregulation of the RAS/MAPK pathway, ie, RASopathy. Melanomas with NF1 mutations typically occur on chronically sun-exposed skin or in older individuals, show a high mutation burden, and are wild-type for BRAF and NRAS. Additionally, NF1 mutations characterize certain clinicopathologic melanoma subtypes, specifically desmoplastic melanoma. This review discusses the current knowledge of the NF1 gene and neurofibromin 1 in neurofibromatosis type I and in melanoma.

  14. Ability to self-detect malignant melanoma decreases with age

    DEFF Research Database (Denmark)

    Trolle, L; Henrik-Nielsen, R; Gniadecki, R


    The prognosis of malignant melanoma depends on the thickness of the tumour. In this study, we analysed the trends in Breslow thickness in 63 patients referred to our institution, a tertiary dermatology referral centre. The mean thickness of melanoma was 0.31 mm, which was lower than the national...... average of 1.10 mm. There was a significant trend towards increased melanoma thickness with increasing age, with a rate of 0.24 mm (95% CI 0.12-0.37) for each additional 10 years of age above the age of 20 years. This trend was only apparent in cases of self-diagnosed melanomas; the thickness of tumours...... diagnosed by a dermatologist did not show any dependence on patient age. As the mortality from melanoma increases with age, this study suggests that dermatologists should include older people in screening programmes for melanoma....

  15. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie


    AIMS: Anorectal melanoma (AM) forms a rare but highly malignant subset of mucosal melanoma with an extremely poor prognosis. Although AMs display histological and immunohistochemical features very similar to cutaneous melanoma (CM), no association exists either with exposure to ultraviolet light...... tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM. METHODS AND RESULTS: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All...... AM cases analysed showed expression of at least three of the classical markers for melanoma. However, immunohistochemistry showed 19 out of 27 AM to be positive for DMBT1, which represented a statistically significant difference (P = 0.0009) compared with CM (six out of 26), which more commonly...

  16. Early Detection and Classification of Melanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Abbas Hanon. Alasadi


    Full Text Available Melanoma is a form of cancer that begins in melanocytes (cells that make the pigment melanin. It can affect the skin only, or it may spread to the organs and bones. It is less common, but more serious and aggressive than other types of skin cancer. Melanoma can be of benign or malignant. Malignant melanoma is the dangerous condition, while benign is not. In order to reduce the death rate due to malignant melanoma skin cancer, it is necessary to diagnose it at an early stage. In this paper, a detection system has been designed for diagnosing melanoma in early stages by using digital image processing techniques. The system consists of two phases: the first phase detects whether the pigmented skin lesion is malignant or benign; the second phase recognizes malignant melanoma skin cancer types. Both first and second phases have several stages. The experimental results are acceptable.

  17. Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genesimplicated in human melanoma%Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genes implicated in human melanoma

    Institute of Scientific and Technical Information of China (English)

    Andrea J. McKinney; Sheri L. Holmen


    The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. Targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms of resistance. Several different genetic alterations identified in human melanoma have been recapitulated in mice. This review outlines recent progress made in the development of mouse models of melanoma and summarizes what these findings reveal about the human disease. We begin with a discussion of traditional models and conclude with the recently developed RCAS/TVA somatic cell gene delivery mouse model of melanoma.

  18. Malignant melanoma with liver and spleen metastases: case report

    Directory of Open Access Journals (Sweden)

    Laura Cotta Ornellas


    Full Text Available CONTEXT: The diagnosis of primary melanoma is easily confirmed after histological analysis of the lesion, whereas it is rarely diagnosed when the patient even has distant metastases. DESIGN: Case report CASE REPORT: Malignant melanoma is responsible for about 1% of all deaths caused by cancer in the USA and only 3% of all malig-nant skin diseases. Malignant melanoma is a rare disease, although it corresponds to 65% of all deaths caused by skin cancer. The liver and spleen are rarely the first sites of melanoma metastases. This paper reports on the clinical picture of a patient with fatal malignant melanoma and hepatic and spleen metastases. As this was an un-usual presentation, the melanoma diagnosis could only be made after pathological analysis of the skin and hepatic lesions.

  19. Malignant uveal melanoma and similar lesions studied by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Mafee, M.F.; Peyman, G.A.; McKusick, M.A.


    Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, the authors noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability as the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.

  20. Therapeutic interventions to disrupt the protein synthetic machinery in melanoma. (United States)

    Kardos, Gregory R; Robertson, Gavin P


    Control of the protein synthetic machinery is deregulated in many cancers, including melanoma, to increase the protein production. Tumor suppressors and oncogenes play key roles in protein synthesis from the transcription of rRNA and ribosome biogenesis to mRNA translation initiation and protein synthesis. Major signaling pathways are altered in melanoma to modulate the protein synthetic machinery, thereby promoting tumor development. However, despite the importance of this process in melanoma development, involvement of the protein synthetic machinery in this cancer type is an underdeveloped area of study. Here, we review the coupling of melanoma development to deregulation of the protein synthetic machinery. We examine existing knowledge regarding RNA polymerase I inhibition and mRNA translation focusing on their inhibition for therapeutic applications in melanoma. Furthermore, the contribution of amino acid biosynthesis and involvement of ribosomal proteins are also reviewed as future therapeutic strategies to target deregulated protein production in melanoma.

  1. Detection of chondroitin sulfate proteoglycan 4 (CSPG4) in melanoma. (United States)

    Wang, Yangyang; Sabbatino, Francesco; Wang, Xinhui; Ferrone, Soldano


    The tumor antigen chondroitin sulfate proteoglycan 4 (CSPG4) appears to be a useful biomarker to identify melanoma cells and an attractive target to apply antibody-based immunotherapy for the treatment of melanoma. Here we described the reverse transcription-polymerase chain reaction (RT-PCR) method and the immunohistochemical (IHC) staining method to detect the expression of CSPG4 in melanoma cells and tissues.

  2. Clinical systemic lupeol administration for canine oral malignant melanoma


    YOKOE, INORU; AZUMA, Kazuo; Hata, Keishi; MUKAIYAMA, TOSHIYUKI; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; ITOH, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu


    Canine oral malignant melanoma (COMM) is the most aggressive malignant tumor in dogs. Lupeol is a triterpene extracted from various fruits and vegetables that reportedly inhibits melanoma cell proliferation in vitro and in vivo. In this study, the efficacy of subcutaneous lupeol for spontaneous COMM was evaluated. A total of 11 dogs (3, 5 and 3 dogs diagnosed with clinical stage I, II and III melanoma, respectively) were evaluated. Subcutaneous lupeol (10 mg/kg) was administered postoperative...

  3. Surgery and radiotherapy in the treatment of cutaneous melanoma

    DEFF Research Database (Denmark)

    Testori, A; Rutkowski, P; Marsden, J;


    Adequate surgical management of primary melanoma and regional lymph node metastasis, and rarely distant metastasis, is the only established curative treatment. Surgical management of primary melanomas consists of excisions with 1-2 cm margins and primary closure. The recommended method of biopsy...... on individual circumstances. Radiotherapy is indicated as a treatment option in select patients with lentigo maligna melanoma and as an adjuvant in select patients with regional metastatic disease. Radiotherapy is also indicated for palliation, especially in bone and brain metastases....

  4. Para-Phenylenediamine Induces Apoptotic Death of Melanoma Cells and Reduces Melanoma Tumour Growth in Mice

    Directory of Open Access Journals (Sweden)

    Debajit Bhowmick


    Full Text Available Melanoma is one of the most aggressive forms of cancer, usually resistant to standard chemotherapeutics. Despite a huge number of clinical trials, any success to find a chemotherapeutic agent that can effectively destroy melanoma is yet to be achieved. Para-phenylenediamine (p-PD in the hair dyes is reported to purely serve as an external dyeing agent. Very little is known about whether p-PD has any effect on the melanin producing cells. We have demonstrated p-PD mediated apoptotic death of both human and mouse melanoma cells in vitro. Mouse melanoma tumour growth was also arrested by the apoptotic activity of intraperitoneal administration of p-PD with almost no side effects. This apoptosis is shown to occur primarily via loss of mitochondrial membrane potential (MMP, generation of reactive oxygen species (ROS, and caspase 8 activation. p-PD mediated apoptosis was also confirmed by the increase in sub-G0/G1 cell number. Thus, our experimental observation suggests that p-PD can be a potential less expensive candidate to be developed as a chemotherapeutic agent for melanoma.

  5. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression. (United States)

    Kim, Sun-Hee; Hashimoto, Yuuri; Cho, Sung-Nam; Roszik, Jason; Milton, Denái R; Dal, Fulya; Kim, Sangwon F; Menter, David G; Yang, Peiying; Ekmekcioglu, Suhendan; Grimm, Elizabeth A


    COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy.

  6. Dendritic cells in melanoma - immunohistochemical study and research trends. (United States)

    Nedelcu, Roxana Ioana; Ion, Daniela Adriana; Holeab, Cosmin Adrian; Cioplea, Mirela Daniela; Brînzea, Alice; Zurac, Sabina Andrada


    Cutaneous dendritic cells play multiple physiological roles and are involved in various pathophysiological processes. Research studies of dendritic cells abound in the medical literature. Nevertheless, the role of dendritic cells in melanoma regression phenomenon is not completely understood. We conducted a scientometric analysis in order to highlight the current state on research regarding dendritic cells and melanoma. We also performed an immunohistochemical study, using specific markers for dendritic cells (CD1a, langerin). We evaluated the frequency and distribution of dendritic cells in areas of tumor regression compared to the areas of inflammatory infiltrate of melanoma without regression. The immunohistochemical study we performed revealed that dendritic cells are more frequent in the regressed areas, comparing with non-regressed ones. In regressed areas, dendritic cells have a predominant nodular pattern (19 cases), followed by diffuse isolate pattern (eight cases) and mixed pattern (diffuse and nodular) (three cases). In melanoma without regression, most cases presented a diffuse pattern (27 cases) of dendritic cells distribution. In conclusion, our immunohistochemical study stressed differences between frequency and distribution of dendritic cells located in the melanoma with regression and melanoma without regression. These data suggest that dendritic cells are involved in the regression phenomenon. Following the literature analysis we obtained, we observed that dendritic cells profile in melanoma with regression was poorly studied. Insights into antitumor immune response and dendritic cells may be essential for the understanding of the potential prognostic role of dendritic cells in melanoma and for the development of new promising therapeutic strategies for melanoma.

  7. Histopathological diagnosis of acral lentiginous melanoma in early stages. (United States)

    Fernandez-Flores, Angel; Cassarino, David S


    Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma.

  8. Multiple cutaneous melanomas associated with gastric and brain metastases* (United States)

    Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro


    The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified.

  9. [Melanoma: from molecular studies to the treatment breakthrough]. (United States)

    Imianitov, E N


    Melanoma holds a leading position in the mortality from skin tumors. Standard treatment of metastatic melanoma allows tumor remission to be achieved only in a small subset of patients. Studies on melanoma molecular pathogenesis led to the identification of several causative genetic events and, consequently, to the development of novel targeted drugs. More than a half of melanomas contain amine acid substitutions in serine-threonine kinase BRAF. Clinical trials involving specific BRAF inhibitors--vemurafenib and dabrafenib--demonstrated high efficacy of these agents towards BRAF-mutated melanoma. MEK inhibitors may show activity against both BRAF--and NRAS-driven tumors. Mucosal and acral melanomas frequently contain mutation in KIT receptor and can be successfully treated by imatinib. There are novel therapeutic monoclonal antibodies targeted against immunosuppressive molecules CTLA4, PD-1 and PD-L1. In some instances these drugs allow to obtain exceptionally prolonged responses. Whole genome sequencing led to the identification of new melanoma genes, e.g. GRIN2A, TRRAP, PREX2, RAC1, STK19, PPP6C, etc. Molecular testing, especially BRAF mutation analysis, has become a mandatory part of melanoma diagnosis. Nevertheless, despite the revolution in melanoma treatment, the prevention of excessive ultraviolet exposure, cancer awareness and early diagnosis remain the main tools for the management of this disease.

  10. Metastatic melanoma mimicking solitary fibrous tumor: report of two cases. (United States)

    Bekers, Elise M; van Engen-van Grunsven, Adriana C H; Groenen, Patricia J T A; Westdorp, Harm; Koornstra, Rutger H T; Bonenkamp, Johannes J; Flucke, Uta; Blokx, Willeke A M


    Malignant melanomas are known for their remarkable morphological variation and aberrant immunophenotype with loss of lineage-specific markers, especially in recurrences and metastases. Hot spot mutations in BRAF, NRAS, GNAQ, and GNA11 and mutations in KIT are oncogenic events in melanomas. Therefore, genotyping can be a useful ancillary diagnostic tool. We present one case each of recurrent and metastatic melanoma, both showing histological and immunohistochemical features of solitary fibrous tumor (SFT). Mutational analysis detected BRAF and NRAS mutations in the primary and secondary lesions, respectively. This result confirmed the diagnosis of recurrent/metastastic melanoma.

  11. Prognosis of thin cutaneous head and neck melanoma (

    DEFF Research Database (Denmark)

    Andersson, A P; Dahlstrøm, Karin Kjærgaard; Drzewiecki, K T


    Thin malignant melanomas, i.e. tumours less than 1 mm, are generally considered to have a good prognosis. The records of 148 patients with thin invasive melanomas located to the head and neck region were reviewed. All patients were followed for the excision of the primary tumour until death...... of these 16 patients (75%) died of disseminated melanoma. We conclude that thin head and neck melanomas do not necessarily carry an excellent prognosis. Prognosis is not dependent upon tumour thickness when less than 1.00 mm....

  12. Identification of donor melanoma in a renal transplant recipient. (United States)

    Wilson, L J; Horvat, R T; Tilzer, L; Meis, A M; Montag, L; Huntrakoon, M


    A patient with chronic renal failure received a closely matched cadaveric kidney. Approximately 3 months after transplantation, the patient developed a metastatic malignant melanoma. A large retroperitoneal mass consisting of large pleomorphic polygonal neoplastic cells was found close to the donated kidney. This tumor was diagnosed as a malignant melanoma. DNA analysis of this tumor, the donated kidney, and the recipient indicated that the melanoma originated from the donor. Although this is not the first report of a donated melanoma, it is the first report of definitive DNA analysis of the origin of the malignant cells.

  13. Molecular biology of normal melanocytes and melanoma cells. (United States)

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya


    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  14. Primary cerebello-pontine angle malignant melanoma : a case report.

    Directory of Open Access Journals (Sweden)

    Desai K


    Full Text Available A rare case of primary malignant melanoma in the cerebello-pontine angle, in a 17 year old girl is presented. The patient presented with one month history of headache, diplopia, facial asymmetry and ataxia. The computerised tomography (CT scan and magnetic resonance imaging (MRI revealed a large cerebello-pontine angle mass with features suggestive of a melanoma. The typical black coloured, solid and vascular melanoma was excised completely. Cerebello-pontine angle melanoma are extremely rare tumours with dismal long term outcome in majority of these cases.

  15. [Systemic treatment of melanoma brain metastases]. (United States)

    Le Rhun, É; Mateus, C; Mortier, L; Dhermain, F; Guillot, B; Grob, J-J; Lebbe, C; Thomas, M; Jouary, T; Leccia, M-T; Robert, C


    Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase).

  16. Relationship between Latitude and Melanoma in Italy. (United States)

    Crocetti, Emanuele; Buzzoni, Carlotta; Chiarugi, Alessandra; Nardini, Paolo; Pimpinelli, Nicola


    Objective. Evaluate the ecological relationship between skin melanoma epidemiology and latitude in Italy. Methods. We used data from the Italian network of cancer registries (Airtum). In a Poisson model, we evaluated the effect on incidence, mortality, and survival of latitude, adjusting for some demographic, social, phenotypic, and behavioural variables. Results. Incidence increased in Italy by 17% for each degree of increase in latitude. The effect of latitude was statistically significantly present also adjusting for other variables (incidence rate ratio = 1.08). The effect of latitude on increasing mortality (mortality rate ratio = 1.27) and improving survival (relative excess risk of death = 0.93) was no longer present in the multivariate model. Conclusion. Melanoma incidence, mortality, and survival vary in Italy according to latitude. After adjustment for several confounders, incidence still grows with growing latitude. Presumably, latitude expresses other variables that might be related to individual susceptibility and/or local care.

  17. Lessons from Cancer Immunoediting in Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Mariana Aris


    Full Text Available We will revisit the dual role of the immune system in controlling and enabling tumor progression, known as cancer immunoediting. We will go through the different phases of this phenomenon, exposing the most relevant evidences obtained from experimental models and human clinical data, with special focus on Cutaneous Melanoma, an immunogenic tumor per excellence. We will describe the different immunotherapeutic strategies employed and consider current models accounting for tumor heterogeneity. And finally, we will propose a rational discussion of the progress made and the future challenges in the therapeutics of Cutaneous Melanoma, taking into consideration that tumor evolution is the resulting from a continuous feedback between tumor cells and their environment, and that different combinatorial therapeutic approaches can be implemented according to the tumor stage.

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

    LENUS (Irish Health Repository)

    Karde, Supriya Ramesh


    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.


    Shada, Amber L.; Dengel, Lynn T.; Petroni, Gina R.; Smolkin, Mark E.; Acton, Scott; Slingluff, Craig L.


    Background Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. Materials and methods Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0–5, >5–15, >15–30, and >30 mm. Images were scored on a scale from −1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. Results IR imaging was able to determine the malignancy of small (0–5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5–15 mm, sensitivity was 58% and specificity 98%. For lesions >15–30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%–100% across all strata, and the negative predictive value was 95% for >15–30 mm lesions and 80% for >30 mm lesions. Conclusions Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies. PMID:23043862

  20. Hypoxia independent drivers of melanoma angiogenesis

    Directory of Open Access Journals (Sweden)

    Svenja eMeierjohann


    Full Text Available Tumor angiogenesis is a process which is traditionally regarded as the tumor`s response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a prerequisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia independent mechanisms of tumor angiogenesis in melanoma.

  1. Primary melanoma of Meckel's cave: case report. (United States)

    Falavigna, Asdrubal; Borba, Luis A B; Ferraz, Fernando Antonio Patriani; Almeida, Giovana Camargo de; Krindges Júnior, José Valentim


    We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months did not show abnormalities.

  2. Primary melanoma of Meckel's cave: case report


    Falavigna,Asdrubal; Luis A. B. Borba; Ferraz, Fernando Antonio Patriani [UNIFESP; Almeida,Giovana Camargo de; Krindges Júnior,José Valentim


    We present a case of trigeminal neuralgia with cranial normal magnetic resonance image (MRI) and computed tomography. The pain was not relieved by carbamazepine and microvascular decompression surgery was done. After two months the pain was similar to the condition before surgery. At this time, MRI showed an expansive lesion in Meckel's cave that was treated with radical resection by extra-dural approach. The pathologic examination revealed a primary melanoma. The follow-up after six months d...

  3. CDC Vital Signs-Preventing Melanoma

    Centers for Disease Control (CDC) Podcasts


    This podcast is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  4. Histology of melanoma and nonmelanoma skin cancer. (United States)

    Müller, Cornelia S L


    Incidence of skin tumors is increasing among elderly patients, and the multi-morbidities which occur in the elderly are a great challenge for dermatologists. Basis of every treatment of skin cancer patients is a reliable diagnosis. Therefore, histopathology serves as the gold standard in clinical dermatooncology and dermatologic surgery. This chapter provides a comprehensive review on the main types of melanoma and nonmelanoma skin cancers, including precursor lesions.

  5. [Malignant melanoma (review of 68 cases)]. (United States)

    Sittart, J A; Valente, N Y; Stevale, J N


    A clinica pathologic revision was performed about 68 patients with malignant melanoma of the Hospital dos Servidores Publicos do Estado de São Paulo. The authors had checked the data concerning to color, age and sex of the patients, localisation, clinical aspect of the lesions and clinical evolution of the cases. They made comments on the histopathology related to Clark's levels, the depth of tumors (Breslow), solar elastosis and inflammatory infiltrate, in relation with the clinical evolution of the cases.

  6. Primary malignant melanoma of cervix and vagina (United States)

    Lee, Jae Hoon; Yun, Jisun; Seo, Jung-Won; Bae, Go-Eun; Lee, Jeong-Won


    Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains. PMID:27668208

  7. Right Atrial Metastatic Melanoma with Unknown Primaries

    Directory of Open Access Journals (Sweden)

    Robin Kuriakose


    Full Text Available A 54-year-old male with history of anemia and rheumatoid arthritis presented with a three-month history of dyspnea on exertion and lower extremity edema. Patient was referred for a transthoracic echocardiogram that revealed a large right atrial mass with reduced ejection fraction of 40% and an incidental large liver mass. Subsequent cardiac MRI revealed a lobulated right atrial mass measuring 5.4 cm × 5.3 cm with inferior vena cava compression and adjacent multiple large liver lesions confirmed to be malignant melanoma through biopsy. Interestingly, no primaries were found in the patient. PET/CT imaging displayed hypermetabolic masses within the right atrium and liver that likely represent metastases, as well as bilateral pleural effusions, most likely due to heart failure. Preoperative coronary angiogram demonstrated perfusion to the mass by a dense network of neovasculature arising from the mid right coronary artery. The cardiac melanoma was surgically removed, and the right atrium was reconstructed with a pericardial patch. After surgery, all cardiac chambers appeared normal in size and function with associated moderate tricuspid regurgitation. The patient is currently being administered ipilimumab for systemic therapy of metastatic melanoma.

  8. Melanoma detection using a mobile phone app (United States)

    Diniz, Luciano E.; Ennser, K.


    Mobile phones have had their processing power greatly increased since their invention a few decades ago. As a direct result of Moore's Law, this improvement has made available several applications that were impossible before. The aim of this project is to develop a mobile phone app, integrated with its camera coupled to an amplifying lens, to help distinguish melanoma. The proposed device has the capability of processing skin mole images and suggesting, using a score system, if it is a case of melanoma or not. This score system is based on the ABCDE signs of melanoma, and takes into account the area, the perimeter and the colors present in the nevus. It was calibrated and tested using images from the PH2 Dermoscopic Image Database from Pedro Hispano Hospital. The results show that the system created can be useful, with an accuracy of up to 100% for malign cases and 80% for benign cases (including common and atypical moles), when used in the test group.

  9. Gamma knife radiosurgery for uveal melanoma ineligible for brachytherapy by the Collaborative Ocular Melanoma Study criteria

    Directory of Open Access Journals (Sweden)

    Nicola G Ghazi


    Full Text Available Nicola G Ghazi1, Christopher S Ketcherside1, Jason Sheehan2, Brian P Conway11Department of Ophthalmology and 2Neurosurgery, University of Virginia Health System, Charlottesville, VA, USAPurpose: To report outcomes of Gamma Knife radiosurgery (GKRS in treating uveal melanoma lesions ineligible for standard brachytherapy.Methods: A retrospective interventional case series of uveal melanoma patients treated with GKRS between 1996 and 2004 was performed. The main outcome measures were local tumor control, metastasis, and death.Results: Four patients with uveal melanoma treated with GKS were identified. Three tumors involved the ciliary body and one was macular with its border within 2 mm of the optic disc. Adequate globe stabilization was achieved by retrobulbar anesthesia in all cases. Pretreatment mean visual acuity was 20/30. Tumor volume as determined by magnetic resonance imaging ranged from 0.05 to 0.30 cc. Ultrasonographic greatest tumor diameter and height ranged from 11 to 18 mm (mean 14.5 mm and 2.9 to 4.5 mm (mean 3.6 mm, respectively. The peripheral dose varied from 16.5 to 30 Gray. Local tumor control was achieved in all cases over a follow up period of 6 to 96 months. Mean final visual acuity was 20/50. One eye was enucleated for neovascular glaucoma and one patient died from liver and lung metastasis.Conclusions: GKRS for uveal melanoma appears to be safe and effective. The metastasis and mortality rates appear to be comparable to those following brachytherapy and enucleation. Moreover, local tumor control and enucleation rates are similar to those following brachytherapy. The findings in this small series suggest a role for GKRS in the treatment of selected cases of uveal melanomas.Keywords: gamma knife radiosurgery, radiation therapy, uveal melanoma

  10. 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.  Created: 10/19/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 10/19/2011.

  11. Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. (United States)

    Nihal, Minakshi; Ahmad, Nihal; Mukhtar, Hasan; Wood, Gary S


    Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

  12. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C


    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.

  13. Prevalence of left-sided melanomas in an Irish population.

    LENUS (Irish Health Repository)

    de Blacam, C


    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.

  14. Hemosideric heterochromia iridum in malignant melanoma of the choroid. (United States)

    Awan, K J


    A case is reported in which hyperchromic heterochromia iridum developed due to blood staining of an eye with malignant melanoma of the choroid in which massive hemorrhage developed. It is suggested that a possibility of the malignant melanoma of the choroid be kept in mind where hemosiderin deposits are suspected to be the cause of heterochromia but no intraocular iron foreign body is present.

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

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali


    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.

  16. Metastatic melanoma mimicking solitary fibrous tumor: report of two cases

    NARCIS (Netherlands)

    Bekers, E.M.; Engen-van Grunsven, A.C.H. van; Groenen, P.J.T.A.; Westdorp, H.; Koornstra, R.H.; Bonenkamp, J.J.; Flucke, U.E.; Blokx, W.A.M.


    Malignant melanomas are known for their remarkable morphological variation and aberrant immunophenotype with loss of lineage-specific markers, especially in recurrences and metastases. Hot spot mutations in BRAF, NRAS, GNAQ, and GNA11 and mutations in KIT are oncogenic events in melanomas. Therefore

  17. Balloon Cell Urethral Melanoma: Differential Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    M. McComiskey


    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.

  18. The European approach to in-transit melanoma lesions

    NARCIS (Netherlands)

    Hoekstra, H. J.


    The biological behavior of melanoma is unpredictable. Three to five per cent of melanoma patients will develop in-transit lesions and the median time to recurrence ranges between 13-16 months. At the time of recurrence the risk of occult nodal metastasis, with clinically negative regional lymph node

  19. Black Pleural Effusion: A Unique Presentation of Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    Akansha Chhabra


    Full Text Available Metastatic melanoma is a rare form of skin cancer, but one that comes with a high mortality rate. Pulmonary involvement is frequently seen in metastatic melanoma with only 2% of malignant melanoma patients with thorax metastasis presenting with pleural effusions. Herein, we report an extremely rare case of black pleural effusion from thoracic metastasis of cutaneous malignant melanoma. A 74-year-old man with known metastatic melanoma presented with a 1-month history of worsening lower back and hip pain and was found to have extensive osseous metastatic disease and multiple compression fractures. The patient underwent an uneventful kyphoplasty; however, the following day, he became acutely hypoxic and tachypneic with increased oxygen requirements. Radiographic evaluation revealed new bilateral pleural effusions. Bedside thoracentesis revealed a densely exudative, lymphocyte-predominant black effusion. Cytological examination showed numerous neoplastic cells with melanin deposition. A diagnosis of thoracic metastasis of malignant melanoma was established based on the gross and microscopic appearance of the pleural fluid. To the best of our knowledge, this is the first reported case of black pleural effusions secondary to metastatic melanoma in the United States. Despite the rarity of this presentation, it is important to determine the etiology of the black pleural effusion and to keep metastatic melanoma as a differential diagnosis.

  20. Ambulatory Melanoma Care Patterns in the United States

    Directory of Open Access Journals (Sweden)

    Andrew L. Ji


    Full Text Available Objective. 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 ( 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, of the population increase in age (0.23 year per interval year. There was a nonsignificant 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.

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

    DEFF Research Database (Denmark)

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


    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...

  2. The Nodal Location of Metastases in Melanoma Sentinel Lymph Nodes

    DEFF Research Database (Denmark)

    Riber-Hansen, Rikke; Nyengaard, Jens; Hamilton-Dutoit, Stephen;


    BACKGROUND: The design of melanoma sentinel lymph node (SLN) histologic protocols is based on the premise that most metastases are found in the central parts of the nodes, but the evidence for this belief has never been thoroughly tested. METHODS: The nodal location of melanoma metastases in 149...

  3. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

    Björnhagen, V; Månsson-Brahme, E; Lindholm, J;


    Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark's level II-III. However, stereological measurements could be performed in only 57 thin melanomas due to too sparse cellularity. Thus, 21 thin metastasizing...

  4. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.


    A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

  5. Cardiac thrombi mistaken for metastasis in recurrent melanoma. (United States)

    Galiuto, Leonarda; Locorotondo, Gabriella; Fedele, Elisa; Danza, Maria L; De Vito, Elena; Masi, Ambra; Favoccia, Carla; Rebuzzi, Antonio G; Crea, Filippo


    Intra-cardiac thrombi can be incidentally found in recurrent melanoma and need careful assessment. An 81-year-old woman, with a history of malignant nasopharyngeal melanoma, was evaluated by echocardiography and cardiac magnetic resonance due to the detection of undefined masses localized both in right atrium and ventricle during contrast-enhanced thoraco-abdominal computed tomography.

  6. Comparative analysis of methods of preinvasive melanoma diagnostics

    Directory of Open Access Journals (Sweden)

    Kozlov S.V.


    Full Text Available The article discusses one of the problems of oncology — skin melanoma. The research objective is to study and to compare diagnostic methods of preinvasive melanoma including fluorescence diagnosis, dermatoscopy and microwave radiometry. Materials and Methods: The survey has used dermatoscope of Heine Delta 20 Company, the unit RTM-01-RES and the instrument of fluorescent diagnostics «Spectrum-Cluster.» The results suggest the possibility of early detection of melanoma with the use of dermatoscopy. The method may be applied to radiometry screening study. Fluorescence diagnostics is effective for the differential diagnosis of melanoma and melanocytic nevi. In conclusion it has been proved the need for an integrated approach to the diagnostics of melanoma of skin, depending on the different clinical situations.

  7. Expression of Integrin Alpha10 Is Induced in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ann-Kathrin Wenke


    Full Text Available Recently, integrin alpha10 was described as a collagen type II-binding integrin expressed mainly in chondrocytes. However, by array studies we detected integrin alpha10 also to be upregulated in malignant melanoma compared to primary melanocytes. Subsequent analysis of melanoma cell lines and melanoma tumor samples confirmed this finding. Further, we demonstrated that expression of integrin alpha10 is controlled by AP-2 and Ets-1, two transcription factors known to be involved in melanoma development and progression. To investigate the functional relevance of integrin alpha10, expression was downregulated via stable antisense transfection. Proliferation assays and colony forming assays revealed no differences comparing antisense integrin alpha10 cell clones with control and wild type melanoma cells, respectively. However, antisense integrin alpha10 cell clones and Mel Im cells treated with an inhibitory antibody against integrin alpha10 showed a reduced migratory potential.

  8. Social Network Analysis of an Online Melanoma Discussion Group (United States)

    Durant, Kathleen T.; McCray, Alexa T.; Safran, Charles


    We have developed tools to explore social networks that share information in medical forums to better understand the unmet informational needs of patients and family members facing cancer treatments. We define metrics that demonstrate members discussing interleukin-2 receive a stronger response from the melanoma discussion group than a typical topic. The interleukin-2 network has a different topology than the melanoma network, has a higher density, and its members are more likely to have a higher intimacy level with another member and a lower inquisitiveness level than a typical melanoma user. Members are more likely to join the interleukin-2 network to answer a question than in the melanoma network (probability =.2 ±.05 p-value=.001). Within the melanoma network 20% of the questions posed to the community do not get an answer. In the interleukin-2 network, 1.3% of the questions (one question) do not get a response. PMID:21347134

  9. POLE mutations in families predisposed to cutaneous melanoma

    DEFF Research Database (Denmark)

    Aoude, Lauren G; Heitzer, Ellen; Johansson, Peter


    Germline mutations in the exonuclease domain of POLE have been shown to predispose to colorectal cancers and adenomas. POLE is an enzyme involved in DNA repair and chromosomal DNA replication. In order to assess whether such mutations might also predispose to cutaneous melanoma, we interrogated...... whole-genome and exome data from probands of 34 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, BAP1, TERT, POT1, ACD and TERF2IP. We found a novel germline mutation, POLE p.(Trp347Cys), in a 7-case cutaneous melanoma family....... Functional assays in S. pombe showed that this mutation led to an increased DNA mutation rate comparable to that seen with a Pol ε mutant with no exonuclease activity. We then performed targeted sequencing of POLE in 1243 cutaneous melanoma cases and found that a further ten probands had novel or rare...

  10. Dissection of T-cell antigen specificity in human melanoma

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Albæk Thrue, Charlotte; Junker, Niels


    Tumor-infiltrating lymphocytes (TIL) isolated from melanoma patients and expanded in vitro by interleukin (IL)-2 treatment can elicit therapeutic response after adoptive transfer, but the antigen specificities of the T cells transferred have not been determined. By compiling all known melanoma......-associated antigens and applying a novel technology for high-throughput analysis of T-cell responses, we dissected the composition of melanoma-restricted T-cell responses in 63 TIL cultures. T-cell reactivity screens against 175 melanoma-associated epitopes detected 90 responses against 18 different epitopes...... from different fragments of resected melanoma lesions. In summary, our findings provide an initial definition of T-cell populations contributing to tumor recognition in TILs although the specificity of many tumor-reactive TILs remains undefined....

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

    Directory of Open Access Journals (Sweden)

    Anita Munde


    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.

  12. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

    Directory of Open Access Journals (Sweden)

    Scott F. Lindsey


    Full Text Available 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.

  13. Primary malignant melanoma of the liver: A case report

    Institute of Scientific and Technical Information of China (English)

    Li Gong; Yan-Hong Li; Jian-Ye Zhao; Xu-Xia Wang; Shao-Jun Zhu; Wei Zhang


    Primary malignant melanoma of the liver is an exceedingly rare tumor.Only 12 cases have been reported in the worldwide lirerature.We present a case of isolated malignant melanoma of the liver occurring in a 36-year-old Chinese male patient.Comprehensive dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or ocular primary lesion.Other lesions in brain,respiratory tract,lung,gastrointestinal tract and anus,were not demonstrated by serial position emission tomography(PET).Microscopic examination of the resected specimen revealed a malignant melanoma,which was confirmed by immunohistochemical staining for HMB-45,S-100 protein,melanoma-pan and vimentin.Moreover,electron microscopy demonstrated melanosomes in tumor cell cytoplasm.Our case shows that primary malignant melanoma may occur in the liver and should be considered when the histopathological appearance is not typical for other hepatic neoplasm.

  14. Primary malignant melanoma of esophagus at esophagogastric junction: case report

    Institute of Scientific and Technical Information of China (English)

    高玉平; 朱建善; 林维; 郑文钧


    @@ Primary malignant melanoma of the esophagus is a rare tumor that accounts for only 0.1% of primary esophageal neoplasms.1 Although it was once thought that primary melanoma could not arise in the esophagus because of the lack of precursor cells, it has since been shown in autopsy series that 4%-8% of individuals have melanoblasts in the esophageal mucosa.2 To date, approximately 200 cases of primary esophageal malignant melanoma have been reported in global literatures while less than 20 cases of primary esophageal malignant melanoma have been reported in China.2-4 In this report we present a case of primary malignant melanoma of the esophagus in a Chinese man.

  15. First-line treatment of metastatic melanoma: role of nivolumab (United States)

    Force, Jeremy; Salama, April KS


    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.

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

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    Carlos Gustavo Leite Vieira


    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.

  17. Dermatologia comparativa: dermatoscopia em melanoma cutâneo Comparative dermatology: dermatoscopy of cutaneous melanoma

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    Otávio Sérgio Lopes


    Full Text Available Os autores apresentam imagens de dermatoscopia em uma fruta (manga-rosa, contaminada pela antracnose, mostrando sua semelhança com o melanoma extensivo superficial.The authors present images from a dermatoscopy performed in a fruit (mango that was contaminated by anthracnosis, showing its similarity to superficial spreading melanona.

  18. Pesticide exposure in farming and forestry and the risk of uveal melanoma

    DEFF Research Database (Denmark)

    Behrens, Thomas; Lynge, Elsebeth; Cree, Ian;


    Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries.......Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries....

  19. Isolated limb infusion chemotherapy for melanoma: an overview of early experience at the Adelaide Melanoma Unit

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    Giles MH


    Full Text Available Mitchell H Giles,1 Brendon J Coventry2 1Adelaide Melanoma Unit, 2Discipline of Surgery, The University of Adelaide, Royal Adelaide Hospital Adelaide, SA, Australia Background: Isolated limb infusion (ILI using cytotoxic agents has been demonstrated to be an effective and less invasive alternative modality than isolated limb perfusion for the treatment of melanoma localized to a limb. Percutaneous catheters were inserted into the axial artery and vein of the affected limb while using a pneumatic cuff to restrict limb vascular flow proximally to "isolate" the limb from the body and enable delivery of high-dose intra-arterial chemotherapy selectively to the limb. The ILI technique was developed at the Sydney Melanoma Unit (now renamed the Melanoma Institute Australia, and only a few other centers have reported separate results. We report our early results using the ILI technique for management of locally recurrent surgically nonresectable melanoma. Methods and results: Twenty-eight ILI procedures were performed in 20 patients treated with one or more procedures between 1997 and 2007. Patient parameters and clinical responses were evaluated. The median follow-up duration was 15.9 months after the first ILI, with an overall response rate after one or more infusions of 70%, of which 35% were complete responders and 35% were partial responders, with a further 20% showing stable disease, giving a "clinically significant" response rate of 90%. After one ILI (n = 20, the overall response rate was 70%, with 20% complete responders and 50% partial responders, and 20% with stable disease. Low limb toxicities were generally observed, and no amputations were required. Conclusion: ILI chemotherapy is a useful technique, which can be readily repeated for control of melanoma in the limb. It is generally well tolerated, and is capable of achieving a cure, delayed progression, or effective palliation in selected cases. The longest survivors in this series were 8

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

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    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.

  1. Intention to Obtain Genetic Testing for Melanoma among Individuals at Low to Moderate Risk for Hereditary Melanoma (United States)

    Vadaparampil, Susan T.; Azzarello, Lora; Pickard, Jennifer; Jacobsen, Paul B.


    Background: Melanoma is a serious skin cancer that has been on the rise in the United States. Some genetic component is apparent. Purpose: The purpose of this study was to identify demographic, clinical, attitudinal, and health belief factors associated with intention to obtain genetic testing for hereditary melanoma among unaffected first-degree…

  2. Testing New Drugs for Treatment of Melanoma Patients Applying Connectivity Map Database Analysis with Melanoma Gene Signatures (United States)


    AD_________________ Award Number: W81XWH-11-1-0794 TITLE: Testing New Drugs for Treatment of...TYPE Final 3. DATES COVERED 15 September 2011 – 14 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Testing New Drugs for Treatment of...4 Introduction: Project Title: Testing New Drugs for treatment of Melanoma Patients Applying Connectivity Map Database Analysis with Melanoma

  3. Tissue-Based Microarray Expression of Genes Predictive of Metastasis in Uveal Melanoma and Differentially Expressed in Metastatic Uveal Melanoma

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    Hakan Demirci


    Full Text Available Purpose: To screen the microarray expression of CDH1, ECM1, EIF1B, FXR1, HTR2B, ID2, LMCD1, LTA4H, MTUS1, RAB31, ROBO1, and SATB1 genes which are predictive of primary uveal melanoma metastasis, and NFKB2, PTPN18, MTSS1, GADD45B, SNCG, HHIP, IL12B, CDK4, RPLP0, RPS17, RPS12 genes that are differentially expressed in metastatic uveal melanoma in normal whole human blood and tissues prone to metastatic involvement by uveal melanoma. Methods: We screened the GeneNote and GNF BioGPS databases for microarray analysis of genes predictive of primary uveal melanoma metastasis and those differentially expressed in metastatic uveal melanoma in normal whole blood, liver, lung and skin. Results: Microarray analysis showed expression of all 22 genes in normal whole blood, liver, lung and skin, which are the most common sites of metastases. In the GNF BioGPS database, data for expression of the HHIP gene in normal whole blood and skin was not complete. Conclusions: Microarray analysis of genes predicting systemic metastasis of uveal melanoma and genes differentially expressed in metastatic uveal melanoma may not be used as a biomarker for metastasis in whole blood, liver, lung, and skin. Their expression in tissues prone to metastasis may suggest that they play a role in tropism of uveal melanoma metastasis to these tissues.

  4. Trabajo de revisión: melanoma Work of revision: melanoma

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    Z. J. Casariego


    Full Text Available El melanoma maligno es derivado de células dendríticas (névicas proliferantes progenitoras de lesiones. Son importantes en la histogénesis y en el riesgo de desarrollo del melanoma maligno. Del 30% al 37% de los melanomas malignos del tracto aero-digestivo superior están asociados a una lesión premaligna melanótica. Los hallazgos histopatológicos con técnicas convencionales concuerdan en considerar de valor el tamaño del tumor, las células atípicas, la distribución de las células y los márgenes de la lesión. Avances mayores en inmunología de los tumores, llevan a identificar la interacción célula tumoral- célula T. Han sido identificados y caracterizados molecularmente un número de melanomas asociados a antígenos.Advance malignant melanoma is generated from proliferating dendritic (nevic cell progenitors. They are important on the histogenesis and risk of tumor development. From 30% to 37% from high air-digestic track melanoms, there are associated with premalignant cell dendritic lesions. Histophatological approaches agree in consider size of tumor, atypical cells, distribution of this cells and borders of lesion as valued markers. Major advances in tumor irnmunology, have led to understand tumor cell-T cell interactions. A number of melanom associated antigens have been identified and molecularly characterized.

  5. Patterns of neural differentiation in melanomas

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    Singh Avantika V


    Full Text Available Abstract Background Melanomas, highly malignant tumors arise from the melanocytes which originate as multipotent neural crest cells during neural tube genesis. The purpose of this study is to assess the pattern of neural differentiation in relation to angiogenesis in VGP melanomas using the tumor as a three dimensional system. Methods Tumor-vascular complexes [TVC] are formed at the tumor-stroma interphase, by tumor cells ensheathing angiogenic vessels to proliferate into a mantle of 5 to 6 layers [L1 to L5] forming a perivascular mantle zone [PMZ]. The pattern of neural differentiation is assessed by immunopositivity for HMB45, GFAP, NFP and synaptophysin has been compared in: [a] the general tumor [b] tumor-vascular complexes and [c] perimantle zone [PC] on serial frozen and paraffin sections. Statistical Analysis: ANOVA: Kruskal-Wallis One Way Analysis of Variance; All Pairwise Multiple Comparison Procedures [Tukey Test]. Results The cells abutting on the basement membrane acquire GFAP positivity and extend processes. New layers of tumor cells show a transition between L2 to L3 followed by NFP and Syn positivity in L4&L5. The level of GFAP+vity in L1&L2 directly proportionate to the percentage of NFP/Syn+vity in L4&L5, on comparing pigmented PMZ with poorly pigmented PMZ. Tumor cells in the perimantle zone show high NFP [65%] and Syn [35.4%] positivity with very low GFAP [6.9%] correlating with the positivity in the outer layers. Discussion From this study it is seen that melanoma cells revert to the embryonic pattern of differentiation, with radial glial like cells [GFAP+ve] which further differentiate into neuronal positive cells [NFP&Syn+ve] during angiogenic tumor-vascular interaction, as seen during neurogenesis, to populate the tumor substance.


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    Hansa H


    Full Text Available Conjunctival malignant melanoma is a rare pigmented tumor occurring during fifth and sixth decade typically involving limbus with high recurrence rate . A 65 yr male presented with complaints of slowly growing dark colored swelling in his left eye since 2 months . No systemic complaints . A black mass was seen on limbus with lobulated appearance . On USG ocular coats were normal . UBM shows 8*5 mm mass . Excision of mass was done and biopsy confirmed diagnosis . Mass excision was supplemented with cryotherapy . Now patient i s cosmetically and visually satisfied .

  7. Melanoma de corpo ciliar e coróide: relato de caso Choroidal and ciliary body melanoma: case report

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    Aline Amaral Fulgêncio da Cunha


    Full Text Available Melanomas oculares correspondem a 5% de todos os melanomas e 85% deles têm origem no trato uveal. Melanoma uveal é o tumor maligno intraocular primário mais comum no adulto. Relatamos neste artigo um caso de melanoma uveal em paciente, sexo feminino, 31 anos, com quadro de fotopsia, hiperemia e baixa da acuidade visual no olho esquerdo com evolução de quatro meses. Apresentava ao exame oftalmológico acuidade visual menor que 20/400, grande massa tumoral na região nasal retroiriana, com deslocamento anterior do cristalino, estreitamento da câmara anterior e descolamento seroso da retina. A ecografia sugeriu tratar-se de grande massa tumoral suspeita de melanoma de coróide com invasão do corpo ciliar. A confirmação diagnóstica foi possível por meio do exame anatomopatológico.Ocular melanomas correspond to 5% of all melanomas and 85% of them have its origin in the uveal tract. Uveal melanoma is the most commom primary intraocular malignant tumor in the adult. In this article, a case of uveal melanoma in a 31 year-old female patient, with photopsia, hyperemia and low visual acuity in the left eye with evolution of 4 months is presented. In the ophthalmologic examination, visual acuity was lower than 20/400, a large tumoral mass was noted at the nasal region behind the iris with anterior lens displacement, anterior chamber narrowing and serous retinal detachment. The ocular echography suggested a large tumoral mass as a choroidal melanoma extending to the ciliary body. The confirmation diagnosis was possible through the histopathologic examination.

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

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    Jason Ezra Hawkes


    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.

  9. Novel alpha-MSH peptide analogs for melanoma targeting (United States)

    Flook, Adam Michael

    Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in

  10. De novo Evolution of a Small Choroidal Melanoma (United States)

    Aleksidze, Nino; Medina, Carlos A.; Singh, Arun D.


    Aim To report the evolution of a de novo choroidal melanoma. Method This is a case report of a 22-year-old white male patient who has been undergoing periodic examination for a choroidal ‘freckle’ since 10 years of age. Results In 2007, a fundus photograph of the left eye showed a nondescript area of choroidal hyperpigmentation temporal to the fovea. Progressive growth was observed and, by 2012, the lesion had become well circumscribed and raised. One year later, a 4.5 × 4.5 × 1.5 mm, dome-shaped, pigmented, choroidal mass with subretinal fluid and orange pigmentation was evident. The lesion was classified as a small choroidal melanoma. Six months after plaque radiotherapy, tumor regression with total resolution of the subretinal fluid was documented. Conclusion The distinction between small choroidal melanoma and choroidal nevus is not absolute; therefore, some choroidal melanomas may initially be mislabeled as choroidal nevi because of their small size until continued growth identifies them to be small choroidal melanomas. In our case, the documented growth of the choroidal lesion on each consecutive visit and its high-risk features strongly suggest that it had been a melanoma from the beginning. To our knowledge, this is only the second documented case of a de novo evolution of a small choroidal melanoma. PMID:27231689

  11. ZBTB7A suppresses melanoma metastasis by transcriptionally repressing MCAM (United States)

    Liu, Xue-Song; Genet, Matthew D; Haines, Jenna E; Mehanna, Elie K; Wu, Shaowei; Chen, Hung-I Harry; Chen, Yidong; Qureshi, Abrar A; Han, Jiali; Chen, Xiang; Fisher, David E; Pandolfi, Pier Paolo; Yuan, Zhi-Min


    The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated down-regulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, down-regulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens. Implications Together these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications. PMID:25995384

  12. Lethal melanoma in children: a clinicopathological study of 12 cases. (United States)

    Prieto-Granada, Carlos N; Lezcano, Cecilia; Scolyer, Richard A; Mihm, Martin C; Piris, Adriano


    Melanoma in children is rare, representing 3% of paediatric malignancies and melanomas. Very few detailed descriptions of bona fide lethal childhood melanomas exist in the literature. We performed a retrospective clinicopathological review of 12 paediatric (≤16 years) melanoma patients who died of metastatic disease, including detailed assessment of architectural and cytomorphological features. There were nine prepubertal patients (median age 7 years old) and three postpubertal cases (median age 15 years old). The patients died on average 45.7 months after diagnosis with the prepubertal subcohort showing a relatively longer time from diagnosis to death. The tumours were bulky (average tumour thickness=10mm), showed brisk mitotic activity (average mitotic count per mm(2)=7), and were formed by large expansile nodules with sheet-like growth pattern and infiltrative borders in the majority of cases (83%). Cytologically, large grossly pleomorphic epithelioid cells with massive eosinophilic macronucleoli were present in most cases (75%). In this cohort, we did not identify specific features of melanoma that were unique to children. Although melanomas are extremely rarely encountered in childhood, the above-cited unequivocal malignant features should prompt an outright diagnosis of melanoma even in a paediatric patient.

  13. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

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    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)


    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.

  14. GNA11 Mutation in a Patient With Cutaneous Origin Melanoma (United States)

    Patel, Sapna P.; Kim, Dae Won; Lacey, Carol L.; Hwu, Patrick


    Abstract The rapid advances in the molecular biology and genetics have improved the understanding of molecular pathogenesis of v-Raf murine sarcoma viral oncogene homolog B (BRAF), feline sarcoma viral oncogene v-kit (KIT), and neuroblastoma v-Ras oncogene homolog (NRAS) mutant melanomas with the subsequent development of targeted therapeutic agents. However, only limited data are available for melanoma harboring other somatic than BRAF, KIT, and NRAS mutations. Mutations in guanine nucleotide-binding protein Q polypeptide (GNAQ) and guanine nucleotide-binding protein alpha-11 (GNA11), alpha subunits of heterotrimeric G proteins, constitutively activate mitogen-activated protein kinase (MAPK) pathway in uveal melanoma. However, there are no reports of GNA11 mutations in cutaneous melanomas. A 48-year-old woman was diagnosed with cutaneous nodular melanoma on the left scalp. Mutation analysis of the tumor revealed a GNA11 Q209L mutation. There was no evidence of uveal melanoma or malignant blue nevus in ophthalmologic exam, imaging studies, and pathology review. To our knowledge, this is the first case report to demonstrate cutaneous origin melanoma harboring a GNA11 Q209L mutation. PMID:26825879

  15. AKT1 Activation Promotes Development of Melanoma Metastases

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    Joseph H. Cho


    Full Text Available Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAFV600E/Cdkn2aNull mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice, respectively. Silencing of PTEN in BRAFV600E/Cdkn2aNull melanomas cooperated with activated AKT1, resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance our knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease.

  16. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma. (United States)

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J; Rotte, Anand


    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

  17. Coffee, tea, and melanoma risk among postmenopausal women. (United States)

    Wu, Haotian; Reeves, Katherine W; Qian, Jing; Sturgeon, Susan R


    Laboratory research suggests that components in coffee and tea may have anticarcinogenic effects. Some epidemiologic studies have reported that women who consume coffee and tea have a lower risk for melanoma. We assessed coffee, tea, and melanoma risk prospectively in the Women's Health Initiative - Observational Study cohort of 66,484 postmenopausal women, followed for an average of 7.7 years. Coffee and tea intakes were measured through self-administered questionnaires at baseline and at year 3 of follow-up. Self-reported incident melanomas were adjudicated using medical records. Cox proportional hazard models were used to estimate risk, adjusting for covariates, with person-time accumulation until melanoma diagnosis (n=398), death, loss to follow-up, or through 2005. Daily coffee [hazard ratio (HR)=0.87, 95% confidence interval (CI) 0.68-1.12] and tea (HR=1.03, 95% CI 0.81-1.31) intakes were not significantly associated with melanoma risk compared with nondaily intake of each beverage. No significant trends were observed between melanoma risk and increasing intakes of coffee (P for trend=0.38) or tea (P for trend=0.22). Women who reported daily coffee intake at both baseline and year 3 had a significantly decreased risk compared with women who reported nondaily intake at both time points (HR=0.68, 95% CI 0.48-0.97). Consistent daily tea intake was not associated with decreased melanoma risk. Overall, there is no strong evidence that increasing coffee or tea consumption can lead to a lower melanoma risk. We observed a decrease in melanoma risk among long-term coffee drinkers, but the lack of consistency in the results by dose and type cautioned against overinterpretation of the results.

  18. Pembrolizumab: A Review in Advanced Melanoma. (United States)

    Deeks, Emma D


    Pembrolizumab (Keytruda(®)) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006. These studies were conducted in ipilimumab-naïve and/or ipilimumab-experienced patients and assessed varying pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks. In the trials with active comparator arms, pembrolizumab regimens significantly improved progression-free survival (PFS), overall survival (OS) and overall response rates (ORR) relative to ipilimumab in ipilimumab-naïve patients (KEYNOTE 006), and significantly improved PFS and ORR, but not OS (although OS data are immature), relative to chemotherapy in ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive (KEYNOTE 002). Pembrolizumab has an acceptable tolerability profile, with immune-related adverse events that are generally manageable/reversible. Thus, pembrolizumab is a valuable treatment option for patients with advanced melanoma, including those who have progressed on ipilimumab and BRAF/MEK inhibitors.

  19. Wavelet and statistical analysis for melanoma classification (United States)

    Nimunkar, Amit; Dhawan, Atam P.; Relue, Patricia A.; Patwardhan, Sachin V.


    The present work focuses on spatial/frequency analysis of epiluminesence images of dysplastic nevus and melanoma. A three-level wavelet decomposition was performed on skin-lesion images to obtain coefficients in the wavelet domain. A total of 34 features were obtained by computing ratios of the mean, variance, energy and entropy of the wavelet coefficients along with the mean and standard deviation of image intensity. An unpaired t-test for a normal distribution based features and the Wilcoxon rank-sum test for non-normal distribution based features were performed for selecting statistically correlated features. For our data set, the statistical analysis of features reduced the feature set from 34 to 5 features. For classification, the discriminant functions were computed in the feature space using the Mahanalobis distance. ROC curves were generated and evaluated for false positive fraction from 0.1 to 0.4. Most of the discrimination functions provided a true positive rate for melanoma of 93% with a false positive rate up to 21%.

  20. Progress in the studies of etiology, epidemiology and pathogenesis of ocular melanomas. (United States)

    Hu, Danning; McCormick, Steven A


    Our population-based epidemiological studies demonstrated that the epidemiological aspects of ocular melanomas are different from those in cutaneous melanoma. The incidences of conjunctival melanoma increased in the past decades and was higher in the South (greater sun exposure), which is consistent with the occurrence of cutaneous melanoma. On the contrary, incidences of uveal melanoma are in the opposite direction of cutaneous melanomas. This indicates that solar radiation does not cause an increase of incidences of melanoma in ocular tissues (uveal melanoma) that are not exposed to solar radiation. Solar radiation increases the incidence of melanoma only in tissues exposed to said radiation, such as in conjunctival and eyelid melanomas. Uveal melanoma incidences in light-pigmented individuals are much greater than in dark-pigmented individuals. This result cannot be attributed to a melanin photo-screening effect, and is possibly related to melanin's biophysical and biochemical effects. The difference in incidences between light- and dark-pigmented individuals in conjunctival melanomas, as well as in vulvar and vaginal melanomas, are much lower than that in the uveal and cutaneous melanomas. This difference may be related to the different histological structures in these melanomas; conjunctival and vaginal melanomas occur in the mucous membrane, whereas cutaneous melanomas occur in the skin. Recent molecular biological studies indicate that each type of melanoma has its own molecular changes which are different from the others. Therefore, independent studies are required for each type of melanoma to discover their own etiology and pathogenesis, and to develop relevant novel prevention and treatment procedures.

  1. Management of uveal tract melanoma: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor


    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.

  2. Utilidad del PET 18F-fluordeoxiglucosa en melanoma maligno




    Está establecida en la literatura la utilidad de la tomografía por emisión de positrones (PET) con 18F-flúordeoxiglucosa (FDG) en la etapificación, reetapificación y seguimiento del melanoma maligno. Objetivo: Evaluar los resultados del PET FDG en melanoma maligno en nuestro centro. Material y Método: Entre febrero 2003 y julio 2004, se estudiaron 33 pacientes (edad 49±14 años, 52% sexo masculino) referidos para etapificación y reetapificación de melanoma maligno. El examen fue realizado en e...

  3. Cutaneous malignant melanoma: clinical aspects, imaging modalities and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ak, I.; Stokkel, M.P.M.; Pauwels, E.K.J. [Leiden University Medical Centre, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Bergman, W. [Department of Dermatology, Leiden University Medical Centre, Leiden (Netherlands)


    Cutaneous melanoma is a highly malignant tumour of the melanocytes presenting characteristic metabolic and biological features. Early detection decreases mortality and morbidity and provides the best chance for optimal clinical management. Imaging techniques, including scintigraphy, have assumed an important role in detection strategies. As a functional modality, nuclear medicine offers a variety of possibilities to assist in the clinical management of malignant melanoma. This review discusses the clinical aspects and treatment of melanoma, and the imaging techniques used for its diagnosis, staging and follow-up. A survey of currently available techniques is presented. (orig.)

  4. Vulvar malignant melanoma: a rare tumor with worse prognosis

    Directory of Open Access Journals (Sweden)

    Swati Singh


    Full Text Available Malignant melanoma, which has a highly malignant potential, is a tumor of the skin and mucosal membranes. Malignant melanomas of the female genital tract, including the vulva and vagina, are rare. Their overall prognosis is worse. A 75 year old woman presented with complaint of growth in vulvar region since 4 months. There was history of itching in vulvar region over growth. Surgery is still the best available treatment for the control and potential cure of malignant melanomas [Int J Reprod Contracept Obstet Gynecol 2013; 2(3.000: 494-496

  5. Practice Gaps in Dermatology: Melanocytic Lesions and Melanoma. (United States)

    Marino, Maria L; Carrera, Cristina; Marchetti, Michael A; Marghoob, Ashfaq A


    Early detection remains the most important strategy to reduce melanoma mortality. The identification and evaluation of new or changing skin lesions are important components of melanoma screening and are best performed today using complementary noninvasive imaging technologies, such as total body photography (TBP), dermoscopy, sequential digital dermoscopic imaging (SDDI), and reflectance confocal microscopy (RCM). Despite strong evidence showing that these screening techniques improve diagnostic accuracy for melanoma, they are not widely used by dermatologists. In this practice gaps review, the authors highlight the use, evidence, and rationale for TBP, dermoscopy, SDDI, and RCM.

  6. Umbilical Plugoma Mimics Melanoma Metastasis on FDG PET/CT. (United States)

    Alabed, Yazan Z; Sakellis, Christopher


    An 84-year-old man with history of left forehead melanoma was found on a restaging F-FDG PET/CT scan with hypermetabolic lung nodules and a mildly FDG-avid soft tissue nodule posterior to the umbilicus. Biopsy of a right lower lobe nodule revealed metastatic melanoma. Follow-up posttreatment PET/CT scan showed complete resolution of lung nodules and unchanged FDG uptake at the level of the umbilicus. Review of the patient's medical history revealed a remote history of umbilical hernia repair. We present a case of postsurgical plugoma mimicking the appearance of melanoma metastasis on FDG PET/CT.

  7. Prognostic Significance of Melanoma Differentiation and Trans-Differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Maddodi, Nityanand; Setaluri, Vijayasaradhi, E-mail: [Department of Dermatology, University of Wisconsin School of Medicine and Public Health, 1300 University Avenue, B25, Madison WI 53706 (United States)


    Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.

  8. 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.

  9. Melanoma "in situ" tratado con Imiquimod Melanoma in situ treated with Imiquimod

    Directory of Open Access Journals (Sweden)

    RE Achenbach

    Full Text Available Comunicamos un caso con dos melanomas "in situ", en un varón de 86 años, localizados en ambos lados de la cara con alto riesgo quirúrgico, quien fuera tratado con imiquimod al 5% una vez al día durante dos meses; los resultados hasta el momento, clínicos e histológicos han sido satisfactorios.A 86 years-old man with two melanomas "in situ" at both sides of his face, treated with imiquimod 5% are presented. The patient has a cardiovascular high risk due to isquemic heart disease, for that reason we start the treatment with imiquimod once a day for two months. The clinical and histological response was good and a follow up will be as long as we can.

  10. Primary pulmonary/pleural melanoma in a 13 year-old presenting as pleural effusion. (United States)

    Baniak, Nick; Podberezin, Mark; Kanthan, Selliah C; Kanthan, Rani


    Melanoma in children, adolescents, and young adults is uncommon and reported almost exclusively as cutaneous melanoma. Melanoma presenting as a pleural effusion is very rare in adults and not reported in the pediatric population. Additionally, primary pulmonary melanoma is overall very rare and undocumented in pediatric patients. Furthermore, the distinction between a primary pulmonary/pleural melanoma versus a regressed cutaneous melanoma with pulmonary/pleural metastases remains extremely challenging. We discuss a case of a previously healthy 13-year-old girl that presented with a left-sided pleural effusion. Investigations revealed a large mediastinal mass, left-sided pleural and pulmonary nodules, a sacral mass, and bone marrow infiltration. The neoplasm was subsequently diagnosed by morphology and immunocytochemistry with histological correlation as malignant melanoma. As no mucosal, eye, or cutaneous lesions were identified, we deliberate the likelihood of a regressed cutaneous melanoma with metastases versus primary pulmonary/pleural melanoma with pleural effusion and discuss its diagnostic approach.

  11. Clinical features of the head and neck mucosal melanoma. А review

    Directory of Open Access Journals (Sweden)

    A. V. Ignatova


    Full Text Available Melanoma is an aggressive and rare neoplasm of melanocytic origin. Mucosal melanomas of the head and neck account for 1 % of neoplasms, 0,2–8,0 4 % of all melanomas and over 50 % of all mucosal melanomas. To date, in Russian and foreign literature only few retrospective series and case reports have been reported on mucosal melanoma. Despite melanoma’s common histological origin, head and neck mucosal melanoma presentation has some specific features due to its anatomical localization and poor clinical outcomes compared with those of cutaneous melanomas. Mucosal melanoma has a high metastatic potential. Five-year overall survival does not exceed 30 %. Advances in understanding of the clinical presentation can be used for prediction of behaviour and prognosis of this disease. We considered and analised articles devoted to clinical features of head and neck mucosal melanoma according to its localization.

  12. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  13. New Therapies Offer Valuable Options for Patients with Melanoma (United States)

    Two phase III clinical trials of new therapies for patients with metastatic melanoma presented in June at the 2011 ASCO conference confirmed that vemurafenib and ipilimumab (Yervoy™) offer valuable new options for the disease.

  14. Spotlight on pembrolizumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Rajakulendran T


    Full Text Available Thanashan Rajakulendran,1 David N Adam2 1Department of Medicine, Division of Dermatology, Postgraduate Medical Education, 2Department of Medicine, Division of Dermatology, St Michael’s Hospital, University of Toronto, Toronto, ON, Canada Abstract: Metastatic melanoma is an aggressive cancer with a poor prognosis. Many approved therapies often do not achieve durable responses in patients. This underscores the need for novel therapeutic strategies. Recruiting a robust immune response is an important antineoplastic treatment strategy. Immune checkpoints offer a molecular target for modulating the immune response and a promising therapeutic target in metastatic melanoma. Here we discuss the recent approval of pembrolizumab by the US Food and Drug Administration for the treatment of metastatic melanoma and its impact on future management of the disease. Keywords: pembrolizumab, melanoma, immune checkpoint, PD-1, PD-L1

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

    Directory of Open Access Journals (Sweden)

    Asmar R


    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. Cutaneous malignant melanoma in association with mycosis fungoides. (United States)

    Evans, Alun V; Scarisbrick, Julia J; Child, F J; Acland, Katharine M; Whittaker, Sean J; Russell-Jones, Robin


    We retrospectively analyzed the first 461 cases entered into our cutaneous lymphoma database and found 285 cases of mycosis fungoides. We also identified 6 cases of malignant melanoma, all of which were found in patients with mycosis fungoides. The crude rate of melanoma in the general population in England, United Kingdom, in 1998 was 8.8/100,000 in men and 11.4/100,000 in women. The incidence of melanoma found in our cohort of patients with mycosis fungoides was far higher, and in 4 of the 6 patients cannot be explained on the basis of prior therapy. The reason for this association is unclear, but this report emphasizes the risk of second malignancies for patients with cutaneous T-cell lymphoma and melanoma.

  17. Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Chiarion-Sileni, Vanna; Grob, Jean-Jacques;


    Background On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had...... undergone complete resection of stage III melanoma. Methods After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months...... patients (1.1%) died owing to immune-related adverse events. Conclusions As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo...

  18. Germline TERT promoter mutations are rare in familial melanoma

    DEFF Research Database (Denmark)

    Harland, Mark; Petljak, Mia; Robles-Espinoza, Carla Daniela;


    Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57...... T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers....... The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte...

  19. Methods to Improve Adoptive T-Cell Therapy for Melanoma

    DEFF Research Database (Denmark)

    Donia, Marco; Hansen, Morten; Sendrup, Sarah L


    Further development of adoptive T-cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) has the potential to markedly change the long-term prognosis of patients with metastatic melanoma, and modifications of the original protocol that can improve its clinical efficacy are highly...... desirable. In this study, we demonstrated that a high in vitro tumor reactivity of infusion products was associated with clinical responses upon adoptive transfer. In addition, we systematically characterized the responses of a series of TIL products to relevant autologous short term-cultured melanoma cell...... lines from 12 patients. We provide evidence that antitumor reactivity of both CD8(+) and CD4(+) T cells could be enhanced in most TIL products by autologous melanoma sensitization by pretreatment with low-dose IFN-γ. IFN-γ selectively enhanced responses to tumor-associated antigens other than melanoma...

  20. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

    DEFF Research Database (Denmark)

    Larkin, James; Chiarion-Sileni, Vanna; Gonzalez, Rene


    BACKGROUND: Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] checkpoint inhibitor) have been shown to have complementary activity in metastatic melanoma. In this randomized, double-blind, phase 3 study, nivolumab...... alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma. METHODS: We assigned, in a 1:1:1 ratio, 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone. Progression...... melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-free survival than ipilimumab alone. In patients with PD-L1-negative tumors, the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone. (Funded by Bristol-Myers Squibb; Check...

  1. Transmission of donor melanoma to multiple organ transplant recipients. (United States)

    Morris-Stiff, G; Steel, A; Savage, P; Devlin, J; Griffiths, D; Portman, B; Mason, M; Jurewicz, W A


    Malignant melanoma represents the most common tumour responsible for donor-derived post transplantation malignancies. We report the varied presentation and outcome of three graft recipients (two kidney and hepatic) who developed metastatic melanoma following cadaveric organ transplantation from a single multiorgan donor. Two of the recipients presented with symptomatic metastatic lesions and the third patient, despite being carefully monitored, developed evidence of metastatic cutaneous melanoma. Two of the patients died as a direct result of their melanomas. The recipients of corneal and cardiac grafts remain disease-free. We conclude that despite careful screening, donor-derived tumours remain a not uncommon clinical entity. The identification of a lesion in one recipient should prompt immediate examination and investigation of the remaining recipients of multiorgan donations.

  2. Dermoscopy of Melanomas on the Trunk and Extremities in Asians.

    Directory of Open Access Journals (Sweden)

    Je-Ho Mun

    Full Text Available The incidence of melanoma among the Asian population is lower compared to that among the Western European population. These populations differed in their most common histopathologic subtypes, acral lentiginous melanoma being the most common in the Asian population. Although the dermoscopic features of the melanomas on the acral skin have been thoroughly investigated in the Asian population, studies concerning the dermoscopic patterns of melanomas on the non-acral skin have been scarce. The aim of this study was to investigate the dermoscopic patterns of melanomas on the trunk and extremities in the Asian population. To achieve this, we evaluated the dermoscopic patterns of 22 primary melanomas diagnosed at two university hospitals in Korea. In addition, 100 benign melanocytic lesions were included as the control group for comparative analysis. A P value less than 0.05 was regarded as statistically significant. Melanoma-associated dermoscopic features such as asymmetry (odds ratio [OR], 30.00, multicolor pattern (OR, 30.12, blotches (OR, 13.50, blue white veils (OR, 15.75, atypical pigment networks (OR, 9.71, irregular peripheral streaks (OR, 6.30, atypical vascular patterns (OR, 11.50, ulcers (OR, 15.83, atypical dots/globules (OR, 3.15, shiny white lines (OR, 5.88, and regression structures (OR, 7.06 were more commonly observed in patients with melanomas than in patients of the control group. The mean dermoscopic scores obtained on the 7-point checklist, revised 7-point checklist, 3-point checklist, ABCD rule, and CASH algorithm were 5.36, 3.41, 2.05, 6.89, and 9.68, respectively, in the primary melanomas, and 1.33, 0.93, 0.46, 2.45, and 3.60, respectively, in the control group (all, P < 0.001. The present study showed that melanoma-related dermoscopic patterns were common in Asian patients. Dermoscopy is a reliable diagnostic tool for the melanomas of the trunk and extremities in the Asian populations.

  3. The role of the Hippo pathway in melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Bruce Charles Baguley


    Full Text Available The Hippo signalling pathway comprises a series of cytoplasmic tumour suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory signalling arising from cell shape and polarity, as well as by a variety of extracellular signalling molecules. When active, the pathway maintains the transcriptional activators YAP and TAZ in phosphorylated forms in the cytoplasm, preventing cell proliferation. When the Hippo pathway is inactivated, YAP and TAZ are translocated to the nucleus and induce the expression of a variety of proteins concerned with entry into the cell division cycle, such as cyclin D1 and Fox M1, as well as the inhibition of apoptosis. The failure of the Hippo pathway has been implicated in the development of many different types of cancer but there is limited information available as to its involvement in melanoma. We hypothesise here firstly that the Hippo pathway is involved in maintaining density of cutaneous melanocytes on the basement membrane at the junction of the epidermis and the dermis, and secondly, that its function is disturbed in melanoma. We have analysed a series of 23 low passage human melanoma lines as well as in cultures of normal melanocytes, and find that melanocytes, as well as all melanoma cell lines examined express TAZ. Melanocytes and most melanoma lines also express YAP. E-cadherin, an upstream regulator of the Hippo pathway, and Axl, a receptor tyrosine kinase regulated by the Hippo pathway, are expressed in melanocytes and in several melanoma cell lines. These observations, together with published evidence for the presence of Merlin, Lats1/2 and MST1/2 in melanocytes and melanoma cells, support the hypothesis that the Hippo pathway is an important component of melanocyte and melanoma behaviour.

  4. Ipilimumab: from preclinical development to future clinical perspectives in melanoma. (United States)

    Letendre, Paul; Monga, Varun; Milhem, Mohammed; Zakharia, Yousef


    The arsenal for the treatment of metastatic melanoma is limited. A new approach to therapy using checkpoint blockade has improved overall survival in this patient population. Ipilimumab a CTLA-4 monoclonal antibody is a first in class drug that has pioneered this revolution. In this review, the authors provide an account of the different stages that led to the development of ipilimumab, its approval in the clinical setting for the treatment of advanced melanoma and ongoing investigations of combinatorial immune therapy.

  5. Predicting outcome in melanoma: where are we now?

    LENUS (Irish Health Repository)

    Jennings, L


    Melanoma incidence continues to rise in most countries. This is of grave concern, given the mortality rate in a relatively young population. Current staging tools are limited in their ability to predict accurately those at risk of metastatic disease, relapse and treatment failure. This overview comprehensively reviews relevant literature, with the focus on the last 5 years, and discusses the current state of traditional and emerging novel methods of staging for melanoma and their effect on prognosis in this population.

  6. Equipment for Dynamic Electron Contact Thermography of Skin Melanoma

    Directory of Open Access Journals (Sweden)

    Biloshenko, V.A.


    Full Text Available The computer-assisted equipment complex for dynamic electron contact thermography of skin melanoma was developed. The cooling device on the basis of Peltier cell, matrix scanner with intellectual converters «temperature/digital code» and original customized software for visualizing temperature maps and their primary mathematical processing were created. Prospects in combined use of complex and dermatoscopy to improve the validity of skin melanoma early diagnostics are experimentally proved.

  7. Nuclear stiffening inhibits migration of invasive melanoma cells


    Ribeiro, Alexandre J. S.; Khanna, Payal; Sukumar, Aishwarya; Dong, Cheng; Dahl, Kris Noel


    During metastasis, melanoma cells must be sufficiently deformable to squeeze through extracellular barriers with small pore sizes. We visualize and quantify deformability of single cells using micropipette aspiration and examine the migration potential of a population of melanoma cells using a flow migration apparatus. We artificially stiffen the nucleus with recombinant overexpression of Δ50 lamin A, which is found in patients with Hutchison Gilford progeria syndrome and in aged individuals....

  8. Spectral regions contributing to melanoma: a personal view. (United States)

    Setlow, R B


    Although human cutaneous melanoma is a complicated disease, the principal etiologic agent for its incidence in fair skin individuals is exposure to sunlight. In order to understand the epidemiology of melanoma - temporal effects, latitude effects, sunscreen effects, albino susceptibility, and differences from nonmelanoma skin cancer -one must approach the problem by obtaining clues indicating which wavelengths in sunlight are effective in inducing melanomas. One way is to use an animal model. At present, the only suitable model is a backcross hybrid of small tropical fish of the genus Xiphophorus, bred to have only one tumor suppressor gene. Single UV exposures to 7-d-old fish induce melanomas readily observable by 4 mo. The initial slopes of dose-response curves for exposures at 302, 313, 365, 405, 436, and 547 nm yield sensitivity as a function of wavelength. This action spectrum does not look like the spectrum for light absorption by DNA (mostly in the UVB), but has appreciable sensitivities in the UVA and visible regions, and looks like a direct effect of light on DNA plus a large indirect effect on DNA by absorption of light by the intracellular melanin. Because the UVB is only a fraction of solar irradiance, one may calculate that 90% of melanoma induction in humans arises from UVA and visible, assuming the human spectrum is similar to the fish spectrum. The implications of this calculation are that (i) depletion of stratospheric ozone will not affect melanoma incidence, (ii) an increase in sun exposure time as a result of using UVB sunscreens could increase the risk of melanoma, and (iii) the use of high UVA sun tanning devices could increase the risk of melanoma.

  9. The behavior of reticulin fibers in and around melanomas. (United States)

    Leviatan, A; Steigleder, G K


    A previous study confirmed the correlation between the vertical diameter of malignant melanomas and prognosis. In 72 of these tumors we examined the pattern and number of reticulin fibers (RF) around and within the melanomas. An increase in vertical diameter was accompanied by an increase of RF within the tumor and a decrease of RF on its edges. The differences were not sufficienty signficant to allow firm prognosis.

  10. Molecular targets in melanoma: time for `ethnic personalization'


    Morita, Shane Y; Markovic, Svetomir N.


    Worldwide, the incidence of melanoma continues to rise. Although not the most common cutaneous malignancy, it is the most lethal. Until recently, while other oncologic patients benefited from the nuances of targeted therapy, those afflicted with melanoma lacked that option. In 2011, the US FDA approved an oral agent that targets the BRAF oncogene. As this information is promising, it is essential that other populations (in addition to Caucasians) are examined, in order to further comprehend t...

  11. Unravelling molecular mechanisms underlying therapy resistance in cutaneous melanoma


    Azimi, Alireza


    For many years the standard treatment of advanced metastatic melanoma with chemotherapeutic agents, including temozolomide (TMZ) and dacarbazine (DTIC), has been unsuccessful. The paradigm shift in melanoma treatment occurred with the identification of mutations in the BRAF gene that leads to a constitutively active BRAF V600E protein. This resulted in the development of BRAF mutant targeted therapies with small molecule inhibitors and showed favorable response in patient...

  12. Antiangiogenic Metargidin Peptide (AMEP) Gene Therapy in Disseminated Melanoma

    DEFF Research Database (Denmark)

    Spanggaard, Iben; Gehl, Julie


    Gene delivery by electroporation is an efficient method for transfecting genes into various tissues including tumors. Here we present the treatment protocol used in a phase 1 study on gene electrotransfer of plasmid DNA encoding an antiangiogenic peptide into cutaneous melanoma.......Gene delivery by electroporation is an efficient method for transfecting genes into various tissues including tumors. Here we present the treatment protocol used in a phase 1 study on gene electrotransfer of plasmid DNA encoding an antiangiogenic peptide into cutaneous melanoma....

  13. Screening for reducing morbidity and mortality in malignant melanoma

    DEFF Research Database (Denmark)

    Johansson, Minna; Brodersen, John; Gøtzsche, Peter C.


    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects on morbidity and mortality of screening for malignant melanoma in the general population.......This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects on morbidity and mortality of screening for malignant melanoma in the general population....

  14. Do hormones influence melanoma? Facts and controversies. (United States)

    Gupta, Amie; Driscoll, Marcia S


    The issue of whether hormones influence malignant melanoma (MM) has been controversial for many years. Although early case reports demonstrated a negative effect of hormones, recent evidence has not supported a potential role for hormones in MM. We address whether exogenous and endogenous hormones influence a woman's risk for MM or affect her prognosis if diagnosed with MM. Multiple epidemiologic studies show the use of oral contraceptives or hormone replacement therapy does not appear to increase a woman's risk for MM. Pregnancy does not appear to influence a woman's risk of MM, nor does pregnancy appear to affect prognosis in the woman diagnosed with MM. When counseling the woman who is diagnosed with MM during pregnancy or during the childbearing years, future use of oral contraceptives or hormone replacement therapy is not contraindicated; counseling concerning future pregnancies should be done on a case-by-case basis, with emphasis placed on established prognostic factors for MM.

  15. Functional specialization in proline biosynthesis of melanoma.

    Directory of Open Access Journals (Sweden)

    Jessica De Ingeniis

    Full Text Available Proline metabolism is linked to hyperprolinemia, schizophrenia, cutis laxa, and cancer. In the latter case, tumor cells tend to rely on proline biosynthesis rather than salvage. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C, and then to proline via pyrroline-5-carboxylate reductases (PYCRs. Here, the role of three isozymic versions of PYCR was addressed in human melanoma cells by tracking the fate of (13C-labeled precursors. Based on these studies we conclude that PYCR1 and PYCR2, which are localized in the mitochondria, are primarily involved in conversion of glutamate to proline. PYCRL, localized in the cytosol, is exclusively linked to the conversion of ornithine to proline. This analysis provides the first clarification of the role of PYCRs to proline biosynthesis.

  16. Functional Specialization in Proline Biosynthesis of Melanoma (United States)

    Richardson, Adam D.; Scott, David A.; Aza-Blanc, Pedro; De, Surya K.; Kazanov, Marat; Pellecchia, Maurizio; Ronai, Ze'ev; Osterman, Andrei L.; Smith, Jeffrey W.


    Proline metabolism is linked to hyperprolinemia, schizophrenia, cutis laxa, and cancer. In the latter case, tumor cells tend to rely on proline biosynthesis rather than salvage. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). Here, the role of three isozymic versions of PYCR was addressed in human melanoma cells by tracking the fate of 13C-labeled precursors. Based on these studies we conclude that PYCR1 and PYCR2, which are localized in the mitochondria, are primarily involved in conversion of glutamate to proline. PYCRL, localized in the cytosol, is exclusively linked to the conversion of ornithine to proline. This analysis provides the first clarification of the role of PYCRs to proline biosynthesis. PMID:23024808

  17. Parkin Somatic Mutations Link Melanoma and Parkinson's Disease. (United States)

    Levin, Lotan; Srour, Shani; Gartner, Jared; Kapitansky, Oxana; Qutob, Nouar; Dror, Shani; Golan, Tamar; Dayan, Roy; Brener, Ronen; Ziv, Tamar; Khaled, Mehdi; Schueler-Furman, Ora; Samuels, Yardena; Levy, Carmit


    Epidemiological studies suggest a direct link between melanoma and Parkinson's disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson's disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases.

  18. Using risk factors for detection and prognostication of uveal melanoma

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    Pukhraj Rishi


    Full Text Available The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF, symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large, local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis.

  19. TANGO is a tumor suppressor of malignant melanoma. (United States)

    Arndt, Stephanie; Bosserhoff, Anja K


    The TANGO gene was originally identified as a new family member of the melanoma inhibitory activity gene family. The gene codes for a 14 kDa protein of so far unknown function. In our study we revealed that TANGO was downregulated or lost in 9 melanoma cell lines when compared to normal melanocytes and in most of the 8 tumor samples analyzed. The losses were associated with advanced stage of the disease. These results were confirmed in situ by immunohistochemistry on 10 paraffin-embedded sections of human malignant melanoma primary tumors and melanoma skin metastases. A small reduction of TANGO was also seen in different benign and atypical nevi when compared to normal skin. For functional analysis of TANGO we evaluated TANGO re-expressing melanoma cell clones and antisense TANGO cell clones with a complete loss of TANGO. Functional assays with TANGO transfected or treated cell lines revealed that TANGO expression reduces motility, whereas reduction of TANGO enhances migration. Our studies, therefore, indicate that reduction of TANGO expression contributes to tumor progression. These results taken together provide the first indications for a tumor suppressor role of TANGO gene in human malignant melanoma.

  20. The effect of pentamidine on melanoma ex vivo. (United States)

    Smith, Jason; Stewart, Benjamin J; Glaysher, Sharon; Peregrin, Katharine; Knight, Louise A; Weber, David J; Cree, Ian A


    Pentamidine is a small molecule inhibitor of the Ca(+)-binding protein S100B and disrupts the S100B-p53 protein-protein interaction; this is thought to restore wild-type p53 tumour suppressor function in melanoma. Additional anticancer effects may be the result of inhibition of regenerating liver family phosphatases. In this study, we have used a standardized ATP-tumour chemosensitivity assay to investigate the effect of pentamidine on cells derived from 18 skin melanoma samples and one uveal melanoma sample. The cells were tested at six concentrations from which the IC(50) and IC(90) were calculated. To allow comparison between samples, an index(sum) was calculated based on the percentage of tumour growth inhibition at each concentration. Of the skin melanoma samples tested, 78% exhibited an index(sum) less than 300 indicating strong inhibition. The median index(sum) of 237 also indicates considerable activity against these samples. The median IC(90) (30.2 micromol/l) may be clinically achievable in a proportion of patients. The uveal melanoma sample exhibited an index(sum) of 333 indicating moderate inhibition, and 86% inhibition at test drug concentration (37.96 micromol/l). These results show that pentamidine has activity against melanoma, and support the prospect of its development for therapeutic use.

  1. Comparison of molecular abnormalities in vulvar and vaginal melanomas. (United States)

    Aulmann, Sebastian; Sinn, Hans P; Penzel, Roland; Gilks, C Blake; Schott, Sarah; Hassel, Jessica C; Schmidt, Dietmar; Kommoss, Friedrich; Schirmacher, Peter; Kommoss, Stefan


    Malignant melanoma of the vulva and vagina is relatively uncommon and accounts for melanomas in women. The aim of our study was to establish the biological properties and evaluate potential therapeutic targets in these tumors. We collected a series of 65 cases from three centers and re-evaluated the tumor tissue for predominant growth pattern (superficial spreading, nodular, and mucosal lentiginous) and tumor thickness. KIT (CD117) expression was detected immunohistochemically. In addition, tumors were screened for BRAF, NRAS, and KIT mutations by PCR and DNA sequencing as well as for KIT amplifications by fluorescence in situ hybridization. None of the cases contained BRAF mutations. NRAS mutations and KIT amplifications were detected in similar frequency (∼12%) in tumors of the vulva and vagina. In contrast, KIT mutations were present in 18% of primary melanomas of the vulva, but in none of the tumors arising in the vagina. Moderate or strong KIT protein expression was detected in 30 cases, including all tumors with KIT mutations and 6 of the 7 with KIT amplifications. In conclusion, BRAF mutations are virtually absent in melanomas originating from the vulva or vagina, whereas NRAS mutations and KIT amplifications occur in both locations. KIT mutations appear to be specific for melanomas of the vulva, suggesting that in spite of the anatomic proximity, the development of vulvar and vaginal melanomas involves different molecular alterations which may be targeted by novel treatment approaches.

  2. CRAF R391W is a melanoma driver oncogene (United States)

    Atefi, Mohammad; Titz, Bjoern; Tsoi, Jennifer; Avramis, Earl; Le, Allison; Ng, Charles; Lomova, Anastasia; Lassen, Amanda; Friedman, Michael; Chmielowski, Bartosz; Ribas, Antoni; Graeber, Thomas G.


    Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas. PMID:27273450


    Institute of Scientific and Technical Information of China (English)

    Shui-qing Ma; Chun-mei Bai; Sen Zhong; Xiao-hong Yu; Jing-he Lang


    Objective To investigate the clinical and pathological characteristics of primary cervical malignant melanoma,and its prognosis.Methods The clinical and pathological data of four patients with primary malignant melanoma of the cervix were analyzed retrospectively. Nerve tissue protein S-100 and monoclonal antibody to melanoma (HMB-45) were measured in all cases by immunohistochemical method. All four patients received radical hysterectomy. Three of them received chemotherapy preoperation or postoperation, and one of them received biotherapy with interferon-γ and interleukin-2 at the same time. All the cases were followed up.Results The average age of four patients was 45 years. Clinical symptoms presented with irregular vaginal bleeding,postcoital bleeding, or increase of vaginal discharge. Gynecologic examination showed polypus papilla cauliflower-shaped or nodulated black-brown or black-blue mass on the cervix. All the four cases were pathologically diagnosed with cervical malignant melanoma. S-100 and HMB-45 were positive in all patients. Two patients died at 6 and 41 months postoperation, respectively. The other two patients survived for 3.5 and 7 years postoperation, respectively.Conclusions S-100 protein and HMB-45 play very important roles in the diagnosis of primary malignant melanoma of cervix. Radical hysterectomy, chemotherapy combined with dimethyl triazemo imidazole carboxamide and biological therapies may improve the prognosis of the primary malignant melanoma of cervix ifthe disease could be diagnosed in an early stage.

  4. Prognostic significance of autoimmunity during treatment of melanoma with interferon. (United States)

    Krauze, Michal T; Tarhini, Ahmad; Gogas, Helen; Kirkwood, John M


    Since the pivotal cooperative group trials in the 1980's-90's,, high-dose interferon (HDI) has been the standard of adjuvant therapy. Despite multiple other trials evaluating potential new therapies in melanoma, HDI remains the only FDA-approved therapy for stage IIB and III melanoma. Initial reports from the more recent phase III international trials of modifications of the original HDI regimen linked the appearance of autoimmunity with improved outcomes of disease. Trials of high-dose interleukin-2, many years earlier, reported anecdotal observations that were consistent with the hypothesis that autoimmunity and clinical benefit of immunotherapies of melanoma are linked with one another. The only prospectively conducted study examining the appearance of clinical and laboratory evidence of autoimmunity during HDI therapy was published by Gogas and colleagues, demonstrating statistically significant impact on relapse-free survival and overall survival. Retrospectively conducted studies of different intermediate dosage regimens of interferon (IFN) have not fully confirmed the linkage of serological evidence of autoimmunity and improved survival outcomes. With the emergence of new immunotherapies in treatment of melanoma, this review highlights the importance of autoimmunity for future applications in melanoma and reviews significant differences of past studies evaluating the appearance of autoimmunity during IFN therapy in high-risk melanoma.

  5. miR-148 regulates Mitf in melanoma cells.

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    Benedikta S Haflidadóttir

    Full Text Available The Microphthalmia associated transcription factor (Mitf is an important regulator in melanocyte development and has been shown to be involved in melanoma progression. The current model for the role of Mitf in melanoma assumes that the total activity of the protein is tightly regulated in order to secure cell proliferation. Previous research has shown that regulation of Mitf is complex and involves regulation of expression, splicing, protein stability and post-translational modifications. Here we show that microRNAs (miRNAs are also involved in regulating Mitf in melanoma cells. Sequence analysis revealed conserved binding sites for several miRNAs in the Mitf 3'UTR sequence. Furthermore, miR-148 was shown to affect Mitf mRNA expression in melanoma cells through a conserved binding site in the 3'UTR sequence of mouse and human Mitf. In addition we confirm the previously reported effects of miR-137 on Mitf. Other miRNAs, miR-27a, miR-32 and miR-124 which all have conserved binding sites in the Mitf 3'UTR sequence did not have effects on Mitf. Our data show that miR-148 and miR-137 present an additional level of regulating Mitf expression in melanocytes and melanoma cells. Loss of this regulation, either by mutations or by shortening of the 3'UTR sequence, is therefore a likely factor in melanoma formation and/or progression.

  6. Nodal Melanoma Metastasis under Infliximab Therapy in a Patient with Nevoid Melanoma First Misdiagnosed as Benign Nevus: A Potentially Dangerous Diagnostic Pitfall in the Era of Biologic Therapies

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    Gilles Safa


    Full Text Available We report the case of a 53-year-old Caucasian woman who developed nodal melanoma metastasis under infliximab therapy 2 years after the removal of a nevoid melanoma, which was initially misdiagnosed as a benign compound nevus. This case illustrates the potential link between tumor necrosis factor (TNF-α inhibition and the reactivation of latent melanoma. Furthermore, this case highlights the need for a complete skin examination before using anti-TNF-α therapy to rule out atypical malignant lesions or melanomas that can easily be missed because of presentations such as nevoid melanoma.

  7. Diagnostic utility of epithelial and melanocitic markers with double sequential immunohistochemical staining in differentiating melanoma in situ from invasive melanoma. (United States)

    Parra-Medina, Rafael; Morales, Samuel David


    Identification of melanoma in situ and its distinction from invasive melanoma is important because of its significant impact on morbidity and mortality. However, this interpretation can cause pitfalls in the diagnosis even with the use of immunohistochemistry. The aim of this study is to evaluate the diagnostic utility of epithelial makers (AE1/AE3, CK5/6, and p63) combined with melanocytic markers (HMB-45, S-100, or Melan-A) using dual-color immunohistochemical staining, performed on a single slide by sequentially applying the antibodies. In this study, we show 4 cases in which examination of routine hematoxylin and eosin slides did not allow for clear-cut distinction between in situ and invasive melanoma and highlight the utility of the double-staining method. Therefore, we recommend this double-staining method with melanocytic and epithelial markers as a helpful adjunct to the diagnosis of cases with a differential diagnosis between in situ and invasive melanoma.

  8. Future perspectives in melanoma research: meeting report from the "Melanoma Bridge", Napoli, December 5th-8th 2013. (United States)

    Ascierto, Paolo A; Grimaldi, Antonio M; Anderson, Ana Carrizosa; Bifulco, Carlo; Cochran, Alistair; Garbe, Claus; Eggermont, Alexander M; Faries, Mark; Ferrone, Soldano; Gershenwald, Jeffrey E; Gajewski, Thomas F; Halaban, Ruth; Hodi, F Stephen; Kefford, Richard; Kirkwood, John M; Larkin, James; Leachman, Sancy; Maio, Michele; Marais, Richard; Masucci, Giuseppe; Melero, Ignacio; Palmieri, Giuseppe; Puzanov, Igor; Ribas, Antoni; Saenger, Yvonne; Schilling, Bastian; Seliger, Barbara; Stroncek, David; Sullivan, Ryan; Testori, Alessandro; Wang, Ena; Ciliberto, Gennaro; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena


    The fourth "Melanoma Bridge Meeting" took place in Naples, December 5 to 8th, 2013. The four topics discussed at this meeting were: Diagnosis and New Procedures, Molecular Advances and Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers.

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

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    Nouritza M. Torossian


    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.

  10. Termoterapia transpupilar em melanoma maligno da coróide Transpupillary thermotherapy for malignant choroidal melanoma

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    Martha M. Motomo Chojniak


    Full Text Available Objetivo: Vários métodos vem sendo utilizados para o tratamento dos melanomas da coróide. A proposta deste trabalho preliminar é avaliar a eficácia da termoterapia transpupilar (TTT como tratamento primário de melanomas da coróide pequenos. Métodos: Foi realizado um trabalho prospectivo e não-randomizado para avaliar os aspectos clínicos, resposta do tumor, complicações e resultados visuais de pacientes portadores de melanomas da coróide pequenos (até 4,0 mm de espessura e 12 mm de diâmetro basal tratados por termoterapia transpupilar utilizando-se sucessivas aplicações de laser diodo contínuo de 810 nm. Resultados: Foram tratados 11 pacientes portadores de melanomas da coróide pequenos. O tumor era único e pigmentado em 100% dos casos. Crescimento documentado esteve presente em 5 pacientes (45,45% previamente ao tratamento e fatores de risco para crescimento ou metástase estavam presentes em todos os pacientes. O tempo de seguimento destes pacientes a partir do tratamento foi em média de 5,72 meses (3 - 8 meses. Foram utilizadas 3 sessões de laser em 5 pacientes (45,45% e 4 sessões em 6 pacientes (64,64%. As lesões apresentavam, por ocasião do diagnóstico, uma espessura média de 2,65 mm (1,85-3,86 mm, com maior diâmetro basal médio de 7,98 mm (4,2-11,33 mm. Após o tratamento, a espessura média foi de 1,83 mm (0,98-2,93 mm e o maior diâmetro basal médio foi de 6,59 mm (3,81 mm -10,67 mm. Das lesões tratadas, 100% apresentaram diminuição da altura e do máximo diâmetro basal, tendo sido a diminuição média da espessura de 0,89 mm e do máximo diâmetro basal de 1,39 mm. A acuidade visual manteve-se inalterada em 5 casos (45,45% e piorou após o tratamento em 6 casos (54,54%. Ocorreram complicações em 9 casos, tendo sido considerada complicação grave 1 caso de descolamento parcial da retina (9,09%; as outras complicações foram consideradas leves: pequenas hemorragias intra-retinianas em 7 pacientes (63

  11. Ultraviolet A does not induce melanomas in a Xiphophorus hybrid fish model. (United States)

    Mitchell, David L; Fernandez, André A; Nairn, Rodney S; Garcia, Rachel; Paniker, Lakshmi; Trono, David; Thames, Howard D; Gimenez-Conti, Irma


    We examined the wavelength dependence of ultraviolet (UV) ra-diation (UVR)-induced melanoma in a Xiphophorus backcross hybrid model previously reported to be susceptible to melanoma induction by ultraviolet A (UVA) and visible light. Whereas ultraviolet B (UVB) irradiation of neonates yielded high frequencies of melanomas in pigmented fish, UVA irradiation resulted in melanoma frequencies that were not significantly different from unirradiated fish. Spontaneous and UV-induced melanoma frequencies correlated with the degree of pigmentation as expected from previous studies, and the histopathology phenotypes of the melanomas were not found in significantly different proportions in UV-treated and -untreated tumor-bearing fish. Our results support the conclusion that a brief early-life exposure to UVB radiation causes melanoma formation in this animal model. These data are consistent with an essential role for direct DNA damage, including cyclobutane dimers and (6-4) photoproducts, in the etiology of melanoma.

  12. A novel fully-humanised 3D skin equivalent to model early melanoma invasion (United States)

    Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O’Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E


    Metastatic melanoma remains incurable, emphasising the acute need for improved research models to investigate the underlying biological mechanisms mediating tumour invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully-humanised 3D skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumour invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth phase melanoma invasion. PMID:26330548

  13. A multilingual assessment of melanoma information quality on the Internet. (United States)

    Bari, Lilla; Kemeny, Lajos; Bari, Ferenc


    This study aims to assess and compare melanoma information quality in Hungarian, Czech, and German languages on the Internet. We used country-specific Google search engines to retrieve the first 25 uniform resource locators (URLs) by searching the word "melanoma" in the given language. Using the automated toolbar of Health On the Net Foundation (HON), we assessed each Web site for HON certification based on the Health On the Net Foundation Code of Conduct (HONcode). Information quality was determined using a 35-point checklist created by Bichakjian et al. (J Clin Oncol 20:134-141, 2002), with the NCCN melanoma guideline as control. After excluding duplicate and link-only pages, a total of 24 Hungarian, 18 Czech, and 21 German melanoma Web sites were evaluated and rated. The amount of HON certified Web sites was the highest among the German Web pages (19%). One of the retrieved Hungarian and none of the Czech Web sites were HON certified. We found the highest number of Web sites containing comprehensive, correct melanoma information in German language, followed by Czech and Hungarian pages. Although the majority of the Web sites lacked data about incidence, risk factors, prevention, treatment, work-up, and follow-up, at least one comprehensive, high-quality Web site was found in each language. Several Web sites contained incorrect information in each language. While a small amount of comprehensive, quality melanoma-related Web sites was found, most of the retrieved Web content lacked basic disease information, such as risk factors, prevention, and treatment. A significant number of Web sites contained malinformation. In case of melanoma, primary and secondary preventions are of especially high importance; therefore, the improvement of disease information quality available on the Internet is necessary.

  14. ABT-737 synergizes with Bortezomib to kill melanoma cells

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    Steven N. Reuland


    The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-XL, or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.

  15. Treatment of cutaneous melanoma: current approaches and future prospects

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    Alain P Algazi


    Full Text Available Alain P Algazi1, Christopher W Soon2, Adil I Daud11Department of Medicine, Division of Hematology and Oncology, 2Department of Dermatology, University of California, San Francisco San Francisco, CA, USAAbstract: Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible.Keywords: melanoma, resection, immune modulation, small molecule kinase inhibitors, chemotherapy, clinical trials

  16. Epidemiología del melanoma cutáneo Epidemiology of cutaneous melanoma

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    R M C Leitner


    Full Text Available Durante las últimas décadas hubo un aumento de la incidencia del melanoma cutáneo en la población caucásica del mundo, aunque este tumor puede afectar a cualquier grupo étnico. En la actualidad se considera a la exposición solar intermitente como un factor de riesgo cierto, en el desarrollo del melanoma cutáneo. La incidencia del melanoma cutáneo en Auckland, Nueva Zelanda, es la mayor del mundo. En Europa, la incidencia y la mortalidad fue creciente hasta que en la década de los 80 se estabilizó. En EEUU también se observó una estabilización de la incidencia. Con respecto a la edad, según la bibliografía consultada la incidencia aumenta a partir de los 20 años; en algunos pacientes con más de 200 nevos y sin pautas de protección solar antes de los 5 años de vida. También se observa aumento de la incidencia en los adultos mayores de 60 años de edad. Con respecto al sexo, en los EEUU y la Argentina es más frecuente en los hombres y en Europa en el sexo femenino.During the last decades there was an increase of incidence of cutaneous melanoma in Caucasian population worldwide, but this tumor can affect any ethnic group. Nowadays, the intermittent solar exposition is a well known predisposing factor. The incidence in Auckland, New Zealand, is the highest in the world. In Europe and in the USA, the incidence and mortality rates decreased until the 80's when it stabilized. Regarding the age of appearance, the incidence increases starting at 20 years of age in patients with more than 200 nevi and without history of sun protection in childhood. There was also an increase in the incidence in adults (>60 y-o. The distribution by sex in USA and Argentina is more frequent in males and in Europe in females.

  17. CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma


    Price, Matthew A.; Wanshura, Leah E. Colvin; Yang, Jianbo; Carlson, Jennifer; Xiang, Bo; Li, Guiyuan; Ferrone, Soldano; Dudek, Arkadiusz Z.; Turley, Eva A.; McCarthy, James B.


    Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified as a highly immunogenic tumor antigen on the surface of melanoma cells, is associated with melanoma tumor formation and poor prognosis in certain melanomas and several other tumor types. The complex mechanisms by which CSPG4 affects melanoma progression have started to be defined, in particular the association with other cell surface proteins and receptor tyrosine kinases (RTKs) and its central role...

  18. Primary intracranial malignant melanoma in an adolescent girl: A case report


    Sajeeb Mondal; Rajashree Pradhan; Subrata Pal; Supratik Bhattacharya; Arindam Banerjee; Debosmita Bhattacharyya


    Primary intracranial malignant melanoma is a very rare tumor, and most of the central nervous system melanomas are metastatic diseases. Diagnosis needs extensive dermatological, opthalmological, and radiological workup to exclude metastatic melanoma. Histologically, it should be differentiate from benign melanocytic lesions, pigmented choroid plexus carcinoma, and pigmented papillary medulloblastoma. Here, we are reporting a case of primary malignant melanoma of posterior fossa in an adolesce...

  19. Recent advances in sunlight-induced carcinogenesis using the Xiphophorus melanoma model✰


    Fernandez, André A.; Paniker, Lakshmi; Garcia, Rachel; Mitchell, David L.


    Unlike breast and prostate cancers, the nature and sequence of critical genetic and epigenetic events involved in the initiation and progression of melanoma is not well understood. A contributing factor to this dilemma, especially given our current understanding of the importance of UV light in melanoma etiology, is the lack of quality UV-inducible melanoma animal models. In this study we elaborate on the capability of UV light to induce cutaneous malignant melanomas (CMM) in Xiphophorus fish...

  20. 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.

  1. Fine needle aspiration biopsy to reestablish cell culture in an animal model of uveal melanoma


    Correa, Zelia Maria da Silva; Marshall,Jean-Claude; Souza Filho,João Pessoa de; Odashiro, Alexandre Nakao; Burnier, Jr.,Miguel Noel


    PURPOSE: To access the reliability of fine-needle aspiration biopsy in harvesting a sufficient amount of viable melanoma cells to establish a cell culture and maintain a melanoma cell line from an animal model of uveal melanoma. METHODS: For this study, fifteen male New Zealand albino rabbits had their right eye surgically inoculated with uveal melanoma cell line 92.1. The animals were immunosupressed with cyclosporine A using a dose schedule previously published. The animals were followed fo...

  2. Frequency and Characteristics of Familial Melanoma in Spain: The FAM-GEM-1 Study (United States)

    Márquez-Rodas, Iván; Martín González, Manuel; Nagore, Eduardo; Gómez-Fernández, Cristina; Avilés-Izquierdo, Jose Antonio; Maldonado-Seral, Cayetana; Soriano, Virtudes; Majem-Tarruella, Margarita; Palomar, Virginia; Maseda, Rocio; Martín-Carnicero, Alfonso; Puertolas, Teresa; Godoy, Elena; Cerezuela, Pablo; Ochoa de Olza, Maria; Campos, Begoña; Perez-Ruiz, Elisabeth; Soria, Ainara; Gil-Arnaiz, Irene; Gonzalez-Cao, Maria; Galvez, Elisa; Arance, Ana; Belon, Joaquin; de la Cruz-Merino, Luis; Martín-Algarra, Salvador


    Introduction 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. Patients and methods 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. Results 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. Conclusions 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. PMID:25874698

  3. Radiosensitivity of Human Melanoma Cell Lines

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R. M.; Medina, V.; Cricco, G.; Mohamed, N.; Martin, G.; Nunez, M.; Croci, M.; Crescenti, E. J.; Rivera, E. S.


    Cutaneous melanoma is a skin cancer resulting from the malign transformation of skin-pigment cells, the melanocytes. The radiotherapy, alone or in combination with other treatment, is an important therapy for this disease. the objective of this paper was to determine in vitro the radiosensitivity of two human melanoma cell lines with different metastatic capability: WM35 and MI/15, and to study the effect of drugs on radiobiological parameters. The Survival Curves were adjusted to the mathematical Linear-quadratic model using GrapsPad Prism software. Cells were seeded in RPMI medium (3000-3500 cells/flask), in triplicate and irradiated 24 h later. The irradiation was performed using an IBL 437C H Type equipment (189 TBq, 7.7 Gy/min) calibrated with a TLD 700 dosimeter. The range of Doses covered from 0 to 10 Gy and the colonies formed were counted at day 7th post-irradiation. Results obtained were: for WM35, {alpha}=0.37{+-}0.07 Gy''-1 and {beta}=0.06{+-}0.02 Gy''-2, for M1/15m {alpha}=0.47{+-}0.03 Gy''-1 and {beta}=0.06{+-}0.01 Gy''-2. The {alpha}/{beta} values WM35: {alpha}/{beta} values WM35: {alpha}/{beta}=6.07 Gy and M1/15: {alpha}/{beta}{sub 7}.33 Gy were similar, independently of their metastatic capabillity and indicate that both lines exhibit high radioresistance. Microscopic observation of irradiated cells showed multinuclear cells with few morphologic changes non-compatible with apoptosis. By means of specific fluorescent dyes and flow cytometry analysis we determined the intracellular levels of the radicals superoxide and hydrogen peroxide and their modulation in response to ionizing radiation. The results showed a marked decreased in H{sub 2}O{sub 2} intracellular levels with a simultaneous increase in superoxide that will be part of a mechanism responsible for induction of cell radioresistance. This response triggered by irradiated cells could not be abrogated by different treatments like histamine or the

  4. Screening Program Reduced Melanoma Mortality at the Lawrence Livermore National Laboratory, 1984-1996

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, MD, J S; II, PhD, D; MD, PhD, M


    Worldwide incidence of cutaneous malignant melanoma has increased substantially, and no screening program has yet demonstrated reduction in mortality. We evaluated the education, self examination and targeted screening campaign at the Lawrence Livermore National Laboratory (LLNL) from its beginning in July 1984 through 1996. The thickness and crude incidence of melanoma from the years before the campaign were compared to those obtained during the 13 years of screening. Melanoma mortality during the 13-year period was based on a National Death Index search. Expected yearly deaths from melanoma among LLNL employees were calculated by using California mortality data matched by age, sex, and race/ethnicity and adjusted to exclude deaths from melanoma diagnosed before the program began or before employment at LLNL. After the program began, crude incidence of melanoma thicker than 0.75 mm decreased from 18 to 4 cases per 100,000 person-years (p = 0.02), while melanoma less than 0.75mm remained stable and in situ melanoma increased substantially. No eligible melanoma deaths occurred among LLNL employees during the screening period compared with a calculated 3.39 expected deaths (p = 0.034). Education, self examination and selective screening for melanoma at LLNL significantly decreased incidence of melanoma thicker than 0.75 mm and reduced the melanoma-related mortality rate to zero. This significant decrease in mortality rate persisted for at least 3 yr after employees retired or otherwise left the laboratory.

  5. File list: ALL.Epd.20.AllAg.Melanoma [Chip-atlas[Archive

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  17. Detection of circulating tumor lysate-reactive CD4+ T cells in melanoma patients

    DEFF Research Database (Denmark)

    Ladekarl, Morten; Agger, Ralf; Fleischer, Charlotte C


    PURPOSE: We wanted to study whether an allogeneic melanoma lysate would be a feasible stimulatory antigen source for detection of a peripheral CD4+ T-cell immune response in patients with medically untreated malignant melanoma. The lysate was produced from a melanoma cell line (FM3.29) which expr...

  18. Important risk factors in melanoma from the Dermato-Oncologic Unit of Brescia, Italy. (United States)

    Manganoni, Ausilia Maria; Zanotti, Federica; Farisoglio, Camillo; Feroldi, Piero; Facchetti, Fabio; Calzavara-Pinton, Piergiacomo


    One of the most significant risk factors for melanoma is a positive family history of the disease. It is estimated that approximately 10 percent of melanoma cases report a first-or second-degree relative with melanoma. We reported the experience of the Dermato-Oncologic Unit of Brescia, Italy.

  19. MicroRNA miR-125b induces senescence in human melanoma cells

    DEFF Research Database (Denmark)

    Glud, Martin; Manfé, Valentina; Biskup, Edyta


    in malignant melanoma producing lymph node micrometastases than in nonmetastasizing tumors. To get further insight into the functional role of miR-125b, we assessed whether its overexpression or silencing affects apoptosis, proliferation, or senescence in melanoma cell lines. We showed that overexpression...... in an early cutaneous malignant melanoma can contribute to the increased metastatic capability of this tumor....

  20. 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)


    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 teleph

  1. Side Effects and Toxicities of Targeted Therapies in Stage IV Melanoma

    DEFF Research Database (Denmark)

    Ascierto, Paolo A; Bastholt, Lars; Hersey, Peter;


    As the incidence of melanoma continues to increase worldwide, the search for new therapies for advanced (stage IV) melanoma brings with it new patterns of toxicity to contend with. This review covers the toxicity profiles of new treatments for advanced melanoma currently in development. Therefore...

  2. Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics

    Directory of Open Access Journals (Sweden)

    Chen J


    Full Text Available Jiezhong Chen,1,2 Renfu Shao,3 Xu Dong Zhang,4 Chen Chen1 1School of Biomedical Sciences, University of Queensland, Brisbane, QLD, Australia; 2Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia; 3GeneCology Research Centre, School of Science, Education and Engineering, University of the Sunshine Coast, Maroochydore, QLD, Australia; 4School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia Abstract: Melanoma is the most aggressive type of skin cancer and has very high rates of mortality. An early stage melanoma can be surgically removed, with a survival rate of 99%. However, metastasized melanoma is difficult to cure. The 5-year survival rates for patients with metastasized melanoma are still below 20%. Metastasized melanoma is currently treated by chemotherapy, targeted therapy, immunotherapy and radiotherapy. The outcome of most of the current therapies is far from optimistic. Although melanoma patients with a mutation in the oncogene v-Raf murine sarcoma viral oncogene homolog B1 (BRAF have an initially higher positive response rate to targeted therapy, the majority develop acquired drug resistance after 6 months of the therapy. To increase treatment efficacy, early diagnosis, more potent pharmacological agents, and more effective delivery systems are urgently needed. Nanotechnology has been extensively studied for melanoma treatment and diagnosis, to decrease drug resistance, increase therapeutic efficacy, and reduce side effects. In this review, we summarize the recent progress on the development of various nanoparticles for melanoma treatment and diagnosis. Several common nanoparticles, including liposome, polymersomes, dendrimers, carbon-based nanoparticles, and human albumin, have been used to deliver chemotherapeutic agents, and small interfering ribonucleic acids (siRNAs against signaling molecules have also been tested for the treatment of melanoma. Indeed

  3. Influence of sun exposures during childhood and during adulthood on melanoma risk. EPIMEL and EORTC Melanoma Cooperative Group. European Organisation for Research and Treatment of Cancer. (United States)

    Autier, P; Doré, J F


    Sun exposure in both childhood and adult life represents the main environmental risk determinant for cutaneous melanoma. However, little is known about the joint effects of sun exposure during early and later life on melanoma risk. A case-control study in Belgium, Germany and France conducted in 1991-1992 suggests that the melanoma risks attached to indicators related to sun exposure appear to combine their effects in an additive way. We therefore constructed composite indices of sun exposure during childhood and during adulthood, assuming additive combinations of melanoma risk associated with each indicator of sun exposure. Logistic regression modeling showed that the melanoma risk associated with a given level of sun exposure during adulthood increased with higher sun exposure during childhood, but the increase in risk was higher than the simple addition of melanoma risk associated with sun exposure during childhood or adulthood. In turn, high sun exposure during childhood constituted a significant risk factor for melanoma only if there was substantial sun exposure during adult life. We thus suggest that sun exposure during childhood and during adulthood would be interdependent as far as their impact on melanoma risk is concerned. Our results support the hypothesis by which the important contribution of sun exposure during childhood in melanoma occurrence is not properly assessed by retrospective epidemiologic studies. Sun avoidance during childhood would have a greater impact on melanoma risk than sun avoidance during adulthood.

  4. 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


    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.

  5. Anorectal malignant melanomas: Retrospective experience with surgical management

    Institute of Scientific and Technical Information of China (English)

    Xu Che; Dong-Bing Zhao; Yong-Kai Wu; Cheng-Feng Wang; Jian-Qiang Cai; Yong-Fu Shao; Ping Zhao


    AIM: To present the experience and outcomes of the surgical treatment for the patients with anorectal melanoma from the Cancer Hospital, Chinese Academy of Medical Sciences. METHODS: Medical records of the diagnosis, surgery, and follow-up of 56 patients with anorectal melanoma who underwent surgery between 1975 and 2008 were retrospectively reviewed. The factors predictive for the survival rate of these patients were identified using multivariate analysis. RESULTS: The 5-year survival rate of the 56 patients with anorectal melanoma was 20%, 36 patients underwent abdominoperineal resection (APR) and 20 patients underwent wide local excision (WLE). The rates of local recurrence of the APR and WLE groups were 16.13% (5/36) and 68.75% (13/20), (P = 0.001), and the median survival time was 22 mo and 21 mo, respectively (P = 0.481). Univariate survival analysis demonstrated that the number of tumor and the depth of invasion had significant effects on the survival (P < 0.05). Multivariate analysis showed that the number of tumor [P = 0.017, 95% confidence interval (CI) = 1.273-11.075] and the depth of invasion (P = 0.015, 95% CI = 1.249-7.591) were independent prognostic factors influencing the survival rate. CONCLUSION: Complete or R0 resection is the first choice of treatment for anorectal melanoma, prognosis is poor regardless of surgical approach, and early diagnosis is the key to improved survival rate for patients with anorectal melanoma.

  6. BPTF transduces MITF-driven prosurvival signals in melanoma cells. (United States)

    Dar, Altaf A; Majid, Shahana; Bezrookove, Vladimir; Phan, Binh; Ursu, Sarah; Nosrati, Mehdi; De Semir, David; Sagebiel, Richard W; Miller, James R; Debs, Robert; Cleaver, James E; Kashani-Sabet, Mohammed


    Microphthalmia-associated transcription factor (MITF) plays a critical and complex role in melanocyte transformation. Although several downstream targets of MITF action have been identified, the precise mechanisms by which MITF promotes melanocytic tumor progression are incompletely understood. Recent studies identified an oncogenic role for the bromodomain plant homeodomain finger transcription factor (BPTF) gene in melanoma progression, in part through activation of BCL2, a canonical target of MITF signaling. Analysis of the BPTF promoter identified a putative MITF-binding site, suggesting that MITF may regulate BPTF expression. Overexpression of MITF resulted in up-regulation of BPTF in a panel of melanoma and melanocyte cell lines. shRNA-mediated down-regulation of MITF in melanoma cells was accompanied by down-regulation of BPTF and BPTF-regulated genes (including BCL2) and resulted in reduced proliferative capacity of melanoma cells. The suppression of cell growth mediated by MITF silencing was rescued by overexpression of BPTF cDNA. Binding of MITF to the BPTF promoter was demonstrated using ChIP analysis. MITF overexpression resulted in direct transcriptional activation of BPTF, as evidenced by increased luciferase activity driven by the BPTF promoter. These results indicate that BPTF transduces key prosurvival signals driven by MITF, further supporting its important role in promoting melanoma cell survival and progression.

  7. In situ photoimmunotherapy for melanoma: preliminary clinical results (United States)

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


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

  8. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A


    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.

  9. Joint effect of multiple common SNPs predicts melanoma susceptibility.

    Directory of Open Access Journals (Sweden)

    Shenying Fang

    Full Text Available Single genetic variants discovered so far have been only weakly associated with melanoma. This study aims to use multiple single nucleotide polymorphisms (SNPs jointly to obtain a larger genetic effect and to improve the predictive value of a conventional phenotypic model. We analyzed 11 SNPs that were associated with melanoma risk in previous studies and were genotyped in MD Anderson Cancer Center (MDACC and Harvard Medical School investigations. Participants with ≥15 risk alleles were 5-fold more likely to have melanoma compared to those carrying ≤6. Compared to a model using the most significant single variant rs12913832, the increase in predictive value for the model using a polygenic risk score (PRS comprised of 11 SNPs was 0.07(95% CI, 0.05-0.07. The overall predictive value of the PRS together with conventional phenotypic factors in the MDACC population was 0.69 (95% CI, 0.64-0.69. PRS significantly improved the risk prediction and reclassification in melanoma as compared with the conventional model. Our study suggests that a polygenic profile can improve the predictive value of an individual gene polymorphism and may be able to significantly improve the predictive value beyond conventional phenotypic melanoma risk factors.

  10. NF1 Mutations Are Common in Desmoplastic Melanoma. (United States)

    Wiesner, Thomas; Kiuru, Maija; Scott, Sasinya N; Arcila, Maria; Halpern, Allan C; Hollmann, Travis; Berger, Michael F; Busam, Klaus J


    Desmoplastic melanoma (DM) is a rare variant of melanoma with distinct clinical, histopathologic, and immunohistochemical features. Clinically, DM differs from conventional melanoma by a higher propensity for local recurrence and less frequent metastatic spread to regional lymph nodes. In its pure form, DM has a distinct appearance displaying a low density of fusiform melanocytes in a collagen-rich matrix. Whereas a number of mutations have been identified in primary melanoma, including BRAF, NRAS, GNAQ, GNA11, and KIT, and the occurrence of these mutations has been found to correlate to some extent with the histopathologic features, anatomic site, and/or mode of sun exposure, no distinct set of mutations has so far been reported for DM. To study the potential association of neurofibromin (NF1) mutations with DM, we examined 15 desmoplastic and 20 non-DMs by next-generation sequencing. Mutations of the NF1 gene were found in 14 of 15 (93%) DMs and 4 of 20 (20%) non-DMs. The high frequency of NF1 mutations in DMs suggests an important role for NF1 in the biology of this type of melanoma.

  11. Psychoeducational intervention for patients with cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Ross, Lone; Frederiksen, Kirsten


    PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifica......PURPOSE: In 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few...... modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned...... significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up. CONCLUSION: The findings of this study support the results of an earlier intervention study among patients with malignant melanoma and indicate...

  12. Chromosome 7 Aneusomy. A Marker for Metastatic Melanoma?

    Directory of Open Access Journals (Sweden)

    Martin Udart


    Full Text Available Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR play an important role in a variety of malignant neoplasias, making the search for aberrations in the relevant chromosomes an important issue. Differential expression of the EGFR gene was investigated by reverse transcriptase (RT-PCR on tissue samples of normal skin, nevi, primary melanomas, and melanoma metastases. The EGFR gene is located on chromosome 7p12.3-p12.1. To determine the number of chromosomes 7 in cell nuclei of the mentioned tissue samples we performed fluorescence in situ hybridization (FISH on touch preparations, using a DNA probe that hybridizes specifically to the centromeric region of chromosome 7. Additionally, chromosome 7 number in interphase nuclei was determined in short-term primary cell cultures of nevi, primary melanomas, and metastases. The highest EGFR gene expression frequency was found in melanoma metastases. By FISH we detected the highest fraction of cell nuclei with more than two chromosomes 7 in the group of metastases. Our results suggest that overexpression of the EGFR gene might play an important role in metastasis of malignant melanoma. This is well reflected by polysomy 7, possibly accounting for an increased EGFRgene copy number.

  13. Saphenous Vein Sparing Superficial Inguinal Dissection in Lower Extremity Melanoma

    Directory of Open Access Journals (Sweden)

    Muhammed Beşir Öztürk


    Full Text Available Aim. The classic inguinal lymph node dissection is the main step for the regional control of the lower extremity melanoma, but this surgical procedure is associated with significant postoperative morbidity. The permanent lymphedema is the most devastating long-term complication leading to a significant decrease in the patient’s quality of life. In this study we present our experience with modified, saphenous vein sparing, inguinal lymph node dissections for patients with melanoma of the lower extremity. Methods. Twenty one patients (10 women, 11 men who underwent saphenous vein sparing superficial inguinal lymph node dissection for the melanoma of lower extremity were included in this study. The effects of saphenous vein sparing on postoperative complications were evaluated. Results. We have observed the decreased rate of long-term lymphedema in patients undergoing inguinal lymphadenectomy for the lower extremity melanoma. Conclusion. The inguinal lymphadenectomy with saphenous vein preservation in lower extremity melanoma patients seems to be an oncologically safe procedure and it may offer reduced long-term morbidity.

  14. The Hydrogen Sulfide Releasing Molecule Acetyl Deacylasadisulfide Inhibits Metastatic Melanoma (United States)

    De Cicco, Paola; Panza, Elisabetta; Armogida, Chiara; Ercolano, Giuseppe; Taglialatela-Scafati, Orazio; Shokoohinia, Yalda; Camerlingo, Rosa; Pirozzi, Giuseppe; Calderone, Vincenzo; Cirino, Giuseppe; Ianaro, Angela


    Melanoma is the most common form of skin cancer. Given its high mortality, the interest in the search of preventive measures, such as dietary factors, is growing significantly. In this study we tested, in vitro and in vivo, the potential anti-cancer effect of the acetyl deacylasadisulfide (ADA), a vinyl disulfide compound, isolated and purified from asafoetida a foul-smelling oleo gum-resin of dietary and medicinal relevance. ADA markedly suppressed proliferation of human melanoma cell lines by inducing apoptosis. Moreover, treatment of melanoma cells with ADA reduced nuclear translocation and activation of NF-κB, decreased the expression of the anti-apoptotic proteins c-FLIP, XIAP, and Bcl-2 and inhibited the phosphorylation and activation of both AKT and ERK proteins, two of the most frequently deregulated pathways in melanoma. Finally, the results obtained in vitro were substantiated by the findings that ADA significantly and dose-dependently reduced lung metastatic foci formation in C57BL/6 mice. In conclusion, our findings suggest that ADA significantly inhibits melanoma progression in vivo and could represent an important lead compound for the development of new anti-metastatic agents. PMID:28289382

  15. Primary Malignant Melanoma of the Lung: A Case Report

    Directory of Open Access Journals (Sweden)

    Karagianni Evangelia


    Full Text Available Abstract Background Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. Case presentation A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. Conclusions Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment.

  16. Proteome serological determination of tumor-associated antigens in melanoma.

    Directory of Open Access Journals (Sweden)

    Michael Forgber

    Full Text Available Proteome serology may complement expression library-based approaches as strategy utilizing the patients' immune responses for the identification pathogenesis factors and potential targets for therapy and markers for diagnosis. Melanoma is a relatively immunogenic tumor and antigens recognized by melanoma-specific T cells have been extensively studied. The specificities of antibody responses to this malignancy have been analyzed to some extent by molecular genetic but not proteomics approaches. We screened sera of 94 melanoma patients for anti-melanoma reactivity and detected seropositivity in two-thirds of the patients with 2-6 antigens per case detected by 1D and an average of 2.3 per case by 2D Western blot analysis. For identification, antigen spots in Western blots were aligned with proteins in 2-DE and analyzed by mass spectrometry. 18 antigens were identified, 17 of which for the first time for melanoma. One of these antigens, galectin-3, has been related to various oncogenic processes including metastasis formation and invasiveness. Similarly, enolase has been found deregulated in different cancers. With at least 2 of 18 identified proteins implicated in oncogenic processes, the work confirms the potential of proteome-based antigen discovery to identify pathologically relevant proteins.

  17. Spitzoid melanoma in a child with Li-Fraumeni syndrome. (United States)

    Kollipara, Ramya; Cooley, Linda D; Horii, Kimberly A; Hetherington, Maxine L; Leboit, Philip E; Singh, Vivekanand; Zwick, David L


    Spitzoid melanoma of childhood is a rare malignancy. The histological features are at the upper end of a range encompassing Spitz nevus and atypical Spitz tumor, the unifying features including large oval, fusiform or polygonal melanocytes with abundant homogeneous-appearing cytoplasma and large vesicular nuclei. The presence of a "bottom-heavy" pattern, strikingly enlarged nuclei and nucleoli in both the upper and lower portions of the lesion, and deep mitotic figures are among the findings that distinguish most of the Spitzoid melanomas from Spitz nevi and atypical Spitz tumors. There are no syndromic associations reported for this malignancy. We report the occurrence of choroid plexus carcinoma, Spitzoid melanoma, and myelodysplasia in a child who was found to carry a germline mutation for TP53. While choroid plexus carcinoma and myelodysplasia have relatively frequently been described, melanomas have been very rarely described in Li-Fraumeni syndrome. The association of Spitzoid melanoma with Li-Fraumeni syndrome, especially in a pediatric patient, has not been reported before.

  18. Homeopathic treatment of malignant melanoma in a dog. Tratamiento homeopático de melanoma maligno en un perro. Tratamiento homeopático de melanoma maligno num cachorro.

    Directory of Open Access Journals (Sweden)

    Priscilla A. Melville


    Full Text Available Malignant melanoma is the most frequently diagnosed of canine’s oral tumors. Conventional treatment’s efficacy – surgical excision, radio and chemotherapy – is very low and the prognostics are very reserved. The present article presents a case of homeopathically treated malignant melanoma in a dog, with successful results. It may be concluded that following the guidelines suggested by Hahnemann for Psora cases might heal the homeopathic treatment of canine malignant melanoma.

  19. Epidemiological aspects of cutaneous malignant melanoma (review). (United States)

    Serraino, D; Fratino, L; Gianni, W; Campisi, C; Pietropaolo, M; Trimarco, G; Marigliano, V


    There is an increasing interest in the etiology of cutaneous malignant melanoma (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the eighteenth in Great Britain. The growing scientific concern on the urgent need to highlight the cause/s of CMM is well documented by the large number of well-designed and well-conducted epidemiological studies reported in the last two decades. Such studies facilitated testing of many etiological hypotheses derived from earlier descriptive investigations and contributed to significant progress in understanding the etiology of such disease. The quantification of the extent to which the increases in CMM incidence and mortality rates are related to new lifestyles and to new patterns of exposure to potential carcinogenetic agents is essential in order to establish an appropriate preventive strategy. In population of mainly European origin a substantial proportion of the increased incidence of CMM is attributable to steady change from predominantly occupational to predominantly recreational exposure to solar radiation. Therefore the present review puts particular emphasis on exposure to sunlight as well as to artificial ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and other potential risk factors for the development of CMM will also be briefly reviewed.

  20. Metástases intestinais de melanoma Metastatic melanoma of the small bowel

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    Flávio Daniel Saavedra Tomasich


    Full Text Available OBJETIVO: O melanoma maligno é a causa mais comum de doença metastática envolvendo o trato gastrointestinal, e o intestino delgado o sítio mais freqüentemente envolvido. Este estudo foi realizado com a finalidade de avaliar o quadro clínico, tratamento, evolução e relatar a experiência com o tratamento cirúrgico do melanoma metastático para intestino delgado. MÉTODO: Foram revisados 11 casos operados no período setembro/1987 a setembro/2000, e estudados os dados referentes ao sexo, idade, localização e estadiamento do tumor primário, tempo e manifestação clínica da metástase intestinal. Também foram avaliados o tipo de cirurgia realizada, a ocorrência de complicações e necessidade de reoperações,a presença de outros sítios metastáticos e sobrevida. RESULTADOS: A média de idade dos pacientes foi de 43,3 anos, sendo 54,5% do sexo masculino. Os membros inferiores foram o sítio primário mais freqüente (54,5%, e em 18,2% dos casos a metástase intestinal foi a primeira manifestação da doença. Dor abdominal (72,7%, obstrução intestinal (36,3% e massa abdominal (27,2% foram os sintomas mais comuns. Enterectomia com enteroanastomose foi realizada em 72,7% dos pacientes, em caráter emergencial em mais de 50% dos casos. O tempo de sobrevida variou de 6 dias a 90 meses, e a mortalidade foi de 72,7%. CONCLUSÕES: As metástases intestinais devem ser consideradas em qualquer paciente que apresente sintomas gastrointestinais e uma história prévia de lesão melanocítica de pele, e o tratamento cirúrgico, apesar do caráter paliativo, pode ocasionalmente resultar em sobrevida longa.BACKGROUND: Malignant melanoma is the most common metastatic tumor involving the gastrointestinal tract, the small bowel being the localization most frequently involved. The aim of the present study is to evaluate the clinical presentation, treatment, evolution, and relate our experience with the surgical treatment of metastatic melanoma of

  1. Analysis of losses of heterozygosity of the candidate tumour suppressor gene DMBT1 in melanoma resection specimens

    DEFF Research Database (Denmark)

    Deichmann, M; Mollenhauer, J; Helmke, B


    , hence we screened primary melanoma samples for losses of heterozygosity (LOH), and acquired melanocytic naevi and melanomas for transcription of DMBT1 and protein expression. Of 38 informative melanomas, 1 nodular melanoma and 2 subcutaneous metastases showed LOH of both microsatellites flanking...

  2. Prospective study of melanoma in the Paris Region in 2004

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    Souques, M.; Baccard, M.; Barrazza, V.; Havard, S.; Verrier, A.; Wechsler, J. [Prevention et Epidemiologie des Tumeurs en Region Ile de France (PETRI), Domus Medica, 75 - Paris (France)


    Introduction: Melanoma remains an important public health problem because of its increasing incidence and its responsibility for the deaths of young individuals. A first study was carried out by the P.E.T.R.I. association in 1994 to estimate the incidence of melanoma in the Paris region. A second one was carried out in 2004, with the same methodology, to estimate the increase of melanoma incidence in the Paris region and the main clinical and histological characteristics of these cancers, comparing to 1994 data. Methodology: Every pathologist of the region has been contacted to fill a questionnaire for each primary cutaneous melanoma excised between January 1. and December 31. 2004, from patients living in the Paris region (departments 75, 77, 91, 92, 93, 94, 95). The information requested included melanoma characteristics (localisation, type, Breslow thickness, Clark level, regression signs, pre existence of a nevus) and demographic data (age, sex, zip code of residence). Results: 98 % of pathologists in the region agree to participate in the study. They send 1453 questionnaires, among them 160 were excluded (double, non cutaneous melanoma, secondary lesion, non resident in the region, diagnoses out of the inclusion dates, biopsy followed by exeresis). The analyse included 1293 lesions in 1269 patients. More than 2/3 of diagnoses were confirmed by 2 laboratories and 10 laboratories (on 98) reported 86 % of the diagnoses. Incidence:The crude incidence of melanoma in the Paris region during 2004 was 11.4 cases per 100 000 inhabitants, by sex:11.1 per 100 000 males and 12.4 cases per 100 000 females. The sex ratio men/women was 0.82. The crude incidence of invasive melanoma (Clark 2 to 5) was 8,9 cases per 100 000 inhabitants, 9,2 per 100 000 women and 8,6 per 100 000 men, with a sex ratio men/women of 0,93. Demographic characteristics: Melanoma diagnosis was more often in women (54.9 %) than in men (45.1 %). The patients mean age was 59.3 years (S.D.: 17.3). The

  3. Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hernandez Jackie


    Full Text Available Abstract Background Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b was tested in a multicenter two stage phase 2 study with centralized DC manufacturing. Methods The vaccine (IDD-3 consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF and interleukin-13 (IL-13, pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity. Results Among 33 patients who received IDD-3 there was one complete response (CR, two partial responses (PR, and six patients had stable disease (SD lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%. IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by in vitro immune monitoring assays. Conclusions The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma. Clinical trial registration NCT00107159.

  4. Delayed presentation of tattoo lymphadenopathy mimicking malignant melanoma lymphadenopathy. (United States)

    Bordea, C; Latifaj, B; Jaffe, W


    Tattooing is a popular cosmetic practice and the technique has been adopted in breast reconstruction. Pigment injected intradermally is transported to lymph nodes leading to permanent pigmentation. Differential diagnosis between melanoma and tattoo pigmentation of lymph nodes is done microscopically. We present the case study of a patient who presented with palpable and pigmented axillary lymph nodes, 2 years after excision of melanoma and 20 years after tattooing. Intraoperative finding of enlarged, pigmented lymph nodes is not a certain sign of metastasis, as causes other then melanoma can lead to pigmented lymphadenopathy. The diagnostic and investigation process should start with history (including history of previous tattooing) and fine needle aspiration (FNA) of enlarged lymph node. If FNA is negative an open biopsy should be performed for confirmation of diagnosis before proceeding to completion lymphadenectomy.

  5. Nanomedicine as a potent strategy in melanoma tumor microenvironment. (United States)

    Pautu, Vincent; Leonetti, Daniela; Lepeltier, Elise; Clere, Nicolas; Passirani, Catherine


    Melanoma originated from melanocytes is the most aggressive type of skin cancer. Despite considerable progresses in clinical treatment with the discovery of BRAF or MEK inhibitors and monoclonal antibodies, the durability of response to treatment is often limited to the development of acquired resistance and systemic toxicity. The limited success of conventional treatment highlights the importance of understanding the role of melanoma tumor microenvironment in tumor developement and drug resistance. Nanoparticles represent a promising strategy for the development of new cancer treatments able to improve the bioavailability of drugs and increase their penetration by targeting specifically tumors cells and/or tumor environment. In this review, we will discuss the main influence of tumor microenvironment in melanoma growth and treatment outcome. Furthermore, third generation loaded nanotechnologies represent an exciting tool for detection, treatment, and escape from possible mechanism of resistance mediated by tumor microenvironment, and will be highlighted in this review.

  6. Clinical systemic lupeol administration for canine oral malignant melanoma. (United States)

    Yokoe, Inoru; Azuma, Kazuo; Hata, Keishi; Mukaiyama, Toshiyuki; Goto, Takahiro; Tsuka, Takeshi; Imagawa, Tomohiro; Itoh, Norihiko; Murahata, Yusuke; Osaki, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu


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

  7. Calcium Channel Expression and Applicability as Targeted Therapies in Melanoma

    Directory of Open Access Journals (Sweden)

    A. Macià


    Full Text Available The remodeling of Ca2+ signaling is a common finding in cancer pathophysiology serving the purpose of facilitating proliferation, migration, or survival of cancer cells subjected to stressful conditions. One particular facet of these adaptive changes is the alteration of Ca2+ fluxes through the plasma membrane, as described in several studies. In this review, we summarize the current knowledge about the expression of different Ca2+ channels in the plasma membrane of melanoma cells and its impact on oncogenic Ca2+ signaling. In the last few years, new molecular components of Ca2+ influx pathways have been identified in melanoma cells. In addition, new links between Ca2+ homeostasis and specific cell processes important in melanoma tumor progression have been unveiled. Thus, not only do Ca2+ channels appear to have a potential as prognostic markers, but their pharmacological blockade or gene silencing is hinted as interesting therapeutic approaches.

  8. Management of a patient with advanced BRAF-mutant melanoma. (United States)

    Ashworth, Michelle T; Daud, Adil


    A 49-year-old man initially diagnosed in 1995 with cutaneous melanoma presented to the authors' institution in 2009 with metastatic, BRAF V600E-mutant melanoma. His treatment course to date has included surgery, adjuvant radiotherapy, and interferon, metastasectomies, granulocyte-macrophage colony-stimulating factors, a clinical trial with the BRAF inhibitor vemurafenib (PLX-4032), clinical trial with combination BRAF plus MEK inhibition with vemurafenib plus GDC-0973, and combination targeted and immune therapy with vemurafenib plus the anti-CTLA4 antibody ipilimumab. This case report illustrates the long-term management of a patient with metastatic melanoma using targeted and immune therapy, evolution in treatment guidelines, next directions in research, and the critical role of clinical trials in advancement of patient care.

  9. Melanoma molecular classes and prognosis in the postgenomic era. (United States)

    Tremante, Elisa; Ginebri, Agnese; Lo Monaco, Elisa; Frascione, Pasquale; Di Filippo, Franco; Terrenato, Irene; Benevolo, Maria; Mottolese, Marcella; Pescarmona, Edoardo; Visca, Paolo; Natali, Pier Giorgio; Giacomini, Patrizio


    Gene expression profiling is a powerful method to classify human tumours on the basis of biological aggressiveness, response to therapy, and outcome for the patient, but its application in melanoma lags behind that of other cancers. From more than 100 articles available on the topic, we selected 14 focusing on patients' outcome. We review and briefly discuss salient findings, and list ten reasons why melanoma molecular classes are not yet used in clinical diagnosis and prognosis. The available evidence suggests that we are on the verge of creating a framework for the use of melanoma molecular classes in prognosis, but so far there is little consensus to put together informative diagnostic and prognostic gene sets.

  10. Adoptive cell transfer in the treatment of metastatic melanoma

    DEFF Research Database (Denmark)

    Straten, Per thor; Becker, Jürgen C


    Adoptive cell therapy (ACT) for metastatic cancer is the focus of considerable research effort. Rosenberg's laboratory demonstrated a 50% response rate in stage IV melanoma patients treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) and high-dose IL-2 administered after nonmyelo......Adoptive cell therapy (ACT) for metastatic cancer is the focus of considerable research effort. Rosenberg's laboratory demonstrated a 50% response rate in stage IV melanoma patients treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) and high-dose IL-2 administered after...... nonmyeloablative conditioning (Dudley et al., 2002a). Because early attempts to use expanded TILs in melanoma therapy failed to demonstrate better efficacy than high-dose IL-2 (Rosenberg et al., 1994), the efficacy of TILs and nonmyeloablative conditioning in combination implies that patient conditioning...

  11. The Pediatric Choroidal and Ciliary Body Melanoma Study

    DEFF Research Database (Denmark)

    Al-Jamal, Rana'a T; Cassoux, Nathalie; Desjardins, Laurence


    PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18...... entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma-related mortality. RESULTS: Cumulative frequency...... type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P...

  12. Detection of Melanoma Skin Cancer in Dermoscopy Images (United States)

    Eltayef, Khalid; Li, Yongmin; Liu, Xiaohui


    Malignant melanoma is the most hazardous type of human skin cancer and its incidence has been rapidly increasing. Early detection of malignant melanoma in dermoscopy images is very important and critical, since its detection in the early stage can be helpful to cure it. Computer Aided Diagnosis systems can be very helpful to facilitate the early detection of cancers for dermatologists. In this paper, we present a novel method for the detection of melanoma skin cancer. To detect the hair and several noises from images, pre-processing step is carried out by applying a bank of directional filters. And therefore, Image inpainting method is implemented to fill in the unknown regions. Fuzzy C-Means and Markov Random Field methods are used to delineate the border of the lesion area in the images. The method was evaluated on a dataset of 200 dermoscopic images, and superior results were produced compared to alternative methods.

  13. Fuzzy logic color detection: Blue areas in melanoma dermoscopy images. (United States)

    Lingala, Mounika; Stanley, R Joe; Rader, Ryan K; Hagerty, Jason; Rabinovitz, Harold S; Oliviero, Margaret; Choudhry, Iqra; Stoecker, William V


    Fuzzy logic image analysis techniques were used to analyze three shades of blue (lavender blue, light blue, and dark blue) in dermoscopic images for melanoma detection. A logistic regression model provided up to 82.7% accuracy for melanoma discrimination for 866 images. With a support vector machines (SVM) classifier, lower accuracy was obtained for individual shades (79.9-80.1%) compared with up to 81.4% accuracy with multiple shades. All fuzzy blue logic alpha cuts scored higher than the crisp case. Fuzzy logic techniques applied to multiple shades of blue can assist in melanoma detection. These vector-based fuzzy logic techniques can be extended to other image analysis problems involving multiple colors or color shades.

  14. Novel Anti-Melanoma Immunotherapies: Disarming Tumor Escape Mechanisms

    Directory of Open Access Journals (Sweden)

    Sivan Sapoznik


    Full Text Available The immune system fights cancer and sometimes temporarily eliminates it or reaches an equilibrium stage of tumor growth. However, continuous immunological pressure also selects poorly immunogenic tumor variants that eventually escape the immune control system. Here, we focus on metastatic melanoma, a highly immunogenic tumor, and on anti-melanoma immunotherapies, which recently, especially following the FDA approval of Ipilimumab, gained interest from drug development companies. We describe new immunomodulatory approaches currently in the development pipeline, focus on the novel CEACAM1 immune checkpoint, and compare its potential to the extensively described targets, CTLA4 and PD1. This paper combines multi-disciplinary approaches and describes anti-melanoma immunotherapies from molecular, medical, and business angles.

  15. Salvage surgery for a giant melanoma on the back

    Directory of Open Access Journals (Sweden)

    Joost Klaase


    Full Text Available We report a case of a giant melanoma on the back with a very extreme Breslow thickness. On physical examination a large odorous and ulcerating tumour was seen adjacent to two large crusted lesions, probably in transit metastases. In the right and left axilla enlarged lymph nodes were palpated. The patient underwent salvage surgery consisting of a complete wide excision of the tumors on the back as well as axillary lymph node dissection on both sides. Histopathology showed a malignant melanoma with a Breslow thickness of 48 mm. Four of fifteen nodes in the right axilla and one of nine nodes in the left axilla, were positive for metastatic disease. Also various in transit and subcutaneous metastases were found in the wide excision specimen. The interest of our observation relies in the rarity of a melanoma with such an extreme Breslow thickness and the difficulty in performing adequate palliative therapy that offers quality of life by means of tumor control.

  16. Skin lesion image segmentation using Delaunay Triangulation for melanoma detection. (United States)

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


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

  17. [Cutaneous melanoma - "black death" of modern times? Traces in contemporary literature]. (United States)

    Bahmer, F A; Bahmer, J A


    Cutaneous melanoma, sometimes labeled as "black skin cancer", is increasing in frequency and becoming a more common literary motive. In US literature, Sylvia Plath and Charles Bukowski depicted melanoma more than 50 years ago, later Stephen King and Thomas C. Boyle. In German literature, Charlotte Roche shortly mentioned this tumor. Jörg Pönnighaus, both poet and dermatologist, intensively deals in his poems with the effects melanoma has on patients and doctors alike. Melanoma definitely is not the "Black Death" of modern times. However, the perception of this tumor as extremely malignant and as life-threatening makes melanoma a metaphor of the deadly danger of cancer.

  18. Primary intracranial malignant melanoma in an adolescent girl: A case report

    Directory of Open Access Journals (Sweden)

    Sajeeb Mondal


    Full Text Available Primary intracranial malignant melanoma is a very rare tumor, and most of the central nervous system melanomas are metastatic diseases. Diagnosis needs extensive dermatological, opthalmological, and radiological workup to exclude metastatic melanoma. Histologically, it should be differentiate from benign melanocytic lesions, pigmented choroid plexus carcinoma, and pigmented papillary medulloblastoma. Here, we are reporting a case of primary malignant melanoma of posterior fossa in an adolescent girl diagnosed in squash cytology as well as in histology and confirmed by immunohistochemistry and by excluding metastatic melanoma.

  19. Boronated monoclonal antibodies for potential neutron capture therapy of malignant melanoma and leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Tamat, S.R.; Patwardhan, A.; Moore, D.E.; Kabral, A.; Bradstock, K.; Hersey, P.; Allen, B.J.

    The authors report a preparation and characterisation of boronated melanoma and leukaemia antibodies and the separation from native antibody by anion exchange liquid chromatography. Two types of biodistribution experiments were performed with the boronated melanoma antibody 225.28S using Balb/c derived nude mice in which melanoma tumours had been raised in the thigh by subcutaneous injection of a human malignant melanoma cell line, designated CMC. From these experiments, one may conclude that the boronated antibody has the ability to localise in the melanoma following systemic injection, but more efficient use of the preparation is achieved with perilesional administration.

  20. Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Johansen, Julia S


    Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients...... with metastatic melanoma. IL-6 was measured by ELISA in serum samples from 103 patients with metastatic melanoma obtained before IL-2-based immunotherapy. Patients with metastatic melanoma had higher serum IL-6 than healthy individuals (median 3.4 ng/l, range 0.3-93 ng/l vs. median 1.4 ng/l, range 0.25-22.5 ng...

  1. [Malignant mucosal melanoma of the head and neck]. (United States)

    Slavícek, A; Astl, J; Válková, D; Betka, J; Petruzelka, L


    Mucosal melanoma comparison to cutaneous melanoma of the head and neck are rare and do poorly. Approximately 0.5-2% of all melanomas occur from the mucous membranes of aerodigestive tract. Most common site of the tumor are the nasal cavity and paranasal sinuses but melanoma of the oral cavity are described too. Therapy usually consists of surgical resection with or without postoperative radiotherapy and immunochemotherapy eventually. The definite role of a kind of therapy in the treatment of mucosal melanoma is not remains to be defined as the small number of cases make prospective study challenging. This article reviews 19 patients with mucosal melanoma of the head and neck treated at the Department of ENT and Head and Neck Surgery Charles University of Prague since 1980 to 1999. Clinical data were obtained from the patient's charts. Analysis of the metastatic disease, type of therapy and follow-up was retrospectively reviewed. The site of the tumor was the lateral wall of the nasal cavity (five cases), nasal septum (four cases), maxilar cavity (two cases), and ethmoidal cavity, orbitoethmoidal complex, nasopharynx, saccus lacrimalis to ethmoidal sinuses diffused, tonsilla (one case each) and hypopharynx (two cases). Primary treatment was surgical resection in ten cases, in one case with radiation therapy, and in seven cases chemotherapy. In three cases were diagnostic surgery only and one patient was without therapy. Three patients received radical neck dissection more. Four patients were treated radiation therapy and three chemotherapy after surgery. In two cases were surgery after primary radiotherapy. For nine cases of recurrence of the disease were surgery (in five cases) and chemotherapy (in four cases). Overal and disease free interval was from 2 to 22 month, approximately 9.3 month and 3-year survival was 41.18%.

  2. Immunotherapy in melanoma: Recent advances and future directions. (United States)

    Franklin, C; Livingstone, E; Roesch, A; Schilling, B; Schadendorf, D


    Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma. Ipilimumab, a monoclonal antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4) as well as nivolumab and pembrolizumab which target the programmed cell death protein 1 (PD-1) have been shown to prolong overall survival in patients with advanced melanoma. The latter substances seem to have an increased response rate and more tolerable safety profile compared to ipilimumab. The combination of a CTLA-4 and a PD-1 inhibitor seems to be superior to the monotherapies, especially in patients with PD-L1 negative tumours. Checkpoint inhibitors are currently being tested in the adjuvant setting with initial data for ipilimumab suggesting efficacy in this context. Talimogene laherparepvec (TVEC) is the first oncolytic virus approved in the therapy of metastatic melanoma offering a treatment option especially for patients with limited disease. In this review, data on these recently developed and approved immunotherapies are presented. However, further studies are necessary to determine the optimal duration, sequencing and combinations of immunotherapies to further improve the outcome of patients with advanced melanoma.

  3. Upcoming strategies for the treatment of metastatic melanoma. (United States)

    Spagnolo, Francesco; Queirolo, Paola


    Prognosis for advanced and metastatic melanoma is poor, with a 5-year survival of 78, 59 and 40% for patients with stage IIIA, IIIB and IIIC, respectively, and a 1-year survival of 62% for M1a, 53% for M1b and 33% for M1c. The unsatisfactory results of actual standard therapies for metastatic melanoma highlight the need for effective new therapeutic strategies. Several drugs, including BRAF, KIT and MEK inhibitors, are currently being evaluated after promising data from Phase I and Phase II studies; Vemurafenib, a BRAF-inhibitor agent, has been approved by the Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation after a significant impact on both progression-free and overall survival was demonstrated compared with dacarbazine in a Phase III trial. Ipilimumab, an immunotherapeutic drug, has proven to be capable of inducing long-lasting responses and was approved for patients with advanced melanoma in first- and second-line treatment by the FDA and in second-line treatment by the European Medicines Agency. Furthermore, a significant survival benefit of the combination of ipilimumab with dacarbazine compared with dacarbazine alone for first-line treatment was reported. In the near future, patients with BRAF mutations could have the chance to benefit from treatment with BRAF inhibitors; patients harboring BRAF or NRAS mutations could be treated with MEK inhibitors; finally, the subgroup of patients with acral, mucosal or chronic sun-damaged melanoma harboring a KIT mutation could benefit from KIT inhibitors. Ipilimumab could become a standard treatment for metastatic melanoma, both as a single agent and in combination; its efficacy has been proven, and researchers should now address their efforts to understanding the predictive variables of response to treatment.

  4. The molecular profile of metastatic melanoma in Australia. (United States)

    Lyle, Megan; Haydu, Lauren E; Menzies, Alexander M; Thompson, John F; Saw, Robyn P M; Spillane, Andrew J; Kefford, Richard F; Mann, Graham J; Cooper, Wendy A; Yu, Bing; Scolyer, Richard A; O'Toole, Sandra A; Long, Georgina V


    Targeted therapy directed at driver oncogenic mutations offers an effective treatment option for select patients with metastatic melanoma. The aim of this study was to assess the prevalence of clinically significant somatic mutations, specifically BRAF, NRAS and KIT, in a large cohort of Australian patients with metastatic melanoma. We performed a cross-sectional cohort study of consecutive patients with American Joint Committee on Cancer (AJCC) stage IIIc unresectable or stage IV melanoma managed at Melanoma Institute Australia, and affiliated sites, that underwent molecular testing between 22 June 2009 and 19 July 2013. Additionally, we examined the change in BRAF testing methodology and patient population over time, and how this influenced the prevalence of mutations. A total of 767 molecular tests were conducted for 733 patients. BRAF V600 mutation testing was performed for 713 patients (97.2%), with an overall mutation prevalence of 37.7% (269/713); 74.3% (200/269) were the V600E genotype and 22.3% (60/269) V600K. The BRAF mutation prevalence and proportion of BRAF V600E and V600K genotypes varied across the study period, as did testing methodology and the median age of the cohorts. Of 222 patients who underwent NRAS testing, 58 (26.1%) had a mutation identified. The overall prevalence of KIT mutations was 3.7% (11/296). In Australia the prevalence of BRAF mutations is lower than initially reported, although this remains the most common mutation identified in metastatic melanoma and an important therapeutic target. NRAS mutations are more prevalent than initially described; however, other mutations reported in melanoma, including KIT, are rare in an unselected population of patients.


    Directory of Open Access Journals (Sweden)



    Full Text Available A 52 year old woman presented with a history of asymptomatic skin lesions over left leg for the past 4 months. On examination she had multiple skin coloured papules and plaques over left leg. Oedema was also seen over left leg. Histopathology and immunohistochemistry proved the diagnosis of malignant melanoma. Radiological investigation showed metastasis to lung, liver and brain. The patient was asymptomatic at the time of admission but she developed rapid metastasis within a very short span of time. This case is reported for the rare atypical presentation of malignant melanoma.

  6. Clear cell sarcoma: A case mimicking primary cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Rodriguez-Martin M


    Full Text Available Clear cell sarcoma (CCS is a recently described variant of sarcoma characterized by prominent clear cells showing features similar to clear cell melanoma. This neoplasm was first described by Dr. Franz M. Erzinger. Primary CCS usually arises in deeper soft tissues, in association with fascia, tendons, or aponeuroses. Characteristic translocation t(12;22 (q13;q12 has been considered pathognomonic for CCS. Prognosis is related to tumor size. An early recognition and initial radical surgery is the key to a favourable outcome. We present a patient with an unusual neoplasm that resembled malignant melanoma.

  7. What's new in the treatment of cutaneous melanoma? (United States)

    Olhoffer, I H; Bolognia, J L


    As surveyors of the skin, it is important for dermatologists to be aware of recent developments in the management of melanoma. Revised recommendations for surgical margins will be reviewed as will the use of Mohs micrographic surgery for the excision of melanoma, in particular lentigo maligna. An explanation of the technique of sentinel node biopsy is followed by a discussion of the results of recent clinical trials. Adjuvant immunotherapy in the form of vaccines and high-dose alpha-interferon is outlined as is the concept of biochemotherapy for more advanced disease.

  8. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R


    characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known...... to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...

  9. Early detection of cutaneous melanoma by sequential digital dermatoscopy (SDD). (United States)

    Kraus, Sophie Luise; Haenssle, Holger Andreas


    The early diagnosis and excision of cutaneous melanoma is essential for an improved prognosis of the disease. Besides the investigation of pigmented lesions with the unaided eye and conventional dermatoscopy, long-term sequential digital dermatoscopy has been shown to improve the sensitivity of melanoma detection, especially in high-risk patients. In addition to the static clinical and dermatoscopic assessment, the sequential digital dermatoscopy strategy helps to detect changes over time. This review summarizes the latest developments in the field of sequential digital dermatoscopy, describes current strategies for the selection of patients and lesions to monitor, and suggests objective criteria that should lead to an excisional biopsy.

  10. Stathmin 1 is a potential novel oncogene in melanoma. (United States)

    Chen, J; Abi-Daoud, M; Wang, A; Yang, X; Zhang, X; Feilotter, H E; Tron, V A


    In previous studies, we demonstrated that miR-193b expression is reduced in melanoma relative to benign nevi, and also that miR-193b represses cyclin D1 and Mcl-1 expression. We suggested that stathmin 1 (STMN1) might be a target of miR-193b. STMN1 normally regulates microtubule dynamics either by sequestering free tubulin heterodimers or by promoting microtubule catastrophe. Increased expression of STMN1 has been observed in a variety of human malignancies, but its association with melanoma is unknown. We now report that STMN1 is upregulated during the progression of melanoma relative to benign nevi, and that STMN1 is directly regulated by miR-193b. Using an experimental cell culture approach, overexpression of miR-193b using synthetic microRNAs repressed STMN1 expression, whereas inhibition of miR-193b with anti-miR oligos increased STMN1 expression in melanoma cells. The use of a luciferase reporter assay confirmed that miR-193b directly regulates STMN1 by targeting the 3'-untranslated region of STMN1 mRNA. We further demonstrated that STMN1 is overexpressed in malignant melanoma compared with nevi in two independent melanoma cohorts, and that its level is inversely correlated with miR-193b expression. However, STMN1 expression was not significantly associated with patient survival, Breslow depth, mitotic count or patient age. STMN1 knockdown by small-interfering RNA in melanoma cells drastically repressed cell proliferation and migration potential, whereas ectopic expression of STMN1 using lentivirus increased cell proliferation and migration rates. Subsequent gene expression analysis indicated that interconnected cytoskeletal networks are directly affected following STMN1 knockdown. In addition, we identified deregulated genes associated with proliferation and migration, and revealed that p21(Cip1/Waf1) and p27(Kip) could be downstream effectors of STMN1 signaling. Taken together, our study suggests that downregulation of miR-193b may contribute to increased

  11. Microenvironment-derived factors driving metastatic plasticity in melanoma

    DEFF Research Database (Denmark)

    Kim, Isabella S; Heilmann, Silja; Kansler, Emily R


    Cellular plasticity is a state in which cancer cells exist along a reversible phenotypic spectrum, and underlies key traits such as drug resistance and metastasis. Melanoma plasticity is linked to phenotype switching, where the microenvironment induces switches between invasive/MITF(LO) versus...... proliferative/MITF(HI) states. Since MITF also induces pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments that induce a MITF(HI)/differentiated/proliferative state. Zebrafish imaging demonstrates that after extravasation, melanoma cells become pigmented and enact...

  12. Malignant melanoma of the cerebello-pontine angle region

    Directory of Open Access Journals (Sweden)

    F. Menezes Braga


    Full Text Available A case of malignant melanoma in the cerebello-pontine angle region is presented in a 72 years old female patient, who had neurological examination and CT scan suggestive of acoustic neuroma. The surgical finding and the histological examination provided the diagnosis. As a primary focus was not found on clinical examination and although autopsy was not carried out, there is a possibility of the diagnosis being a primary malignant melanoma in CNS. This specific location for this kind of tumor was found to be rare when literature is looked up.

  13. [Treatment of choroid melanoma by Gamma-Knife radiosurgery]. (United States)

    Devin, F; Regis, J; Berros, P; Manera, L; Porcheron, D; Sedan, R; Peragut, J C; Saracco, J B


    Conservative treatment of uveal melanomas by Gamma Knife Radiosurgery is based on the use of cross fire technique with 201 Cobalt60 sources. A following of 13 months is available for the first case operated by Gamma-Knife Surgery in France. Technical baselines and one year preliminary results are reported. The diagnosis of uveal melanoma T3NOMO was established by converging results of clinical examination, angiography and echography. The definition of the target was based on stereotactic MRT examination. We delivered a dose of 50 Gys to the marginal isodose (50%). Today, one year after treatment the tumor decreased, the visual function was preserved. There were no side effect or complication.

  14. In vitro chemosensitivity tests on xenografted human melanomas.



    An in vitro chemosensitivity test has been applied to malignant melanoma cells from 5 patients. The tumour cells were first grown as xenografts in immune-suppressed mice, so that the results of the in vitro test could be compared with precise measurements of the sensitivity of the melanoma cells when exposed to chemotherapeutic drugs in vivo in the mouse. The in vitro assay involved exposing the tumour cells to each of 8 drugs, after which cell survival was determined by colony assay in soft ...

  15. Primary malignant melanoma of female urethra: a rare neoplasm. (United States)

    Pandey, Praveen K; Vijay, Mukesh K; Goel, Hemant; Shukla, Suruchi


    Primary malignant melanoma of urethra is an extremely rare entity. It has very poor prognosis. A 62-year-old post-menopausal female presented with complaints of voiding difficulty and a mass projecting from external urethral meatus. External genital examination revealed a growth arising from urethral meatus with blood-stained discharge from its surface. Biopsy from lesion confirmed the diagnosis to be malignant melanoma. Metastatic work up for the malignancy was negative. We describe the surgical management of this pathology at our tertiary care center and discuss the various treatment options possible in this scenario.

  16. Primary malignant melanoma of female urethra: A rare neoplasm

    Directory of Open Access Journals (Sweden)

    Praveen K Pandey


    Full Text Available Primary malignant melanoma of urethra is an extremely rare entity. It has very poor prognosis. A 62-year-old post-menopausal female presented with complaints of voiding difficulty and a mass projecting from external urethral meatus. External genital examination revealed a growth arising from urethral meatus with blood-stained discharge from its surface. Biopsy from lesion confirmed the diagnosis to be malignant melanoma. Metastatic work up for the malignancy was negative. We describe the surgical management of this pathology at our tertiary care center and discuss the various treatment options possible in this scenario.

  17. Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations. (United States)

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


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

  18. Chondroitin sulfate proteoglycan-4: a biomarker and a potential immunotherapeutic target for canine malignant melanoma. (United States)

    Mayayo, Saray Lorda; Prestigio, Simone; Maniscalco, Lorella; La Rosa, Giuseppe; Aricò, Arianna; De Maria, Raffaella; Cavallo, Federica; Ferrone, Soldano; Buracco, Paolo; Iussich, Selina


    Chondroitin sulfate proteoglycan-4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), is a membrane-bound chondroitin sulfate proteoglycan highly expressed by human melanoma cells. This phylogenetically conserved tumour antigen plays an important biological role in human melanoma, where it is used as a marker to diagnose forms with unusual characteristics, such as desmoplastic melanoma, and to detect melanoma cells in lymph nodes and peripheral blood, and as a target for immunotherapy because of its restricted distribution in normal tissues. To identify suitable targets to develop novel approaches of treating canine melanoma, CSPG4 was studies to see whether it is expressed in canine malignant melanomas. Immunohistochemical staining of 65 canine malignant melanomas with an anti-human CSPG4-specific antibody detected CSPG4 in 37 cases (56.9%). Positive staining was more frequent, albeit not significantly, in amelanotic compared to melanotic tumours and was statistically associated with tumours having both melanin and the epithelioid histotype. The frequency of CSPG4 expression was similar to that of other melanoma antigens used as diagnostic markers for canine malignant melanoma, such as Melan A and the protein recognized by the PNL2 monoclonal antibody. The results suggest that CSPG4 constitutes a new potential immunohistochemical marker of canine malignant melanoma and may represent an immunotherapeutic target as in humans.

  19. Natural Killer cell recognition of melanoma: new clues for a more effective immunotherapy

    Directory of Open Access Journals (Sweden)

    Raquel eTarazona


    Full Text Available Natural killer cells participate in the early immune response against melanoma and also contribute to the development of an adequate adaptive immune response by their crosstalk with dendritic cells and cytokine secretion. Melanoma resistance to conventional therapies together with its high immunogenicity justifies the development of novel therapies aimed to stimulate effective immune responses against melanoma. However, melanoma cells frequently escape to CD8 T cell recognition by the down-regulation of major histocompatibility complex class I molecules. In this scenario, Natural killer cells emerge as potential candidates for melanoma immunotherapy due to their capacity to recognize and destroy melanoma cells expressing low levels of major histocompatibility complex class I molecules. In addition, the possibility to combine immune checkpoint blockade with other NK cell potentiating strategies (e.g. cytokine induction of activating receptors has opened new perspectives in the potential use of adoptive NK cell-based immunotherapy in melanoma.

  20. DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR. (United States)

    Micevic, Goran; Muthusamy, Viswanathan; Damsky, William; Theodosakis, Nicholas; Liu, Xiaoni; Meeth, Katrina; Wingrove, Emily; Santhanakrishnan, Manjula; Bosenberg, Marcus


    DNA methyltransferase DNMT3B is frequently overexpressed in tumor cells and plays important roles during the formation and progression of several cancer types. However, the specific signaling pathways controlled by DNMT3B in cancers, including melanoma, are poorly understood. Here, we report that DNMT3B plays a pro-tumorigenic role in human melanoma and that DNMT3B loss dramatically suppresses melanoma formation in the Braf/Pten mouse melanoma model. Loss of DNMT3B results in hypomethylation of the miR-196b promoter and increased miR-196b expression, which directly targets the mTORC2 component Rictor. Loss of RICTOR in turn prevents mTORC2 activation, which is critical for melanoma formation and growth. These findings establish Dnmt3b as a regulator of melanoma formation through its effect on mTORC2 signaling. Based on these results, DNMT3B is a potential therapeutic target in melanoma.

  1. Differentiation-inducing and anti-proliferative activities of lupeol on canine melanoma cells. (United States)

    Ogihara, Kikumi; Naya, Yuko; Okamoto, Yoshiharu; Hata, Keishi


    Canine melanoma is the most common oral malignant tumor reported in the field of veterinary medicine. We found that lupeol, a lupine triterpene, inhibited mouse melanoma cell growth in vitro and in vivo by inducing cell differentiation. In the present study, we examined the differentiation-inducing activities of lupeol on 4 canine melanoma cells in vitro and in vivo. The induction of canine melanoma cell differentiation by lupeol was confirmed by evaluating some differentiation markers such as tyrosinase with real-time RT-PCR. Furthermore, we transplanted canine melanoma cells into a severe combined immunodeficiency mouse, and studied the anti-progressive effects of lupeol on tumor tissue. The gene expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-2, which are markers of pigment cell differentiation, was induced in 4 canine oral malignant melanoma cells by lupeol, and the agent markedly inhibited tumor progression in canine melanoma-bearing mice.

  2. Germline RAD51B truncating mutation in a family with cutaneous melanoma

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Golmard, Lisa


    Known melanoma predisposition genes only account for around 40% of high-density melanoma families. Other rare mutations are likely to play a role in melanoma predisposition. RAD51B plays an important role in DNA repair through homologous recombination, and inactivation of RAD51B has been implicated...... in tumorigenesis. Thus RAD51B is a good candidate melanoma susceptibility gene, and previously, a germline splicing mutation in RAD51B has been identified in a family with early-onset breast cancer. In order to find genetic variants associated with melanoma predisposition, whole-exome sequencing was carried out...... on blood samples from a three-case cutaneous melanoma family. We identified a novel germline RAD51B nonsense mutation, and we demonstrate reduced expression of RAD51B in melanoma cells indicating inactivation of RAD51B. This is only the second report of a germline truncating RAD51B mutation. While...

  3. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue (United States)

    He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi


    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

  4. Radioiodinated methylene blue--a promising agent for melanoma scintigraphy: labelling, stability and in vitro uptake by melanoma cells. (United States)

    Sobal, Grazyna; Rodrigues, Margarida; Sinzinger, Helmut


    Melanoma is a tumor of continuously increasing incidence for which new methods of imaging and targeted therapy are widely sought. Radioiodinated methylene blue is a promising tracer, showing selective uptake in human pigmented melanoma cells. We performed 131I-labeling of the tracer using 1% methylene blue injection United States Pharmacopeia (USP) and 131I sodium iodide. For quality control, a Merck high performance liquid chromatography (HPLC) system was used. We developed a new HPLC procedure using 0.1% trifluoroacetic acid, 90% acetonitrile and 10% water as solvent for isocratic elution of the tracer and applied a TLC method using ITLC-SG strips and the same solvent. The stability of the preparation was studied for 15 min, 3 h and 6 h. In order to evaluate the potential relevance of 131I-labeled methylene blue for melanoma detection, the in vitro uptake of 131I-methylene blue was investigated in SK-MEL 28 and 518A2 melanoma cells. Time and a temperature influence on uptake of 1311 methylene blue by these two melanoma cells were investigated. The radiochemical purity obtained by the HPLC method was 99.97 +/- 0.08% (n=8), while that by the TLC method was 99.88 +/- 0.16% (n=8). This indicates the excellent agreement between these two methods. The stability was persistent over 6 h and amounted to 99.75% +/- 0.21% (n=8). The uptake of 131I methylene blue was time and temperature dependent by both melanoma cells lines. The net cellular uptake on incubation at 37 degrees C of 131I methylene blue by SK-MEL 28 cells was high at 56.3-61.8% and that by 518A2-cells was 36.3-56.0%. Uptake by these cells was also investigated at 22 degrees C. The uptake by both cell types was also high at this temperature, but lower than that at 37 degrees C, amounting to 45.0-51.7% and 25.6-36.3%, respectively. Due to its easy handling and quite high uptake by melanoma cells, we expect that this tracer could be successfully used in routine application for melanoma imaging or eventual

  5. Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells


    TANG, Li; Yi, Xue-Mei; Chen, Jia; Chen, Fu-Juan; Lou, Wei; Gao, Yun-Lu; Zhou, Jing; Su, Li-Na; Xu, Xin; Lu, Jia-Qing; Ma, Jun; Yu, Ning; Ding, Yang-Feng


    Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinom...

  6. CDC Signos Vitales-La prevención del melanoma (Preventing Melanoma)

    Centers for Disease Control (CDC) Podcasts


    Este podcast se basa en la edición de junio del 2015 del informe Signos Vitales de los CDC. El cáncer de piel es el tipo de cáncer más común en los Estados Unidos. En el 2011, hubo más de 65 000 casos de melanoma, el tipo de cáncer de piel más mortal. Sepa cómo todos pueden ayudar a prevenir el cáncer de piel.  Created: 6/2/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 6/2/2015.

  7. An approach to unsupervised hair removal from skin melanoma image (United States)

    Xie, Feng-Ying; Qin, Shi-Yin; Jiang, Zhi-Guo; Meng, Ru-Song; Xu, Bin


    Hair removal from skin melanoma image is one of the key problems for the precise segmentation and analysis of the skin malignant melanoma. In this paper, an automatically hair removal algorithm in dermoscopy images of pigmented skin lesions is proposed. This algorithm includes three steps: firstly, the melanoma image with hairs are enhanced by morphologic closing-based top-hat operator and then segmented through statistic threshold; secondly, the hairs are extracted based on the elongate of connected region; thirdly, the hair-occluded information is repaired by replacing the hair pixels with the nearby non-hair pixels. As a matter of fact, with the morphologic closing-based top-hat operator both strong and weak hairs can be enhanced simultaneously, and the elongate state of band-like connected region can be correctly described by the elongate function proposed in this paper so as to measure the hair effectively. Therefore, the unsupervised hair removal problem in dermoscopy melanoma image can be resolved very well through combining the hair extraction with information repair. The experiment results show that various hairs can be extracted accurately and the repaired effect of textures can satisfy the requirement of medical diagnosis.

  8. Treatment with levodopa and risk for malignant melanoma

    DEFF Research Database (Denmark)

    Olsen, Jørgen H; Tangerud, Karina; Wermuth, Lene


    of the drug. We conclude that the increased rate of malignant melanoma observed in patients treated at hospital for Parkinson's disease is restricted to those with idiopathic Parkinson's disease, however, unrelated to the treatment with levodopa. (c) 2007 Movement Disorder Society....


    NARCIS (Netherlands)



    Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atyical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocyti

  10. Melanoma conjuntival multifocal recidivado originado de nevus pigmentado preexistente

    Directory of Open Access Journals (Sweden)

    Marcos Leandro Pereira


    Full Text Available O melanoma conjuntival multifocal recidivado originado de nevus preexistente é extremamente raro, ocorrendo em uma pessoa para cinco milhões de habitantes. Seu estudo é de extrema relevância, devido sua potencial letalidade. Este estudo objetiva descrever um caso de melanoma conjuntival multifocal recidivado proveniente de nevus pigmentado preexistente ocorrido em Patos de Minas, MG. Este é um estudo de caso com revisão de literatura. O diagnóstico histopatológico e o estadiamento precoce da lesão conjuntival é de fundamental importância para designar a conduta frente ao paciente. O procedimento terapêutico mais utilizado nos dias atuais é a excisão cirúrgica com crioterapia adjuvante associada à mitomicina C. O prognóstico do melanoma conjuntival multifocal recidivado originado de nevus preexistente é o pior dentre todos os melanomas oculares, apresentando alta taxa de mortalidade, 12% a 20% em 5 anos e 30% em 10 anos de desenvolvimento patológico.

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

    DEFF Research Database (Denmark)

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


    nine haematoxylin and eosin (HE)-negatives, all of which were found by immunohistochemistry. The false negative rate for the SNB procedure was 4% (2/55). The complication rate was 6% after SNB and 29% after complete node dissection. In conclusion, SN status is a strong prognostic factor in melanoma...

  12. Photoacoustic imaging of single circulating melanoma cells in vivo (United States)

    Wang, Lidai; Yao, Junjie; Zhang, Ruiying; Xu, Song; Li, Guo; Zou, Jun; Wang, Lihong V.


    Melanoma, one of the most common types of skin cancer, has a high mortality rate, mainly due to a high propensity for tumor metastasis. The presence of circulating tumor cells (CTCs) is a potential predictor for metastasis. Label-free imaging of single circulating melanoma cells in vivo provides rich information on tumor progress. Here we present photoacoustic microscopy of single melanoma cells in living animals. We used a fast-scanning optical-resolution photoacoustic microscope to image the microvasculature in mouse ears. The imaging system has sub-cellular spatial resolution and works in reflection mode. A fast-scanning mirror allows the system to acquire fast volumetric images over a large field of view. A 500-kHz pulsed laser was used to image blood and CTCs. Single circulating melanoma cells were imaged in both capillaries and trunk vessels in living animals. These high-resolution images may be used in early detection of CTCs with potentially high sensitivity. In addition, this technique enables in vivo study of tumor cell extravasation from a primary tumor, which addresses an urgent pre-clinical need.

  13. Evidence of melanoma in wild marine fish populations.

    Directory of Open Access Journals (Sweden)

    Michael Sweet

    Full Text Available The increase in reports of novel diseases in a wide range of ecosystems, both terrestrial and marine, has been linked to many factors including exposure to novel pathogens and changes in the global climate. Prevalence of skin cancer in particular has been found to be increasing in humans, but has not been reported in wild fish before. Here we report extensive melanosis and melanoma (skin cancer in wild populations of an iconic, commercially-important marine fish, the coral trout Plectropomus leopardus. The syndrome reported here has strong similarities to previous studies associated with UV induced melanomas in the well-established laboratory fish model Xiphophorus. Relatively high prevalence rates of this syndrome (15% were recorded at two offshore sites in the Great Barrier Reef Marine Park (GBRMP. In the absence of microbial pathogens and given the strong similarities to the UV-induced melanomas, we conclude that the likely cause was environmental exposure to UV radiation. Further studies are needed to establish the large scale distribution of the syndrome and confirm that the lesions reported here are the same as the melanoma in Xiphophorus, by assessing mutation of the EGFR gene, Xmrk. Furthermore, research on the potential links of this syndrome to increases in UV radiation from stratospheric ozone depletion needs to be completed.

  14. Does Melanoma Begin in a Melanocyte Stem Cell?

    Directory of Open Access Journals (Sweden)

    James D. Hoerter


    Full Text Available 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 zebrafish model. Zebrafish 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 zebrafish to investigate how UVA- (320–400 nm and UVB- (290–320 nm 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.


    NARCIS (Netherlands)



    Tumor nuclear DNA content was determined by flow cytometry in routinely prepared paraffin blocks from 25 primary malignant melanomas of the extremities. Twelve of the tumors were aneuploid, and 13 were euploid. In this series the presence of aneuploidy appeared to have no prognostic value.

  16. Stereologic estimation of nucleolar volume in ocular melanoma

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Gamel, J W; McCurdy, J


    The aim of this study was to investigate the relationships between one-, two-, and three-dimensional histomorphometric estimators of nucleolar size in ordinary histologic sections of uveal melanomas from 144 patients. In addition, the prognostic value of the various size parameters was studied...

  17. Socioeconomic status and cutaneous malignant melanoma in Northern Europe

    DEFF Research Database (Denmark)

    Idorn, L W; Wulf, H C


    Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM), also in Northern Europe despite equal access to health care. SES per se is not responsible for this association which must be ascribed to important risk factors for CMM such as intermittent UVR exposure, and screening...

  18. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T


    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast...

  19. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker


    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...

  20. Keratinocytes drive melanoma invasion in a reconstructed skin model.

    NARCIS (Netherlands)

    Kilsdonk, J.W.J. van; Bergers, M.; Kempen, L.C.L.T. van; Schalkwijk, J.; Swart, G.W.


    Melanoma progression is a multistep progression from a common melanocytic nevus through the radial growth phase, the invasive vertical growth phase finally leading to metastatic spread into distant organs. Migration and invasion of tumor cells requires secretion of proteases to facilitate remodeling

  1. Insights in tumorigenesis and metastasis of uveal melanoma

    NARCIS (Netherlands)

    Notting, Irene Christa


    For a long time enucleation has been the treatment of choice for uveal melanoma. New treatment modalities have been developed e.g. transscleral thermotherapy (TTT), proton beam radiation, stereotactic radiotherapy and ruthenium application 1-3 . These treatment options offer a better chance to spare

  2. The genetic basis of new treatment modalities in melanoma. (United States)

    Kunz, Manfred


    In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2. Also mutated c-KIT has been identified as a promising target. Meanwhile, evidence has been provided that combinations between BRAF inhibitors and MEK1/2 inhibitors are more promising than single-agent treatments. Moreover, new treatment algorithms favor sequential treatment using BRAF inhibitors and newly developed immunotherapies targeting common T lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1). In depth molecular analyses have uncovered new mechanisms of treatment resistance and recurrence, which may impact on future treatment decisions. Moreover, next-generation sequencing data have shown that recurrent lesions harbor specific genetic aberrations. At the same time, high throughput sequencing studies of melanoma unraveled a series of new treatment candidates for future treatment approaches such as ERBB4, GRIN2A, GRM3, and RAC1. More recent bioinformatic technologies provided genetic evidence for extensive tumor heterogeneity and tumor clonality of solid tumors, which might also be of relevance for melanoma. However, these technologies have not yet been applied to this tumor. In this review, an overview on the genetic basis of current treatment of melanoma, treatment resistance and recurrences including new treatment perspectives based on recent high-throughput sequencing data is provided. Moreover, future aspects of individualized treatment based on each patient's individual mutational landscape are discussed.

  3. Neoantigen landscape dynamics during human melanoma-T cell interactions

    DEFF Research Database (Denmark)

    Verdegaal, Els M. E.; De Miranda, Noel F. C. C.; Visser, Marten;


    is constant over time is unclear. Here we analyse the stability of neoantigen-specific T-cell responses and the antigens they recognize in two patients with stage IV melanoma treated by adoptive T-cell transfer. The T-cell-recognized neoantigens can be selectively lost from the tumour cell population, either...

  4. Expression of basement membrane antigens in spindle cell melanoma. (United States)

    Prieto, V G; Woodruff, J M


    Spindle cell melanoma (SCM) is an uncommon form of melanoma that may be confused histologically with other tumors, including malignant peripheral nerve sheath tumors (MPNST). Tumors with neural differentiation and melanocytic nevi may both show basement membrane immunohistochemically and at the ultrastructural level. However, most ultrastructural studies of melanoma have failed to demonstrate well formed basement membrane around tumor cells. The presence of basement membrane has been used by some authors as evidence favoring MPNST, as opposed to SCM. To evaluate this distinction immunohistochemically, 22 primary and metastatic cutaneous melanomas having a spindle cell component (SCM) were studied using monoclonal antibodies against laminin and Type IV collagen. S100 protein and HMB45 antigen expression were also studied. All but one of the SCM were reactive for S100 protein in at least 25% of the cells. Thirteen of 20 tumors (65%) were focally reactive with HMB45. Laminin was expressed in 42% of the tumors (only membranous pattern in 3; cytoplasmic and membranous in 5). Seventeen tumors (77%) expressed type IV collagen (only membranous pattern in 7; cytoplasmic and membranous pattern in 10). Laminin and type IV collagen, known components of basement membrane, are often found in SCM. Therefore, their detection cannot be used to distinguish SCM from MPNST.

  5. Pelvis metastasis from primary choroidal melanoma: a case report

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    Xiong Y


    Full Text Available Yan Xiong, Yun Lang, Chongqi Tu, Hong Duan Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China Abstract: The patient, a 16-year-old girl, was admitted to our hospital with complaints of right hip pain and claudication. Her past medical history indicated that 2 years earlier she had undergone enucleation of her left eye for a primary choroidal melanoma. Imaging studies revealed a osteolytic destruction with soft tissue mass involving the right hemipelvis (zone I–II. Single-photon emission computed tomography (SPECT and positron emission tomography–computed tomography (PET–CT showed no other sites of metastases. Consequently, the patient underwent hemipelvic prosthesis reconstruction after tumor resection. Postoperative pathological diagnosis was metastatic malignant melanoma. Thirty months after treatment, imaging studies indicated no evidence of recurrence, and functional recovery was excellent. To our knowledge, the literature does not reveal any previously reported cases of ocular choroidal melanoma that metastasized to pelvis, meanwhile was carried out hemipelvic prosthesis reconstruction after pelvic tumor resection. Keywords: melanoma, metastasis, pelvis, tumor, reconstruction

  6. Immunotherapy in the management of melanoma: current status

    Directory of Open Access Journals (Sweden)

    Alston D


    Full Text Available Dylan Alston,1 Jerry D Brewer21Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, IL, 2Mayo Clinic, Rochester, MN, USAAbstract: As the rate of melanoma continues to increase, so does the need for more effective and durable therapies. Despite considerable research, the management of advanced disease remains challenging. Numerous therapies are being investigated, many of which aim at upregulating the immune system's innate ability to attack the tumor. Cytotoxic T lymphocyte antigen 4 antibodies are immune stimulants that act as negative regulators of the immune system by modifying an antitumor T-cell response. Ipilimumab, one such cytotoxic T lymphocyte antigen 4 antibody, and vemurafenib, a BRAF competitive inhibitor, were approved as first-line therapies in 2011 due to improved survival rates versus standard chemotherapy. Allovectin-7 is a lipid plasmid that encodes for major histone compatibility complex DNA sequences. It has led to increases in cytotoxic T-cell production, which subsequently attacks the tumor. OncoVEX, an oncolytic herpes virus, and PV-10, a chemoablative agent, have yielded promising results in metastatic lesions and have demonstrated a unique "bystandarder" phenomenon. In this paper we review the basics of melanoma from the pathophysiology, risk factors, signs, diagnostic approaches, and current status of immunologic management of melanoma.Keywords: melanoma, immunotherapy, ipilimumab, vemurafenib, OncoVEX, Allovectin-7

  7. Primary gastric melanoma: case report of a rare malignancy

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn


    Full Text Available We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.

  8. Characterization of the Melanoma miRNAome by Deep Sequencing.

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    Mitchell S Stark

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are 18-23 nucleotide non-coding RNAs that regulate gene expression in a sequence specific manner. Little is known about the repertoire and function of miRNAs in melanoma or the melanocytic lineage. We therefore undertook a comprehensive analysis of the miRNAome in a diverse range of pigment cells including: melanoblasts, melanocytes, congenital nevocytes, acral, mucosal, cutaneous and uveal melanoma cells. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced 12 small RNA libraries using Illumina's Genome Analyzer II platform. This massively parallel sequencing approach of a diverse set of melanoma and pigment cell libraries revealed a total of 539 known mature and mature-star sequences, along with the prediction of 279 novel miRNA candidates, of which 109 were common to 2 or more libraries and 3 were present in all libraries. CONCLUSIONS/SIGNIFICANCE: Some of the novel candidate miRNAs may be specific to the melanocytic lineage and as such could be used as biomarkers to assist in the early detection of distant metastases by measuring the circulating levels in blood. Follow up studies of the functional roles of these pigment cell miRNAs and the identification of the targets should shed further light on the development and progression of melanoma.

  9. Spontaneous regression of metastases from melanoma: review of the literature

    DEFF Research Database (Denmark)

    Kalialis, Louise Vennegaard; Drzewiecki, Krzysztof T; Klyver, Helle


    Regression of metastatic melanoma is a rare event, and review of the literature reveals a total of 76 reported cases since 1866. The proposed mechanisms include immunologic, endocrine, inflammatory and metastatic tumour nutritional factors. We conclude from this review that although the precise...

  10. Desmoplastic melanoma morphology on Thinprep: a report of two cases

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    Van Ells Becky L


    Full Text Available Abstract Background Desmoplastic melanoma is a variant of malignant melanoma that can range in appearance from sarcomatoid to scar-like. Cytomorphology of desmoplastic melanoma has been previously described on conventional smears; however, to our knowledge, detailed cytomorphology on ThinPrep has so far not been described. Herein, we describe the cytomorphology of two cases of desmoplastic melanoma on fine needle aspiration processed as ThinPrep slides and compare it to that seen on conventional smears. Pertinent immunocytochemical stains, performed on ThinPrep slides are also discussed. Case presentation The first case is a woman with a history of desmoplastic melanoma of the scalp with previous local recurrences and lymph node metastasis with a new submandibular mass. The second case is a man with a previously resected desmoplastic melanoma with his first local recurrence. Conventional smears, including air-dried Diff-Quik-stained and alcohol-fixed Papanicolaou-stained smears, demonstrated aggregates of pleomorphic spindle cells admixed with fibrous stroma and single spindle cells. In both cases, nuclei were elongated and plump with irregular nuclear contours, deep grooves, and folds. Chromatin was dark and coarse with either inconspicuous or multiple prominent nucleoli. Cytoplasm was located at the nuclear poles and was fine, wispy, and delicate. The background was clean with no evidence of necrosis or melanin pigment. Papanicolaou-stained ThinPrep slides were prepared from needle rinses and demonstrated excellent correlation of nuclear and cytoplasmic detail of single spindle cells to that seen on conventional smears with the exception of only slight decrease in nuclear size; however, nuclear and cytoplasmic detail of spindle cells embedded in stroma was markedly attenuated. Confirmatory immunostain for S-100 protein in both cases was performed on ThinPrep slides demonstrating crisp cytoplasmic staining in the spindle cells. Conclusion The

  11. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma. (United States)

    Khoja, Leila; Lorigan, Paul; Zhou, Cong; Lancashire, Matthew; Booth, Jessica; Cummings, Jeff; Califano, Raffaele; Clack, Glen; Hughes, Andrew; Dive, Caroline


    The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P<0.011) for patients with ≥ 2 CTCs vs. <2 CTCs, respectively). In multivariate analysis, CTC number was an independent prognostic biomarker of OS (hazard ratio (HR) 2.403, 95% confidence interval (CI) 1.303-4.430, P=0.005). Patients receiving treatment in whom CTC number remained ≥ 2 CTCs during treatment had shorter median OS than those who maintained <2 CTCs (7 vs. 10 months, HR 0.34, 95% CI 0.14-0.81, log-rank test P=0.015). In conclusion, CTC number in metastatic cutaneous melanoma patients is prognostic for OS with a cutoff of 2 CTCs per 7.5 ml blood. CTC number measured before and throughout treatment provided additional prognostic information. Larger studies are warranted to confirm CTC biomarker utility in melanoma patients.

  12. Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients. (United States)

    Roh, Mi Ryung; Park, Kyu-Hyun; Chung, Kee Yang; Shin, Sang Joon; Rha, Sun Young; Tsao, Hensin


    Telomerase reverse transcriptase (TERT) is the reverse transcriptase component of the telomeric complex, which synthesizes terminal DNA to protect chromosomal ends and to maintain genomic integrity. In melanoma, mutation in TERT promoter region is a common event and theses promoter variants have been shown to be associated with increased gene expression, decreased telomere length and poorer outcome. In this study, we determined the frequency of TERT promoter mutation in 88 Korean primary melanoma patients and aimed to see the association of TERT promoter mutation status to other major molecular features, such as BRAF, NRAS, KIT mutations and correlate with clinicopathological features. In our study, acral melanoma (n=46, 52.3%) was the most common type. Overall, TERT promoter mutation was observed in 15 cases (17%) with ten c. -124C>T altertions and five c. -146C>T alterations. None of our samples showed CC>TT mutation which is considered pathognomonic of UV induction. Among the 46 acral melanoma patients, 5 patients (10.9%) harbored TERT promoter mutation. Tumors with TERT promoter mutation showed significantly greater Breslow thickness compared to WT tumors (P=0.039). A combined analysis for the presence of TERT promoter and BRAF mutations showed that patients with both TERT promoter and BRAF mutation showed decreased survival compared with those with only TERT promoter mutation, only BRAF mutation, or without mutations in either TERT promoter or BRAF (P=0.035). Our data provides additional evidence that UV-induced TERT promoter mutation frequencies vary depending on melanoma subtype, but preserves its prognostic value.

  13. Clonal architectures and driver mutations in metastatic melanomas.

    Directory of Open Access Journals (Sweden)

    Li Ding

    Full Text Available To reveal the clonal architecture of melanoma and associated driver mutations, whole genome sequencing (WGS and targeted extension sequencing were used to characterize 124 melanoma cases. Significantly mutated gene analysis using 13 WGS cases and 15 additional paired extension cases identified known melanoma genes such as BRAF, NRAS, and CDKN2A, as well as a novel gene EPHA3, previously implicated in other cancer types. Extension studies using tumors from another 96 patients discovered a large number of truncation mutations in tumor suppressors (TP53 and RB1, protein phosphatases (e.g., PTEN, PTPRB, PTPRD, and PTPRT, as well as chromatin remodeling genes (e.g., ASXL3, MLL2, and ARID2. Deep sequencing of mutations revealed subclones in the majority of metastatic tumors from 13 WGS cases. Validated mutations from 12 out of 13 WGS patients exhibited a predominant UV signature characterized by a high frequency of C->T transitions occurring at the 3' base of dipyrimidine sequences while one patient (MEL9 with a hypermutator phenotype lacked this signature. Strikingly, a subclonal mutation signature analysis revealed that the founding clone in MEL9 exhibited UV signature but the secondary clone did not, suggesting different mutational mechanisms for two clonal populations from the same tumor. Further analysis of four metastases from different geographic locations in 2 melanoma cases revealed phylogenetic relationships and highlighted the genetic alterations responsible for differential drug resistance among metastatic tumors. Our study suggests that clonal evaluation is crucial for understanding tumor etiology and drug resistance in melanoma.

  14. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

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    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  15. β-Catenin signaling increases during melanoma progression and promotes tumor cell survival and chemoresistance.

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    Tobias Sinnberg

    Full Text Available Beta-catenin plays an important role in embryogenesis and carcinogenesis by controlling either cadherin-mediated cell adhesion or transcriptional activation of target gene expression. In many types of cancers nuclear translocation of beta-catenin has been observed. Our data indicate that during melanoma progression an increased dependency on the transcriptional function of beta-catenin takes place. Blockade of beta-catenin in metastatic melanoma cell lines efficiently induces apoptosis, inhibits proliferation, migration and invasion in monolayer and 3-dimensional skin reconstructs and decreases chemoresistance. In addition, subcutaneous melanoma growth in SCID mice was almost completely inhibited by an inducible beta-catenin knockdown. In contrast, the survival of benign melanocytes and primary melanoma cell lines was less affected by beta-catenin depletion. However, enhanced expression of beta-catenin in primary melanoma cell lines increased invasive capacity in vitro and tumor growth in the SCID mouse model. These data suggest that beta-catenin is an essential survival factor for metastatic melanoma cells, whereas it is dispensable for the survival of benign melanocytes and primary, non-invasive melanoma cells. Furthermore, beta-catenin increases tumorigenicity of primary melanoma cell lines. The differential requirements for beta-catenin signaling in aggressive melanoma versus benign melanocytic cells make beta-catenin a possible new target in melanoma therapy.

  16. Interpretation on Expert Consensus for Diagnosis and Treatment of Melanoma in China

    Institute of Scientific and Technical Information of China (English)

    DU Fu-rong; WU Yin-ping; YANG Xue; YU Li-fang; YE Zhen-hua


    In recent years, melanoma has become a tumor with the fastest increase of morbidity in all malignant tumors, and its annual increase is 3%-5%. Both morbidity and mortality of melanoma are low in China, but they are showing an increasing tendency in recent years. However, the morbidity of melanoma is increasing in most European and American countries, but the mortality keeps stable and is not in an increasing tendency along with the increasing morbidity, demonstrating that there are great differences between China and Western countries in the diagnosis and treatment of melanoma. At present, melanoma has become one of the diseases that severely threaten human health. Compared with other common malignant tumors, there are signiifcant differences in the clinical diagnosis and specific treatment of melanoma. To better adapt the rapid development of treatment for melanoma, and to make the clinical practice of melanoma more specific and internationalized in China, Expert Committee on Melanoma, Chinese Society of Clinical Oncology, has updated the Guidelines for Diagnosis and Treatment of Melanoma in China. Therefore, the editorial board of this journal interpreted this guideline in details, aiming to provide the lastest and most practical evidence-based evidence for clinical oncologists in China.

  17. Expression of Phosphorylated-STAT3 and Osteopontin and Their Correlation in Melanoma

    Institute of Scientific and Technical Information of China (English)

    Yan WU; Ping JIANG; Yun LIN; Siyuan CHEN; Nengxing LIN; Jiawen LI


    The expressions of p-STAT3 and osteopontin in 22 cases of normal nevi and 43 cases of malignant melanoma were immunohistochemically detected,and the correlation between p-STAT3 and osteopontin in malignant melanoma and the correlations of p-STAT3 (or osteopontin) with invasion,metastasis and thickness of malignant melanoma were examined.The results showed p-STAT3 was expressed in 2 of 22 cases of normal nevi and 30 of 43 cases of malignant melanoma,while osteopontin was expressed in 3 cases of normal nevi and 29 cases of malignant melanoma.The expressions of p-STAT3 and osteopontin in melanoma were significantly higher than that in benign nevi.There existed significant correlations between the expression of p-STAT3 and that of osteopontin in melanoma.Furthermore,the expression rates of p-STAT3 were significantly higher in invasive or metastatic melanomas than that their non-invasive or non-metastatic counterparts,and the expression rates of osteopontin were significantly higher in invasive melanomas than that in non-invasive ones.It is concluded that p-STAT3 and osteopontin may play important roles in the pathogenesis of malignant melanoma.

  18. Subcutaneous adipocytes promote melanoma cell growth by activating the Akt signaling pathway: role of palmitic acid. (United States)

    Kwan, Hiu Yee; Fu, Xiuqiong; Liu, Bin; Chao, Xiaojuan; Chan, Chi Leung; Cao, Huihui; Su, Tao; Tse, Anfernee Kai Wing; Fong, Wang Fun; Yu, Zhi-Ling


    Tumorigenesis involves constant communication between tumor cells and neighboring normal cells such as adipocytes. The canonical function of adipocytes is to store triglyceride and release fatty acids for other tissues. This study was aimed to find out if adipocytes promoted melanoma cell growth and to investigate the underlying mechanism. Here we isolated adipocytes from inguinal adipose tissue in mice and co-cultured with melanoma cells. We found that the co-cultured melanoma had higher lipid accumulation compared with mono-cultured melanoma. In addition, fluorescently labeled fatty acid BODIPY® FLC16 signal was detected in melanoma co-cultured with the adipocytes that had been loaded with the fluorescent dye, suggesting that the adipocytes provide fatty acids to melanoma cells. Compared with mono-cultured melanoma, co-cultured melanoma cells had a higher proliferation and phospho-Akt (Ser-473 and Thr-450) expression. Overexpression of Akt mutants in melanoma cells reduced the co-culture-enhanced proliferation. A lipidomic study showed that the co-cultured melanoma had an elevated palmitic acid level. Interestingly, we found that palmitic acid stimulated melanoma cell proliferation, changed the cell cycle distribution, and increased phospho-Akt (Ser-473 and Thr-450) and PI3K but not phospho-PTEN (phosphophosphatase and tensin homolog) expressions. More importantly, the palmitic acid-stimulated proliferation was further enhanced in the Akt-overexpressed melanoma cells and was reduced by LY294002 or knockdown of endogenous Akt or overexpression of Akt mutants. We also found that palmitic acid-pretreated B16F10 cells were grown to a significantly larger tumor in mice compared with control cells. Taken together, we suggest that adipocytes may serve as an exogenous source of palmitic acid that promotes melanoma cell growth by activating Akt.

  19. KIT amplification and gene mutations in acral/mucosal melanoma in Korea. (United States)

    Yun, Jina; Lee, Jeeyun; Jang, Jiryeon; Lee, Eui Jin; Jang, Kee Taek; Kim, Jung Han; Kim, Kyoung-Mee


    Mucosal and acral melanomas have demonstrated different genetic alterations and biological behavior compared with more common cutaneous melanomas. It was recently reported that gain-of-function KIT mutations and/or copy number increases are more common in mucosal and acral melanomas. Thus, we studied the frequency and pattern of KIT aberrations in mucosal and acral melanomas in Korea. We analyzed 97 patients who were pathologically confirmed with mucosal or acral melanoma between 1997 and 2010 at Samsung Medical Center. Of the 97 melanoma patients, 92 were screened for mutations in KIT exons 11, 13, 17, and 18, BRAF and NRAS genes. KIT copy number was assessed by quantitative, real-time PCR. Of the 97 patients, 55 (56.7%) were mucosal, 40 (41.2%) were acral melanoma, and two were of unknown primary origin. Among seven cases with KIT mutation, five (60.0%) occurred in exon 11, one (20.0%) in exon 17, and one (20.0%) in exon 13. Point mutations were the most common, resulting in substitutions in exon 11 (K558R, T574A, L576P, and V559A), exon 13 (N655K), and exon 17 (N822K). A novel Thr574Ala (c.1720A>G) KIT mutation, which has not been reported in melanoma or other tumor types, was identified in one genital melanoma case. Of the 97 mucosal or acral melanoma specimens, 49 were tested for KIT gene copy number changes using quantitative PCR. Increased KIT copy number was identified in 15 patients: seven (40%) of 20 acral melanomas and eight (31%) of 26 mucosal melanomas. Our study implicates that a significant proportion of acral and mucosal melanomas have KIT mutations in Asian population.

  20. Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry (United States)

    Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin


    Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. The raw signal detected from target cells often contains some noise caused by electronic devices, such as background noise and thermal noise. We choose the Wavelet denoising method to effectively distinguish the target signal from background noise. Processing in time domain and frequency domain would be combined to analyze the signal after denoising. This algorithm contains time domain filter and frequency transformation. The frequency spectrum image of the signal contains distinctive features that can be used to analyze the property of target cells or particles. The processing methods have a great potential for analyzing signals accurately and rapidly. By counting circulating melanoma cells termly, we obtain the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.