Science.gov

Sample records for malignant melanoma experience

  1. Bronchial malignant melanoma.

    PubMed

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

    1980-01-01

    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.

  2. Primary malignant melanoma of prostate.

    PubMed

    Doublali, M; Chouaib, A; Khallouk, A; Tazi, M F; El Fassi, M J; Farih, My H; Elfatmi, H; Bendahou, M; Benlemlih, A; Lamarti, O

    2010-05-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

  3. Lymphoscintigraphy in malignant melanoma

    SciTech Connect

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

    1992-01-01

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

  4. Primary cerebral malignant melanoma

    PubMed Central

    Tang, Kai; Kong, Xiangyi; Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi; Du, Shiwei

    2017-01-01

    Abstract Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma—a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers’ reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. PMID:28121927

  5. Prevention of malignant melanoma

    PubMed Central

    Chaidemenos, G; Stratigos, A; Papakonstantinou, M; Tsatsou, F

    2008-01-01

    The results of Primary Prevention programs, aiming at the decrease of melanoma incidence, were less encouraging than those of Secondary prevention which aims at an early diagnosis of malignant melanoma. Australia was the country with the best results obtained in both Prevention strategies, especially in avoiding intense, though intermittent, UV exposure. The success of these programs encouraged health authorities to initiate their application to other disorders. New sunscreens containing substances correcting the UV-damaged DNA may offer a promising result in the decades to come. However, so far no one epidemiological study has proved the prevention of malignant melanoma with the use of sun protecting agents. A meta-analysis verified the connection between melanoma and solarium use. The protective role of vitamin D in the development of prostate, breast and colon cancer was shown in a meta-analysis. The authors, however, suggest that fair-skinned persons should take oral supplementation of vitamin D, instead of exposing themselves to the sun. The Hellenic Society of Dermatology and Venereology published the results of 5-year-prevention programs in Greece. Their favorable results in the early diagnosis of melanoma justify an intense continuation of these efforts. PMID:18923759

  6. Primary malignant melanoma of prostate

    PubMed Central

    Doublali, M.; Chouaib, A.; Khallouk, A.; Tazi, M. F.; El Fassi, M. J.; Farih, My. H.; Elfatmi, H.; Bendahou, M.; Benlemlih, A.; Lamarti, O.

    2010-01-01

    Primary genitourinary melanoma accounts for less than one per cent of all cases of melanoma. Most cases attributed to the prostate actually originate from the prostatic urethra. Due to its infrequency, primary malignant melanoma of the genitourinary tract presents a difficult diagnostic and management challenge. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate. PMID:20882159

  7. Primary pineal malignant melanoma

    PubMed Central

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

    2011-01-01

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

  8. Basic and clinical aspects of malignant melanoma

    SciTech Connect

    Nathanson, L. )

    1987-01-01

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

  9. Malignant melanoma of the skin

    PubMed Central

    Armstrong, B. K.; Holman, C. D. J.

    1987-01-01

    Ultra-violet radiation (UVR) in sunlight is thought to be the main cause of malignant melanoma in lightly-pigmented populations. Individuals with fair skin, fair hair, blue eyes and/or a tendency to burn rather than tan when exposed to the sun are at particularly high risk of melanoma and should be given special attention in primary prevention programmes. Intermittent exposure to the sun, as in recreational exposure, may be a more potent cause of melanoma than more continuous exposure. Primary prevention offers the best prospects for a substantial reduction in mortality from malignant melanoma. However, there is little evidence available to judge the effectiveness of primary prevention of melanoma through reduction of exposure to the sun. Education for reducing exposure to the sun is common in high-risk populations but has never been evaluated adequately. Mortality from melanoma could also possibly be reduced by earlier diagnosis through education or screening of high-risk groups. Regular screening of patients with the familial dysplastic naevus syndrome should reduce their mortality from melanoma. PMID:3301043

  10. Malignant melanoma of the foot and ankle.

    PubMed

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

    2000-04-01

    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.

  11. Cutavirus in Cutaneous Malignant Melanoma

    PubMed Central

    Fridholm, Helena; Vinner, Lasse; Kjartansdóttir, Kristín Rós; Friis-Nielsen, Jens; Asplund, Maria; Herrera, Jose A.R.; Steiniche, Torben; Mourier, Tobias; Brunak, Søren; Willerslev, Eske; Izarzugaza, Jose M.G.; Hansen, Anders J.; Nielsen, Lars P.

    2017-01-01

    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 investigated. PMID:28098541

  12. Primary retroperitoneal malignant melanoma: A case report

    PubMed Central

    LIU, GUO-BING; WU, GUANG-YAO; GHIMIRE, PRASANNA; ZHANG, ZAI-PENG

    2011-01-01

    Primary malignant melanoma occurring at an extra cutaneous site is rare. A case of primary malignant melanoma located in the retroperitoneum of an 18-year-old female is presented in this study. Histopathological examination of the tissue biopsies at laparotomy with immunohistochemical stains confirmed a diagnosis of malignant melanoma. Further extensive clinical and radiological investigations proved the retroperitoneum to be the primary site. PMID:22848275

  13. Malignant rectal melanoma. Case report.

    PubMed

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

    2015-03-26

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

  14. Isolated Pancreatic Metastasis from Malignant Melanoma: Is Pancreatectomy Worthwile?

    PubMed Central

    Birnbaum, David Jérémie; Moutardier, Vincent; Turrini, Olivier; Gonçalves, Anthony; Delpero, Jean Robert

    2013-01-01

    Isolated pancreatic metastasis from malignant melanoma (IPMMM) is rare because most melanoma patients already have a widespread disease at diagnosis. No adjuvant systemic treatment is known to be efficient in this setting. Experience with pancreatic resection for IPMMM is limited and controversial. We report here the case of an IPMMM patient successfully treated by pancreaticoduodenectomy with a prolonged survival of 6 years. PMID:24741425

  15. Genetic progression of malignant melanoma.

    PubMed

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

    2016-03-01

    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

  16. Canine olfactory detection of malignant melanoma

    PubMed Central

    Campbell, Leon Frederick; Farmery, Luke; George, Susannah Mary Creighton; Farrant, Paul B J

    2013-01-01

    Our patient is a 75-year-old man who presented after his pet dog licked persistently at an asymptomatic lesion behind his right ear. Examination revealed a nodular lesion in the postauricular sulcus. Histology confirmed malignant melanoma, which was subsequently excised. Canine olfactory detection of human malignancy is a well-documented phenomenon. Advanced olfaction is hypothesised to explain canine detection of bladder, breast, colorectal, lung, ovarian, prostate and skin cancers. Further research in this area may facilitate the development of a highly accurate aid to diagnosis for many malignancies, including melanoma. PMID:24127369

  17. [Malignant melanoma of the oral cavity].

    PubMed

    A, Burgos; R, Kaplan; N, Rodríguez; Meza, Vetanzo; Morelatto, R; Piccinni, D

    2008-01-01

    Malignant melanoma of the oral cavity is a rare neoplasm and it is only 0.5% of the malignant neoplasms of the oral cavity, and less than 10% of all the malignant melanomas. The mean age for patients with oral melanoma is from 40 to 70 years; with a higher frequency between the 50 and 60 years. Pigmentation areas are frequently noted before diagnosis of this neoplasm. Some predisposing factors are mechanical traumas resulting from not well adapted prostheses, solar radiation, and chem-icals. Although oral cavity melanomas can remain asymptomatic during a time, the clinical presentations include hemorrhage, ulceration and pain. Melanomas grow fast, generally in a vertical growth phase, with early invasion of bones and lymphatic nodes. The prognosis for patients with melanoma is poor with a 5-year survival rate. The election treatment is surgical. The early diagnosis, the recognition of the lesions for doctors and odontologists, and the biopsy of recent or old pigmentation areas in the mouth that they have some changes (ulceration, bleeding, etc.) will contribute to offer patients a more effective treatment and a higher survival rate. We will present the case study of a 78-year-old male patient with a tumor in the dental ridge surrounded by melanotic spots, which was diagnosed as invasive melanoma and confirmed with immunohistochemical techniques.

  18. Fluorescent Antibody Studies in Malignant Melanoma

    PubMed Central

    Whitehead, R. H.

    1973-01-01

    Sera from 57 patients with malignant melanoma and 39 control patients were tested by immunofluorescence techniques against 6 melanoma cell lines. Thirty-two per cent of tests with sera from melanoma patients showed fluorescence with these cell lines whereas only 17% of tests with control sera were positive. Reactions occurred in 21% of tests with sera from patients with primary melanoma compared with 40% with secondary melanomata and 54% with “cured” melanomata. The cell lines varied in antigenicity but this did not correlate with either pigmentation or length of time in culture. The cell lines which were most reactive with sera from melanoma patients were also most reactive with control sera. PMID:4205845

  19. Fli-1 expression in malignant melanoma.

    PubMed

    Torlakovic, Emina E; Slipicevic, Ana; Flørenes, Vivi Ann; Chibbar, Richa; DeCoteau, John F; Bilalovic, Nurija

    2008-11-01

    Friend leukemia integration site 1 (Fli-1) has been reported as the first nuclear marker of endothelial differentiation; it is expressed in leukocytes and recently demonstrated in melanomas. Formalin-fixed, paraffin-embedded tissue sections from 97 melanomas including 69 cases of primary and 28 metastatic melanomas were evaluated by immunohistochemistry. Five melanoma cell lines were evaluated by Western blot and immunocytochemistry. Fli-1 expression was observed in all cell lines. Fli-1 expression was higher in metastatic than in primary tumors (r=0.208, p=0.041, Spearman correlation), it positively correlated with Ki-67 expression (r=0.233, p=0.022, Spearman correlation), and the presence of an ulcer in the primary tumor (r=0.267, p=0.030, Spearman correlation). Therefore, the expression of Fli-1 in malignant melanoma appears to be associated with biologically more aggressive tumors.

  20. Malignant Melanoma Arising in Red Tattoo Ink

    PubMed Central

    Duff, Gerald; McKenna, Dermot; Regan, Padraic James

    2015-01-01

    We report the case of a 33-year-old male who presented with a malignant melanoma on his anterior chest wall. The lesion was only found in the red ink pigment of the tattoo, as were several in-transit dermal metastases. Possible explanations include a pre-existing lesion which was seeded with red ink or the possibility of the red ink causing an inflammatory reaction leading to malignant transformation. This is the first reported case of a melanoma developing in the red ink pigment of a multi-colored tattoo. PMID:26217569

  1. Malignant melanoma at a scientific laboratory

    SciTech Connect

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

    1985-11-15

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

  2. Experimental ocular malignant melanoma in Sinclair swine.

    PubMed

    Burns, R P; Tidwell, M

    1986-04-01

    An animal model of malignant melanoma of the eye was established by transplanting a cell suspension from cutaneous melanomas into the anterior chamber of the eye in Sinclair Farm miniature swine. The frequency of tumor takes in the eye was increased from 8.9% to 22% by treating the animals simultaneously with subconjunctival triamcinolone acetonide. As an animal model for hematoporphyrin derivative--photoradiation treatment of human malignant melanoma of the eye, this does not appear to be a good research tool because of the sporadic incidence of tumor takes, the rapid growth of tumor within the eye causing glaucoma, and the dark iris pigmentation of successful tumor takes, which hides extensive underlying ciliary body tumor.

  3. Wavelengths effective in induction of malignant melanoma.

    PubMed Central

    Setlow, R B; Grist, E; Thompson, K; Woodhead, A D

    1993-01-01

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented backcross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. We irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and scored the irradiated animals for melanomas 4 months later. We used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. We interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths > 320 nm--the UV-A and visible spectral regions. Images Fig. 4 PMID:8341684

  4. Wavelengths effective in induction of malignant melanoma

    SciTech Connect

    Setlow, R.B.; Grist, E.; Thompson, K.; Woodhead, A.D. )

    1993-07-15

    It is generally agreed that sunlight exposure is one of the etiologic agents in malignant melanoma of fair-skinned individuals. However, the wavelengths responsible for tumorigenesis are not known, although DNA is assumed to be the target because individuals defective in the repair of UV damage to DNA are several thousandfold more prone to the disease than the average population. Heavily pigmented back-cross hybrids of the genus Xiphophorus (platyfish and swordtails) are very sensitive to melanoma induction by single exposures to UV. The authors irradiated groups of five 6-day-old fish with narrow wavelength bands at 302, 313, 365, 405, and 436 nm and score the irradiated animals for melanomas 4 months later. They used several exposures at each wavelength to obtain estimates of the sensitivity for melanoma induction as a function of exposure and wavelength. The action spectrum (sensitivity per incident photon as a function of wavelength) for melanoma induction shows appreciable sensitivity at 365, 405, and probably 436 nm, suggesting that wavelengths not absorbed directly in DNA are effective in induction. They interpret the results as indicating that light energy absorbed in melanin is effective in inducing melanomas in this animal model and that, in natural sunlight, 90-95% of melanoma induction may be attributed to wavelengths >320 nm-the UV-A and visible spectral regions. 25 refs., 4 figs., 1 tab.

  5. Ukrain monotherapy in malignant melanoma (case report).

    PubMed

    Hamler, F; Hiesmayr, W; Korsh, O; Melnyk, A

    1996-01-01

    A patient with a metastasizing malignant melanoma (stage III) was treated with Ukrain monotherapy. Before and during the first Ukrain course of treatment the patient excreted melanin in the urine. After the third course melanin was no more detectable and the patient has been without any symptoms of disease for the last 12 years.

  6. [Advances in cellular immunotherapy for malignant melanoma].

    PubMed

    López, Mercedes; Escobar, Alejandro; Alfaro, Jorge; Fodor, Miguel; Larrondo, Milton; Ferrada, Carlos; Salazar-Onfray, Flavio

    2004-09-01

    An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy. The immunotherapeutical use of cells of the immune system, like dendritic cells (DC), is being explored in different clinical protocols. Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates. Our results indicate that the subcutaneous application of DCs do not produce adverse effects. We also observed an increase of tumor specific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients. In most cases, an stability in the disease was observed, although without a significant association between vaccination and survival. Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985. However, problems associated to the toxicity of IL-2 still restrict its massive use. Our direct experience with the use of IL-2, indicates that low doses and its subcutaneous application, maintains the beneficial effects for patients, eliminating the adverse effects. Based on the accumulated evidence during last the five years, we decided to implement an optimized clinical protocol, which alternatively combines dendritic cells vaccines with the use of low doses of IL-2 for the reinforcement of the immunological system.

  7. Primary Retroperitoneal Melanoma Presented in a Rare Extracutaneous Site for Malignant Melanoma.

    PubMed

    Alsharedi, Mohamed; Zgheib, Nadim Bou; Khelfa, Yousef; Raufi, Ali; Elmsherghi, Nabiha; Lebowicz, Yehuda

    2016-09-05

    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.

  8. Toward automated detection of malignant melanoma

    NASA Astrophysics Data System (ADS)

    Huang, Billy; Gareau, Daniel S.

    2009-02-01

    In vivo reflectance confocal microscopy shows promise for the early detection of malignant melanoma (MM). Two hallmarks of MM have been identified: the presence of pagetoid melanocytes in the epidermis and the breakdown of the dermal papillae. For detection of MM, these features must be identified qualitatively by the clinician and qualitatively through automated pattern recognition. A machine vision algorithm was developed for automated detection. The algorithm detected pagetoid melanocytes and breakdown of the dermal/epidermal junction in a pre-selected set of five MMs and five benign nevi for correct diagnosis.

  9. Tracheal malignant melanoma: successful outcome with tracheal resection.

    PubMed

    Terra, Ricardo Mingarini; Minamoto, Helio; Junqueira, Jader J M; Falzoni, Roberto; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

    2008-07-01

    Primary tracheal malignant melanomas are uncommon neoplasms: only five cases have been reported. Different therapeutic approaches are described, with a short life expectancy observed. We report a case of a young woman with a primary tracheal malignant melanoma who underwent complete tracheal resection and is free of disease 4 years after surgical treatment.

  10. Metastatic Malignant Melanoma in an alpaca (Vicugna pacos)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Malignant melanoma in a 7-year old, intact male alpaca with a chronic, non-healing wound on the left nares, weight loss and inappetance is described. Malignant melanoma was diagnosed in punch biopsy specimens from a mass on the maxilla associated with the non-healing wound and from a mass in the su...

  11. Hemosideric heterochromia iridum in malignant melanoma of the choroid.

    PubMed

    Awan, K J

    1975-08-01

    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.

  12. Pigmented mammary paget disease misdiagnosed as malignant melanoma.

    PubMed

    Lee, Ji Hye; Kim, Tae Hyung; Kim, Soo-Chan; Kim, You Chan; Roh, Mi Ryung

    2014-12-01

    Pigmented mammary Paget disease is a very rare clinicopathologic variant of mammary Paget disease. Diagnosis is often difficult because its clinical and histological features are very similar to those of malignant melanoma. Herein, we report a case of pigmented mammary Paget disease misdiagnosed as malignant melanoma.

  13. Primary malignant melanoma of cervix and vagina

    PubMed Central

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

    2016-01-01

    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

  14. False negative clinical diagnoses of malignant melanoma.

    PubMed

    Osborne, J E; Bourke, J F; Graham-Brown, R A; Hutchinson, P E

    1999-05-01

    The false negative rate for the clinical diagnosis (FNR) for malignant melanoma is reported to be of the order of 20-50%. The aim of this study was to investigate possible predictor variables for FNR, with particular reference to the features and score of the seven-point check-list within the total population (778) of histologically proved malignant melanomas presenting in Leicestershire between 1982 and 1996. The FNR was 18.5%. The check-list would have failed as a referral indication in only 0.8-1. 1% of the lesions. The major check-list features occurred more commonly than the minor features, excepting size >/= 7 mm, confirming the diagnostic importance of the major criteria. The FNR was unaffected by age or sex. More rarely involved sites had higher rates (31-42%), and the face was a particularly difficult diagnostic site. Clinical features of lesions associated with a higher FNR were lack of irregular pigmentation and shape, altered sensation, the presence of inflammation and size < 7 mm. The FNR was inversely related to the total score and major feature score, but directly related to the minor score. The minor features, in addition to the major features, are potentially valuable in avoiding false negative diagnoses and we suggest their retention as part of the check-list. There was only one patient, in whom the diagnosis of melanoma was initially missed and who was not biopsied on presentation to hospital, who re-presented after 1 year. However, the study illustrates the importance of avoiding a false negative diagnosis as there was marked delay in the excision of such lesions.

  15. Classification of malignant melanomas: a view of the current controversy.

    PubMed

    Lieblich, L M

    1982-10-01

    The Clark classification of malignant melanomas into four types is well known and widely used. This classification system has been recently challenged by Ackerman and subsequently defended by Elder, Jucovy, Tuthill, and Clark. Four areas of disagreement among these opposing authors are discussed. They include the reliability of the criteria used for distinguishing the four types of malignant melanomas, the possible site dependence of the four types of malignant melanomas, the differing definitions given to radial-growth phase, horizontal-growth phase, and vertical-growth phase; and whether a malignant melanoma can exist in a "pure" vertical-growth phase (nodular melanoma). An analogy to the classification of warts is made. The view of this paper is that all classification systems are arbitrary and thus are types of models. Like other models, they should be evaluated only in terms of their usefulness in explaining pathogenesis or predicting clinical outcome.

  16. Primary Intracranial Malignant Melanoma with Extracranial Metastasis

    PubMed Central

    Hirota, Kengo; Yoshimura, Chika; Kubo, Osami; Kasuya, Hidetoshi

    2017-01-01

    We report a case of primary intracranial malignant melanoma (PIMM) with extracranial metastases. The patient was an 82-year-old woman diagnosed with PIMM under the left cerebellar tentorium. We performed a tumor resection followed by gamma knife surgery. An magnetic resonance imaging at 11 months after surgery showed a local intracranial recurrence. At 12 months, vertebral metastasis was suspected, and 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) showed multiple extracranial metastases. She died at 13 months after surgery. Although extracranial metastases of PIMM are extremely rare, we should carefully follow up extracranial metastases together with intracranial ones, especially by FDG-PET/CT, even at an early asymptomatic stage. PMID:28061499

  17. Human malignant melanoma heterotransplanted to nude mice.

    PubMed

    Tropé, C; Johnsson, J E; Alm, P; Landberg, T; Olsson, H; Wennerberg, J

    1981-01-01

    Five different human malignant melanoma were heterotransplanted subcutaneously to nude mice. When small tissue pieces were used 3 out of 5 tumors grew. Subcutaneous injections of suspended tumor cells were also made, but all failed to take. Metastatic or infiltrative growth was never seen in the mice observed for up to 2.5 months. The successful grafts largely retained the original morphologicaL features. The three successfully transplanted tumors could all be serially transferred with 100% tumor take. In one case passage time was reduced from 40 days to 15 days. As measured with 3H-thymidine incorporation the proliferation rate increased during the passages. These changes might be due to a selection of more rapidly growing tumor cells in the nudes.

  18. Solar radiation and malignant melanoma of the skin

    SciTech Connect

    Houghton, A.N.; Viola, M.V.

    1981-01-01

    Several observations suggest that a majority of cases of malignant melanoma of the skin are linked to sun exposure. Evidence includes higher occurrence of melanoma on anatomic areas heavily exposed during recreation, development of melanoma more frequently in lightly pigmented persons, and correlation of melanoma incidence and mortality with proximity to the equator. The role of the sun exposure in the pathogenesis of melanoma remains unclear, however. Many cases of melanoma may be related to heavy doses of solar radiation received during recreation. Chronic sun exposure is not so clearly linked to the development of melanoma (except in the uncommon lentigo maligna variety). Sunspot cycles have been associated with changes in melanoma incidence; an excess of melanoma cases has been observed every 9 to 12 years after peak sunspot activity. These excess cases may be caused by more intense exposure to solar ultraviolet radiation during sunspot maxima, perhaps related to changes in the stratospheric ozone layer. These epidemiologic and clinical clues suggest that many cases of melanoma are related to sun exposure triggering the appearance of clinically evident melanoma. In this regard, solar radiation behaves as a cocarcinogen or promoter, rather than a dose-dependent carcinogen. These observations also suggest that other factors may be involved in the pathogenesis of melanoma, e.g., nevi, heredity, or exposure to chemical carcinogens.

  19. [Utilization of melanin precursors for experimental chemotherapy of malignant melanoma].

    PubMed

    Jimbow, K; Miura, S; Ito, Y; Kasuga, T; Ito, S

    1984-10-01

    Melanin synthesis is a metabolic pathway unique and specific to melanocytes. It occurs by conversion of tyrosine to dopa and dopaquinone in the presence of tyrosinase. It is highly accelerated in malignant melanoma with a marked increase of tyrosinase activity. This study summarizes the recent progress in experimental chemotherapeutic approaches to malignant melanoma by utilizing melanin precursors, and presents our current results. Our studies indicated (a) that hydroquinone and 4-isopropylcatechol are selectively toxic to melanocytes and melanoma cells, (b) that their actions are mediated through tyrosinase, and (c) that dopa is selectively and highly incorporated into melanoma cells and melanocytes depending on the tyrosinase activity. In addition, our new compounds, i.e., 4-S-cysteinylphenol and 4-S-cysteaminylphenol were highly toxic to melanoma cells, increasing the life span of B16 melanoma bearing mice and decreasing melanoma growth in C57 BL mice. Other synthetic compounds, e.g., cysteinylcatechols and their devivatives, were, however, not toxic to melanoma cells. 4-S-cysteinylphenol and 4-S-cysteaminylphenol appeared to exert their cytotoxicity through the action of tyrosinase present in melanoma cells, thus providing a kind of "guided missile" approach to melanoma chemotherapy.

  20. Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance.

    PubMed

    Krumm, Andrea; Barckhausen, Christina; Kücük, Pelin; Tomaszowski, Karl-Heinz; Loquai, Carmen; Fahrer, Jörg; Krämer, Oliver Holger; Kaina, Bernd; Roos, Wynand Paul

    2016-05-15

    DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance of melanomas to the alkylating drugs temozolomide, dacarbazine, and fotemustine. Here, we report on the impact of class I HDACs on the response of malignant melanoma cells treated with alkylating agents. The data show that malignant melanomas in situ contain a high level of HDAC1/2 and malignant melanoma cells overexpress HDAC1/2/3 compared with noncancer cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes malignant melanoma cells to apoptosis following exposure to alkylating agents, while not affecting primary melanocytes. Inhibition of HDAC1/2/3 caused sensitization of melanoma cells to temozolomide in vitro and in melanoma xenografts in vivo HDAC1/2/3 inhibition resulted in suppression of DNA double-strand break (DSB) repair by homologous recombination because of downregulation of RAD51 and FANCD2. This sensitized cells to the cytotoxic DNA lesion O(6)-methylguanine and caused a synthetic lethal interaction with the PARP-1 inhibitor olaparib. Furthermore, knockdown experiments identified HDAC2 as being responsible for the regulation of RAD51. The influence of class I HDACs on DSB repair by homologous recombination and the possible clinical implication on malignant melanoma therapy with temozolomide and other alkylating drugs suggests a combination approach where class I HDAC inhibitors such as valproic acid or MS-275 (entinostat) appear to counteract HDAC- and RAD51/FANCD2-mediated melanoma cell resistance. Cancer Res; 76(10); 3067-77. ©2016 AACR.

  1. Malignant melanoma showing a rapid response to nivolumab.

    PubMed

    Tsutsumi, Miho; Asai, Jun; Wada, Makoto; Takenaka, Hideya; Katoh, Norito

    2016-02-01

    Malignant melanoma is a highly aggressive skin tumour, with a recent rise in incidence. Nivolumab is a recently developed anti-programmed cell death-1 immune checkpoint inhibitor and its usage has resulted in a significant improvement in the overall survival of patients with metastatic melanomas. We report a case of advanced melanoma that showed a significant and rapid response to nivolumab treatment. The patient displayed multiple melanoma-associated vitiligo prior to treatment; this symptom was theorised to indicate potentially immunoreactive melanoma and the need for nivolumab. In addition, interferon-β was injected prior to nivolumab treatment. The significant rapid response to nivolumab suggested the induction of a marked immune response against melanoma by interferon-β. Therefore, interferon-β could be a useful and effective adjuvant for nivolumab therapy.

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

    SciTech Connect

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

    1985-08-01

    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.

  3. Primary malignant melanoma of female urethra: a rare neoplasm.

    PubMed

    Pandey, Praveen K; Vijay, Mukesh K; Goel, Hemant; Shukla, Suruchi

    2014-01-01

    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.

  4. Malignant melanoma of gingiva: Report of a rare case.

    PubMed

    Vikey, Ashok; Kapoor, Prakhar; Kathariya, Rahul; Vikey, Deepali; Kukreja, Ipsita

    2015-01-01

    According to the World Health Organization, oral malignant melanoma (OMM) is a rare disease, accounting for only 0.8% of all melanomas, 8% of head and neck melanomas, and up to 0.5% of all oral malignancies. OMM presents as a pigmented lesion with asymmetrical borders, irregular surface characteristics, and a distinct color. Melanoma-associated pigmented lesion of the oral cavity does not possess clinical specificity and frequently divert the clinical diagnosis; hence, differential diagnosis becomes mandatory. Furthermore, the unpredictable pathophysiological behavior and delayed detection, contributes for poor prognosis of the disease. As a result, the 5 years survival rate is only 10-25%. Commonly OMM is seen in maxillary gingiva of males. However, we report a rare case of a middle-aged female having pigmentations and growth over mandibular gingiva.

  5. Cutaneous malignant melanoma in association with mycosis fungoides.

    PubMed

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

    2004-05-01

    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.

  6. Rhabdomyosarcoma and late malignant melanoma of the orbit

    SciTech Connect

    Leff, S.R.; Henkind, P.

    1983-10-01

    Forty-five years following surgical excision and radiation for a childhood rhabdomyosarcoma of the left orbit, a patient with primary lymphedema developed an ipsilateral malignant melanoma of the anterior orbital tissue. This was excised, but a metastasis of the melanoma occurred in the contralateral upper lid. This is the first case report of treated rhabdomyosarcoma of the orbit followed by a second primary tumor occurring in the field of radiation.

  7. Cutaneous malignant melanoma arising in an acquired naevus of Ota.

    PubMed

    Patterson, Clare R S; Acland, Katharine; Khooshabeh, Ramona

    2009-11-01

    Naevus of Ota is a dermal melanocytosis most commonly found in black or Asian skin and is usually a benign malformation, but with a low risk of melanoma. We describe a 32-year-old Caucasian man with an acquired naevus of Ota with subtle pigmentation, in which a melanocytic papule developed. The lesion, deceptively, had no clinically suspicious features, but investigation revealed an aggressive cutaneous malignant melanoma, extensive orbital ring melanocytosis and metastatic brain and subsequent liver disease.

  8. [Case of primary amelanotic malignant melanoma of the female urethra].

    PubMed

    Yoshii, Takahiko; Horiguchi, Akio; Shirotake, Suguru; Tobe, Musashi; Tasaki, Shinsuke; Hayakawa, Masamichi; Sumitomo, Makoto; Asano, Tomohiko

    2010-09-01

    We report a rare case of primary amelanotic malignant melanoma of the female urethra. A 58-year-old female with complaint of nodule on the external urethral meatus was referred to our hospital. Pathological diagnosis of the biopsy specimen from the nodule was malignant melanoma. Computed tomography of the chest and abdomen as well as bone scan showed no evidence of metastasis. Sentinel biopsy from the inguinal lymph nodes revealed no metastasis. Thereafter, the patient underwent radical urethrectomy, whose limits of resection were the bulbocavernosal muscles bilaterally, the arch of the pubic symphysis anteriorly, the anterior vaginal wall posteriorly, and the urethra up to the level of the bladder neck superiorly. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received six cycles of DAV-Feron (dacarbazine, nimustine, vincristine, and interferon-beta) in an adjuvant setting, and there is no sign of recurrence 25 months after operation.

  9. [Is UV-A a cause of malignant melanoma?].

    PubMed

    Moan, J

    1994-03-20

    The first action spectrum for cutaneous malignant melanoma was published recently (2). This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B-solaria rather than UV-A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagnetic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filters (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert.

  10. TANGO is a tumor suppressor of malignant melanoma.

    PubMed

    Arndt, Stephanie; Bosserhoff, Anja K

    2006-12-15

    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.

  11. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  12. [Cutaneous malignant melanoma and the new drugs].

    PubMed

    Nieweg, Omgo E; Gallegos-Hernández, José Francisco

    2015-01-01

    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.

  13. [Sentinel lymph node in malignant melanoma].

    PubMed

    Salas, Carmen; Pérez, Natividad

    2004-06-01

    The authors describe the technique called sentry ganglion, the ganglion which has the highest risk of receiving neoplastic cells and towards which a primary tumor directs its metastasis. The authors explain the procedure for carrying out a biopsy on this ganglion and its warnings regarding different neoplasias and specifically regarding melanoma.

  14. Citrus Consumption and Risk of Cutaneous Malignant Melanoma

    PubMed Central

    Wu, Shaowei; Han, Jiali; Feskanich, Diane; Cho, Eunyoung; Stampfer, Meir J.; Willett, Walter C.; Qureshi, Abrar A.

    2015-01-01

    Purpose Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption. Methods A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records. Results Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001). Conclusion Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications. PMID:26124488

  15. (14C)deoxyglucose uptake and imaging in malignant melanoma

    SciTech Connect

    Kern, K.A. )

    1991-06-01

    Since malignant tumors utilize more glucose than normal tissues, tumor uptake and autoradiographic imaging studies using the 14C-labeled glucose analog 2-deoxyglucose (DG) provide a useful preclinical system to determine if similar human tumors will image in vivo with positron emission tomography (PET) using 18F-labeled DG (FDG-PET). We studied B16 murine melanomas of increasing metastatic potential (F1, low; BL-6, intermediate; F10, high) as a feasibility study to determine the potential for human melanoma imaging using FDG-PET. Male C57BL-6 mice (50 g) were implanted sc with 1-mm3 fragments of B16 melanomas. Fourteen days later mice were injected ip with 1.25 muCi of {sup 14}CDG. Sixty minutes later tumor (T) and gastrocnemius muscle (M) were harvested, solubilized, and counted for {sup 14}CDG dpm/mg to estimate glucose utilization. Autoradiographic imaging was carried out similarly, using 2.0 muCi or {sup 14}CDG with 30-day exposure of T and M tissue sections (20 microns thick) to x-ray film. The uptake of {sup 14}CDG (expressed as dpm/mg; % injected dose/g; and tumor-to-muscle uptake ratios) was 6 to 10 times higher in tumors than in muscle tissue (P less than 0.001). All three melanoma cell lines imaged successfully with {sup 14}CDG autoradiography. Tumor uptake of {sup 14}CDG did not correlate with increasing metastatic potential. The experimental B16 murine melanomas F1, BL-6, and F10 extract glucose at higher rates than muscle tissue, a property necessary for successful PET imaging of cutaneous melanoma. The lack of correlation between glucose extraction and metastatic potential suggests that the demands for glucose during tumor growth and metastasis are not related. This is the first laboratory study to predict that human malignant melanoma will image with FDG-PET.

  16. Cytological diagnosis of metastatic malignant melanoma by fine-needle aspiration biopsy.

    PubMed

    Lindsey, Kathryn G; Ingram, Courtney; Bergeron, Joseph; Yang, Jack

    2016-07-01

    Despite increased surveillance and public awareness, the incidence of melanoma is increasing. Frequently, fine-needle aspiration is employed for the diagnosis of metastatic disease, and aspirated material is used for cytogenetic and molecular studies to guide treatment options. The pairing of a significant diagnosis with the numerous morphologic variants of melanoma can make the cytologic evaluation disquieting. We present selected examples of our experiences and a brief review of the literature to provide cytodiagnostic clues for this malignancy. The clinical history is foremost, although the fine-needle aspiration (FNA) of metastatic melanoma can provide a diagnosis before identification of the primary lesion in up to 20% of cases. If a history of melanoma is assured, negative results in sampling of pulmonary and subcutaneous nodules should be suspected as false negatives. The smearing pattern usually features poorly cohesive cells. Frankly malignant, spindled, and epithelioid cell shapes are most common, and cytoplasmic vacuoles, if sought on Romanowsky-stained specimens, can usually be found. The telltale feature of melanin production, although diagnostic, is only present in 50% of cases. Finally, eccentric placement of nuclei, nucleoli, and nuclear pseudoinclusions are accessory features for the cytologic interpretation of melanoma. Numerous morphologic patterns of melanoma are potentially seen, but a stepwise approach to diagnosis usually produces a successful result.

  17. Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas

    NASA Astrophysics Data System (ADS)

    Chen, Kevin G.; Valencia, Julio C.; Lai, Barry; Zhang, Guofeng; Paterson, Jill K.; Rouzaud, François; Berens, Werner; Wincovitch, Stephen M.; Garfield, Susan H.; Leapman, Richard D.; Hearing, Vincent J.; Gottesman, Michael M.

    2006-06-01

    Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. cancer | melanosomes | skin | tumor therapy | multidrug resistance

  18. Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma.

    PubMed

    Babiker, Hani M; Riaz, Irbaz Bin; Husnain, Muhammad; Borad, Mitesh J

    2017-01-01

    The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients. This is certainly a burgeoning time in immunotherapy drug development, and the aforementioned efforts along with the recent US Food and Drug Administration approval of talimogene laherparepvec (T-VEC), a recombinant oncolytic herpes virus, have paved the way to exploring the role of additional oncolytic viruses, such as the echovirus Rigvir, as new and innovative treatment modalities in patients with melanoma. Herein, we discuss the current standard of care treatment in melanoma with an emphasis on immunotherapy and oncolytic viruses in development.

  19. Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma

    PubMed Central

    Babiker, Hani M; Riaz, Irbaz Bin; Husnain, Muhammad; Borad, Mitesh J

    2017-01-01

    The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients. This is certainly a burgeoning time in immunotherapy drug development, and the aforementioned efforts along with the recent US Food and Drug Administration approval of talimogene laherparepvec (T-VEC), a recombinant oncolytic herpes virus, have paved the way to exploring the role of additional oncolytic viruses, such as the echovirus Rigvir, as new and innovative treatment modalities in patients with melanoma. Herein, we discuss the current standard of care treatment in melanoma with an emphasis on immunotherapy and oncolytic viruses in development. PMID:28224120

  20. Management of conjunctival malignant melanoma: a review and update

    PubMed Central

    Wong, James R.; Nanji, Afshan A.; Galor, Anat; Karp, Carol L.

    2014-01-01

    Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It is an uncommon but potentially devastating tumor that may invade the local tissues of the eye, spread systemically through lymphatic drainage and hematogenous spread, and recur in spite of treatment. Despite its severity, the rarity of available cases has limited the evidence for diagnosis and management. This review will provide an overview of the epidemiology, presentation, diagnosis, management, and surveillance of conjunctival melanoma, with an emphasis on recent advances in biological therapies to treat this disease. PMID:25580155

  1. The classification of malignant melanoma, its histological reporting and registration: a revision of the 1972 Sydney classification.

    PubMed

    McGovern, V J; Cochran, A J; Van der Esch, E P; Little, J H; MacLennan, R

    1986-01-01

    A group of pathologists with an interest in malignant melanoma met in Sydney in 1982 to update the classification of melanoma formulated in Sydney in 1972. The group recommended that malignant melanoma be classified as follows: malignant melanoma with an adjacent component of superficial spreading type, malignant melanoma with an adjacent component of lentigo maligna type, malignant melanoma with an adjacent component of acral lentiginous type, malignant melanoma with an adjacent component of mucosal lentiginous type, malignant melanoma with no adjacent component, malignant melanoma of unclassifiable histogenetic type. The data recorded in the surgical pathology report should include: diagnosis of primary malignant melanoma, histogenetic classification, presence/absence of ulceration, micrometer-measured thickness, microanatomical level, mitotic rate/mm2, presence/absence of vascular invasion, presence/absence of regression, completeness of resection. The recommendations for the examination of specimens and the recording of data for research purposes and for tumour registries are described.

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

    ClinicalTrials.gov

    2016-05-06

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

  3. Use of computed body tomography in malignant melanoma

    SciTech Connect

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

    1988-05-20

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

  4. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    SciTech Connect

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. )

    1991-05-01

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

  5. Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical techniques

    PubMed Central

    Wainstein, Alberto JA; Drummond-Lage, Ana P; Kansaon, Milhem JM; Bretas, Gustavo O; Almeida, Rodrigo F; Gloria, Ana LF; Figueiredo, Ana RP

    2015-01-01

    Background The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN) biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure. Methods Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens). Results Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility. Conclusion Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. PMID:25565762

  6. Carbon nanotubes in the diagnosis and treatment of malignant melanoma.

    PubMed

    Naderi, Naghmeh; Madani, Seyed Y; Ferguson, Elaine; Mosahebi, Afshin; Seifalian, Alexander M

    2013-01-01

    The potential role of carbon nanotubes (CNTs) in the diagnosis and treatment of malignant melanoma (MM) is still an emerging area of research. To date, there is strong evidence for the efficiency of CNTs in this therapeutic area, despite their unique physical, mechanical and biological properties. In this review, the application of CNTs in cancer diagnostics and treatment is reviewed, and consideration is given to the toxicity issues associated with their use.

  7. Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma.

    PubMed

    Ronan, S G; Farolan, M J; McDonald, A; Manaligod, J R; Das Gupta, T K

    1994-12-01

    Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

  8. Impact of hypothyroidism on primary anal malignant melanoma: a rare entity.

    PubMed

    Singh, Siddharth; Verma, Satyajeet; Kala, Sanjay

    2014-01-01

    Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

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

    PubMed

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

    2016-01-01

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

  10. Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

    PubMed Central

    Capoluongo, Ettore

    2011-01-01

    Insulin and insulin-like growth factors (IGFs) are important regulators of energy metabolism and growth. Several findings have outlined an important role played by this family of molecules in both tumor maintenance and development. Despite the established contribution of the IGF system in carcinogenesis, little and contrasting data have been reported concerning the intertwined relationships between melanoma and this family of molecules. The present minireview aims to summarize the main topics and evidence concerning this malignant skin cancer, with a focus on the following: i) melanoma and cell proliferation effects induced by the IGF system, ii) in vitro and in vivo experimental data, and iii) targeting studies. Because of consistent findings regarding the role of the IGF-1 receptor in the modulation of IGF-1 activity, possible therapeutic strategies combining the use of antisense oligonucleotides against IGF-1 receptor mRNA could be applied in the future. PMID:21224039

  11. Malignant Melanoma on a Thermal Burn Scar with an Interval of More Than 70 Years

    PubMed Central

    Uchida, Shusuke; Oiso, Naoki; Shiga, Kuriko; Narita, Tomohiko; Kawada, Akira

    2016-01-01

    Cases of malignant melanoma on thermal burn scars have occasionally been reported. We report a 78-year-old Japanese female with malignant melanoma on a thermal burn scar with an interval of more than 70 years. Our case reemphasizes the importance of regular examinations in persons with thermal burn scars. PMID:27721752

  12. Synchronous primary oesophageal malignant melanoma and sigmoid adenocarcinoma

    PubMed Central

    Malik, Ahsan; Bansil, Sandeep; Junglee, Naushad; Sutton, Jonathon; Gasem, Jaber; Ahmed, Waqar

    2011-01-01

    The authors present a case of a gentleman in his 70s who was referred to the gastroenterology outpatient clinic with dysphagia. An oesophagogastroduodenoscopy was performed which showed a polypoidal black coloured mass in the oesophagus. Endoscopic biopsies confirmed malignant melanoma. Further staging investigations were organised to assess suitability for surgery which revealed a mass in the sigmoid colon. Subsequent colonoscopy and biopsy confirmed adenocarcinoma. As this was an unusual case to associate these two malignancies at the same time, there was no ideal or recognised management plan available. Different treatment options were considered and a consensus was developed regarding best surgical approach but due to the lapse in time a repeat staging CT scan was organised which unfortunately now demonstrated lymph node metastasis. Patient was managed conservatively from this point onwards and he died 12 months later. PMID:22689833

  13. Chondroitin sulfate proteoglycan-4: a biomarker and a potential immunotherapeutic target for canine malignant melanoma.

    PubMed

    Mayayo, Saray Lorda; Prestigio, Simone; Maniscalco, Lorella; La Rosa, Giuseppe; Aricò, Arianna; De Maria, Raffaella; Cavallo, Federica; Ferrone, Soldano; Buracco, Paolo; Iussich, Selina

    2011-11-01

    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.

  14. Malignant neurocristic hamartoma: a tumor distinct from conventional melanoma and malignant blue nevus.

    PubMed

    Linskey, Katy R; Dias-Santagata, Dora; Nazarian, Rosalynn M; Le, Long P; Lam, Quynh; Bellucci, Kirsten S W; Robinson-Bostom, Leslie; Mihm, Martin C; Hoang, Mai P

    2011-10-01

    Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials--the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi.

  15. Expression of Estrogen Receptor Alpha in Malignant Melanoma

    PubMed Central

    Rajabi, Parvin; Bagheri, Marzieh; Hani, Mohsen

    2017-01-01

    Background: Features of malignant melanoma (MM) vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α) in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC). Results: In this study, 38 patients (female/male; 20/18) with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM. PMID:28299306

  16. Popliteal lymph node dissection for metastases of cutaneous malignant melanoma.

    PubMed

    Teixeira, Frederico; Moutinho, Vitor; Akaishi, Eduardo; Mendes, Gabriella; Perina, Andre; Lima, Tiberio; Lallee, Margareth; Couto, Sergio; Utiyama, Edivaldo; Rasslan, Samir

    2014-05-01

    Popliteal lymph node dissection is performed when grossly metastatic nodal disease is encountered in the popliteal fossa or after microscopic metastasis is found in interval sentinel nodes during clinical staging of cutaneous malignant melanoma. Initially, an S-shaped incision is made to gain access to the popliteal fossa. A careful en bloc removal of fat tissue and lymph nodes is made to preserve and avoid the injury of peroneal and tibial nerves as well as popliteal vessels, following the previous recommendations. This rare surgical procedure was successfully employed in a patient with cutaneous malignant melanoma and nodal metastases at the popliteal fossa. The technique described by Karakousis was reproduced in a step-by-step fashion to allow anatomical identification of the neurovascular structures and radical resection with no post-operative morbidity and prompt recovery. Popliteal lymph node dissection is a rarely performed operative procedure. Following a lymphoscintigraphic examination of the popliteal nodal station, surgeons can be asked to explore the popliteal fossa. Detailed familiarity of the operative procedure is necessary, however, to avoid complications.

  17. MicroRNA-15a inhibits the growth and invasiveness of malignant melanoma and directly targets on CDCA4 gene.

    PubMed

    Alderman, Christopher; Sehlaoui, Ayoub; Xiao, Zhaoyang; Yang, Yixin

    2016-10-01

    MicroRNAs can affect behaviors of tumor cells by modulating the expression of the target genes that involve tumor growth, invasiveness, and death. The goal of this research is to examine the effects of miR-15a on the proliferation and invasiveness of malignant melanoma cells in vitro, as well as the therapeutic effect of miR-15a in a mouse melanoma model. miR-15a displayed inhibitory effects on proliferation and invasiveness of several malignant melanoma cell lines. miR-15a also caused cell cycle arrest at G1/G0 phase. miRNA 15a downregulated the expressions of CDCA4 and AKT-3 in melanoma cell lines. In vivo, experiment showed that miRNA 15a significantly retarded the growth of melanoma tumors in the mouse model. The luciferase reporter assay demonstrated that miR15a can suppress gene expression through the binding site in the 3 'UTR of CACD4, which is a bona fide target of miRNA 15a. In conclusion, miRNA 15a suppressed the growth and invasiveness of melanoma cells, suggesting that miRNA 15a may represent a viable microRNA-based therapy against melanoma.

  18. Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.

    PubMed

    Masugi, Yohei; Tanese, Keiji; Emoto, Katsura; Yamazaki, Ken; Effendi, Kathryn; Funakoshi, Takeru; Mori, Mariko; Sakamoto, Michiie

    2015-12-01

    Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well-conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma.

  19. Induction of exportin-5 expression during melanoma development supports the cellular behavior of human malignant melanoma cells

    PubMed Central

    Ott, Corinna Anna; Linck, Lisa; Kremmer, Elisabeth; Meister, Gunter; Bosserhoff, Anja Katrin

    2016-01-01

    Regulation of gene expression via microRNAs is known to promote the development of many types of cancer. In melanoma, miRNAs are globally up-regulated, and alterations of miRNA-processing enzymes have already been identified. However, mis-regulation of miRNA transport has not been analyzed in melanoma yet. We hypothesized that alterations in miRNA transport disrupt miRNA processing. Therefore, we investigated whether the pre-miRNA transporter Exportin-5 (XPO5) was involved in altered miRNA maturation and functional consequences in melanoma. We found that XPO5 is significantly over-expressed in melanoma compared with melanocytes. We showed enhanced XPO5 mRNA stability in melanoma cell lines which likely contributes to up-regulated XPO5 protein expression. In addition, we identified MEK signaling as a regulator of XPO5 expression in melanoma. Knockdown of XPO5 expression in melanoma cells led to decreased mature miRNA levels and drastic functional changes. Our data revealed that aberrant XPO5 expression is important for the maturation of miRNAs and the malignant behavior of melanoma cells. We suggest that the high abundance of XPO5 in melanoma leads to enhanced survival, proliferation and metastasis and thereby supports the aggressiveness of melanoma. PMID:27556702

  20. Assessment of immunological techniques in the diagnosis and prognosis of ocular malignant melanoma.

    PubMed Central

    Cochran, A. J.; Foulds, W. S.; Damato, B. E.; Trope, G. E.; Morrison, L.; Lee, W. R.

    1985-01-01

    Tests of cell mediated immunity (one and two stage leucocyte migration inhibition assays) and humoural immunity (membrane immunofluorescence and serum effects on leucocyte migration) were done with leucocytes and sera from 36 patients with uveal melanoma, five with conjunctival melanoma, 21 with non-malignant ocular disease, and 189 with cutaneous melanoma. Cell mediated reactivity with melanoma extracts and serum reactivity with cultured melanoma cells were significantly more frequent in the melanoma patients, but control donor reactivity was also relatively high. Maximum reactivity was found with cells or serum from those patients in whom, on pathological examination, the intraocular melanoma had penetrated the sclera and in patients with conjunctival melanoma. Maximum separation of melanoma patients from control donors was achieved by consideration of the results of several tests done simultaneously. These immunopathological studies were made during the period from 1972 to 1978. At follow-up in 1983 four of the five patients suffering from conjunctival melanoma had died from metastases, and 10 of the 36 with uveal melanoma had died from metastatic disease. The immunological reactions, while of some value in separating melanoma patients from those without melanoma, did not predict whether a particular patient with uveal melanoma would die of metastatic disease or would survive. PMID:3884037

  1. Malignant Melanoma of the Foot in Black Patients: A Case Report and Literature Survey

    PubMed Central

    Haverkamp, John; Rodman, O. G.

    1979-01-01

    Malignant melanoma in black patients is not the rare entity previously supposed if the numerous reported accounts are considered. In black patients, the tumor appears most commonly in the pedal region. The plantar surface appears to be most frequently involved. The literature on melanoma in blacks provides confusing statistics. Malignant melanoma in blacks represents a small, well-delineated subset of melanomas possibly with its own incidence and prognosis. A case report is presented, with a search of the Walter Reed Army Medical Center Tumor Registry and a review of pertinent current dermatological literature. ImagesFigure 1 PMID:439168

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

    PubMed

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

    2016-06-01

    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).

  3. Cutaneous Malignant Melanoma in Jamaica, 1958 to 2007

    PubMed Central

    Liburd, CG; Gibson, TN; Hanchard, B; Waugh, N; McNaughton, D

    2014-01-01

    ABSTRACT Objective: To document the epidemiology of cutaneous malignant melanoma (CMM) in Jamaica over the 50-year period, 1958–2007. Methods: All cases of CMM recorded in the Jamaica Cancer Registry (JCR), for the period 1958–2007 were collected. For each case, we documented method of ascertainment, age, gender and anatomical location. Age standardized incidence rates (ASRs) for the seven five-year periods from 1973–2007 were also obtained from the JCR. Results: There were 220 cases of CMM from 218 patients (131 females, 87 males; male:female ratio 1:1.5), ranging in age from 21 to 98 years (median age 62 years). The majority of cases (94%) were ascertained via biopsy. The ASRs fluctuated around 0.9 per 100 000 per year from 1973 to 2007, ranging from 0.6–1.4 per 100 000 per year in females and 0.5–1.1 per 100 000 per year in males. Cutaneous malignant melanoma was most common in the lower limb (59% of males and 69% of females). The foot was the most common lower limb site (female: 77%, male: 83%) and the commonest site overall (female: 53%, male: 49%). Conclusion: In Jamaica, CMM is more common in females than in males. In both genders, the ASRs were noted to be low and fluctuated around 0.9 per 100 000 per year since 1973. The lower limb is the commonest anatomical site, with the majority of cases involving the foot. These findings are similar to those documented in other predominantly Black populations. PMID:25867558

  4. Molecular Biology and Genetic Mechanisms in the Progression of the Malignant Skin Melanoma.

    PubMed

    Pejkova, Sofija; Dzokic, Gjorgje; Tudzarova-Gjorgova, Smilja; Panov, Sasho

    2016-11-01

    Malignant skin melanoma is a tumor deriving from transformed skin melanocytes as a result of complex interactions between genetic and environmental factors. This melanoma has a potential to metastasize early and very often it is resistant to the existing modalities of the systemic therapy. As in any other neoplasms, certain types of melanoma may skip certain stages of progression. The progression from one stage to another is accompanied by specific biological changes. Several key changes in the melanoma tumorogenesis influence the regulation of the cell proliferation and vitality, including the RAS-RAF-ERK, PI3K-AKT, and p16INK4/CDK4/RB pathways. A key role in the dissreguarity of the RAS-RAF-ERK (MAPK) pathway in the malignant melanoma development have been demonstrated by many studies. To date, the molecular genetic alterations during melanoma development have been partially known. In the pathogenesis of the malignant melanoma, there are mutations of various genes such as NRAS, BRAF, and PTEN and mutations and deletions of CDKN2A. In the past years, great advance has been made in the insights of the molecular aspects of the melanoma pathogenesis. However, this field yet poses a challenge to discover new details about the melanoma molecular characteristics. The research results are focused towards the improvement of the melanoma patients prognosis by introducing personalized targeted therapy.

  5. Automatic Detection of Malignant Melanoma using Macroscopic Images

    PubMed Central

    Ramezani, Maryam; Karimian, Alireza; Moallem, Payman

    2014-01-01

    In order to distinguish between benign and malignant types of pigmented skin lesions, computerized procedures have been developed for images taken by different equipment that the most available one of them is conventional digital cameras. In this research, a new procedure to detect malignant melanoma from benign pigmented lesions using macroscopic images is presented. The images are taken by conventional digital cameras with spatial resolution higher than one megapixel and by considering no constraints and special conditions during imaging. In the proposed procedure, new methods to weaken the effect of nonuniform illumination, correction of the effect of thick hairs and large glows on the lesion and also, a new threshold-based segmentation algorithm are presented. 187 features representing asymmetry, border irregularity, color variation, diameter and texture are extracted from the lesion area and after reducing the number of features using principal component analysis (PCA), lesions are determined as malignant or benign using support vector machine classifier. According to the dermatologist diagnosis, the proposed processing methods have the ability to detect lesions area with high accuracy. The evaluation measures of classification have indicated that 13 features extracted by PCA method lead to better results than all of the extracted features. These results led to an accuracy of 82.2%, sensitivity of 77% and specificity of 86.93%. The proposed method may help dermatologists to detect the malignant lesions in the primary stages due to the minimum constraints during imaging, the ease of usage by the public and nonexperts, and high accuracy in detection of the lesion type. PMID:25426432

  6. [Genetic counseling and DNA testing in patients with increased risks for malignant melanoma].

    PubMed

    Itin, P H; Fistarol, S K

    2003-08-01

    There are numerous risk factors for the development of malignant melanoma. It has been documented that genetic predisposition exists but exogenous factors are also very important. In familial melanomas it has been well established that mutation in the CDKN2A gene which is located at chromosome 9 leads to a marked risk for malignant melanoma. This tumor-suppressor gene is important for the regulation of the cell cycle and mutation in this gene is associated also with an increased rate of pancreas cancer. The penetrance of this mutation is influenced by UV-energy. In addition it has been shown that a second cluster for the familial atypical nevus syndrome is located at chromosome 1p36. Patients with the rare disease xeroderma pigmentosum have a defect in the DNA-repair mechanism inherited in an autosomal recessive trait and therefore develop within the first 20 years of life numerous malignant skin tumours including malignant melanomas. But also in non-syndromic patients a decrease of DNA-repair ability may occur. It has been shown recently that reduced DNA-repair ability is an independent risk factor for malignant melanoma and may contribute to susceptibility to sunlight-induced melanoma among the general population. Other constitutional risk factors for the development of malignant melanoma are fair skin, red hair and blue eyes. The most important exogenous risk factor is UV-exposition. Extensive and repetitive sunburns before the age of 15 years are especially predisposing to malignant melanoma. The most important preventive measures are continuous sun-protection including avoidance of sun in noon time on tropical and subtropical places, wearing a hut and sunglasses and application of sun-screens with high sun-protection factor. Furthermore a regular check for changing moles is indicated in persons with multiple atypical nevi or a familial melanoma syndrome. Nowadays molecular genetic screenings are available within research projects for members of melanoma

  7. Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemistry and tumor stage.

    PubMed

    Korabiowska, Monika; Cordon-Cardo, Carlos; Jaenckel, Fredericke; Stachura, Jerzy; Fischer, Gösta; Brinck, Ulrich

    2004-12-01

    Defects in DNA mismatch-repair genes MLH1 and MSH2 reported primarily in hereditary nonpolyposis colorectal carcinoma are present in many sporadic tumors, including malignant melanomas. The main aim of this study was to investigate the expression of these genes in malignant melanomas in relation to tumor stage. An experiment was performed on paraffin-embedded tissue microarrays of malignant melanomas applying in situ hybridization with probes produced by our research group and immunohistochemical techniques. In situ hybridization demonstrated MLH1 expression in 45 of 59 melanomas and MSH2 expression in 51 of 59 melanomas. Immunohistochemistry detected MLH1 expression in 46 of 59 melanomas and MSH2 expression in 50 of 59 melanomas. Down-regulation of expression of both DNA mismatch repair genes in malignant melanomas was observed. The findings obtained by in situ hybridization and immunohistochemistry correlated significantly. Our study demonstrates the suitability of in situ hybridization with MLH1 and MSH2 probes for paraffin-embedded tissue. Tissue microarrays can be used successfully in both in situ hybridization and immunohistochemistry to analyze the expression of DNA mismatch-repair genes.

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

    PubMed

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

    2017-02-01

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

  9. Analysis of KIT expression and KIT exon 11 mutations in canine oral malignant melanomas.

    PubMed

    Murakami, A; Mori, T; Sakai, H; Murakami, M; Yanai, T; Hoshino, Y; Maruo, K

    2011-09-01

    KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for anti-cancer therapy. In humans, its expression and mutations have been identified in malignant melanomas and therapies using molecular-targeted agents have been promising in these tumours. As human malignant melanoma, canine malignant melanoma is a fatal disease with metastases and the poor response has been observed with all standard protocols. In our study, KIT expression and exon 11 mutations in dogs with histologically confirmed malignant oral melanomas were evaluated. Although 20 of 39 cases were positive for KIT protein, there was no significant difference between KIT expression and overall survival. Moreover, polymerase chain reaction amplification and sequencing of KIT exon 11 in 17 samples did not detect any mutations and proved disappointing. For several reasons, however, KIT expression and mutations of various exons including exon 11 should be investigated in more cases.

  10. Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

    DOEpatents

    Gabel, D.

    1991-06-04

    The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

  11. Malignant melanoma arising in an in vitro fertilisation pregnancy: A case report.

    PubMed

    Pabuccu, Recai; Kiseli, Mine; Kahyaoğlu, Inci; Cağlar, Gamze Sinem; Yılmaz, Müşerref Banu

    2013-01-01

    Malignant melanoma diagnosed during pregnancy results in confusion about staging and management. In this case report, a 39-year-old pregnant woman, who had undergone conception via in vitro fertilisation, was diagnosed with malignant melanoma of a growing lesion on her back in the 20th week of gestation. She delivered her baby by caesarean section in the 38th week. Metastasis was not found by chest X-ray, ultrasonography and positron emission tomography after delivery. She has been disease free for 6 months postpartum. Surgical resection of malignant melanoma and postponing of the sentinel lymph node biopsy has been proposed. Risk of adverse perinatal outcomes has not been increased; but the prognosis of malignant melanoma is known to be poorer when diagnosed during pregnancy. As a conclusion, any pigmentary change in the nevi should be assessed carefully during pregnancy.

  12. Primary glottic malignant melanoma of the larynx (PGMML): a very rare entity.

    PubMed

    Aggarwal, Sumeet; Kaushal, Vivek; Singla, Sujata; Sen, Rajeev

    2015-11-20

    Primary glottic malignant melanoma of the larynx (PGMML) is a very rare clinical entity with less than 20 cases reported in the literature so far. The most frequently reported subsite in primary malignant melanomas of the larynx is the supraglottic larynx. The vocal cord as a subsite for primary malignant melanoma is very rare. The present case is a primary glottic malignant melanoma involving both vocal cords. PGMML may present early due to associated hoarseness of voice, unlike other non-cutaneous melanomas in the head and neck. Non-cutaneous malignant melanomas in the head and neck are historically very aggressive in nature and known for poor outcomes and survival. Most non-cutaneous melanomas described in the literature have been superficial spreading or ulcerative in nature, unlike the present case, in which proliferative, polypoidal growth was seen. No associated risk factor was present in this case. Every reported case of this rare entity further adds to the better understanding of tumour biology and expression.

  13. Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

    PubMed Central

    Arroyo-Berdugo, Yoana; Alonso, Santos; Ribas, Gloría; Ibarrola-Villava, Maider; Peña-Chilet, María; Martínez-Cadenas, Conrado; Gardeazabal, Jesús; Ratón-Nieto, Juan Antonio; Sánchez-Díez, Ana; Careaga, Jesús María; Pérez-Yarza, Gorka; Carretero, Gregorio; Martín-González, Manuel; Gómez-Fernández, Cristina; Nagore, Eduardo; Asumendi, Aintzane; Boyano, María Dolores

    2014-01-01

    Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12–1.48; p-value = 4×10−4). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocytes. PMID:24743186

  14. Analysis of association between sunscreens use and risk of malignant melanoma

    PubMed Central

    Xie, Fang; Xie, Tingting; Song, Qi; Xia, Shan; Li, Hengjin

    2015-01-01

    Background: Epidemiological studies evaluating the association between sunscreens use and malignant melanoma risk have produced inconsistent results. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of sunscreens use with the risk of malignant melanoma. Methods: Pertinent studies were identified by a search in PubMed and Web of Knowledge up to October 2014. Random-effect model was used to combine the results. Publication bias was estimated using Egger’s regression asymmetry test. Results: Twenty-one studies including 7150 malignant melanoma cases about sunscreens use with the risk of malignant melanoma were included in this meta-analysis. The combined relative risk (RR) of malignant melanoma associated with sunscreens use was 1.145 (95% CI=0.912-1.438). The association was significant neither in the case-control studies nor in the cohort studies. No publication biases were found. Conclusions: Our analysis indicated that sunscreens use is not associated with the risk of malignant melanoma. PMID:25932176

  15. Characteristics of malignant melanoma cells in the treatment with fast neutrons

    SciTech Connect

    Tsunemoto, H.; Morita, S.; Mori, S. )

    1989-07-01

    The radioresistance of malignant melanoma cells has been explained by the wide shoulder of the dose-cell-survival curve of the cells exposed to photon beams. Fast neutrons, 30 MeV d-Be, were used to treat patients who had malignant melanoma in order to confirm the biological effects of high linear energy transfer (LET) radiation for tumor control. Seventy-two patients suffering from malignant melanoma participated in the clinical trials with fast neutrons between November 1975 and December 1986. Of 72 patients, 45 had melanoma of the skin, 20 had melanoma of the head and neck, and seven had choroidal melanoma. Five-year survival rate of the patients who had previously untreated melanoma of the skin was 61% and for patients who received postoperative irradiation, it was 35.7% whereas no patients who had recurrent tumor survived over 4 years. Of 22 patients who had melanoma of the skin, stage I, local control in four cases was achieved by irradiation alone, whereas local control was achieved in 17 of 18 patients who required salvage surgery after fast-neutron therapy. The results of pathological studies performed with specimens obtained from salvage surgery have shown that melanoma cells growing in intradermal tissue are radioresistant, compared with cells growing in intraepidermal tissue. This might suggest that melanoma cells acquire radioresistance when the connective tissue is involved. Five-year survival rate of the patients who had locally advanced melanoma of the head and neck, previously untreated, was 15.4%. Radiation therapy with accelerated protons was suitable for patients suffering from choroidal melanoma.

  16. Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis.

    PubMed

    Jahn, Stephan W; Kashofer, Karl; Halbwedl, Iris; Winter, Gerlinde; El-Shabrawi-Caelen, Laila; Mentzel, Thomas; Hoefler, Gerald; Liegl-Atzwanger, Bernadette

    2015-07-01

    Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.

  17. An epidemiologic study of unreported cutaneous malignant melanoma among residents of Alameda and Contra Costa Counties

    SciTech Connect

    West, D.W.; Whittemore, A.S. Stanford Univ., CA ); Zippin, C.; Lum, D. ); Holly, E. )

    1991-11-12

    Because of a reported excess of cutaneous malignant melanoma cases at the Lawrence Livermore National Laboratory during the 1970's this study was funded to: determine if the number of cases in Alameda and Contra Costa Counties may have been underreported during 1973--1985 (this is the comparison group used to report an excess of melanoma at the LLNL), and determine if melanoma cases at the LLNL had different melanomas from the comparison population in terms of tumor thickness and therefore aggressiveness of tumors. The results of these two objectives are reported in the form of two papers, each dealing with one of the objectives.

  18. [Genetic diversity and immunological characteristics of malignant melanoma: the therapeutic spectrum].

    PubMed

    Doma, Viktória; Gulya, Ernő

    2015-04-01

    Malignant melanoma, originating from pigment cells, is a highly aggressive tumour affecting patients of any age group. Its incidence is rapidly growing. The most common form can be easily diagnosed by any physician. There are some well-known genetic (skin-, eye-, hair colour, naevi, melanoma in the personal/family history) and environmental (ultraviolet radiation) predisposing factors. Treatment is based on early diagnosis and excision. When metastasis occurs, the traditional chemo- and radiotherapy gives a low response rate. Recently some newly approved targeted therapies and immunomodulant drugs have become available. This review focuses on the classification and novel therapeutic approaches of malignant melanoma to provide guidance to clinicians.

  19. Primary Malignant Melanoma of Pleura: A Case Report and Literature Review.

    PubMed

    Agarwal, Poojan; Nambiyar, Kaniyyapan; Manju Kaushal; Bhardwaj, Minakshi

    2016-07-01

    Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648-652. © 2016 Wiley Periodicals, Inc.

  20. Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors.

    PubMed Central

    Westerdahl, J.; Olsson, H.; Måsbäck, A.; Ingvar, C.; Jonsson, N.

    1996-01-01

    In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was found that certain specific types of prescribed drugs, i.e. beta-blockers, hydralazines and benzodiazepines, may increase the risk of melanoma development. However, these associations were diminished, at least for benzodiazepines, after controlling for host factors. As these findings are unconfirmed, and may be due to chance or confounding, further studies are warranted. The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits. Our results do not suggest an association between oral contraceptives and melanoma. Furthermore, reproductive factors were not independent risk factors for melanoma. However, increasing number of live births seemed to be protective (P for trend = 0.01). There is a need for further research to be able to draw firm conclusions on the relation between number of live births and melanoma. The results based on histopathological re-examinations and those based on tumour registry data were essentially the same. PMID:8624275

  1. Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma.

    PubMed Central

    Wang, X; Heller, R; VanVoorhis, N; Cruse, C W; Glass, F; Fenske, N; Berman, C; Leo-Messina, J; Rappaport, D; Wells, K

    1994-01-01

    BACKGROUND. The presence or absence of lymph node metastases in patients with malignant melanoma is the most powerful prognostic factor for predicting survival. If regional nodal metastases are found, the 5-year survival for the patient decreases approximately 50%. If the presence or absence of regional nodal metastases will determine which patients receive formal dissections or which patients enter adjuvant trials, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination routinely underestimates the number of patients with metastases. This study was initiated to develop a highly sensitive clinically applicable method to detect micrometastases by examining lymph nodes for the presence of tyrosinase messenger RNA (mRNA). The hypothesis was that if mRNA for tyrosinase is found in the lymph node preparation, that finding is good evidence that metastatic melanoma cells are present. METHODS. The assay is accomplished using the combination of reverse transcription and double-round polymerase chain reaction (RT-PCR). The amplified samples are examined on a 2% agarose gel and tyrosinase cDNA is seen as a 207 base pair fragment. Lymph node preparations from 29 patients who were clinically stage I and II and undergoing elective node dissections were analyzed both by standard pathologic staining and RT-PCR. RESULTS. Eleven of 29 lymph node (38%) samples from 29 patients with intermediate thickness melanoma were pathologically positive. Nineteen of the 29 lymph node preparations (66%) were RT-PCR-positive, and these included all of the pathologically positive samples, so that the false-negative rate was 0. In a spiking experiment, one SK-Mel-28 melanoma cell in a background of one million normal lymphocytes could be detected, thus indicating the sensitivity of this method. In addition, analysis by restriction enzyme mapping showed that the amplified 207-bp PCR product produced is part of the tyrosinase gene

  2. Metastatic malignant melanoma of the urinary bladder: A case report and review of the literature.

    PubMed

    Topal, Cumhur Selcuk; Kır, Gözde; Daş, Taner; Sarbay, Billur; Tosun, Muzaffer İlkay

    2016-01-01

    Metastatic bladder tumors constitute <5% of all bladder tumors and metastatic malignant melanoma of the urinary bladder is very rare. We present a case report of a metastatic malignant melanoma of the urinary bladder. A 70-year-old woman without any apparent significant clinical history was admitted to the Department of Urology for gross hematuria. Microscopic findings of the transurethral resection specimen revealed fascicles, sheets, and diffuse areas composed of oval and fusiform cells with focal pigmentation. Immunohistochemical analysis revealed that the tumor cells were positive for human melanoma black-45, Melan-A, and S100, and negative for pancytokeratin. Subsequently, we contacted the patient and learned that she was admitted to the Department of Ophthalmology for painless and progressive visual field loss 15 years ago. She had been diagnosed with a primary ocular (uveal) melanoma. A detailed patient history coupled with histological and immunohistochemical findings were necessary to make the final diagnosis of metastatic melanoma.

  3. Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma

    PubMed Central

    Yip, King Tuo; Zhong, Xue Yin; Seibel, Nadia; Pütz, Stefanie; Autzen, Jasmin; Gasper, Raphael; Hofmann, Eckhard; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-01-01

    Melanoma inhibitory activity (MIA), an extracellular protein highly expressed by malignant melanoma cells, plays an important functional role in melanoma development, progression, and metastasis. After its secretion, MIA directly interacts with extracellular matrix proteins, such as fibronectin (FN). By this mechanism, MIA actively facilitates focal cell detachment from surrounding structures and strongly promotes tumour cell invasion and migration. Hence, the molecular understanding of MIA’s function provides a promising target for the development of new strategies in malignant melanoma therapy. Here, we describe for the first time the discovery of small molecules that are able to disrupt the MIA-FN complex by selectively binding to a new druggable pocket, which we could identify on MIA by structural analysis and fragment-based screening. Our findings may inspire novel drug discovery efforts aiming at a therapeutically effective treatment of melanoma by targeting MIA. PMID:27151361

  4. Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review

    PubMed Central

    Kyriakopoulos, Christos; Zarkavelis, George; Andrianopoulou, Artemis; Papoudou-Bai, Alexandra; Stefanou, Dimitrios

    2017-01-01

    Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are extremely rare. Published data on primary pulmonary malignant melanomas are limited. Up to now 40 relevant cases have been reported in the English literature. Herein, we report a case of a 56-year-old female patient who presented with intracranial metastases due to primary pulmonary melanoma. She underwent bronchoscopy and died 5 months after the initial diagnosis despite the administered biochemotherapy and subsequent immunotherapy. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin was excluded by detailed examination and radiographic imaging. Moreover, an extensive review of the literature regarding this rare entity has been performed. PMID:28352484

  5. Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant melanoma.

    PubMed

    Wang, Y L; Uhara, H; Yamazaki, Y; Nikaido, T; Saida, T

    1996-02-01

    p16INK4 gene, which encodes a specific inhibitor of cyclin-dependent kinase 4 (CDK4), has been recently reported as an important tumour suppressor gene. It is mapped to chromosome 9p21, which is frequently deleted or mutated in many tumour cell lines including malignant melanoma. Since the CDK4/cyclin D complex propels a cell to go through the G1 check point of the cell cycle, a critical phase of cell division, alteration of the p16INK4 gene could lead a cell to uncontrolled proliferation and malignant transformation. To clarify any role for p16INK4 and CDK4 proteins in the development of human malignant melanoma, we have examined, immunohistochemically, the expression of these two proteins in melanocytic neoplasms including 19 primary lesions of non-familial melanoma. Intense nuclear and/or cytoplasmic expression of the CDK4 protein was observed in 11 of 19 cases (58%) of melanoma. In contrast, virtually no nuclear or cytoplasmic staining for CDK4 protein was detected in 28 benign melanocytic naevi, including six Spitz naevi. Expression of p16INK4 protein was observed in three of 19 melanomas (16%) and in 17 of 28 benign naevi (61%). Inverse expression of CDK4 and p16INK4, at individual cell level, was detected in one case of melanoma. The present study suggests that CDK4 overexpression is characteristic for malignant melanoma, and probably reflects its autonomous accelerated cell proliferation. The expression rate of p16INK4 protein in malignant melanoma was lower than that in benign naevi, although the significance of p16INK4 deletion in melanoma development has not been definitely confirmed.

  6. Lectin binding to cutaneous malignant melanoma: HPA is associated with metastasis formation

    PubMed Central

    Thies, A; Moll, I; Berger, J; Schumacher, U

    2001-01-01

    Changes in protein glycosylation of tumour cells, as detected by lectin histochemistry, have been associated with metastasis formation in several human malignancies. This study analysed the association between lectin binding and metastasis in cutaneous malignant melanoma. In a 10-year retrospective study, sections of 100 primary cutaneous malignant melanomas were histochemically stained for the following 5 lectins: HPA, SNA-I, MAA, WGA and PHA-L, differing in their carbohydrate specificity. Since differences in the results of HPA binding depending on methodology have been reported, an indirect and a biotinylated method were employed for HPA. Kaplan–Meier analysis of time to first metastasis revealed a positive correlation between HPA binding and metastasis for both methods, with the biotinylated HPA method (P< 0.0001) being superior to the ‘indirect’ method (P = 0.0006). Cox regression analysis demonstrated that even after adjustment for stage, HPA positivity is an independent predictor for metastasis. The results of the present study indicate that N -acetyl-galactosamine/-glucosamine residues, recognized by HPA, are linked to metastasis in malignant melanoma. In contrast, β1-6 branched oligosaccharides or sialic acid residues, both of which were correlated with metastasis in other malignancies, are of no functional importance for metastasis formation in malignant melanoma. Thus, HPA proved to be a useful and independent prognostic marker for the metastatic phenotype of melanoma. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259098

  7. Video-Assisted Thoracoscopic Surgery Lobectomy for Pulmonary Malignant Melanoma Metastasis

    PubMed Central

    Samancilar, Ozgur; Kaya, Seyda Ors; Akcay, Onur; Akcam, Tevfik Ilker; Ceylan, Kenan Can; Yener, Ali Galip

    2015-01-01

    Malign melanoma (MM) develops as a result of malign transformation of the melanocytes and constitutes 2–4% of all skin cancers, while being the most common cause of mortality among all skin cancers. In addition to other organs, distant organ metastases also include lung metastasis. A metastasectomy is an acceptable treatment option in cases of malign melanoma with isolated lung metastasis. The current report presents a case with isolated lung metastasis that underwent a right upper VATS (video-assisted thoracoscopic surgery) lobectomy due to tumour localization. PMID:26644775

  8. Malignant melanoma cure by selective thermal neutron capture therapy

    SciTech Connect

    Mishima, Y.; Ichihashi, M.; Hatta, S.

    1986-01-01

    Thermal neutrons are easily absorbed by the nonradioactive isotope /sup 10/B, resulting in the emission of alpha particles and lithium atoms, which release an energy of 2.33 MeV for up to a 14-..mu..m-diam melanoma cell. Thus, if /sup 10/B can be selectively accumulated in melanoma, it can be destroyed without injury to the surrounding normal tissues by concentrating high linear energy transfer particles. The authors have synthesized seven melanoma-seeking /sup 10/B compounds, two of which, /sup 10/B12-chlorpromazine(/sup 10/B/sup 12/-CPZ) and /sup 10/B/sub 1/-p-boronophenylalanine(/sup 10/B/sub 1/-BPA), are found to be highly effective. The enhanced melanoma-killing effect of the /sup 10/B compounds is found by in vitro radiobiological analysis. A chemical assay and alpha-track analysis 28 h after systemic administration to melanoma-bearing hamsters reveals a /sup 10/B melanoma/blood ratio of 11.5 and a melanoma/liver ratio of 15. Establishment of a clinical therapeutic method for curing human melanoma without failure is underway by correlating biophysical, biochemical, biological, and therapeutic data analysis. Recently, the authors have also been working to develop neutron capture therapy using /sup 10/B-monoclonal antibodies for melanoma and were able to make some /sup 10/B conjugates with the specific m259-0 antibody.

  9. The GIST of targeted therapy for malignant melanoma.

    PubMed

    Bello, Danielle M; Dematteo, Ronald P; Ariyan, Charlotte E

    2014-06-01

    The high response rates to the tyrosine kinase inhibitor imatinib in KIT-mutated gastrointestinal stromal tumors (GIST) has led to a paradigm shift in cancer treatment. In a parallel fashion, the field of melanoma is shifting with the utilization of targeted therapy to treat BRAF-mutated melanoma. We reviewed published literature in PubMed on GIST and melanoma, with a focus on both past and current clinical trials. The data presented centers on imatinib, vemurafenib, and most recently dabrafenib, targeting KIT and BRAF mutations and their outcomes in GIST and melanoma. The BRAF(V600E) melanoma mutation, like the KIT exon 11 mutation in GIST, has the highest response to therapy. High response rates with inhibition of KIT in GIST have not been recapitulated in KIT-mutated melanoma. Median time to resistance to targeted agents occurs in ~7 months with BRAF inhibitors and 2 years for imatinib in GIST. In GIST, the development of secondary mutations leads to resistance; however, there have been no similar gatekeeper mutations found in melanoma. Although surgery remains an important component of the treatment of early GIST and melanoma, surgeons will need to continue to define the thresholds and timing for operation in the setting of metastatic disease with improved targeted therapies. Combination treatment strategies may result in more successful clinical outcomes in the management of melanoma in the future.

  10. Towards automatic detection of malignant melanoma by laser speckle

    NASA Astrophysics Data System (ADS)

    Lee, T. K.; Tchvialeva, L.; Lui, H.; Zeng, H.; McLean, D. I.

    2010-09-01

    The incidence of malignant melanoma (MM), the most aggressive and deadly form of skin cancer, has been increasing rapidly since the last few decades. Clinical differentiation between MM and pigmented benign skin lesions based on visual assessment can be challenging because some of benign lesions such as melanocytic lesions (ML) and seborrheic keratoses (SK) resemble MM. In this paper we introduce a novel, non-invasive, "optical biopsy" method based on laser speckle. Propagating inside the skin tissues, photons undergo optical path dispersion due to scattering. Therefore the emerging light loses the initial state of coherence, which influences the backscattered speckle pattern if the light optical path deviation in a tissue is comparable with the length of coherence. Speckle contrast is a measure of this decorrelation process. Histology shows that MM, ML, and SK have diverse morphology. We hypothesized that the morphological differences can be detected by polychromatic speckle, and the technique can be used to differentiate these lesions in vivo. In a study with 12 MMs, 24 MLs, and 37 SKs, we computed the speckle contrast related to their superficial skin region. The mean contrast of MM, ML and SK were 0.78 (standard error (SE) = 0.02, 0.63 (SE = 0.01), and 0.67 (SE = 0.01), respectively. Statistical test showed that there was a significant difference among the contrast of the three types of lesions (p < 0.001, Kruskal-Wallis), and intergroup pair-wise tests showed significant differences in distribution between all three groups. Potentially, speckle imaging can differentiate these lesions.

  11. Risk factors for cutaneous malignant melanoma among aircrews and a random sample of the population

    PubMed Central

    Rafnsson, V; Hrafnkelsson, J; Tulinius, H; Sigurgeirsson, B; Hjaltalin, O

    2003-01-01

    Aims: To evaluate whether a difference in the prevalence of risk factors for malignant melanoma in a random sample of the population and among pilots and cabin attendants could explain the increased incidence of malignant melanoma which had been found in previous studies of aircrews. Methods: A questionnaire was used to collect information on hair colour, eye colour, freckles, number of naevi, family history of skin cancer and naevi, skin type, history of sunburn, sunbed, all sunscreen use, and number of sunny vacations. Results: The 239 pilots were all males and there were 856 female cabin attendants, which were compared with 454 males and 1464 females of the same age drawn randomly from the general population. The difference in constitutional and behavioural risk factors for malignant melanoma between the aircrews and the population sample was not substantial. The aircrews had more often used sunscreen and had taken more sunny vacations than the other men and women. The predictive values for use of sunscreen were 0.88 for pilots and 0.85 for cabin attendants and the predictive values for sunny vacation were 1.36 and 1.34 respectively. Conclusion: There was no substantial difference between the aircrew and the random sample of the population with respect to prevalence of risk factors for malignant melanoma. Thus it is unlikely that the increased incidence of malignant melanoma found in previous studies of pilots and cabin attendants can be solely explained by excessive sun exposure. PMID:14573711

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

    SciTech Connect

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

    1989-05-01

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

  13. Metastatic malignant melanoma in a prehensile-tailed porcupine (Coendou prehensilis).

    PubMed

    Guthrie, Amanda; deMaar, Thomas

    2011-03-01

    A 14-yr-old male, prehensile-tailed porcupine (Coendou prehensilis) presented for an ulcerated, bleeding lesion of the right flank. The wound presented similar to a bite wound and was treated with antibiotics. After 2 mo, the lesion had increased in size and was nonhealing, so surgical excision was elected. Histopathology diagnosed this lesion as a malignant melanoma with incomplete margins. Radiographs showed no evidence of pulmonary metastasis. At 6 mo, another skin lesion was removed and was diagnosed as malignant melanoma with clean surgical margins. At 8 mo, another four dermal masses were surgically excised and, again, these were melanomas that were completely excised. The animal was euthanized approximately 15 mo after initial presentation due to continued growth of dermal masses, dyspnea, and decreased appetite. Necropsy and histopathology revealed metastatic melanoma present in skin, kidneys, and lung.

  14. Ultrasonographic evaluation of a uterine malignant melanoma presenting as a large pelvic mass.

    PubMed

    Varras, Michail; Kassanos, Demetrios; Tzaida, Olympia; Bournas, Nikolaos; Panagiotopoulos, Nikolaos; Chrelias, Charalambos; Salamalekis, Emmanuel

    2005-10-01

    The uterus is an extremely rare location for a primary or metastatic melanoma. We describe the ultrasonographic appearance of a malignant melanoma of the uterus presenting clinically as a large mass in a 78-year-old woman. Transabdominal sonography revealed a solid uterine mass measuring 13 x 11.5 x 8.5 cm with inhomogeneous echotexture and bright internal echoes. The tumor showed a diffuse spread inside the uterine corpus, and the endometrium was not demonstrated ultrasonographically.

  15. Is cutaneous malignant melanoma associated with the use of antibacterial soaps?

    PubMed

    Arbesman, H

    1999-07-01

    Since 1960, the incidence of melanoma has increased dramatically in Caucasians worldwide, and during the past decade has risen at a rate of 6% a year in the USA. A hypothesis regarding this increased incidence suggests that the prevalent use of antibacterial soaps that contain photosensitizing compounds may be a risk factor for the development of cutaneous malignant melanoma. These antibacterial soaps were introduced in the 1960s and compounds with photosensitizing properties are still present in various soaps throughout the industrialized world. The use of these antibacterial soaps, in combination with sun exposure, leads to free radical production in the skin. These free radicals are hypothesized to cause damage to melanocytes, leading to the development of melanoma. Various epidemiological findings regarding melanoma are consistent with this hypothesis. A significant reduction in the number of new cases of melanoma could be achieved if this hypothesis is correct.

  16. Ureteric Obstruction From Malignant Melanoma in Both Right Double Moiety and Left Single Moiety Ureters.

    PubMed

    March, Brayden; Calopedos, Ross John Spero; Latif, Edward; Ouyang, Rupert

    2017-02-16

    We report the first documented case of malignant melanoma obstructing ureters of both moieties of a duplex kidney and contralateral single moiety ureter in a 51-year-old male. The patient presented with fever, coryzal symptoms, and liver function test derangement several years after 2 superficial spreading melanomas were excised with clear margins. Ultrasonography demonstrated hydronephroureter in both moieties of a complete right-sided duplex kidney. Retrograde pyelograms showed bilateral hydronephroureter and filling defects in all 3 ureters. Biopsied tumor cells were positive for S100, Melan A, and HMB45. Cutaneous melanoma metastasizing to ureters is a rare phenomenon and can present a diagnostic challenge to clinicians if clinically silent.

  17. Primary malignant melanoma, of head and neck: a comprehensive review of literature.

    PubMed

    Vikey, A K; Vikey, Deepali

    2012-05-01

    Malignant melanoma; since long time is considered as deadly disease, but risk factor is minimized due to new technologies, substantial literatures, and promising treatments. The diverse etiopathogenesis; including physical carcinogens, bio-molecules, biological behavior, anatomical locations, and negligence; contribute to complexity of disease. So even after advanced medical technology, malignant melanoma is the challenge to doctors as well as common public. There is increase in incidence rate day by day, which directly attributes to recent concept of sun beds or tanning beds and global climate. After considering its severity, different researches are carried out in the field of radiology and biotechnology. But again these are not sufficient to control the disease. However; to reduce the mortality there is need of general public awareness regarding causative factors and preventive measures. Many literatures recently advocate for long time survival of malignant melanoma, after its early detection and treatment.

  18. Recurrent Malignant Melanoma Presenting as Isolated Pleural Metastases in a Patient with Chronic Lymphocytic Leukemia

    PubMed Central

    Anand, Kartik; Cingam, Shashank; Peddi, Prakash

    2017-01-01

    Isolated pleural metastasis with pleural effusion is a rare occurrence in malignant melanoma. We report an unusual case of a patient with chronic lymphocytic leukemia (CLL) and recurrent pleural effusions. The pleural fluid cytology and immunohistochemistry profile were consistent with the diagnosis of CLL. However, chemotherapy with pentostatin, cyclophosphamide, and rituximab did not result in any meaningful clinical response. A video-assisted thoracoscopic surgery and biopsy of the affected nodular parietal layer of the pleura were consistent with malignant melanoma. Our case underlines the importance of having a suspicion for secondary causes of effusion in patients with CLL. We briefly discuss the mechanisms of an increased incidence of secondary cancers in CLL and the diagnosis of isolated pleural metastases in malignant melanoma. PMID:28203169

  19. Bipolar cellular morphology of malignant melanoma in unstained human melanoma skin tissue

    NASA Astrophysics Data System (ADS)

    Zhang, Kai; Zhang, Wenkai; Yang, Chia-Yi; Yang, Haw

    2009-03-01

    Microstructures of unstained human melanoma skin tissues have been examined by multimodal nonlinear optical microscopy. The polarized shape of the individual melanoma cell can be readily recognized-a phenotype that has been identified in laboratory cultures as characteristic of proliferating melanocytes but has not been demonstrated in clinical instances. The results thus provide snapshots of invading melanoma cells in their native environment and suggest a practical means of connecting in vitro laboratory studies to in vivo processes.

  20. Therapeutic vaccination for the treatment of malignant melanoma.

    PubMed

    Walden, Peter

    2007-01-01

    With increasing knowledge of tumor-associated antigens and T cell epitopes, and the mechanisms of induction and regulation of T-cellular immune responses, therapeutic vaccination is increasingly being explored as a treatment option for cancer. Several clinical cancer vaccination trials, the majority of them with melanoma patients, have demonstrated efficient induction of tumor-specific cellular immune responses in patients. However, these immune responses, in most cases, do not translate into clinical responses. The clinical response rates in these trials are relatively low. The most likely causes for the lack of correlation of immunological and clinical responsiveness are loss of antigenicity and immune suppression. Nonetheless, many patients in the vaccination trials have experienced extended survival compared to clinical experience. Therapeutic vaccination thus appears suited for maintenance therapy where cure is not possible and is an interesting option for adjuvant therapy after surgical tumor resection. While the clinical efficacy of vaccination is expected to be better for early-stage cancer, advancement of the treatment of advanced-stage disease will require combination with other therapeutic principles.

  1. Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.

    PubMed

    Pritchard-Jones, R O; Dunn, D B A; Qiu, Y; Varey, A H R; Orlando, A; Rigby, H; Harper, S J; Bates, D O

    2007-07-16

    Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGF(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) P<0.001 metastatic vs nonmetastatic), irrespective of tumour thickness, while the surrounding epidermis showed no difference in expression. Staining for total VEGF expression showed staining in metastatic and nonmetastatic melanomas, and normal epidermis. An absence of VEGF(xxx)b expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.

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

    PubMed

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

    2010-04-01

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

  3. Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

    SciTech Connect

    Moan, J.; Setlow, R.; Cicarma, E.; Porojnicu, A. C.; Grant, W. B.; Juzeniene, A.

    2010-01-01

    In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. There is a marked north - south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe as a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant, or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.

  4. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation.

    PubMed

    Molven, Anders; Grimstvedt, Magne B; Steine, Solrun J; Harland, Mark; Avril, Marie-Françoise; Hayward, Nicholas K; Akslen, Lars A

    2005-09-01

    Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene.

  5. [Malignant mucosal melanoma of the head and neck].

    PubMed

    Slavícek, A; Astl, J; Válková, D; Betka, J; Petruzelka, L

    2000-01-01

    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%.

  6. Sentinel node biopsy in the management of malignant melanoma.

    PubMed

    Russell-Jones, R; Acland, K

    2001-09-01

    The technique of sentinel lymph node (SLN) biopsy has been in use for almost a decade, but its effect on survival has not yet been established. It is however the most accurate method for staging patients with primary cutaneous melanoma who lack clinical evidence of metastatic disease. This article discusses the rationale and logistics of SLN biopsy, and the management strategies that can be employed in those patients who are SLN positive. Future therapeutic trial in patients with primary cutaneous melanoma will only be meaningful if the SLN status of the subjects is established.

  7. Progression in Cutaneous Malignant Melanoma Is Associated with Distinct Expression Profiles

    PubMed Central

    Alonso, Soledad R.; Ortiz, Pablo; Pollán, Marina; Pérez-Gómez, Beatriz; Sánchez, Lydia; Acuña, Ma Jesús; Pajares, Raquel; Martínez-Tello, Francisco J.; Hortelano, Carlos M.; Piris, Miguel A.; Rodríguez-Peralto, José L.

    2004-01-01

    Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow’s index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16INK4a (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27KIP1 (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma, that provided a predictor model with four antibodies (Ki67, p16INK4a, p21CIP1, and Bcl-6). This predictor model was validated using an independent series of 72 vertical growth phase melanoma patients. PMID:14695333

  8. Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.

    PubMed

    Qin, Jin; Li, Sha; Zhang, Chao; Gao, Dong-Wei; Li, Qiang; Zhang, Hong; Jin, Xiao-Dong; Liu, Yang

    2017-01-01

    This study aims to investigate the influence of high linear energy transfer (LET) heavy ion ((12)C(6+)) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion ((12)C(6+)) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion ((12)C(6+)). High LET heavy ion ((12)C(6+)) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion ((12)C(6+)) presented special advantages in terms of treating malignant melanoma.

  9. Notification of workers about an excess of malignant melanoma: a case study.

    PubMed

    Mazzuckelli, L F; Schulte, P A

    1993-01-01

    In January 1991, NIOSH completed a retrospective cohort mortality study of 3,588 Westinghouse Electric Corporation workers who had been engaged in the manufacture of electrical capacitors. The study evolved from a NIOSH Health Hazard Evaluation, which was conducted at the request of the Indiana State Board of Health because of its concern about PCB exposures among the Westinghouse workers. Life table analysis revealed a fourfold excess of deaths due to malignant melanoma. Though the workers were principally exposed to PCBs, the available exposure data did not lend itself to constructing an exposure-response curve that could relate PCB exposure to development of malignant melanomas. This was further complicated by the lack of substantial corroboration from other studies of PCB-exposed cohorts. Because of the magnitude of the malignant melanoma excess and the fact that malignant melanoma is probably more amenable to treatment and remediation than most other cancers, NIOSH determined that notification of the individual cohort members was a prudent and necessary public health action. This article describes the notification process from the time the decision to notify was made through the postnotification period. It details the interaction between NIOSH, the former and current plant owners, the two labor organizations that represented the workers at the plant, and the recipients of the notification materials. Scientific and other issues surrounding this notification effort are also discussed. A number of lessons were learned about the notification process; these are described for the benefit of others who conduct notifications.

  10. Cutaneous malignant melanomas occurring under cyclosporin A therapy: a report of two cases.

    PubMed

    Mérot, Y; Miescher, P A; Balsiger, F; Magnenat, P; Frenk, E

    1990-08-01

    Two patients are reported with cutaneous malignant melanoma who had been on treatment with cyclosporin A. The first case was a 44-year-old man with systemic sclerosis and the second a 52-year-old woman who had a renal transplant. In both cases cyclosporin A was administered with a low dose of prednisone.

  11. PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1.

    PubMed

    Fang, Xian-Ying; Song, Ran; Chen, Wei; Yang, Yuan-Yuan; Gu, Yan-Hong; Shu, Yong-Qian; Wu, Xu-Dong; Wu, Xue-Feng; Sun, Yang; Shen, Yan; Xu, Qiang

    2015-09-01

    Phosphatase of regenerating liver-3 (PRL-3) has been reported to have a critical role in metastatic progression of cancers. Here, we investigate how PRL-3 increases the malignant degree of melanoma cells. The expression of PRL-3 increased gradually during the malignant progression of melanoma. The phosphorylation of Akt was elevated in highly malignant melanoma cells, which was accompanied by a decrease in nuclear phosphatase and tensin homolog (PTEN). The phosphorylation of NHERF1 in the serine site was regulated by PRL-3 and showed cytoplasmic translocation upon dephosphorylation, which resulted in a decrease in nuclear PTEN. The co-translocation of NHERF1 and PTEN from the nucleus to the cytoplasm was observed during the malignant progression of melanoma cells. Tumor growth was inhibited significantly, and the survival was prolonged upon knockdown of cytoplasmic NHERF1 in B16BL6 cells prior to the inoculation into mice. Taken together, to our knowledge previously unreported, we have identified NHERF1 as a potential substrate of PRL-3. Its phosphorylation status as well as its change in cellular localization and association with PTEN correlated with the malignant progression of melanoma. Our data provide an explanation for how PRL-3 promotes the malignant progression of melanoma, as well as a diagnostic marker or therapeutic target for malignant melanoma.

  12. Correlations Between Cutaneous Malignant Melanoma and Other Cancers: An Ecological Study in Forty European Countries

    PubMed Central

    Serrano, Pablo Fernandez-Crehuet; Serrano, Jose Luis Fernandez-Crehuet; Allam, Mohamed Farouk; Navajas, Rafael Fernandez-Crehuet

    2016-01-01

    Background: The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Methods: Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson's correlation test. Results: In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI): 0.68–0.89]), myeloma (r = 0.68 [95% CI: 0.46–0.81]), prostatic carcinoma (r = 0.66 [95% CI: 0.43–0.80]), and non-Hodgkin lymphoma (NHL) (r = 0.63 [95% CI: 0.39–0.78]). In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64–0.88]), colorectal cancer (r = 0.72 [95% CI: 0.52–0.83]), and NHL (r = 0.71 [95% CI: 0.50–0.83]). Conclusions: These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular. PMID:27217938

  13. Cytokeratin positivity in paraffin-embedded malignant melanomas: comparative study of KL1, A4 and Lu5 antibodies.

    PubMed

    Korabiowska, Monika; Fischer, Gösta; Steinacker, Anja; Stachura, Jerzy; Cordon-Cardo, Carlos; Brinck, Ulrich

    2004-01-01

    The unclear role of cytokeratin (CK) in the progression and diagnostics of malignant melanomas stimulated us to compare the reactivity of three antibodies directed to CK in 109 paraffin-embedded melanomas. By far the majority of melanomas did not express cytokeratin even at the<1% level, only vimentin. In about 6% of melanomas it was possible to find CK expression ranging between 3 and 40% of melanoma cells. There was a correlation between CK expression and pT-stage. Cytokeratin-expressing tumours were found in the more advanced pT-stages. The independent prognostic values of none of the three CK antibodies investigated could be shown.

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

    PubMed

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

    2016-05-01

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

  15. Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.

    PubMed

    Shimizu, Akira; Kaira, Kyoichi; Mori, Keita; Kato, Madoka; Shimizu, Kimihiro; Yasuda, Masahito; Takahashi, Ayumi; Oyama, Tetsunari; Asao, Takayuki; Ishikawa, Osamu

    2016-05-01

    Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma.

  16. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    PubMed Central

    He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

    2016-01-01

    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. PMID:27445171

  17. Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

    NASA Astrophysics Data System (ADS)

    He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

    2016-07-01

    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.

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

    PubMed Central

    2016-01-01

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

  19. Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

    PubMed Central

    Yano, Shuya; Takehara, Kiyoto; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. PMID:26701857

  20. Boron neutron capture therapy for malignant melanoma: An experimental approach

    SciTech Connect

    Larsson, B.S.; Larsson, B.; Roberto, A. )

    1989-07-01

    Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.

  1. Melanoma

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Melanoma KidsHealth > For Teens > Melanoma Print A A A ... to the moles on your skin. What Is Melanoma? Melanoma is a type of cancer that begins ...

  2. Melanoma

    MedlinePlus

    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 ...

  3. Decreased expression of Ku70/Ku80 proteins in malignant melanomas of the oral cavity.

    PubMed

    Korabiowska, Monika; Tscherny, Michael; Grohmann, Ulrike; Hönig, Johannes F; Bartkowski, Stanislaw B; Cordon-Cardo, Carlos; Brinck, Ulrich

    2002-01-01

    Ku70/80 are genes responsible for the repairing of DNA double-strand breaks and they function as a regulatory subunit of the DNA-dependent protein kinase. Their expression has not yet been investigated in malignant melanomas of the oral cavity. These tumours are characterized by very poor prognosis and etiology independent of UV-radiation. We investigated 29 malignant melanomas of the oral cavity for the expression of Ku70/80 proteins. Ku70 expression was preserved in 21 out of 29 tumours and the percentage of Ku70-positive cells did not exceed 76%. Ku80 was found in 19 out of 29 tumours and the percentage of Ku80-positive cells peaked at 62%. Correlations between Ku70 and Ku80 expression were lost (p>0.05). We conclude that decreased Ku70/80 expression in malignant melanomas of the oral cavity and loss of correlation between these markers may influence progression of oral melanomas.

  4. Nivolumab: a review of its use in patients with malignant melanoma.

    PubMed

    Deeks, Emma D

    2014-07-01

    Nivolumab (Opdivo(®)) is a fully human monoclonal antibody against programmed death receptor-1, a negative regulatory checkpoint molecule with a role in immunosuppression. The drug is administered intravenously and is approved for the treatment of unresectable malignant melanoma in Japan. The potential for intravenous nivolumab to be used in the treatment of advanced malignancies such as melanoma was initially demonstrated in phase I dose-ranging trials. Subsequently, in a noncomparative, open-label, phase II trial, almost one-quarter of Japanese patients with previously treated stage III/IV melanoma (recurrent or unresectable) achieved a partial tumour response with intravenous nivolumab 2 mg/kg every 3 weeks. The clinical benefit of the drug was durable, with patients surviving free from progression for a median of 172 days and median overall survival not yet reached. Nivolumab had an acceptable tolerability profile in this trial, with fewer than 18 % of patients experiencing grade 3 or 4 adverse events related to the drug, the most common of which was increased γ-glutamyl transferase. Thus, nivolumab is an emerging, promising option for the treatment of malignant melanoma.

  5. Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules

    PubMed Central

    Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom

    2017-01-01

    Objectives Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Design Systematic review. Data sources A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Study selection and data extraction Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. Results From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. Conclusions At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. PMID:28264830

  6. An immunohistochemical and prognostic analysis of cytokeratin expression in malignant uveal melanoma.

    PubMed Central

    Fuchs, U.; Kivelä, T.; Summanen, P.; Immonen, I.; Tarkkanen, A.

    1992-01-01

    A group of 52 patients with malignant uveal melanoma treated by primary enucleation in 1977-1979 was studied to determine the frequency of immunoreactivity for cytokeratins (CK) in primary and metastatic melanoma, the CK types present, and the prognostic significance of CK expression. By immunohistochemistry, monoclonal antibody (MAb) V9 to vimentin reacted with all 52 formalin-fixed, paraffin-embedded primary tumors and all 31 metastases from 11 patients. MAb CAM 5.2 to CK 8 and 18 reacted with 20 and MAb CY-90 to CK 18 with 25 primary melanomas, whereas MAb KS-B17.2 and MAb CK5 to CK 18 labeled 8 and 6 tumors, respectively. Antibodies to CK 13 and CK 19 each labeled single cells in one specimen, and other CK types were not detected. In 6 primary melanomas, only a few tumor cells were immunopositive for CK 8 and 18, but in 17 cases up to one quarter, and in 2 tumors more than one quarter, of them were labeled. The positive cells were spindle, epithelioid, or intermediate in shape, and tended to be more frequent in mixed than in spindle cell melanomas. MAbs CAM 5.2 and CY-90 did not react with any of the 16 liver metastases, but labeled 7 of 15 other metastases. Metastases were somewhat more common when the primary tumor was immunoreactive for CK 8 and 18, apparently because CKs were more frequent in mixed cell melanomas. Although CK expression is of diagnostic significance and can denote low levels of epithelioid differentiation, it is not an independent prognostic factor in malignant uveal melanoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1378696

  7. Pharmacological and biochemical characterization of adenosine receptors in the human malignant melanoma A375 cell line

    PubMed Central

    Merighi, Stefania; Varani, Katia; Gessi, Stefania; Cattabriga, Elena; Iannotta, Valeria; Ulouglu, Canan; Leung, Edward; Borea, Pier Andrea

    2001-01-01

    The present work characterizes, from a pharmacological and biochemical point of view, adenosine receptors in the human malignant melanoma A375 cell line. Adenosine receptors were detected by RT – PCR experiments. A1 receptors were characterized using [3H]-DPCPX binding with a KD of 1.9±0.2 nM and Bmax of 23±7 fmol mg−1 of protein. A2A receptors were studied with [3H]-SCH 58261 binding and revealed a KD of 5.1±0.2 nM and a Bmax of 220±7 fmol mg−1 of protein. A3 receptors were studied with the new A3 adenosine receptor antagonist [3H]-MRE 3008F20, the only A3 selective radioligand currently available. Saturation experiments revealed a single high affinity binding site with KD of 3.3±0.7 nM and Bmax of 291±50 fmol mg−1 of protein. The pharmacological profile of radioligand binding on A375 cells was established using typical adenosine ligands which displayed a rank order of potency typical of the different adenosine receptor subtype. Thermodynamic data indicated that radioligand binding to adenosine receptor subtypes in A375 cells was entropy- and enthalpy-driven. In functional assays the high affinity A2A agonists HE-NECA, CGS 21680 and A2A – A2B agonist NECA were able to increase cyclic AMP accumulation in A375 cells whereas A3 agonists Cl-IB-MECA, IB-MECA and NECA were able to stimulate Ca2+ mobilization. In conclusion, all these data indicate, for the first time, that adenosine receptors with a pharmacological and biochemical profile typical of the A1, A2A, A2B and A3 receptor subtype are present on A375 melanoma cell line. PMID:11704641

  8. [Intradural and cervical primary malignant melanoma. Case report and review of the literature].

    PubMed

    Mlaiki, A; Ksira, I; Ladib, M; Guesmi, H; Krifa, H

    2004-03-01

    Primary malignant melanoma of the central nervous system is an uncommon localization, first reported by Hirsberg in 1906. Since then, to our knowledge, only 39 cases have been reported in the literature. We present a case of primary intradural extra-medullary melanoma which developed in a 51-Year-old man who complained of pain in the lower cervical spine, difficulties in micturition and sexual impotence. The diagnosis was suspected at the MRI which showed a lesion with a paramagnetic signal and was confirmed by the histological examination. The resection was complete and the course has been satisfactory after 19 months follow-up.

  9. Attenuation of genome-wide 5-methylcytosine level is an epigenetic feature of cutaneous malignant melanomas.

    PubMed

    Micevic, Goran; Theodosakis, Nicholas; Taube, Janis M; Bosenberg, Marcus W; Rodić, Nemanja

    2017-04-01

    Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas, the most notable known epigenetic abnormality is the attenuation of 5-hydroxymethylcytosine (5-hmC) residues. However, it remains unknown whether a decrease in 5-hmC represents a primary defect of melanoma cancer epigenome or whether it is secondary to the loss of 5-methylcytosine (5-mC), a chemical substrate for 5-hmC. Here, we evaluated 5-mC levels in a spectrum of melanocytic proliferations. To study the epigenetic features of melanocytic nuclei, we began by measuring 5-mC levels in histologic specimens semiquantitatively by immunohistochemistry. We next treated established melanoma cell lines with S-adenosyl methionine (SAM), a universal methyl group donor, in an effort to cause changes in 5-mC levels. We detected a marked reduction in 5-mC levels in both primary and metastatic melanomas compared with 5-mC levels in benign melanocytic nevi. We also empirically induced changes in 5-mC in melanoma cell lines by incubation with SAM. To our surprise, we observed a significant cytoreductive effect of SAM on all melanoma cell lines examined. At subcytotoxic levels, SAM treatment is accompanied by a genome-wide increase in 5-mC. Moreover, we recorded a dose-dependent increase in genome-wide 5-mC levels in melanoma cell lines following SAM treatment. Taken together, we report that genome-wide attenuation of 5-mC is a hallmark of malignant melanomas. We propose that genome-wide attenuation of 5-mC is not merely an epiphenomenon as it is required for melanoma cell growth, albeit by an as of yet undetermined mechanism. Given its potential benefit in slowing down the growth of melanoma cells, SAM should be studied further to determine its role in epigenome modulation.

  10. New malignancies after squamous cell carcinoma and melanomas: a population-based study from Norway

    PubMed Central

    2014-01-01

    Background Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers. Methods All invasive cutaneous malignant melanomas (CMM, N = 28 069) and squamous cell carcinomas (SCC, N = 24 620) diagnosed in Norway during 1955–2008 were included. Rates of new primary cancers in skin cancer survivors were compared to rates of primary malignancies in the general population using standardized incidence ratios (SIR). Discrete-time logistic regression models were applied to individual-level data to estimate cancer risk among those with and without a prior skin cancer, accounting for residential region, education, income, parenthood, marital status and parental cancer status, using a 20% random sample of the entire Norwegian population as reference. Further analyses of the skin cancer cohort were undertaken to determine risk factors related to subsequent cancers. Results During follow-up, 9608 new primary cancers occurred after an initial skin cancer. SIR analyses showed 50% and 90% increased risks for any cancer after CMM and SCC, respectively (p < 0.01). The logistic regression model suggested even stronger increase after SCC (130%). The highest risk was seen for subsequent skin cancers, but several non-skin cancers were also diagnosed in excess: oral, lung, colon, breast, prostate, thyroid, leukemia, lymphoma and central nervous system. Factors that were associated with increased risk of subsequent cancers include male sex, older age, lower residential latitude, being married and low education and income. Parental cancer did not increase the risk of a subsequent cancer after SCC, but was a significant predictor among younger CMM survivors. Conclusions Our results provide information on shared environmental and genetic risk factors for first and

  11. Phyllodes Tumor of the Breast With Malignant Melanoma Component: A Case Report.

    PubMed

    Vergine, Marco; Guy, Catherine; Taylor, Mark R

    2015-09-01

    Phyllodes tumors of the breast display a wide variation in histological appearance and are classified into benign, borderline, and malignant categories based on a combination of histological parameters. These tumors may include a malignant heterologous component that is believed to originate through a process of multidirectional differentiation from a cancer stem cell. In these cases, the tumor is classified as a malignant phyllodes tumor. Among the heterologous elements that have been described in malignant phyllodes tumors are rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma and angiosarcoma. We present the first case of a phyllodes tumor with a malignant melanoma component in the breast of a 71-year-old lady, discussing the clinical implications of this diagnosis.

  12. An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi

    PubMed Central

    Flake, Darl D.; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G.; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A.; Brown, Krystal L.; Warf, M. Bryan; Roa, Benjamin B.; Wenstrup, Richard J.

    2016-01-01

    BACKGROUND Recently, a 23‐gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. METHODS A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. RESULTS The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. CONCLUSIONS These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617–628. © 2016 American Cancer Society. PMID:27768230

  13. Malignant Melanoma in U.S. Navy Personnel

    DTIC Science & Technology

    1988-07-11

    of cancer after tions (11-14); and that high lifetime exposures to sunlight testicular cancer in males in the US Navy. A wide range of have been...melanoma: Aircrew Survival Equipmentman, SIR = 6.8 in the Navy. (p<O.05); and Engineman, SIR = 2.8 (p<O.05). However, oc- cupations with similar job...because of the puterized Inpatient Follow-up Data System which contains all relationship of sunlight to other skin cancers and the ability

  14. DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines.

    PubMed

    Chen, Ya-Ping; Hou, Xiao-Yang; Yang, Chun-Sheng; Jiang, Xiao-Xiao; Yang, Ming; Xu, Xi-Feng; Feng, Shou-Xin; Liu, Yan-Qun; Jiang, Guan

    2016-08-01

    Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells. This study demonstrates that MGMT expression, CpG island methylation, and histone acetylation vary between melanoma cell lines. Combined treatment with 5-Aza-2'-deoxycytidine and Trichostatin A led to reexpression of MGMT, indicating that DNA methylation and histone deacetylation are associated with silencing of MGMT in melanoma. This study provides information on the role of epigenetic modifications in malignant melanoma that may enable the development of new strategies for treating malignant melanoma.

  15. Trends in incidence of cutaneous malignant melanoma in a Swedish population 1976-1994.

    PubMed

    Månsson-Brahme, Eva; Johansson, Hemming; Larsson, Olle; Rutqvist, Lars E; Ringborg, Ulrik

    2002-01-01

    The incidence of cutaneous malignant melanoma has been increasing in Sweden for several decades. In the Stockholm-Gotland area educational activities for healthcare professionals were started in the late 1970s and public primary and secondary prevention campaigns were initiated in the mid-1980s. Melanoma incidence trends have been studied in Sweden, with special reference to trends in the Stockholm-Gotland area where these prevention campaigns were first started. During 1976-1994 the average annual increase of age-standardized incidence in the Stockholm-Gotland area was about 5%, the increase being associated mainly with thin tumors and melanoma in situ. During the 1990s, the incidence among males leveled off. In contrast, no such shift in trend was observed among females, or among males or females residing outside the Stockholm-Gotland area. The campaigns may have contributed to a trend towards earlier diagnosis but there is still no clear effect of the primary prevention efforts.

  16. An Orbital Malignant Melanoma Arising in Cellular Blue Nevus in a Patient with Nevus of Ota

    PubMed Central

    Ouyang, Jie; Cartwright, Mont

    2016-01-01

    Melanomas arising from orbital melanocytic proliferations are exceedingly rare. Many questions remain regarding their development and malignant transformation. We report on a 45-year-old Caucasian woman with a nevus of Ota that presented with visual disturbances involving her right eye and was found to have a biopsy-proven cellular blue nevus in the orbital space. Five years later, she presented with proptosis and worsening symptoms. Biopsy at that time showed a cellular blue nevus with areas of melanoma. We conclude that patients with a nevus of Ota or an orbital cellular blue nevus, particularly Caucasians, should be monitored for ocular/orbital involvement and followed closely for signs of rapid growth. There may be a progressive evolution to melanoma from a blue nevus.   PMID:27699140

  17. A literature overview of primary cervical malignant melanoma: an exceedingly rare cancer.

    PubMed

    Pusceddu, Sara; Bajetta, Emilio; Carcangiu, Maria Luisa; Formisano, Barbara; Ducceschi, Monika; Buzzoni, Roberto

    2012-02-01

    Primary malignant melanoma (MM) of the uterine cervix is an extremely rare neoplasm, with about 78 cases described in the literature. Since traces of melanocytes in normal cervical epithelium were found in 3.5% of cases primary origin of melanoma at this site cannot be ruled out. It occurs mainly in the sixth decade of life, and it is five time less common than primary vaginal or vulvar MM. Clinical history usually includes abnormal genital bleeding; and physical examination frequently reveals a pigmented, exophytic cervical mass. Diagnosis is confirmed by immuno-histochemical methods and by exclusion of any other primary site of melanoma. Treatment of this condition is not yet standardized, and the overall prognosis is very poor. Diagnostic approaches and therapeutic procedures on primary MM of the uterine cervix are discussed following a review of the literature encompassing more than one century.

  18. Sex differences in rising trends of cutaneous malignant melanoma in Norway, 1954-2008.

    PubMed

    Robsahm, Trude E; Bergva, Gjøril; Hestvik, Unn E; Møller, Bjørn

    2013-02-01

    With more than a seven-fold increase during the last 50 years, the incidence rate of cutaneous malignant melanoma in Norway is amongst the highest worldwide. The present study aims to present the incidence trends of cutaneous malignant melanoma in Norway, 1954-2008, according to period, sex, age, stage of disease, anatomical location and geographical regions, and discuss the results in relation to sun exposure habits over time. All new cases of invasive cutaneous malignant melanoma diagnosed in the Norwegian population between 1 January 1954 and 31 December 2008 were retrieved from the Cancer Registry of Norway (n=31 783). In addition to descriptive analyses, joinpoint and age-period-cohort regression models were used to explore the incidence trends. Throughout the 1980s, a steep increase in the rate of melanoma was observed in both sexes, continuing to increase from the late 1990s. Age-specific incidence rates showed the steepest increase in age groups older than 50 years, and were most pronounced in men. A clear sex-specific anatomical distribution exists, although the trunk has become the most common location for both sexes. During the entire period of follow-up, a two-fold risk was observed in inhabitants of the southern compared with the northern part of Norway. It is reasonable to suggest that the rising incidence rates of melanoma in Norway, in both sexes, reflect a strengthened intermittent sun exposure pattern over time. The particularly strong incidence increase in older men corresponds with their less favourable sun-protective behaviour.

  19. miR-125b induces cellular senescence in malignant melanoma

    PubMed Central

    2014-01-01

    Background Micro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory. Methods We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization. Results In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours. Conclusions Our results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma. PMID:24762088

  20. DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria

    PubMed Central

    Antony, Jayesh; Saikia, Minakshi; V, Vinod.; Nath, Lekshmi. R.; Katiki, Mohana Rao; Murty, M.S.R.; Paul, Anju; A, Shabna; Chandran, Harsha; Joseph, Sophia Margaret; S, Nishanth Kumar.; Panakkal, Elizabeth Jayex; V, Sriramya I.; V, Sridivya I.; Ran, Sophia; S, Sankar; Rajan, Easwary; Anto, Ruby John

    2015-01-01

    Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma. PMID:26061820

  1. In situ malignant melanoma on nevus spilus in an elderly patient.

    PubMed

    Corradin, Maria Teresa; Giulioni, Erika; Fiorentino, Renzo; Santeufemia, Davide Adriano; Re, Giovanni Lo; Vettorello, Angelo

    2014-03-01

    Nevus spilus is the term usually given to a pigmented skin lesion, congenital or acquired, that may occur anywhere on the body, consisting of a large light tan patch with numerous superimposed darker scattered maculae or papulae that are flat or slightly raised. For a long time, nevus spilus was believed to be a benign lesion. However, in 1957 Perkinson reported a melanoma appearing on nevus spilus for the first time. Since then other reports about melanomas developing on nevus spilus have been published, sometimes with a fatal outcome. We describe the case of an 80-year-old male patient with a congenital nevus just above his left knee. The lesion had remained unchanged over time, but some months before his checkup the patient noticed a darker area in the lesion that had continued to enlarge. The lesion was removed and histological examination revealed an in situ malignant melanoma. Although nevus spilus is not normally considered a precursor of melanoma, the potentiality of malignant transformation requires regular monitoring, and careful checkups are recommended and justified.

  2. Boron neutron capture therapy for malignant melanoma: first clinical case report in China

    PubMed Central

    Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

    2016-01-01

    A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

  3. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    PubMed

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog.

  4. Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma.

    PubMed

    Martínez-García, Miguel-Ángel; Martorell-Calatayud, Antonio; Nagore, Eduardo; Valero, Irene; Selma, Maria Jose; Chiner, Eusebi; Landete, Pedro; Montserrat, Josep-Maria; Carrera, Cristina; Pérez-Gil, Amalia; Campos-Rodríguez, Francisco; Farré, Ramón

    2014-06-01

    Some recent studies have shown an association between sleep disordered breathing (SDB) and cancer mortality and incidence but no study has focused on a specific type of cancer. The objective of this study was to analyse the relationship between the severity of SDB and factors related to cutaneous malignant melanoma (CMM) aggressiveness. We performed a multicentre observational study in 82 consecutive patients diagnosed with CMM. 56 patients in whom melanoma measurements were available were finally included in the study. Melanoma measurements of aggressiveness included: tumour mitotic rate, Breslow index, presence of ulceration, stage of disease and growth rate of melanoma. A sleep study was performed in all the included patients. Multivariate analyses were used to examine the independent relationship between SDB severity (apnoea-hypopnea index (AHI) and nocturnal oxygen desaturation indexes (ODI3% and ODI4%)) and measures of CMM aggressiveness. 60.7% of patients had SDB (AHI ≥ 5) and 14.3% severe obstructive sleep apnoea (AHI ≥ 30). In fully adjusted multivariate analyses, AHI (OR 1.08, 95% CI 1.02-1.14), ODI3% (OR 1.08, 95% CI 1.02-1.11) and ODI4% (OR 1.1, 95% CI 1.02-1.2) were independently associated with an increased melanoma growth rate. Furthermore, AHI, ODI4% and ODI3% were significantly correlated with other aggressiveness factors of CMM, such as Breslow index, presence of ulceration and mitotic index. SDB severity markers are associated with some aggressiveness markers of CMM.

  5. Glucose transporter isoform 1 expression enhances metastasis of malignant melanoma cells

    PubMed Central

    Koch, Andreas; Lang, Sven Arke; Wild, Peter Johannes; Gantner, Susanne; Mahli, Abdo; Spanier, Gerrit; Berneburg, Mark; Müller, Martina; Bosserhoff, Anja Katrin; Hellerbrand, Claus

    2015-01-01

    The glucose transporter isoform 1 (GLUT1; SLC2A1) is a key rate-limiting factor in the transport of glucose into cancer cells. Enhanced GLUT1 expression and accelerated glycolysis have been found to promote aggressive growth in a range of tumor entities. However, it was unknown whether GLUT1 directly impacts metastasis. Here, we aimed at analyzing the expression and function of GLUT1 in malignant melanoma. Immunohistochemical analysis of 78 primary human melanomas on a tissue micro array showed that GLUT1 expression significantly correlated with the mitotic activity and a poor survival. To determine the functional role of GLUT1 in melanoma, we stably suppressed GLUT1 in the murine melanoma cell line B16 with shRNA. GLUT1 suppressed melanoma cells revealed significantly reduced proliferation, apoptosis resistance, migratory activity and matrix metalloproteinase 2 (MMP2) expression. In a syngeneic murine model of hepatic metastasis, GLUT1-suppressed cells formed significantly less metastases and showed increased apoptosis compared to metastases formed by control cells. Treatment of four different human melanoma cell lines with a pharmacological GLUT1 inhibitor caused a dose-dependent reduction of proliferation, apoptosis resistance, migratory activity and MMP2 expression. Analysis of MAPK signal pathways showed that GLUT1 inhibition significantly decreased JNK activation, which regulates a wide range of targets in the metastatic cascade. In summary, our study provides functional evidence that enhanced GLUT1 expression in melanoma cells favors their metastatic behavior. These findings specify GLUT1 as an attractive therapeutic target and prognostic marker for this highly aggressive tumor. PMID:26293674

  6. Case report: laparoscopic adrenalectomy in a patient with primary adrenal malignant melanoma.

    PubMed

    Liatsikos, Evangelos N; Papathanassiou, Zafiria; Voudoukis, Theodoros; Repanti, Maria; Sklavou, Christina; Filos, Kriton S; Stolzenburg, Jens-Uwe; Athanasopoulos, Anastasios; Perimenis, Petros; Barbalias, George A

    2006-02-01

    We report a case of laparoscopic management of a primary malignant melanoma of the left adrenal gland. A 42-year-old male presented a 55 x 60-mm round, inhomogeneous, noninvasive mass of the left adrenal gland. Hormone-activity values were within normal range. The mass was removed laparoscopically en bloc along with the left adrenal gland, and its histopathologic evaluation was consistent with the features of a malignant melanocytic tumor. Postoperatively, the patient presented no signs of fever or remarkable blood loss and was discharged on the third day in good clinical condition. He is free of disease 1 year later.

  7. Cutaneous amelanotic signet-ring cell malignant melanoma with interspersed myofibroblastic differentiation in a young cat.

    PubMed

    Hirz, Manuela; Herden, Christiane

    2016-07-01

    The diagnosis of malignant melanoma can be difficult because these tumors can be amelanotic and may contain diverse variants and divergent differentiations, of which the signet-ring cell subtype is very rare and has only been described in humans, dogs, cats, and a hamster. We describe herein histopathologic and immunohistochemical approaches taken to diagnose a case of signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. A tumor within the abdominal skin of a 2-year-old cat was composed of signet-ring cells and irregularly interwoven streams of spindle cells. Both neoplastic cell types were periodic-acid-Schiff, Fontana, and Sudan black B negative. Signet-ring cells strongly expressed vimentin and S100 protein. Spindle cells strongly expressed vimentin and smooth muscle actin; some cells expressed S100, moderately neuron-specific enolase, and others variably actin and desmin. A few round cells expressed melan A, and a few plump spindle cells expressed melan A and PNL2, confirming the diagnosis of amelanotic signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. Differential diagnoses were excluded, including signet-ring cell forms of adenocarcinomas, lymphomas, liposarcomas, leiomyosarcomas, squamous cell carcinomas, basal cell carcinomas, and adnexal tumors.

  8. Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

    SciTech Connect

    Beadle, Beth M.; Guadagnolo, B. Ashleigh Ballo, Matthew T.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Cormier, Janice N.; Mansfield, Paul F.; Ross, Merrick I.; Zagars, Gunar K.

    2009-04-01

    Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

  9. An epidemiologic study of unreported cutaneous malignant melanoma among residents of Alameda and Contra Costa Counties. Final report

    SciTech Connect

    West, D.W.; Whittemore, A.S. |; Zippin, C.; Lum, D.; Holly, E.

    1991-11-12

    Because of a reported excess of cutaneous malignant melanoma cases at the Lawrence Livermore National Laboratory during the 1970`s this study was funded to: determine if the number of cases in Alameda and Contra Costa Counties may have been underreported during 1973--1985 (this is the comparison group used to report an excess of melanoma at the LLNL), and determine if melanoma cases at the LLNL had different melanomas from the comparison population in terms of tumor thickness and therefore aggressiveness of tumors. The results of these two objectives are reported in the form of two papers, each dealing with one of the objectives.

  10. Use of host factors to identify people at high risk for cutaneous malignant melanoma .

    PubMed Central

    Marrett, L D; King, W D; Walter, S D; From, L

    1992-01-01

    OBJECTIVE: To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. DESIGN: Case-control study. SETTING: Southern Ontario. SUBJECTS: The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. INTERVENTION: Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. RESULTS: Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. CONCLUSIONS: Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be

  11. Social inequality and incidence of and survival from malignant melanoma in a population-based study in Denmark, 1994-2003.

    PubMed

    Birch-Johansen, Fatima; Hvilsom, Gitte; Kjaer, Trille; Storm, Hans

    2008-09-01

    The incidence of cutaneous malignant melanoma has increased more than that of any other cancer in most white populations during the past few decades. We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from malignant melanoma in 1994-2003 in Denmark using information from nationwide registries. The analyses were based on data on 6914 patients with malignant melanoma in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. The age- and period-standardised incidence rate was 25 and 29 per 100,000 person-years for men and women, respectively. We found an increased risk for malignant melanoma in the highest socioeconomic groups. In general, survival after a malignant melanoma was better in high socioeconomic groups and better in women than men. Our results support earlier reports that malignant melanoma is associated with higher socioeconomic position.

  12. MITF is a critical regulator of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in malignant melanoma.

    PubMed

    Ullrich, Nico; Löffek, Stefanie; Horn, Susanne; Ennen, Marie; Sánchez-Del-Campo, Luis; Zhao, Fang; Breitenbuecher, Frank; Davidson, Irwin; Singer, Bernhard B; Schadendorf, Dirk; Goding, Colin R; Helfrich, Iris

    2015-11-01

    The multifunctional Ig-like carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is neo-expressed in the majority of malignant melanoma lesions. CEACAM1 acts as a driver of tumor cell invasion, and its expression correlates with poor patient prognosis. Despite its importance in melanoma progression, how CEACAM1 expression is regulated is largely unknown. Here, we show that CEACAM1 expression in melanoma cell lines and melanoma tissue strongly correlates with that of the microphthalmia-associated transcription factor (MITF), a key regulator of melanoma proliferation and invasiveness. MITF is revealed as a direct and positive regulator for CEACAM1 expression via binding to an M-box motif located in the CEACAM1 promoter. Taken together, our study provides novel insights into the regulation of CEACAM1 expression and suggests an MITF-CEACAM1 axis as a potential determinant of melanoma progression.

  13. Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.

    PubMed

    Okano, Yudai; Satoh, Tetsurou; Horiguchi, Kazuhiko; Toyoda, Minoru; Osaki, Aya; Matsumoto, Shunichi; Tomaru, Takuya; Nakajima, Yasuyo; Ishii, Sumiyasu; Ozawa, Atsushi; Shibusawa, Nobuyuki; Shimada, Takehiro; Higuchi, Tetsuya; Chikamatsu, Kazuaki; Yamada, Masanobu

    2016-10-29

    The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6(th) administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7(th) administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7(th) administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.

  14. Comparative microarray analysis of microRNA expression profiles in primary cutaneous malignant melanoma, cutaneous malignant melanoma metastases, and benign melanocytic nevi.

    PubMed

    Sand, Michael; Skrygan, Marina; Sand, Daniel; Georgas, Dimitrios; Gambichler, Thilo; Hahn, Stephan A; Altmeyer, Peter; Bechara, Falk G

    2013-01-01

    Perturbations in microRNA (miRNA) expression profiles have been reported for cutaneous malignant melanoma (CMM) predominantly when examined in cell lines. Despite the rapidly growing number of newly discovered human miRNA sequences, the availability of up-to-date miRNA expression profiles for clinical samples of primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM), and benign melanocytic nevi (BMN) is limited. Specimens excised from the center of tumors (lesional) from patients with PCMM (n=9), CMMM (n=4), or BMN (n=8) were obtained during surgery. An exploratory microarray analysis was performed by miRNA expression profiling based on Agilent platform screening for 1205 human miRNAs. The results from the microarray analysis were validated by TaqMan quantitative real-time polymerase chain reaction. In addition to several miRNAs previously known to be associated with CMM, 19 unidentified miRNA candidates were found to be dysregulated in CMM patient samples. Among the 19 novel miRNA candidates, the genes hsa-miR-22, hsa-miR-130b, hsa-miR-146b-5p, hsa-miR-223, hsa-miR-301a, hsa-miR-484, hsa-miR-663, hsa-miR-720, hsa-miR-1260, hsa-miR-1274a, hsa-miR-1274b, hsa-miR-3663-3p, hsa-miR-4281, and hsa-miR-4286 were upregulated, and the genes hsa-miR-24-1*, hsa-miR-26a, hsa-miR-4291, hsa-miR-4317, and hsa-miR-4324 were downregulated. The results of this study partially confirm previous CMM miRNA profiling studies identifying miRNAs that are dysregulated in CMM. However, we report several novel miRNA candidates in CMM tumors; these miRNA sequences require further validation and functional analysis to evaluate whether they play a role in the pathogenesis of CMM.

  15. Topical CpG enhances the response of murine malignant melanoma to dacarbazine.

    PubMed

    Najar, Hossain M; Dutz, Jan P

    2008-09-01

    Malignant melanoma is a potentially fatal skin cancer that is increasing in incidence. Standard chemoimmunotherapy consisting of dacarbazine (DTIC) given with IFN-alpha has had disappointing results. We describe a chemoimmunotherapy protocol for cutaneous melanoma that combines the administration of DTIC with the topical application of CpG oligodinucleotide (ODN). Subcutaneous B16 melanoma tumors in C57BL/6 mice were treated with intraperitoneal injections of DTIC followed by the topical application of CpG-ODN over the tumors. This therapeutic approach abrogated the growth of established tumors and significantly enhanced survival. Topical CpG application was more effective than intratumoral CpG. Cell depletion studies indicated that the antitumor effect was dependent on both CD4(+) and CD8(+) cells but not on natural killer (NK) cells. Tumor-specific cytotoxic T-lymphocyte activity was generated in treated animals and was highest in topically treated animals. Immunohistochemical analysis revealed that DTIC, but not CpG, enhanced tumor cell apoptosis. Further, topical CpG induced an expansion of a B220(+)CD8(+) subset of dendritic cells and a subset of NK1.1(+) CD11c(+) cells within the tumors. By enhancing both tumor cell death and local immune activation, DTIC/topical CpG chemoimmunotherapy induced an effective T-cell-dependent host-immune response against melanoma.

  16. Workplace investigation of increased diagnosis of malignant melanoma among employees of Lawrence Livermore National Laboratory

    SciTech Connect

    Moore, D.H. II; Patterson, H.W.; Hatch, F.; Discher, D.; Schneider, J.S.; Bennett, D.

    1994-08-01

    Based on rates for the surrounding communities, the diagnosis rate of malignant melanoma for employees of Lawrence Livermore National Laboratory (LLNL) during 1972 to 1977 was three to four times higher than expected. In 1984 Austin and Reynolds concluded, as a result of a case-control study, that five occupational factors were {open_quotes}causally associated{close_quotes} with melanoma risk at LLNL. These factors were: (1) exposure to radioactive materials, (2) work at Site 300, (3) exposure to volatile photographic chemicals, (4) presence at the Pacific Test Site, and (5) chemist duties. Subsequent reviews of the Austin and Reynolds report concluded that the methods used were appropriate and correctly carried out. These reports did determine, however, that Austin and Reynolds` conclusion concerning a causal relationship between occupational factors and melanoma among employees was overstated. There is essentially no supporting evidence linking the occupational factors with melanoma from animal studies or human epidemiology. Our report summarizes the results of further investigation of potential occupational factors.

  17. miR-204-5p acts as a tumor suppressor by targeting matrix metalloproteinases-9 and B-cell lymphoma-2 in malignant melanoma

    PubMed Central

    Luan, Wenkang; Qian, Yao; Ni, Xin; Bu, Xuefeng; Xia, Yun; Wang, Jinlong; Ruan, Hongru; Ma, Shaojun; Xu, Bin

    2017-01-01

    An increasing number of microRNAs have been found to be involved in tumorigenesis, including melanoma tumorigenesis. miR-204-5p is down-regulated and functions as a tumor suppressor in many human malignant tumors. miR-204-5p expression is also decreased in melanoma tissues, but its biological roles and molecular mechanisms in malignant melanoma remain unclear. In this study, the aberrant down-regulation of miR-204-5p was detected in melanoma, especially in metastatic melanoma. miR-204-5p also served as a protective factor for the prognosis of melanoma patients. We determined that miR-204-5p suppresses cell proliferation, migration and invasion, and promotes cell apoptosis in melanoma. Matrix metalloproteinases-9 and B-cell lymphoma-2 are the functional targets of miR-204-5p, through which it plays an important biological role in malignant melanoma. The effect of miR-204-5p on malignant melanoma is verified using a xenograft model. We also determined that miR-204-5p increases 5-fluorouracil and cisplatin (DDP) chemosensitivity in malignant melanoma cells. This finding elucidates new functions and mechanisms for miR-204-5p in melanoma development, and provides potential therapeutic targets for the treatment of melanoma. PMID:28280358

  18. Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma

    PubMed Central

    Yang, Chunhua; Cao, Hang; Liu, Ning; Xu, Kai; Ding, Meng; Mao, Li-jun

    2016-01-01

    Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy. PMID:27895465

  19. Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma.

    PubMed

    Yang, Chunhua; Cao, Hang; Liu, Ning; Xu, Kai; Ding, Meng; Mao, Li-Jun

    2016-01-01

    Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.

  20. A Case of Malignant Melanoma of the Uterine Cervix with Disseminated Metastases throughout the Vaginal Wall

    PubMed Central

    Ota, Nami; Mabuchi, Yasushi; Yagi, Shigetaka; Minami, Sawako; Okuhira, Hisako; Yamamoto, Yuki; Nakamura, Yasushi; Ino, Kazuhiko

    2017-01-01

    Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab) treatment, she died of the disease 13 months after surgery. PMID:28197351

  1. A phase II study of bryostatin 1 in metastatic malignant melanoma.

    PubMed Central

    Propper, D. J.; Macaulay, V.; O'Byrne, K. J.; Braybrooke, J. P.; Wilner, S. M.; Ganesan, T. S.; Talbot, D. C.; Harris, A. L.

    1998-01-01

    Bryostatin 1 is a protein kinase C partial agonist which has both antineoplastic and immune-stimulatory properties, including the induction of cytokine release and expansion of tumour-specific lymphocyte populations. In phase I studies, tumour responses have been observed in patients with malignant melanoma, lymphoma and ovarian carcinoma. The dose-limiting toxicity is myalgia. Sixteen patients (age 35-76 years, median 57 years) with malignant melanoma were treated. All had received prior chemotherapy. In each cycle of treatment, patients received bryostatin 25 degrees g m(-2) weekly for three courses followed by a rest week. The drug was given in PET diluent (10 microg bryostatin ml(-1) of 60% polyethylene glycol, 30% ethanol, 10% Tween 80) and infused in normal saline over 1 h. The principal toxicities were myalgia (grade 2, eight patients and grade 3, six patients) and grade 2 phlebitis (four patients), fatigue (three patients) and vomiting (one patient). Of 15 patients evaluable for tumour response, 14 developed progressive disease. One patient developed stable disease for 9 months after bryostatin treatment. In conclusion, single-agent bryostatin appears ineffective in the treatment of metastatic melanoma in patients previously treated with chemotherapy. It should, however, be investigated further in previously untreated patients. PMID:9823975

  2. [Psychological aspects of immunotherapies in the treatment of malignant melanoma].

    PubMed

    Kovács, Péter; Pánczél, Gitta; Melegh, Krisztina; Balatoni, Tímea; Pörneczy, Edit; Lõrincz, Lenke; Czirbesz, Kata; Gorka, Eszter; Liszkay, Gabriella

    2016-03-02

    Psychological problems may arise in connection with oncomedical treatments in three ways: 1. acute and/or 2. chronic ways, as well as 3. co-morbid psychiatric diseases that already exist must also be taken into account. Immunotherapies have the most common and also clinically relevant psychological side effects. Fatigue, anhedonia, social isolation, psychomotor slowness is reported during treatment. Anti-CTLA-4 antibody (ipilimumab) immunotherapy can present one of the most modern opportunities for adequate treatment for patients having distant metastasis or unresectable tumour. In relation to immunotherapies, acute psychological side effects (acute stress) emerging during treatments develop in a way that can mostly be linked to environmental factors, e.g. notification of diagnosis, hospitalisation, progression, deterioration in quality of life, imminent dates of control. Crisis is a temporary and threatening condition that endangers psychological balance. In such conditions, enhanced psychological vulnerability must be taken into account and doctors play a key role in the rapid recognition of the condition. Chronic psychological problems, which may arise from the depressogenic effect of the applied treatment or originated from a pre-melanoma psychiatric condition, may exceed the diagnostic and psychotherapeutic competences of a clinical psychologist. Even in case of a well-defined depressogenic biological mechanism such as the activation of the pro-inflammatory cytokine pathway, positive environmental effects can reduce symptoms and thus increase compliance. Side effects can be treated successfully using psychotherapeutic methods and/or psychiatric medicines. The application of routinely used complex psychosocial screening packages can provide the easiest method to identify worsening psychological condition during immunotherapy and give rapid feedback to the oncologist and the patient. Team work is of particular importance in a situation like this as it requires

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

    SciTech Connect

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

    2009-03-10

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

  4. Malignant melanoma in the penguin: characterization of the clinical, histologic, and immunohistochemical features of malignant melanoma in 10 individuals from three species of penguin.

    PubMed

    Duncan, Ann E; Smedley, Rebecca; Anthony, Simon; Garner, Michael M

    2014-09-01

    Malignant melanomas are aggressive neoplasms that are relatively common in penguins compared to other avian species. In this study, the clinical and pathologic characteristics of melanocytic neoplasms in five macaroni (Eudyptes chrysolophus), three rock hopper (Eudyptes chrysocome), and two Humboldt (Spheniscus humboldti) penguins are described. Tumors most commonly occurred in the skin of the foot or hock, and were seen in the subcutaneous muscle, especially near the beak/oral cavity. Gross lesions were usually heavily pigmented, becoming raised and ulcerated over time. Humboldt penguins had a unique presentation, forming variably pigmented, cornified lesions in the inguinal area. Original case materials were obtained from all but two cases, and were assessed to define the characteristics of malignancy, evaluate four immunohistochemical markers for melanoma, and look for factors useful to informing prognosis and clinical decisions. Diagnosis was made histologically, based on morphologic features and pigmentation. Though not necessary for diagnosis, PNL-2 was found to be a useful immunohistochemical marker. HMB-45 showed unreliable positive labelling and S-100, Melan-A and Ki67 were not useful. Several factors were associated with prognosis, including gross surface dimension, mitotic index, depth of neoplastic cell invasion, and degree of surface ulceration. Metastatic spread occurred to the liver, lung, adrenal gland, brain, and bone; all lesions showed positive labelling to PNL-2. The average survival after diagnosis was 7 mo, though complete surgical excision of tumors less than 2.0 cm was curative in two cases and radiation therapy prolonged survival in one penguin. The underlying pathogenesis associated with the high prevalence of melanocytic neoplasms in captive penguins could not be identified. Three different molecular methods were performed to look for viral particles and results were negative. Advanced age is the most probable associated risk factor

  5. Comparative study of p63 and p53 expression in tissue microarrays of malignant melanomas.

    PubMed

    Brinck, Ulrich; Ruschenburg, Ilka; Di Como, Charles J; Buschmann, Nadine; Betke, Herbert; Stachura, Jerzy; Cordon-Cardo, Carlos; Korabiowska, Monika

    2002-12-01

    p63 is a known homologue of p53. In contrast to p53, however, p63 mutations are rarely seen in tumours. There have been several reports that p63 plays a regulatory role in the normal differentiation of cells, whereas its role in tumour biology must still be elucidated. The main aim of this study was to compare p63 and p53 expression in tissue microarrays of malignant melanomas and to establish any prognostic significance. p63 expression was found in 2 out of 59 tumours, both pT4. The p63 index did not exceed 30%. p53 expression was found in 27 out of 59 melanomas, with maximal expression in up to 80% of tumour cells. There were no correlations observed between the two markers. Multivariate analysis confirmed the prognostically independent role of p53. This study also confirmed that tissue microarrays can be used effectively for evaluation of the expression of certain tumour markers.

  6. Immunological monitoring in a controlled trial of immunotherapy in stage IIB malignant melanoma.

    PubMed Central

    Embleton, M. J.; Ransom, J. H.; McIllmurray, M. B.; Reeves, W. G.

    1978-01-01

    Fifteen patients undergoing surgery for Stage IIb malignant melanoma were randomly allocated either to a group who received a vaccine of BCG mixed with irradiated autologous melanoma cells, or a control group who received no further treatment. All patients were monitored sequentially for immunological competence and tumour-directed immunity, using a wide range of techniques, and the results were compared retrospectively with their clinical course. Three months after surgery, there was a trend towards inhibition of PHA-induced lymphocyte transformation by autologous serum in patients who developed recurrent tumour within 12 months after treatment. Serum from patients who remained tumour-free for 12 months did not inhibit stimulation of autologous lymphocytes by PHA. Apart from this test, no other immunological parameters correlated either with clinical course or with the type of treatment received. PMID:565645

  7. Malignant melanoma of the vulva: a clinicopathological study of 50 women.

    PubMed

    Bradgate, M G; Rollason, T P; McConkey, C C; Powell, J

    1990-02-01

    A clinicopathological review of 50 primary malignant melanomas of the vulva in the West Midlands region of England is presented. The overall 5-year-survival rate was 35%, when adjusted for age. Significant predictors of survival were clinical stage, patient age, tumour ulceration, cell type and mitotic rate. Tumour thickness was of prognostic importance but as a prognostic variable it did not operate independently of stage and as most lesions were deeply invasive at presentation vulval tumours must be separated for prognostic purposes into bands at greater overall thicknesses than those used for skin melanomas generally. There was no significant relation between survival and type of surgery performed as a primary therapeutic procedure.

  8. c-RET Molecule in Malignant Melanoma from Oncogenic RET-Carrying Transgenic Mice and Human Cell Lines

    PubMed Central

    Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

    2010-01-01

    Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma. PMID:20422010

  9. Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

    PubMed

    Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions.

  10. PRMT5 is upregulated in malignant and metastatic melanoma and regulates expression of MITF and p27(Kip1.).

    PubMed

    Nicholas, Courtney; Yang, Jennifer; Peters, Sara B; Bill, Matthew A; Baiocchi, Robert A; Yan, Fengting; Sïf, Saïd; Tae, Sookil; Gaudio, Eugenio; Wu, Xin; Grever, Michael R; Young, Gregory S; Lesinski, Gregory B

    2013-01-01

    Protein arginine methyltransferase-5 (PRMT5) is a Type II arginine methyltransferase that regulates various cellular functions. We hypothesized that PRMT5 plays a role in regulating the growth of human melanoma cells. Immunohistochemical analysis indicated significant upregulation of PRMT5 in human melanocytic nevi, malignant melanomas and metastatic melanomas as compared to normal epidermis. Furthermore, nuclear PRMT5 was significantly decreased in metastatic melanomas as compared to primary cutaneous melanomas. In human metastatic melanoma cell lines, PRMT5 was predominantly cytoplasmic, and associated with its enzymatic cofactor Mep50, but not STAT3 or cyclin D1. However, histologic examination of tumor xenografts from athymic mice revealed heterogeneous nuclear and cytoplasmic PRMT5 expression. Depletion of PRMT5 via siRNA inhibited proliferation in a subset of melanoma cell lines, while it accelerated growth of others. Loss of PRMT5 also led to reduced expression of MITF (microphthalmia-associated transcription factor), a melanocyte-lineage specific oncogene, and increased expression of the cell cycle regulator p27(Kip1). These results are the first to report elevated PRMT5 expression in human melanoma specimens and indicate this protein may regulate MITF and p27(Kip1) expression in human melanoma cells.

  11. Mucosal Malignant Melanoma of the Head and Neck Treated by Carbon Ion Radiotherapy

    SciTech Connect

    Yanagi, Takeshi Mizoe, Jun-etsu; Hasegawa, Azusa; Takagi, Ryo; Bessho, Hiroki; Onda, Takeshi; Kamada, Tadashi; Okamoto, Yoshitaka; Tsujii, Hirohiko

    2009-05-01

    Purpose: To evaluate the efficacy of carbon ion radiotherapy for mucosal malignant melanoma of the head and neck. Methods and Materials: Between 1994 and 2004, 72 patients with mucosal malignant melanoma of the head and neck were treated with carbon ion beams in three prospective studies. Total dose ranged from 52.8 GyE to 64 GyE given in 16 fixed fractions over 4 weeks. Clinical parameters including gender, age, Karnofsky index, tumor site, tumor volume, tumor status, total dose, fraction size, and treatment time were evaluated in relation to local control and overall survival. Results: The median follow-up period was 49.2 months (range, 16.8-108.5 months). Treatment toxicity was within acceptable limits, and no patients showed Grade 3 or higher toxicity in the late phase. The 5-year local control rate was 84.1%. In relation to local control, there were no significant differences in any parameters evaluated. The 5-year overall and cause-specific survival rates were 27.0% and 39.6%, respectively. For overall survival, however, tumor volume ({>=}100 mL) was found to be the most significant prognostic parameter. Of the patients who developed distant metastasis, 85% were free from local recurrence. Conclusion: Carbon ion radiotherapy is a safe and effective treatment for mucosal malignant melanoma of the head and neck in terms of high local control and acceptable toxicities. Overall survival rate was better than in those treated with conventional radiotherapy and was comparable to that with surgery.

  12. Quantifying lifetime exposure to ultraviolet radiation in the epidemiology of cutaneous malignant melanoma: A pilot study

    SciTech Connect

    Lea, C.S.; Selvin, S. . Dept. of Biomedical and Environmental Health Sciences Lawrence Berkeley Lab., CA ); Buffler, P.A. . Dept. of Biomedical and Environmental Health Sciences); Scotto, J. . Biostatistics Branch); Berwick, M. (Cancer Pre

    1992-10-01

    This pilot study uses a unique method to calculate cumulative lifetime exposure to, ultraviolet radiation-b to determine if this refined method would indicate differences in lifetime cumulative UVB exposure between age and sex matched controls. Forty-four age and sex matched cases and controls demonstrated no significant difference in mean cumulative lifetime UVB exposure based on the duration and location of residence. This pilot study suggests that further analysis of the dataset should be conducted to determine if the cumulative lifetime exposure hypothesis is of primary importance regarding the association between UVB exposure and development of cutaneous malignant melanoma.

  13. The Quinone Methide Aurin Is a Heat Shock Response Inducer That Causes Proteotoxic Stress and Noxa-dependent Apoptosis in Malignant Melanoma Cells*

    PubMed Central

    Davis, Angela L.; Qiao, Shuxi; Lesson, Jessica L.; Rojo de la Vega, Montserrat; Park, Sophia L.; Seanez, Carol M.; Gokhale, Vijay; Cabello, Christopher M.; Wondrak, Georg T.

    2015-01-01

    Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinderTM PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. PMID:25477506

  14. The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.

    PubMed

    Davis, Angela L; Qiao, Shuxi; Lesson, Jessica L; Rojo de la Vega, Montserrat; Park, Sophia L; Seanez, Carol M; Gokhale, Vijay; Cabello, Christopher M; Wondrak, Georg T

    2015-01-16

    Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinder(TM) PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin.

  15. Tumours of the anterior uvea. III. Oxytalan fibres in the differential diagnosis of leiomyoma and malignant melanoma of the iris.

    PubMed Central

    Noor Sunba, M. S.; Rahi, A. H.; Garner, A.; Alexander, R. A.; Morgan, G.

    1980-01-01

    The diagnostic potential of oxytalan fibre demonstration in differentiating between leiomyomas and spindle-cell malignant melanomas of the iris was investigated. It was found that oxytalan fibres were abundant in leiomyomata, both between and around the tumour cells, whereas they were found in small numbers only and usually near the iris muscle in malignant melanomata. Their presence and distribution, therefore, appear to offer a satisfactory method of differentiating between these tumours. Since the human choroid and ciliary body normally contain oxytalan fibres, the above findings are not relevant to malignant melanoma of these structures. Naevi and regressing aggregates of iris melanoma cells away from the main tumour mass may similarly be surrounded by misleading amounts of these fibres. Images PMID:7426559

  16. Argyrophilic nucleolar organizer region counts in malignant melanoma associated with benign intradermal nevus.

    PubMed

    Pich, A; Aloi, F; Margaria, E; Tomasini, C

    1991-01-01

    A silver colloidal technique to demonstrate argyrophilic proteins of the nucleolar organizer regions (AgNORs) was performed on sections of 20 cases of malignant melanoma (MM) associated with underlying benign nevus (BN). In these cases, significant different AgNOR counts were found for MM and BN. In addition, this technique permitted the identification of melanocytic cells located between malignant and benign cells showing AgNOR scores intermediate (5.51) between BN (2.6) and MM (7.71) with a more complex and bizarre morphology than that observed in BN. The AgNOR technique can be suitable in the identification of residual nevus cells in MM, especially when their number is minimal and the common histologic criteria are unsatisfactory; it can also increase the understanding of the natural history of MM.

  17. A mathematical analysis of the ABCD criteria for diagnosing malignant melanoma

    NASA Astrophysics Data System (ADS)

    Lee, Hyunju; Kwon, Kiwoon

    2017-03-01

    The medical community currently employs the ABCD (asymmetry, border irregularity, color variegation, and diameter of the lesion) criteria in the early diagnosis of a malignant melanoma. Although many image segmentation and classification methods are used to analyze the ABCD criteria, it is rare to see a study containing mathematical justification of the parameters that are used to quantify the ABCD criteria. In this paper, we suggest new parameters to assess asymmetry, border irregularity, and color variegation, and explain the mathematical meaning of the parameters. The suggested parameters are then tested with 24 skin samples. The parameters suggested for the 24 skin samples are displayed in three-dimensional coordinates and are compared to those presented in other studies (Ercal et al 1994 IEEE Trans. Biomed. Eng. 41 837–45, Cheerla and Frazier 2014 Int. J. Innovative Res. Sci., Eng. Technol. 3 9164–83) in terms of Pearson correlation coefficient and classification accuracy in determining the malignancy of the lesions.

  18. Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

    PubMed

    Field, S; Deady, S; Fitzgibbon, J; Murphy, M; Comber, H

    2010-02-01

    Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

  19. The Induction of Apoptosis in A375 Malignant Melanoma Cells by Sutherlandia frutescens

    PubMed Central

    van der Walt, Nicola B.; Zakeri, Zahra

    2016-01-01

    Sutherlandia frutescens is a medicinal plant indigenous to Southern Africa and is commonly known as the “cancer bush.” This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against “internal” cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract of S. frutescens could induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action. S. frutescens extract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochrome c from the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show that S. frutescens extract is effective in inducing apoptosis in malignant melanoma cells and indicates that further in vivo mechanistic studies may be warranted. PMID:27656236

  20. Analysis of dose fractionation in the palliation of metastases from malignant melanoma

    SciTech Connect

    Konefal, J.B.; Emami, B.; Pilepich, M.V.

    1988-01-15

    Sixty-five visceral metastases from malignant melanoma were treated with radiation therapy. A variety of total doses and dose fractions were used. Significant palliation was achieved in 40 of 65 (62%) symptomatic lesions. There was no correlation between total dose or dose fraction size and significant palliation. Brain and bone metastases were separately analyzed. Nineteen of 28 (68%) bone metastases were palliated. Appendicular bony metastases were more likely to be palliated than axial bony metastases (88% versus 60%). The palliation of bone metastases did not depend on total dose given or fraction size. Nine of 23 (39%) symptomatic brain metastases were palliated. There was no difference in the rate of palliation between solitary and multiple brain metastases. Palliation of brain lesions was not dependent on fraction size, although there was a trend to better palliation with higher total doses. These findings suggest that unlike treating cutaneous or nodal melanoma lesions for local control, there is no advantage in large fraction size when treating with palliative intent visceral melanoma lesions.

  1. TERT promoter mutations in sinonasal malignant melanoma: a study of 49 cases.

    PubMed

    Jangard, Mattias; Zebary, Abdlsattar; Ragnarsson-Olding, Boel; Hansson, Johan

    2015-06-01

    Sinonasal malignant melanoma (SNMM) comprises less than 1% of all melanomas and is located in the nasal cavity and the paranasal sinuses. The majority of SNMMs have unknown underlying oncogenic driver mutations. The recent identification of a high frequency of driver mutations in the promoter of the telomerase reverse transcriptase (TERT) gene in cutaneous melanoma led us to investigate whether these mutations also occur in SNMM. Our aim was to determine the TERT promoter mutation frequencies in primary SNMMs. Laser capture microdissection and manual dissection were used to isolate tumour cells from 49 formalin-fixed paraffin-embedded tissues. The tumours were screened for TERT promoter mutations by direct Sanger sequencing. Information on NRAS, BRAF and KIT mutation was available from an earlier study. Overall, 8% (4/49) of SNMMs harboured TERT promoter mutations. One of these mutated tumours had a coexistent NRAS mutation and one had a BRAF mutation. Our findings show that TERT promoter mutations are present in a moderate proportion of SNMM. No conclusion can be drawn on their potential influence on the clinical outcome or tumour progression.

  2. Comparison of dermatoscopic ABCD rule and risk stratification in the diagnosis of malignant melanoma.

    PubMed

    Lorentzen, H; Weismann, K; Kenet, R O; Secher, L; Larsen, F G

    2000-01-01

    For didactic and documentation purposes the dermatoscopic ABCD rule and the dermatoscopic risk stratification have been proposed. The aim of this investigation was to compare the ability of the 2 methods to separate patients with cutaneous malignant melanoma from individuals with other pigmented skin lesions. Three dermatologists, experienced users of dermatoscopy, assessed macroscopic clinical and dermatoscopic slides from 258 patients referred to the skin cancer outpatient clinic by the ABCD rule and risk stratification methods. Diagnostic performance of the 2 methods was compared by receiver operating characteristics curve analysis. When all pigmented skin lesions were compared, there was a trend for the observers to perform better using risk stratification. When only lesions with a well-defined pigment network were included, the diagnostic performance of the risk stratification method was superior to the dermatoscopic ABCD rule (areas under the receiver operating characteristics curve median 0.93 vs. 0.80, p<0.004) for all observers. The agreement between the 2 methods was moderate to substantial (kappa coefficient 0.53-0.62). More melanomas were identified when the rules were combined. The dermatoscopic ABCD rule has been accepted as a standard for identifying melanomas with the dermatoscope, but should be considered secondary to pigment network analysis.

  3. The Induction of Apoptosis in A375 Malignant Melanoma Cells by Sutherlandia frutescens.

    PubMed

    van der Walt, Nicola B; Zakeri, Zahra; Cronjé, Marianne J

    2016-01-01

    Sutherlandia frutescens is a medicinal plant indigenous to Southern Africa and is commonly known as the "cancer bush." This plant has traditionally been used for the treatment of various ailments, although it is best known for its claims of activity against "internal" cancers. Here we report on its effect on melanoma cells. The aim of this study was to investigate whether an extract of S. frutescens could induce apoptosis in the A375 melanoma cell line and to outline the basic mechanism of action. S. frutescens extract induced apoptosis in A375 cells as evidenced by morphological features of apoptosis, phosphatidylserine exposure, nuclear condensation, caspase activation, and the release of cytochrome c from the mitochondria. Studies in the presence of a pan-caspase inhibitor allude to caspase-independent cell death, which appeared to be mediated by the apoptosis inducing factor. Taken together, the results of this study show that S. frutescens extract is effective in inducing apoptosis in malignant melanoma cells and indicates that further in vivo mechanistic studies may be warranted.

  4. Mutations in the TP53 gene in human malignant melanomas derived from sun-exposed skin and unexposed mucosal membranes.

    PubMed

    Ragnarsson-Olding, B K; Karsberg, S; Platz, A; Ringborg, U K

    2002-10-01

    Mutations in the p53 tumour suppressor gene ( ) have been linked to several types of cancer. We therefore investigated whether such mutations occur in malignant melanomas and, if so, whether they are linked to ultraviolet (sun) light exposure. For the first time, mutations in mucosal membranes and adjacent tissues shielded from sunlight were compared with those in cutaneous melanomas from sun-exposed skin. Archival tissues were obtained from 35 patients with a primary melanoma taken from unexposed mucosal areas and from 34 patients with a primary melanoma located in chronically sun-exposed head and neck skin. was characterized by means of polymerase chain reaction amplification and single-strand conformation polymorphism assay followed by nucleotide sequencing. The results showed that 17.6% of the primary cutaneous and 28.6% of the primary mucosal melanomas had point mutations in. Among the cutaneous melanomas, one showed three mutations in exon 7, and one had two mutations in exon 5; the mutation was in the same allele in both cases. One mucosal melanoma had two mutations in exon 7, both in the same allele, and another had two mutations, one in exon 7 and one in intron 6, both in the same allele. C<--T mutations at dipyrimidine sites, considered fingerprints for ultraviolet light-induced mutations, were about equally distributed among patients with melanomas from chronically sun-exposed areas (six out of nine; 67%) and those with melanomas from unexposed mucosal areas and adjacent skin (eight out of 14; 57%). Our data, demonstrating the presence of such mutations even in melanomas from mucosal membranes, clearly suggest that factors other than, or additional to, ultraviolet radiation are operational in the induction of mutations in melanomas.

  5. The ''hot spleen'' phenomenon in metastatic malignant melanoma: its incidence and relationship with the immune system

    SciTech Connect

    Wagstaff, J.; Phadke, K.; Adam, N.; Thatcher, N.; Crowther, D.

    1982-02-01

    Of patients with Stage II and III malignant melanoma, 34.7% display reversal of the liver-spleen ratio on technetium-99m-sulfhur colloid isotope scans. Such an occurrence does not suggest a greater likelihood of relapse or a worse survival. The phenomenom is more common in female patients and there is a significant relationship between the presence of a ''hot spleen'' and a high IgM level. Patients with Stage II disease and high IgM levels have relapses more quickly than do those with normal IgM levels. Lymphopenia is common in patients with Stage II and III disease and the survival of these patients is worse than that of those with normal lymphocyte counts. In this report, the data are discussed together with results from other investigations, and a unifying hypothesis is presented which explains the phenomenon and relates it to increased activity of macrophages as a result of the presence of the tumor. The usefulness of isotope liver scanning in stage III malignant melanoma is also discussed.

  6. Diagnosis and treatment of a dermal malignant melanoma in an African lion (Panthera leo).

    PubMed

    Steeil, James C; Schumacher, Juergen; Baine, Katherine; Ramsay, Edward C; Sura, Patricia; Hodshon, Rebecca; Donnell, Robert L; Lee, Nathan D

    2013-09-01

    A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.

  7. First application of dynamic infrared imaging in boron neutron capture therapy for cutaneous malignant melanoma

    SciTech Connect

    Santa Cruz, G. A.; Gonzalez, S. J.; Bertotti, J.; Marin, J.

    2009-10-15

    Purpose: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. Methods: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). In order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. Results: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 deg. C were observed in the larger nodules. Conclusions: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.

  8. [Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line].

    PubMed

    Dong, Wang; Yongjun, Li; Nan, Ding; Junyun, Wang; Qiong, Yang; Yaran, Yang; Yanming, Li; Xiangdong, Fang; Hua, Zhao

    2015-07-01

    Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

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

    ClinicalTrials.gov

    2015-06-01

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

  10. Somatic deletion of the NF1 gene in a neurofibromatosis type 1-associated malignant melanoma demonstrated by digital PCR

    PubMed Central

    Rübben, Albert; Bausch, Birke; Nikkels, Arjen

    2006-01-01

    Background Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous disorder and it is associated with an elevated risk for malignant tumors of tissues derived from neural crest cells. The NF1 gene is considered a tumor suppressor gene and inactivation of both copies can be found in NF1-associated benign and malignant tumors. Melanocytes also derive from neural crest cells but melanoma incidence is not markedly elevated in NF1. In this study we could analyze a typical superficial spreading melanoma of a 15-year-old boy with NF1 for loss of heterozygosity (LOH) within the NF1 gene. Neurofibromatosis in this patient was transmitted by the boy's farther who carried the mutation NF1 c. 5546 G/A. Results Melanoma cells were isolated from formalin-fixed tissue by liquid coverslip laser microdissection. In order to obtain statistically significant LOH data, digital PCR was performed at the intragenic microsatellite IVS27AC28 with DNA of approx. 3500 melanoma cells. Digital PCR detected 23 paternal alleles and one maternal allele. Statistical analysis by SPRT confirmed significance of the maternal allele loss. Conclusion To our knowledge, this is the first molecular evidence of inactivation of both copies of the NF1 gene in a typical superficial spreading melanoma of a patient with NF1. The classical double-hit inactivation of the NF1 gene suggests that the NF1 genetic background promoted melanoma genesis in this patient. PMID:16961930

  11. Host Risk Factors, Ultraviolet Index of Residence, and Incident Malignant Melanoma In Situ Among US Women and Men

    PubMed Central

    Walls, Andrew C.; Han, Jiali; Li, Tricia; Qureshi, Abrar A.

    2013-01-01

    The incidences of malignant melanoma in situ (MMIS) and invasive malignant melanoma are rising in the United States, but few studies have examined risk factors for MMIS. We evaluated the risk of MMIS according to the host phenotype and the ultraviolet index of the state of residence. Prospective data were collected via biennial questionnaires from 250,151 women and men aged ≥20 years in the Nurses' Health Study (1980–2008), the Nurses' Health Study 2 (1989–2009), and the Health Professionals Follow-up Study (1986–2008). During 7,144,820 person-years of follow-up, 888 incident MMIS lesions occurred, representing 33% of all incident malignant melanoma. Meta-analysis across the cohorts demonstrated that the presence of multiple nevi on the extremities conferred the highest relative risk for MMIS (relative risk = 3.18, 95% confidence interval: 2.59, 3.90). Family history of melanoma, number of severe sunburns, sunburn susceptibility, hair color, and Fitzpatrick skin types I, II, and III were significantly associated with an increased risk of MMIS. Conversely, the ultraviolet index of the state of residence at birth, at age 15 years, and at age 30 years was not associated with increased risk of MMIS. Continued study of MMIS and associated risk factors will help identify persons who are most at risk and elucidate the role of MMIS within the spectrum of cutaneous melanoma. PMID:23579556

  12. Metastatic Malignant Melanoma With Complete Loss of Differentiation Markers (Undifferentiated/Dedifferentiated Melanoma): Analysis of 14 Patients Emphasizing Phenotypic Plasticity and the Value of Molecular Testing as Surrogate Diagnostic Marker.

    PubMed

    Agaimy, Abbas; Specht, Katja; Stoehr, Robert; Lorey, Thomas; Märkl, Bruno; Niedobitek, Gerald; Straub, Melanie; Hager, Thomas; Reis, Anna-Carinna; Schilling, Bastian; Schneider-Stock, Regine; Hartmann, Arndt; Mentzel, Thomas

    2016-02-01

    Metastatic malignant melanoma is notorious for its phenotypic diversity and loss of differentiation markers. We herein summarized our experience with 14 metastatic melanomas showing complete loss of immunohistochemical melanocytic markers (with or without heterologous differentiation). Patients included 11 men and 3 women aged 24 to 78 years (median, 67 y). Thirteen patients had histologically confirmed primary skin melanoma, and 1 had metastatic melanoma of unknown primary. Undifferentiated metastasis was diagnosed synchronous to primary tumor (n=1), following skin melanoma by 3 months to 9 years (n=11) and preceding it by 1 year (n=1). Sites of undifferentiated metastases were axillary (3), inguinal (1), or submandibular (1) lymph nodes, digestive tract (2), bone/soft tissue (2), lung/pleura (2), and disseminated (n=3). Histology of metastases mimicked undifferentiated pleomorphic or spindle cell sarcoma with variable myxoid and giant cell areas (n=10) and cytokeratin-positive undifferentiated small cell sarcoma (n=1). Three cases showed heterologous dedifferentiation: pleomorphic rhabdomyosarcoma (n=1), teratocarcinosarcoma-like with prominent rhabdomyoblasts (n=1), and adenocarcinoma-like with metaplastic bone (n=1). All cases were negative for S100, melanoma cocktail, HMB45, Melan A, and SOX10. Other markers showed following results: smooth muscle actin (1/14), p16 (1/14), TP53 (2/12), pancytokeratin (4/14), desmin (5/14), h-caldesmon (0/9), and MDM2/CDK4 (0/5). SMARCB1 was intact in 8/8 cases. Genotyping showed BRAF(V600E) mutation (5/14), NRAS mutation (5/14), and BRAF/NRAS wild-type (4/14). In conclusion, undifferentiated/dedifferentiated metastatic melanoma is likely underrecognized and frequently mistaken for undifferentiated sarcoma or other neoplasms. Diagnosis of undifferentiated sarcoma at sites where melanoma metastasis are frequent (eg, inguinal and axillary region) should be made with great caution and warrants exploration of the remote history

  13. Upregulation of miR-124 by physcion 8-O-β-glucopyranoside inhibits proliferation and invasion of malignant melanoma cells via repressing RLIP76.

    PubMed

    Zhang, Di; Han, Yantao; Xu, Luo

    2016-12-01

    Melanoma is the most malignant type of skin cancer. In recent years, mounting studies have evidenced the involvement of miRNAs in melanoma. One of these miRNAs, miR-124 has been found aberrantly downregulated in a variety of human malignancies. In this study, our results showed that the expression of miR-124 was significantly lower in malignant melanoma tissues and cell lines and miR-124 functioned as a tumor suppressor in melanoma. Moreover, our findings showed that miR-124 exerted anti-tumor effect by directly targeting RLIP76, a stress-inducible non-ABC transporter that plays a crucial role in the development of melanoma. Furthermore, our study also showed that physcion 8-O-β-glucopyranoside, a natural compound from medicinal plant, could inhibit the proliferation and invasion of melanoma cells by targeting miR-124/RLIP76 signaling.

  14. [A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

    PubMed

    Sasaki, Shin; Kojima, Tetsu; Hidemura, Akio; Hatanaka, Kazuhito; Uekusa, Toshimasa; Ishimaru, Masahiro

    2010-10-01

    We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

  15. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    PubMed

    Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

    2014-07-01

    Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38α phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

  16. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance.

    PubMed

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol(®). Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy.

  17. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance

    PubMed Central

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol®. Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy. PMID:28293102

  18. Hair shaft miRNA-221 levels as a new tumor marker of malignant melanoma.

    PubMed

    Inada, Taisuke; Fukushima, Satoshi; Murai, Masayuki; Jinnin, Masatoshi; Miyashita, Azusa; Nakahara, Satoshi; Yamashita, Junji; Aoi, Jun; Masuguchi, Shinichi; Ihn, Hironobu

    2015-02-01

    miRNA-221 (miR-221) is known to be abnormally expressed in many human cancers. The serum levels of miR-221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR-221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR-221 levels could be a marker for MM. The hair shaft miR-221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR-221 levels above the cut-off value were comparable to those of serum 5-S-CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR-221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR-221 and MM, and may provide a new, non-invasive way to screen for melanoma.

  19. MC1R gene variants and sporadic malignant melanoma susceptibility in the Canary Islands population.

    PubMed

    Córdoba-Lanús, Elizabeth; Hernández-Jiménez, José G; Medina-Coello, Chaxiraxi; Espinoza-Jiménez, Adriana; González, Ana; Rodríguez-Pérez, María-Del-Cristo; Carretero-Hernández, Gregorio; Almeida, Pablo; Suárez-Hernández, José; Perera-Molinero, Antonio; Fernández-de-Misa, Ricardo

    2014-01-01

    Several MC1R variants are associated with increased risk of malignant melanoma (MM) in a variety of populations. We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. Overall, 1,046 Caucasian individuals were included in the study. A thousand of them were genotyped for MC1R variants: 509 were sporadic MM patients and 491 were healthy control subjects from general population. The analysis was adjusted for age, sex, hair colour, eye colour, skin phototype and ancestry. We found that carriers of the R151C and R163Q variants were at an increased risk for melanoma OR 2.76 (1.59-4.78) and OR 5.62 (2.54-12.42), respectively. The risk of carrying RHC variants was 3.04 (1.90-4.86). Current study confirms the increased MM risk for R151C carriers. It also supports the association between R163Q variant and MM risk in the population on the Canary Islands, as opposed to reported on northern populations. These results highlight the importance of the sample population selection in this kind of studies.

  20. Coexisting malignant melanoma and blue nevus of the uterine cervix: an unusual combination.

    PubMed

    Parada, David; Peña, Karla B; Riu, Frances

    2012-01-01

    Malignant melanoma (MM) and blue nevi of the uterine cervix are an extremely rare neoplasm, probably derived from embryologic migration of melanocytes from the neural crest. MM displays aggressive behavior with a poor prognosis. We report the case of a 76-year-old postmenopausal woman abnormal vaginal bleeding. She underwent a hysterectomy and bilateral salpingo-oophorectomy with paraaortic-iliac lymphadenectomy. Histopathological and immunohistochemical studies were consistent with the diagnosis of MM and blue nevi in the uterine cervix. Although it is extremely rare, this case suggests that MM of the uterine cervix should be considered in the differential diagnosis of undifferentiated neoplasm. Early diagnosis is essential in order to warrant a better prognosis, although there are no cases of cure described.

  1. Dermoscopic Features of Pigmented Bowen's Disease in a Japanese Female Mimicking Malignant Melanoma

    PubMed Central

    Inoue, Takayuki; Kobayashi, Ken; Sawada, Mizuki; Ishizaki, Sumiko; Ito, Haruo; Fujibayashi, Mariko; Tanaka, Masaru

    2010-01-01

    Various structures have been reported for dermoscopic features of pigmented Bowen's disease (BD), which could be a mimic of various pigmented skin lesions. A 79-year-old Japanese woman presented with a 3-year history of brown-black macule on her right upper arm without symptom. Dermoscopic examination demonstrated irregular flossy streaks, irregular brown dots/globules, blue-whitish regression structures, and overlaying whitish scaly areas. We suspected pigmented skin lesions including seborrheic keratosis, pigmented eccrine poroma, and malignant melanoma and excised completely with a 5 mm margin. Histopathological features were consistent with a diagnosis of pigmented BD. Although similar dermoscopic features might be revealed in pigmented skin lesions and it may occasionally be difficult to distinguish between pigmented BD and other pigmented skin lesions, dermoscopy would be useful in speculating pathologic features of pigmented BD. PMID:20811602

  2. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis.

    PubMed

    Maeda, Osamu; Yokota, Kenji; Atsuta, Naoki; Katsuno, Masahisa; Akiyama, Masashi; Ando, Yuichi

    2016-02-01

    A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten doses of nivolumab. Although a case who died due to MG after administration of nivolumab was reported recently, pre-existing MG is considered not to be always a contraindication of nivolumab.

  3. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

    PubMed

    Law, Matthew H; Bishop, D Timothy; Lee, Jeffrey E; Brossard, Myriam; Martin, Nicholas G; Moses, Eric K; Song, Fengju; Barrett, Jennifer H; Kumar, Rajiv; Easton, Douglas F; Pharoah, Paul D P; Swerdlow, Anthony J; Kypreou, Katerina P; Taylor, John C; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A; Andresen, Per A; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M; Dȩbniak, Tadeusz; Duffy, David L; Elder, David E; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M; Goldstein, Alisa M; Gruis, Nelleke A; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A; Chen, Wei V; Landi, Maria Teresa; Lang, Julie; Lathrop, G Mark; Lubiński, Jan; Mackie, Rona M; Mann, Graham J; Molven, Anders; Montgomery, Grant W; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A; Radford-Smith, Graham L; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C; Craig, Jamie E; Schadendorf, Dirk; Simms, Lisa A; Burdon, Kathryn P; Nyholt, Dale R; Pooley, Karen A; Orr, Nick; Stratigos, Alexander J; Cust, Anne E; Ward, Sarah V; Hayward, Nicholas K; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M; Bishop, Julia A Newton; Demenais, Florence; Amos, Christopher I; MacGregor, Stuart; Iles, Mark M

    2015-09-01

    Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

  4. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

    PubMed Central

    Law, Matthew H.; Bishop, D. Timothy; Martin, Nicholas G.; Moses, Eric K.; Song, Fengju; Barrett, Jennifer H.; Kumar, Rajiv; Easton, Douglas F.; Pharoah, Paul D. P.; Swerdlow, Anthony J.; Kypreou, Katerina P.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Dębniak, Tadeusz; Duffy, David L.; Elder, David E.; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A.; Chen, Wei V.; Landi, Maria Teresa; Lang, Julie; Lathrop, G. Mark; Lubiński, Jan; Mackie, Rona M.; Mann, Graham J.; Molven, Anders; Montgomery, Grant W.; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C.; Craig, Jamie E.; Schadendorf, Dirk; Simms, Lisa A.; Burdon, Kathryn P.; Nyholt, Dale R.; Pooley, Karen A.; Orr, Nick; Stratigos, Alexander J.; Cust, Anne E.; Ward, Sarah V.; Hayward, Nicholas K.; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M.; Bishop, Julia A. Newton; MacGregor, Stuart; Iles, Mark M.

    2015-01-01

    Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10–8), as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes including one involved in telomere biology. PMID:26237428

  5. [Primary malignant melanoma in the brain of a 7-month-old sheep (Ovis aries f. domestica)].

    PubMed

    Breuer, Wolfram; Hafner-Marx, Angela

    2017-02-15

    A case of malignant melanoma in a sheep's brain is described for the first time. In a 7-month-old sheep that had been euthanized due to ataxia, post-mortem and histopathologic examinations were performed. Both the brain and the calvarium were heavily infiltrated with neoplastic tissue. Metastases were found in the liver and kidneys. Histomorphology confirmed the gross pathologic impression of malignancy. Congenital melanosis, which is regularly present in the meninx of sheep, could have been the origin of the malignant melanoma in the present case. The young age of the animal appears to favour this supposition. This case demonstrates that even in farm animals - including sheep - a neoplasm should be considered as a differential diagnosis in diagnostically doubtful cases.

  6. Primary uterine cervix melanoma resembling malignant peripheral nerve sheath tumor: a case report.

    PubMed

    Pusceddu, Sara; Bajetta, Emilio; Buzzoni, Roberto; Carcangiu, Maria Luisa; Platania, Marco; Del Vecchio, Michele; Ditto, Antonino

    2008-10-01

    A rare variant of malignant melanoma (MM) of the uterine cervix that mimics a malignant peripheral nerve sheath tumor (MPNST) is described. A 43-year-old white woman was admitted to the hospital complaining of genital discharge and vaginal bleeding. Neoadjuvant chemotherapy and total abdominal hysterectomy and bilateral salpingo-ovariectomy plus pelvic lymphadenectomy were performed, and the diagnosis was MPNST, FIGO IIB. Pathological examination showed a diffuse proliferation of amelanotic spindle cells and large, highly atypical, frequently multinucleated, bizarre, and S100-, HMB-45-, vimentin-positive cells. The patient remained disease-free for 43 months, when an abdominal computed tomographic scan showed local polypoid vaginal lesions, with histological features of typical MM. A pathological review was obtained in our institution by a gynecological pathologist, who defined the primary neoplasm in the cervix as an MM, with a pattern of growth histologically simulating an MPNST, metastatic to the vagina. To our knowledge, this is the first report in literature of MM of the uterine cervix resembling MPNST. Despite its rarity, this variant of MM should be considered when a diagnosis of cervix MPNST is made. The histological and immunohistochemical features of these different entities should be considered in the differential diagnosis.

  7. Melanoma

    MedlinePlus

    ... flat or raised, large or small, light or dark, and can appear anywhere on our bodies. Sometimes, ... can still get melanoma even if they're dark skinned, young, and have no family history. Even ...

  8. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

    PubMed Central

    Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B.; da Motta, Leonardo L.; Klamt, Fabio; Ibañez, Irene L.; Durán, Hebe

    2016-01-01

    Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy. PMID:27206672

  9. SCD5-induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B.

    PubMed

    Bellenghi, Maria; Puglisi, Rossella; Pedini, Francesca; De Feo, Alessandra; Felicetti, Federica; Bottero, Lisabianca; Sangaletti, Sabina; Errico, Maria Cristina; Petrini, Marina; Gesumundo, Cinzia; Denaro, Massimo; Felli, Nadia; Pasquini, Luca; Tripodo, Claudio; Colombo, Mario Paolo; Carè, Alessandra; Mattia, Gianfranco

    2015-07-01

    A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl-CoA desaturase SCD5 in converting saturated FAs into mono-unsaturated FAs during melanoma progression. SCD5 is down-regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B. Enforced expression of SCD5 or supplementation of its enzymatic product, oleic acid, reduced the intracellular pH (pHe > pHi) and, in turn, vesicular trafficking across plasma membranes as well as melanoma dissemination. This intracellular acidification appears also to depend on SCD5-induced reduction of the C2 subunit of the vacuolar H(+) -ATPase, a proton pump whose inhibition changes the secretion profile of cancer cells. Our data support a role for SCD5 and its enzymatic product, oleic acid, in protection against malignancy, offering an explanation for the beneficial Mediterranean diet. Furthermore, SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment.

  10. Vitamin C at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations.

    PubMed

    Yang, Guang; Yan, Yao; Ma, Younan; Yang, Yixin

    2017-03-30

    Vitamin C has been used in complementary and alternative medicine for cancers regardless of its ineffectiveness in clinical trials and the paradoxical effects antioxidants have on cancer. Vitamin C was found to induce cytotoxicity against cancers. However, the mechanisms of action have not been fully elucidated, and the effects of vitamin C on human malignant melanoma have not been examined. This study revealed that vitamin C at millimolar concentrations significantly reduced the cell viability as well as invasiveness, and induced apoptosis in human malignant melanoma cells. Vitamin C displayed stronger cytotoxicity against the Vemurafenib-resistance cell line A2058 compared with SK-MEL-28. In contrast, vitamin C at micromolar concentrations promoted cell growth, migration and cell cycle progression, and protected against mitochondrial stress. Vemurafenib paradoxically activated the RAS-RAF-MEK-ERK signaling pathway in the Vemurafenib-resistant A2058, however, vitamin C abolished the activations. Vitamin C displayed synergistic cytotoxicity with Vemurafenib against the Vemurafenib-resistant A2058. In vivo assay suggested that lower dosage (equivalent to 0.5g/70kg) of vitamin C administered orally increased the melanoma growth. Therefore, vitamin C may exert pro- or anti-melanoma effect depending on concentration. The combination of vitamin C at high dosage and Vemurafenib is promising in overcoming the action of drug resistance. This article is protected by copyright. All rights reserved.

  11. Cutaneous malignant melanoma: clinical and histopathological review of cases in a Malaysian tertiary referral centre.

    PubMed

    Pailoor, Jayalakshmi; Mun, Kein-Seong; Leow, Margaret

    2012-12-01

    Melanoma is a lethal skin cancer that occurs predominantly among Caucasians. In Malaysia, the incidence of melanoma is low. This is a retrospective study of clinical and histopathological features of patients with cutaneous melanoma who were seen at the University Malaya Medical Centre from 1998 to 2008. Thirty-two patients with cutaneous melanoma were recorded during that period. Of these, 24 had sought treatment at the onset of disease at our centre. Chinese patients constituted the largest group (19 cases). The median age of these 24 patients at the time of presentation was 62 years. 16 patients had melanoma involving the lower limb with 12 affecting the sole of the foot. None had melanoma arising from the face. Histopathology showed nodular melanoma in 22 cases (91.6%), with superficial spreading and acral lentiginous melanoma diagnosed in 1 case each. The majority of patients (62.5%) were found to be in Stage III of the disease at the time of diagnosis.

  12. Development of a practical guide for the early recognition for malignant melanoma of the foot and nail unit

    PubMed Central

    2010-01-01

    Background Malignant melanoma is a rare but potentially lethal form of cancer which may arise on the foot. Evidence suggests that due to misdiagnosis and later recognition, foot melanoma has a poorer prognosis than cutaneous melanoma elsewhere. Methods A panel of experts representing podiatry and dermatologists with a special interest in skin oncology was assembled to review the literature and clinical evidence to develop a clinical guide for the early recognition of plantar and nail unit melanoma. Results A systematic review of the literature revealed little high quality data to inform the guide. However a significant number of case reports and series were available for analysis. From these, the salient features were collated and summarised into the guide. Based on these features a new acronym "CUBED" for foot melanoma was drafted and incorporated in the guide. Conclusions The use of this guide may help clinicians in their assessment of suspicious lesions on the foot (including the nail unit). Earlier detection of suspicious pedal lesions may facilitate earlier referral for expert assessment and definitive diagnosis. The guide is currently being field tested amongst practitioners. PMID:20920168

  13. Unusual Severe Complication Following Transarterial Chemoembolization for Metastatic Malignant Melanoma: Giant Intrahepatic Cyst and Fatal Hepatic Failure

    SciTech Connect

    Ataergin, Selmin; Tasar, Mustafa; Solchaga, Luis; Ozet, Ahmet; Arpaci, Fikret

    2009-03-15

    We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

  14. A case-control study of malignant melanoma among Lawrence Livermore National Laboratory employees: A critical evaluation

    SciTech Connect

    Kupper, L.L.; Setzer, R.W.; Schwartzbaum, J.; Janis, J.

    1987-07-01

    This document reports on a reevaluation of data obtained in a previous report on occupational factors associated with the development of malignant melanomas at Lawrence Livermore National Laboratory. The current report reduces the number of these factors from five to three based on a rigorous statistical analysis of the original data. Recommendations include restructuring the original questionnaire and trying to contact more individuals that worked with volatile photographic chemicals. 17 refs., 7 figs., 22 tabs. (TEM)

  15. Melanoma.

    PubMed

    Gershenwald, J E

    2001-01-01

    The presentations at the American Society of Clinical Oncology 2001 meeting reported or updated the results of phase I, II, and III randomized trials and also reported important meta-analyses and retrospective studies impacting on the management of patients with melanoma. In the treatment of early stage melanoma, the prognostic significance of pathologic status of sentinel lymph nodes was affirmed. With respect to regional nodal involvement (American Joint Committee on Cancer [AJCC] stage III), investigators presented the interim results of the United Kingdom randomized low-dose interferon (IFN) trial, and up-to-date meta-analyses of several IFN trials including a pooled analysis of the Eastern Cooperative Oncology Group trials evaluating interferon in the adjuvant setting. In the advanced disease setting (AJCC stage IV), several studies elucidated the pros and cons of biochemotherapy in patients with metastatic melanoma, with an emphasis on seeking to improve response in the central nervous system and durability of response in general. Thought provoking was new data regarding the potential for lovastatin to act as a chemopreventive agent for melanoma. Translational studies were presented, one supporting the importance of HLA-typing in developing targeted vaccine therapy. Finally, the results of a novel experimental melanoma vaccine were presented using autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96).

  16. In vivo tumor transfection with superantigen plus cytokine genes induces tumor regression and prolongs survival in dogs with malignant melanoma.

    PubMed Central

    Dow, S W; Elmslie, R E; Willson, A P; Roche, L; Gorman, C; Potter, T A

    1998-01-01

    In vivo transfection of established tumors with immunostimulatory genes can elicit antitumor immunity. Therefore, we evaluated the safety and efficacy of intratumoral injections of a bacterial superantigen with a cytokine gene in dogs with malignant melanoma, a spontaneous and highly malignant canine tumor. 26 dogs with melanoma were treated with lipid-complexed plasmid DNA encoding staphylococcal enterotoxin B and either GM-CSF or IL-2. Dogs were evaluated for treatment-associated toxicity, tumor responses, immunologic responses, and survival times. The overall response rate (complete or partial remissions) for all 26 dogs was 46% (12 of 26), and was highest in patients with smaller tumors. Toxicity was minimal or absent in all dogs. Injected tumors developed marked infiltrates of CD4+ and CD8+ T cells and macrophages, and tumor regression was associated with development of high levels of antitumor cytotoxic T lymphocyte activity in peripheral blood lymphocytes. Survival times for animals with stage III melanomas treated by intratumoral gene therapy were prolonged significantly compared with animals treated with surgical tumor excision only. Thus, local tumor transfection with superantigen and cytokine genes was capable of inducing both local and systemic antitumor immunity in an outbred animal with a spontaneously developing malignant tumor. PMID:9616212

  17. Ultraviolet radiation and the risks of cutaneous malignant melanoma and non-melanoma skin cancer: perceptions and behaviours of Danish and American adolescents.

    PubMed

    Savona, M R; Jacobsen, M D; James, R; Owen, M D

    2005-02-01

    The highest prevalence rates of skin malignancy in the northern hemisphere occur in Scandinavia and the United States (USA). Most Danes and Americans receive 50% of their lifetime ultraviolet (UV) radiation before the age of 21, making it important to address sun exposure risks with adolescents. The project was undertaken to determine differences between Danish and American adolescents in knowledge of sun exposure and skin malignancy, activities accounting for sun exposure, and means used for sun protection. Questionnaires regarding skin cancer and sun exposure were distributed to 674 secondary school age students in Hilleroed, Denmark, and to 483 similarly aged students in Winston-Salem, North Carolina, USA. Differences in responses between and within groups were compared. American adolescents had more knowledge of the characteristics and malignant potential of melanoma than did Danish adolescents. Danish youth and females from both countries were significantly more likely to engage in sunbathing and tanning bed use. Black Danish students reported significantly more sunburn and were more likely to sunbathe or use a tanning bed than were black American students. Danish students were more likely than Americans to use sunscreen, however, Americans were more likely to apply sun protective factor (SPF) 15 or greater. In conclusion, given that sunbathing and tanning bed use are associated with the development of precancerous lesions and skin malignancy, Danish teens are at increased risk. The rates of skin malignancy are relatively high in Scandinavia and efforts to improve understanding of exposure and cancer risks should be undertaken in adolescents.

  18. Antiproliferative Effects of 1α-OH-vitD3 in Malignant Melanoma: Potential Therapeutic implications

    PubMed Central

    Spath, Lucia; Ulivieri, Alessandra; Lavra, Luca; Fidanza, Laura; Carlesimo, Marta; Giubettini, Maria; Narcisi, Alessandra; Luciani, Emidio; Bucci, Barbara; Pisani, Daniela; Sciacchitano, Salvatore; Bartolazzi, Armando

    2017-01-01

    Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow’s thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth. 99 out of 105 (94%) melanoma patients had insufficient 25-hydroxycholecalciferol serum levels. Interestingly among the six with vitamin D in the normal range, five had a diagnosis of in situ/microinvasive melanoma. Treatment with 1α-hydroxycholecalciferol induced antiproliferative effects on melanoma cells in vitro and in vivo, modulating the expression of cell cycle key regulatory molecules. Cell cycle arrest in G1 or G2 phase was invariably observed in vitamin D treated melanoma cells. The antiproliferative activity induced by 1α-hydroxycholecalciferol in experimental melanoma models, together with the discovery of insufficient 25-hydroxycholecalciferol serum levels in melanoma patients, provide the rationale for using vitamin D in melanoma adjuvant therapy, alone or in association with other therapeutic options. PMID:28074906

  19. Combined BCG and irradiation treatment of skin metastases originating from malignant melanoma

    SciTech Connect

    Plesnicar, S.; Rudolf, Z.

    1982-09-15

    Treatment with BCG (Bacillus Calmette-Guerin) followed by irradiation was attempted to improve response to therapy by cutaneous metastases from malignant skin melanomas. Both agents were applied in low doses, known to cause minimal side effects. Nineteen patients, divided into three groups, entered the clinical trial. The first group consisted of five patients with numerous, small skin metastases. The nine patients of the second group presented a small number of relatively large metastases that usually appeared as a residual disease in the surgically treated area. Five patients with numerous, large metastases were included in the third group. The treatment sequence consisted of applying BCG intralesionally in doses from 4 x 10/sup 5/ to 1.17 x 10/sup 7/ viable units. After a free interval, the affected area was irradiated with doses from 1500-2500 ret. Patients with numerous small metastases and those with a small number of larger metastases, i.e., patients of the first and second group, showed a complete response and in these cases regression affected all the noninjected nodules and was also effective when regression could not have been achieved by BCG alone.

  20. Fotemustine: an overview of its clinical activity in disseminated malignant melanoma.

    PubMed

    Khayat, D; Avril, M F; Gerard, B; Bertrand, P; Bizzari, J P; Cour, V

    1992-09-01

    Fotemustine is a new chloronitrosourea which is active against disseminated malignant melanoma (DMM), and especially against cerebral metastases (CM). This efficacy has been widely demonstrated through many phase II studies. A multicentre trial of monotherapy was undertaken in 153 evaluable French patients. A response rate (RR) of 24.2% (25.0% RR in CM; 31.8% in non-visceral metastases (NVM) was obtained. Three other phase II studies confirmed these results with respective objective RR of 16.7%, 20.0% and 47.0% and RR in CM of 8.3%, 14.3% and 60.0%. Fotemustine has also been used in combination with dacarbazine (DTIC), in patients with DMM. The RR among 103 patients was 27.2% (26.3% in CM, 37.5% in NVM), confirming the activity of fotemustine. The two drugs have also been administered sequentially, in order to exploit their synergism in interfering with the O6 alkyltransferase. Impressive RR have been achieved, especially in patients with visceral metastases (VM) but at the expense of a pulmonary toxicity that does not arise with other treatment schedules and which precludes its use outside of strictly conducted clinical trials.

  1. Study of IL-2 receptor expression after chemoimmunotherapy in patients treated for metastatic malignant melanoma.

    PubMed Central

    Mouawad, R; Ichen, M; Rixe, O; Benhammouda, A; Vuillemin, E; Weil, M; Khayat, D; Soubrane, C

    1994-01-01

    Using flow cytometry, cellular IL-2 receptors were studied before and following chemoimmunotherapy combination in 20 patients with metastatic malignant melanoma (MMM). Patients received cisplatin (100 mg/m2) at days 1 and 28, recombinant IL-2 by continuous infusion from days 3 to 6, 17 to 21, 31 to 34, and 45 to 49. Interferon-alpha (IFN-alpha) was given subcutaneously three times weekly. In terms of clinical response, we observed 55% objective response (complete: 15%). When pretreatment blood samples were compared with those of healthy donors, we did not observe any change in low (alpha chain) and high affinity receptor (alpha + beta) expression. In contrast, intermediate affinity p75 (beta chain) expression was decreased significantly (P < or = 0.0001) in MMM patients. During treatment, we found a dramatic increase of beta chain as well as high affinity (alpha + beta) expression in responding patients, as soon as IL-2 therapy began. Furthermore, the increase of beta chain expression was limited to natural killer (NK) cells (CD56+). In non-responding patients, on the other hand, increase of both receptors was seen only at day 31. These data suggest the involvement of beta chain expression in the mechanism of cell activation after chemoimmunotherapy. Moreover, this early beta chain expression is correlated with the clinical response to chemoimmunotherapy. PMID:8082289

  2. Automated detection of malignant features in confocal microscopy on superficial spreading melanoma versus nevi

    NASA Astrophysics Data System (ADS)

    Gareau, Dan; Hennessy, Ricky; Wan, Eric; Pellacani, Giovanni; Jacques, Steven L.

    2010-11-01

    In-vivo reflectance confocal microscopy (RCM) shows promise for the early detection of superficial spreading melanoma (SSM). RCM of SSM shows pagetoid melanocytes (PMs) in the epidermis and disarray at the dermal-epidermal junction (DEJ), which are automatically quantified with a computer algorithm that locates depth of the most superficial pigmented surface [DSPS(x,y)] containing PMs in the epidermis and pigmented basal cells near the DEJ. The algorithm uses 200 noninvasive confocal optical sections that image the superficial 200 μm of ten skin sites: five unequivocal SSMs and five nevi. The pattern recognition algorithm automatically identifies PMs in all five SSMs and finds none in the nevi. A large mean gradient ψ (roughness) between laterally adjacent points on DSPS(x,y) identifies DEJ disruption in SSM ψ = 11.7 +/- 3.7 [-] for n = 5 SSMs versus a small ψ = 5.5 +/- 1.0 [-] for n = 5 nevi (significance, p = 0.0035). Quantitative endpoint metrics for malignant characteristics make digital RCM data an attractive diagnostic asset for pathologists, augmenting studies thus far, which have relied largely on visual assessment.

  3. Melanoma Diagnosis

    NASA Astrophysics Data System (ADS)

    Horsch, Alexander

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

  4. Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis and protein expression levels in malignant melanomas.

    PubMed

    Korabiowska, Monika; Brinck, Ulrich; Stachura, Jerzy; Jawien, Jacek; Hasse, Frank Michael; Cordon-Cardos, Carlos; Fischer, Gösta

    2006-01-01

    The mutations of MLH1 and MSH2 have been reported to be responsible for malignant transformation and tumour progression in several sporadic tumours. Eighty-six primary malignant melanomas with known follow-up were investigated. Point mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not found. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13 (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in 22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss of exons correlated strongly with the loss of MLH1 and MSH2 protein expression. In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2, prognostic significance was found only for loss of exon 12 (MSH2) and loss of exon 15 (MLH1).

  5. An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

    PubMed

    Kirby, L C; Banerjee, A; Augustine, T; Douglas, J F

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation.

  6. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    PubMed

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis.

  7. Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors

    PubMed Central

    Rad, Ehsan Bonyadi; Hammerlindl, Heinz; Wels, Christian; Popper, Ulrich; Menon, Dinoop Ravindran; Breiteneder, Heimo; Kitzwoegerer, Melitta; Hafner, Christine; Herlyn, Meenhard; Bergler, Helmut; Schaider, Helmut

    2016-01-01

    The effects of Notch signaling are context-dependent and both oncogenic and tumor-suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial-like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial–mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the reexpression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo. Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E-cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting. PMID:26801977

  8. Several loci at chromosome 9p are involved in early and late stages of growth of cutaneous malignant melanoma

    SciTech Connect

    Puig, S. |; Ruiz, A.; Lazaro, C.

    1994-09-01

    To study the inactivation of a possible tumor suppressor gene at chromosome 9p associated with the development and progression of cutaneous malignant melanoma (CMM), we have analyzed 12 microsatellite markers in 54 paired tumors and normal tissues. Forty-six percent of the tumors (corresponding to 52% of patients) showed loss of heterozygosity (LOH) for at least one marker. The smallest deleted region included markers D9S126, D9S265 and D9S259, spanning 5 centiMorgans of chromosome 9p21. Forty-two percent of the metastasic tumors and 50% of the primary tumors, including two in situ CMM, showed 9p21 deletions. Tumors with the worst prognoses showed larger deletions at 9p, ({chi}{sup 2} = 4.16, p < 0.04), and three cases showed two non-contiguous regions deleted, one telomeric to IFNA and the other centromeric. The presence of large and non-contiguous deletions, in the cases with the worst prognoses, suggests the existence of more than one tumor suppressor gene at 9p involved in the predisposition to, and progression of, malignant melanoma, outside the region of the recently identified p16 gene (MTS1), which has been found deleted in about 60% of melanoma cell lines.

  9. Mutations of the KIT gene and loss of heterozygosity of the PTEN region in a primary malignant melanoma arising from a mature cystic teratoma of the ovary.

    PubMed

    Tate, Genshu; Tajiri, Takuma; Suzuki, Takao; Mitsuya, Toshiyuki

    2009-04-01

    A tumor suppressor gene at 10q23.3, designated PTEN, encoding a dual-specificity phosphatase with lipid and protein phosphatase activity, has been shown to play a pivotal role in the pathogenesis of a variety of human cancers. A frequent loss of heterozygosity (LOH) at 10q is found in melanoma; however, little is known about the role of PTEN in the pathogenesis of a primary malignant melanoma derived from ovarian mature cystic teratoma, which is an extremely rare melanoma. This study examined the genetic alterations involved in the mitogen-activated protein kinase and phosphatidylinositol 3 kinase pathways in an ovarian malignant melanoma. A LOH analysis revealed hemizygous deletion around and in the PTEN gene not only in the ovarian melanoma but also in a mature cystic teratoma. Another case of ovarian mature cystic teratomas in the absence of melanoma also showed allelic loss of the PTEN region. To date, mutations of BRAF, NRAS, and KIT genes have been reported in malignant melanomas. In the present study, D816H and K558E mutations of the KIT gene were revealed in the melanoma arising from a mature cystic teratoma, but not in a mature cystic teratoma. No mutations of the BRAF and NRAS genes were found in the melanoma. These results indicate that LOH of the PTEN region is one of the molecular alterations of an ovarian mature cystic teratoma and a KIT mutation is an additional promotional event associated with the oncogenesis of a melanoma arising from an ovarian mature cystic teratoma.

  10. Multiple pigmentation gene polymorphisms account for a substantial proportion of risk of cutaneous malignant melanoma.

    PubMed

    Duffy, David L; Zhao, Zhen Z; Sturm, Richard A; Hayward, Nicholas K; Martin, Nicholas G; Montgomery, Grant W

    2010-02-01

    We have previously described the role of red hair (melanocortin-1 receptor, MC1R) and blue eye (oculocutaneous albinism type II, OCA2) gene polymorphisms in modulating the risk of cutaneous malignant melanoma (CMM) in a highly sun-exposed population of European descent. A number of recent studies, including genome-wide association studies, have identified numerous polymorphisms controlling human hair, eye, and skin color. In this paper, we test a selected set of polymorphisms in pigmentation loci (ASIP (Agouti signalling protein, nonagouti homolog (mouse) gene), TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), MC1R, OCA2, IRF4 (interferon regulatory factor 4), SLC24A4 (solute carrier family 24, member 4), and SLC45A2 (solute carrier family 45, member 2)) for association with CMM risk in a large Australian population-based case-control study. Variants in IRF4 and SLC24A4, despite being strongly associated with pigmentation in our sample, did not modify CMM risk, but the other six did. Three single nucleotide polymorphisms (rs28777, rs35391, and rs16891982) in the MATP gene (SLC45A2) exhibited the strongest crude association with risk, but this was attenuated to approximately the same effect size as that of a MC1R red hair color allele by controlling for ancestry of cases and controls. We also detected significant epistatic interactions between SLC45A2 and OCA2 alleles, and MC1R and ASIP alleles. Overall, these measured variants account for 12% of the familial risk of CMM in our population.

  11. Positron emission tomography in the follow-up of cutaneous malignant melanoma patients: a systematic review

    PubMed Central

    Danielsen, Maria; Højgaard, Liselotte; Kjær, Andreas; Fischer, Barbara MB

    2014-01-01

    Cutaneous malignant melanoma (CMM) has a high risk of dissemination to regional lymph nodes and visceral organs. Recurrences are most frequently seen within the first 2-3 years after initial treatment, but these patients have a life-long risk of relapse. The prognosis is highly dependent on lymph node involvement and distant metastases, accentuating the importance of close surveillance to identify disease progression at an early stage, and thereby detect recurrences amenable to treatment. Positron emission tomography (PET) has already been proven useful in the staging of CMM, but the utility of PET in follow-up programs for asymptomatic patients in high risk of relapse to detect systemic recurrences has yet to be investigated. We performed a systematic literature search in PUBMED, EMBASE and the Cochrane Controlled Trials Register, and identified 7 original studies on the diagnostic value of FDG-PET in the follow-up of CMM. Sensitivity, specificity, positive and negative predictive values were calculated to examine PET’s diagnostic value in detecting relapse. The mean sensitivity of PET was 96% and the specificity was 92%. The positive and negative predictive values were, respectively, 92% and 95%. Overall, PET has a high diagnostic value and the many advantages of PET indicate utility in the routine follow-up program of CMM. However, the number of prospective studies of high quality is scarce, and as the use of PET and PET/CT is becoming more widespread and the technology is expensive, there is an urgent need for systematic assessment of the diagnostic value. PMID:24380042

  12. Dormancy of Growth-Stunted Malignant Melanoma: Sustainable and Smoldering Patterns

    PubMed Central

    Piérard-Franchimont, Claudine; Hermanns-Lê, Trinh; Delvenne, Philippe; Piérard, Gerald E.

    2014-01-01

    The presentations of primary and metastatic cutaneous malignant melanoma (CMM) are very diverse. Evidence increasingly indicates that single CMM cells spread to distant sites quite early during cancer progression and are soon eliminated before they become clinically detectable. However bulky metastases which appear at a later stage might derive from some of these early neoplastic cells. It seems that local CMM single cell micro-metastases commonly predict sentinel lymph node involvement without overtly reflecting CMM progression to bulky visceral metastases. This study is intended to review the current understanding of the mechanisms underlying two CMM presentations. The first is the long interval, apparently disease-free, with persistent CMM dormancy, which may precede overt metastatic growth. Immunosurveillance may induce dormancy in single CMM cells disseminated in the body by blocking their proliferation cycle. The second is the so-called CMM smoldering phenomenon, which is marked by an alternate progression and regression of CMM locally with metastases that wax and wane for long periods of time over restricted skin areas. These very diverse patterns of CMM progression are likely to be ascribable to a number of biological factors, including the activation of CMM stem cells, and the combined phenotypic heterogeneity and variability in proliferative amplification in CMM cell clusters. Furthermore an adequate stimulation of CMM immune-surveillance and the induction of a specific stromal structure and vascular response are required. In this context, most early CMM tumors are in part controlled by lymphocyte-mediated responses before they become clinically detectable. However both the role of immune-surveillance and the mechanisms underlying both persistent and smoldering CMM dormancy remain unclear. PMID:25992239

  13. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

    PubMed Central

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

  14. Radicality of initial surgery for primary malignant melanoma of the vagina.

    PubMed

    Todo, Yukiharu; Okamoto, Kazuhira; Suzuki, Yoshihiro; Minobe, Shinichiro; Kato, Hidenori

    2016-04-01

    Radical surgery is considered not to improve the prognosis of primary malignant melanoma of the vagina (PMMV). This study was carried out to review the general consensus. A systematic review was performed on the basis of data from 10 patients in our cohort and 147 patients in the previous literature. The radicality of the initial surgery (RAINS) score was defined as the total number of points in terms of the resected organs. The target organs were the vagina, vulva, urethra, bladder, uterus, anus, rectum, pelvic lymph nodes, and inguinal lymph nodes. Overall survival (OS) according to the RAINS score was analyzed using the Kaplan-Meier method. Information on tumor stage, size, and depth of invasion was not obtained in 15, 47, and 43% of patients, respectively. The median follow-up period was 18 months. OS with a RAINS score of at least 7 was significantly longer than that with a RAINS score of up to 6 (median survival time, 41 vs. 19 months; log-rank test, P=0.037), despite the fact that the former group included significantly more patients with advanced-stage disease. A significant difference in OS was not found between patients with a RAINS score of at least 6 and up to 5. The therapeutic significance of radical surgery for PMMV has not been assessed appropriately in previous studies because of the lack of comparability among groups and differences in the definitions of surgical radicality. Patients with PMMV might benefit from initial surgery with appropriate surgical radicality, despite incomplete validation of the RAINS score.

  15. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

    PubMed Central

    Piotrowska, Anna; Wierzbicka, Justyna; Nadkarni, Sharmin; Brown, Geoffrey; Kutner, Andrzej; Żmijewski, Michał A.

    2016-01-01

    Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs. PMID:26760999

  16. Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Upregulation of antioxidant genes correlates with regression of melanoma malignancy and with malignant progression when downregulated

    PubMed Central

    Berenstein, Ariel; Notcovich, Cintia; Cerda, María B.; Klamt, Fabio; Chernomoretz, Ariel; Durán, Hebe

    2016-01-01

    Reactive oxygen species (ROS) are implicated in tumor transformation. The antioxidant system (AOS) protects cells from ROS damage. However, it is also hijacked by cancers cells to proliferate within the tumor. Thus, identifying proteins altered by redox imbalance in cancer cells is an attractive prognostic and therapeutic tool. Gene expression microarrays in A375 melanoma cells with different ROS levels after overexpressing catalase were performed. Dissimilar phenotypes by differential compensation to hydrogen peroxide scavenging were generated. The melanotic A375-A7 (A7) upregulated TYRP1, CNTN1 and UCHL1 promoting melanogenesis. The metastatic A375-G10 (G10) downregulated MTSS1 and TIAM1, proteins absent in metastasis. Moreover, differential coexpression of AOS genes (EPHX2, GSTM3, MGST1, MSRA, TXNRD3, MGST3 and GSR) was found in A7 and G10. Their increase in A7 improved its AOS ability and therefore, oxidative stress response, resembling less aggressive tumor cells. Meanwhile, their decrease in G10 revealed a disruption in the AOS and therefore, enhanced its metastatic capacity. These gene signatures, not only bring new insights into the physiopathology of melanoma, but also could be relevant in clinical prognostic to classify between non aggressive and metastatic melanomas. PMID:27206673

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

    PubMed

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

    2011-12-01

    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 in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function and enhanced growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of integrin, RTK, and ERK1,2 function by CSPG4 modulates numerous aspects of tumor progression. CSPG4 expression has further been correlated to resistance of melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein-protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma.

  18. The Evolving Role of Radiation Therapy in the Management of Malignant Melanoma

    SciTech Connect

    Khan, Niloufer; Khan, Mohammad K.; Almasan, Alex; Singh, Arun D.; Macklis, Roger

    2011-07-01

    The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotactic radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.

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

    PubMed Central

    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.

    2012-01-01

    Summary 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 in modulating the function of these proteins. CSPG4 is essential to the growth of melanoma tumors through its modulation of integrin function and enhanced growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of integrin, RTK, and ERK 1,2 function by CSPG4 modulates numerous aspects of tumor progression. CSPG4 expression has further been correlated to resistance of melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and protein–protein interactions may provide us with novel combinatorial therapies for the treatment of advanced melanoma. PMID:22004131

  20. Construction of Ang2-siRNA chitosan magnetic nanoparticles and the effect on Ang2 gene expression in human malignant melanoma cells.

    PubMed

    Liu, Zhao-Liang; You, Cai-Lian; Wang, Biao; Lin, Jian-Hong; Hu, Xue-Feng; Shan, Xiu-Ying; Wang, Mei-Shui; Zheng, Hou-Bing; Zhang, Yan-Ding

    2016-06-01

    The aim of the present study was to construct angiopoietin-2 (Ang2)-small interfering (si)RNA chitosan magnetic nanoparticles and to observe the interference effects of the nanoparticles on the expression of the Ang2 gene in human malignant melanoma cells. Ang2-siRNA chitosan magnetic nanoparticles were constructed and transfected into human malignant melanoma cells in vitro. Red fluorescent protein expression was observed, and the transfection efficiency was analyzed. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the inhibition efficiency of Ang2 gene expression. Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed, and at a mass ratio of plasmid to magnetic chitosan nanoparticles of 1:100, the transfection efficiency into human malignant melanoma cells was the highest of the ratios assessed, reaching 61.17%. RT-qPCR analysis showed that the magnetic chitosan nanoparticles effectively inhibited Ang2 gene expression in cells, and the inhibition efficiency reached 59.56% (P<0.05). Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed. The in vitro studies showed that the nanoparticles inhibited Ang2 gene expression in human malignant melanoma tumor cells, which laid the foundation and provided experimental evidence for additional future in vivo studies of intervention targeting malignant melanoma tumor growth in nude mice.

  1. The long non-coding RNA NKILA inhibits the invasion-metastasis cascade of malignant melanoma via the regulation of NF-ĸB

    PubMed Central

    Bian, Donghui; Gao, Cong; Bao, Kai; Song, Guodong

    2017-01-01

    The long non-coding RNA (lncRNA) NKILA has been reported to participate in the development of human cancers. The purpose of this study was to explore the potential role of lncRNA-NKILA, which acts through NF-ĸB, in the process of melanoma development. Real-time PCR (qRT-PCR) showed that NKILA was expressed at low levels in human melanoma tissues. The area under the ROC curve of NKILA was 0.875, which indicated that NKILA may be a potential diagnostic biomarker of melanoma. Our results also indicated that NKILA inhibited the progression of cell proliferation, migration, and invasion, and promoted apoptosis of melanoma cells. Furthermore, qRT-PCR showed that NF-κB, which was negatively correlated with NKILA, was highly expressed in human melanoma tissues. Moreover, our results indicated that NKILA inhibited the carcinogenesis of melanoma cells through the inhibition of NF-ĸB in vitro. More importantly, we found that NKILA suppressed the growth of melanoma tumors via NF-ĸB in vivo. In conclusion, NKILA suppressed the development of malignant melanoma via the regulation of NF-ĸB and may be a potential therapeutic target in patients with melanoma. PMID:28123845

  2. Functional reconstruction after subtotal glossectomy in the surgical treatment of an uncommon and aggressive neoplasm in this location: Primary malignant melanoma in the base of the tongue

    PubMed Central

    Manzano-Solo-de-Zaldívar, Damián; Moreno-Sánchez, Manuel; Hernández-Vila, Cristina; Ramírez-Pérez, Francisco-Alejandro; González-Ballester, David; Ruíz-Laza, Luis; González-García, Raúl; Monje-Gil, Florencio

    2014-01-01

    Primary malignant melanoma of the oral cavity is a rare neoplasm, especially on the tongue. We report a case of mucosal melanoma at the base of the tongue, an extremely rare location (only about 30 cases have been reported in literature). The extension study doesn´t revealed distant metastatic lesions. The patient was treated by subtotal glossectomy and bilateral functional neck dissection. Tongue is one of the most difficult structures to reconstruct, because of their central role in phonation, swallowing and airway protection. The defect was reconstructed with anterolateral thigh free flap. Surgical treatment was supplemented with adjuvant immunotherapy. The post-operative period was uneventful. At present, 24 months after surgery, patient is asymptomatic, there isn´t evidence of recurrence of melanoma and he hasn´t any difficulty in swallowing or phonation. Key words:Malignant mucosal melanoma, anterolateral thigh free flap, phonation, swallowing. PMID:25593674

  3. ETM study of electroporation influence on cell morphology in human malignant melanoma and human primary gingival fibroblast cells

    PubMed Central

    Skolucka, Nina; Daczewska, Malgorzata; Saczko, Jolanta; Chwilkowska, Agnieszka; Choromanska, Anna; Kotulska, Malgorzata; Kaminska, Iwona; Kulbacka, Julita

    2011-01-01

    Objective To estimate electroporation (EP) influence on malignant and normal cells. Methods Two cell lines including human malignant melanoma (Me-45) and normal human gingival fibroblast (HGFs) were used. EP parameters were the following: 250, 1 000, 1 750, 2 500 V/cm; 50 µs by 5 impulses for every case. The viability of cells after EP was estimated by MTT assay. The ultrastructural analysis was observed by transmission electron microscope (Zeiss EM 900). Results In the current study we observed the intracellular effect following EP on Me-45 and HGF cells. At the conditions applied, we did not observe any significant damage of mitochondrial activity in both cell lines treated by EP. Conversely, we showed that EP in some conditions can stimulate cells to proliferation. Some changes induced by EP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters of EP (250 and 1 000 V/cm). After applying higher electric field intensities (2 500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications after EP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters of EP. Conclusions We can claim that EP conditions are cell line dependent. In terms of the intracellular morphology, human fibroblasts are more sensitive to electric field as compared with melanoma cells. Optimal conditions should be determined for each cell line. Summarizing our study, we can conclude that EP is not an invasive method for human normal and malignant cells. This technique can be safely applied in chemotherapy for delivering drugs into tumor cells. PMID:23569735

  4. Comparison of participants and non-participants in a randomized psychosocial intervention study among patients with malignant melanoma.

    PubMed

    Boesen, Ellen; Boesen, Sidsel; Christensen, Søren; Johansen, Christoffer

    2007-01-01

    The authors investigated barriers for entering a randomized psychosocial intervention study among patients with malignant melanoma. Data on age, sex, prognostic factors, social class, marital status, mood, coping, social relations, and social desirability from participants and non-participants were compared in a regression model. More patients in lower socioeconomic classes declined participation. Non-participation was associated with low levels of distress and adaptive coping and higher levels of empathy and congruence from spouses. The type of intervention offered in this study may have more appeal to patients belonging to higher socioeconomic classes.

  5. A mitogen-activated protein kinase kinase inhibitor induced compound skin toxicity with oedema in metastatic malignant melanoma.

    PubMed

    Thomas, C L; Mortimer, P S; Larkin, J M; Basu, T N; Gore, M E; Fearfield, L

    2016-04-01

    We report three cases of skin toxicity associated with oral mitogen-activated protein kinase kinase (MEK) inhibitor treatment for metastatic malignant melanoma (MM). All three patients developed oedema, and a single patient experienced eyelash trichomegaly. This is the first known report of eyelash trichomegaly secondary to MEK inhibitor use. We also discuss possible mechanisms for MEK inhibitor-associated oedema development. This series supports the role of the dermatologist in the screening and management of patients in the rapidly developing oncology setting, as new targeted agents can give rise to marked skin toxicity.

  6. Facial resurfacing with a monoblock full-thickness skin graft after multiple malignant melanomas excision in xeroderma pigmentosum.

    PubMed

    Ozmen, Selahattin; Uygur, Safak; Eryilmaz, Tolga; Ak, Betul

    2012-09-01

    Xeroderma pigmentosum is an autosomal recessive disease, characterized by vulnerability of the skin to solar radiation. Increase in sunlight-induced cancer is a direct consequence of an increase in mutated cells of the skin of patients with xeroderma pigmentosum. There is no specific technique for facial resurfacing in patients with xeroderma pigmentosum. In this article, a patient with xeroderma pigmentosum with multiple malignant melanomas on her face and radical excision of total facial skin followed by facial resurfacing with monoblock full-thickness skin graft from the abdomen is presented.

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

    PubMed

    Huang, Sharon K; Hoon, Dave S B

    2016-03-01

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

  8. Genomic rearrangements of the CDKN2A locus are infrequent in Italian malignant melanoma families without evidence of CDKN2A/CDK4 point mutations.

    PubMed

    Vignoli, Marina; Scaini, Maria Chiara; Ghiorzo, Paola; Sestini, Roberta; Bruno, William; Menin, Chiara; Gensini, Francesca; Piazzini, Mauro; Testori, Alessandro; Manoukian, Siranoush; Orlando, Claudio; D'Andrea, Emma; Bianchi-Scarrà, Giovanna; Genuardi, Maurizio

    2008-12-01

    Predisposition to familial cutaneous malignant melanoma has been associated with mutations in the CDKN2A and CDK4 genes. However, only a small subgroup of melanoma pedigrees harbour CDKN2A or CDK4 germline mutations. It is possible that other types of CDKN2A rearrangements, not detectable by routine PCR-based approaches, are involved in a fraction of melanoma cases negative for point sequence changes. In order to gain insights on the possible role of CDKN2A large deletions or duplications in melanoma susceptibility in the Italian population, we screened a series of 124 cutaneous malignant melanoma families referred to five national medical/cancer genetics centres. All probands were negative for point mutations in CDKN2A and CDK4. All samples were tested by MLPA (multiplex ligation-dependent probe amplification), and the results were confirmed by real-time quantitative PCR in a subset of 53 cases. No genomic rearrangements were detected in this series, one of the largest so far investigated. These data suggest that large deletions/duplications in the CDKN2A locus are infrequently involved in the development of familial melanoma in the Italian population. Based on these results, routine search for these rearrangements in CDKN2A- and CDK4-mutation negative melanoma families is not warranted, although it would be reasonable to pursue it in selected cases with very strong family history and/or showing linkage to 9p21.

  9. Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22

    PubMed Central

    Bu, Xuefeng; Xia, Yun; Wang, Jinlong; Djangmah, Henry Siaw; Liu, Xiaohui; You, Yongping; Xu, Bin

    2016-01-01

    Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNAs, is associated with the growth and metastasis of many human tumors, but its biological roles in malignant melanoma remain unclear. In this study, the aberrant up-regulation of MALAT1 was detected in melanoma. We determined that MALAT1 promotes melanoma cells proliferation, invasion and migration by sponging miR-22. MiR-22 was decreased and acted as a tumor suppressor in melanoma, and MMP14 and Snail were the functional targets of miR-22. Furthermore, MALAT1 could modulate MMP14 and Snail by operating as a competing endogenous RNA (ceRNA) for miR-22. The effects of MALAT1 in malignant melanoma is verified using a xenograft model. This finding elucidates a new mechanism for MALAT1 in melanoma development and provides a potential target for melanoma therapeutic intervention. PMID:27564100

  10. Malignancy without immortality? Cellular immortalization as a possible late event in melanoma progression.

    PubMed

    Soo, Julia K; Mackenzie Ross, Alastair D; Kallenberg, David M; Milagre, Carla; Heung Chong, W; Chow, Jade; Hill, Lucy; Hoare, Stacey; Collinson, Rebecca S; Hossain, Mehnaz; Keith, W Nicol; Marais, Richard; Bennett, Dorothy C

    2011-06-01

    Cell senescence is a permanent growth arrest following extended proliferation. Cultured cancer cells including metastatic melanoma cells often appear immortal (proliferate indefinitely), while uncultured benign nevi (moles) show senescence markers. Here, with new explantation methods, we investigated which classes of primary pigmented lesions are typically immortal. Nevi yielded a few proliferating cells, consistent with most nevus cells being senescent. No nevus culture (0/28) appeared immortal. Some thin and thick melanoma cultures proved immortal under these conditions, but surprisingly few (4/37). All arrested cultures displayed three senescence markers in some cells: β-galactosidase, nuclear p16, and heterochromatic foci/aggregates. However, melanoma cultures also showed features of telomeric crisis (arrest because of ultrashort telomeres). Moreover, crisis markers including anaphase bridges were frequent in uncultured vertical growth-phase (VGP) melanomas. Conversely, all immortal melanoma cultures expressed telomerase reverse transcriptase and telomerase, showing aneuploidy. The findings suggest that primary melanomas are typically precrisis, with immortalization/telomere maintenance as a late event.

  11. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography.

    PubMed

    Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R

    2016-01-01

    One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma

  12. Comparison of DNA ploidy status and DNA ploidy-related parameters in malignant melanoma tissue microarrays and full sections.

    PubMed

    Korabiowska, Monika; Cordon-Cardo, Carlos; Buschmann, Nadine; Stachura, Jerzy; Fischer, Gösta; Brinck, Ulrich

    2004-07-01

    A new high-throughput tissue-arraying technique, now frequently used in tumor pathology, requires standardization of methods of DNA analysis, previously applied in full histological sections. The main objectives of this study were to evaluate DNA ploidy status and DNA ploidy-related parameters using the CAS200 image analyzer in malignant melanoma tissue microarrays and to compare them with full histological sections. Comparison of DNA ploidy-related parameters, including percentage of diploid cells, percentage of aneuploid cells between 2c and 4c, percentage of tetraploid cells, percentage of aneuploid cells between 4c and 8c, percentage of octaploid cells, percentage of 16-ploid cells, and 5c exceeding rate, did not reveal any significant differences between malignant melanoma tissue microarrays and full sections. The DNA ploidy status according to Auer differed in 1 out of 59 cases investigated. Our study demonstrated that it is possible to evaluate DNA ploidy status and DNA ploidy-related parameters in tissue microarrays, which is of practical relevance to tumor pathology.

  13. Clustered somatic mutations are frequent in transcription factor binding motifs within proximal promoter regions in melanoma and other cutaneous malignancies

    PubMed Central

    Colebatch, Andrew J.; Di Stefano, Leon; Wong, Stephen Q.; Hannan, Ross D.; Waring, Paul M.; Dobrovic, Alexander

    2016-01-01

    Most cancer DNA sequencing studies have prioritized recurrent non-synonymous coding mutations in order to identify novel cancer-related mutations. Although attention is increasingly being paid to mutations in non-coding regions, standard approaches to identifying significant mutations may not be appropriate and there has been limited analysis of mutational clusters in functionally annotated non-coding regions. We sought to identify clustered somatic mutations (hotspot regions across samples) in functionally annotated regions in melanoma and other cutaneous malignancies (cutaneous squamous cell carcinoma, basal cell carcinoma and Merkel cell carcinoma). Sliding window analyses revealed numerous recurrent clustered hotspot mutations in proximal promoters, with some specific clusters present in up to 25% of cases. Mutations in melanoma were clustered within ETS and Sp1 transcription factor binding motifs, had a UV signature and were identified in other cutaneous malignancies. Clinicopathologic correlation and mutation analysis support a causal role for chronic UV irradiation generating somatic mutations in transcription factor binding motifs of proximal promoters. PMID:27611953

  14. Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases

    PubMed Central

    Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui

    2016-01-01

    Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not

  15. Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

    PubMed Central

    Salazar-Onfray, F; López, M; Lundqvist, A; Aguirre, A; Escobar, A; Serrano, A; Korenblit, C; Petersson, M; Chhajlani, V; Larsson, O; Kiessling, R

    2002-01-01

    The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT–PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a ‘therapeutic window’ to be exploited in cancer immunotherapy. British Journal of Cancer (2002) 87, 414–422. doi:10.1038/sj

  16. [Cutaneous malignant melanoma: a retrospective study of seven years (2006-2012)].

    PubMed

    Moreira, Jorge; Moreira, Elisabete; Azevedo, Filomena; Mota, Alberto

    2014-01-01

    Introdução: O melanoma maligno é a neoplasia cutânea mais agressiva, e a sua incidência tem vindo a aumentar nas últimas décadas. A possibilidade de cura depende de um diagnóstico atempado, sendo fundamental o conhecimento da sua epidemiologia para a implementação de programas de prevenção primária e deteção precoce do melanoma. Material e Métodos: Foi efetuada revisão dos processos clínicos dos doentes com melanoma maligno cutâneo primário, diagnosticados entre janeiro de 2006 e dezembro de 2012, no Centro Hospitalar de São João, Porto. Resultados: Analisaram-se os 148 casos de melanoma diagnosticados neste período, tendo-se observado um predomínio do sexo feminino (razão F:M - 1,6:1). A média etária na altura do diagnóstico foi de 61 anos. As localizações mais frequentemente envolvidas foram os membros inferiores e o tronco. No sexo masculino o dorso foi o local mais afetado, enquanto no sexo feminino as lesões ocorreram, preferencialmente, nas pernas. O melanoma de extensão superficial foi o subtipo predominante em quase todas as faixas etárias. Verificou-se um predomínio dos melanomas finos e o índice mitótico foi intermédio (1-6 mitoses/ mm2) na maioria dos doentes. A ulceração esteve presente em 22,3% dos casos e predominou nos melanomas espessos e no subtipo nodular. A maioria dos doentes encontrava-se no estádio IA. A progressão para doença metastática ocorreu em 20 doentes. Discussão: O perfil do doente com melanoma cutâneo, no Centro Hospitalar de São João, apresenta características relativamente semelhantes às descritas na literatura. Conclusão: O predomínio dos melanomas finos, considerados de melhor prognóstico, é provavelmente, o resultado de um diagnóstico cada vez mais precoce.

  17. Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

    SciTech Connect

    Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

    2011-07-22

    Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

  18. Endogenous μ-opioid peptides modulate immune response towards malignant melanoma.

    PubMed

    Boehncke, Sandra; Hardt, Katja; Schadendorf, Dirk; Henschler, Reinhard; Boehncke, Wolf-Henning; Duthey, Beatrice

    2011-01-01

    Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and μ-opioid receptor-deficient (MOR-/-) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR-/- mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild-type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR-/- leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that μ-opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.

  19. Slit3 inhibits activator protein 1-mediated migration of malignant melanoma cells.

    PubMed

    Denk, Alexandra E; Braig, Simone; Schubert, Thomas; Bosserhoff, Anja K

    2011-11-01

    The repellent factor family of Slit molecules has been described to have repulsive function in the developing nervous system on growing axons expressing the Robo receptors. Alterations of the Slit/Robo system have been observed in various pathological conditions and in cancer. However, until today no detailed studies on Slit function on melanoma migration are available. Therefore, we analysed the mRNA expression in melanoma cells and found induction of Robo3 expression compared to normal melanocytes. Functional assays performed with melanoma cells revealed that treatment with Slit3 led to strong inhibition of migration. Interestingly, we observed down-regulation of AP-1 activity and target gene expression after Slit3 treatment contributing to the negative regulation of migration. Taken together, our data showed that Slit3 reduces the migratory activity of melanoma cells, potentially by repulsion of the cells in analogy to the neuronal system. Further studies will be necessary to prove Slit activity in vivo, but due to its function, Slit3 activity may be helpful in the treatment of melanoma.

  20. Radiotherapy for choroidal melanoma. An 18-year experience with radon

    SciTech Connect

    Davidorf, F.H.; Pajka, J.T.; Makley, T.A. Jr.; Kartha, M.K.

    1987-03-01

    Twenty-three patients were treated with radon therapy for choroidal melanoma at the Ohio State University Hospitals, Columbus, between 1968 and 1976. We present an 18-year experience, including follow-up of at least eight years, in all those receiving therapy. Three patients (13%) died of metastatic disease. Four patients (17.4%) died of other causes. Sixteen patients (69.6%) were alive, with no signs of metastatic disease. Eight patients subsequently required enucleation due to inadequate tumor response. Of the 15 patients who demonstrated successful tumor destruction and retained their eyes, 13 (86.7%) developed substantial irradiation-induced retinopathy, including hard exudates, telangiectasias, neovascularization, microaneurysms, intraretinal and vitreous hemorrhages, secondary glaucoma, and irradiation-induced cataract. Our long-term results indicate a high incidence of both vascular complications and decreased visual acuity.

  1. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955-1977 by cohort, sex, age, and primary tumor site

    SciTech Connect

    Magnus, K.

    1981-11-15

    Incidence data on malignant melanoma of the skin in Norway from 1955-1977, comprising a total of 5108 new cases, were analyzed according to cohort, sex, age, and primary tumor site. A continuous increase in incidence of approximately 7% per year was observed for both sexes during the study period. For trunk and lower limb melanomas, the increase and cohort variations in incidence were much greater than for face and neck melanoma. A difference between these site groups was also observed in the shape of the cohort curves of age-specific rates. This indicated that the trend in carcinogenic exposure through life was different for the face--neck and the trunk--lower limb. For the generations born 1930-1949, the incidence of malignant melanoma per area unit of skin was greater for the trunk and lower limb than for the face--neck. It is suggested that not only the cumulated dose, but also the intensity of solar radiation may be significant in the cause of malignant melanoma.

  2. Conceptual Knowledge Discovery in Databases for Drug Combinations Predictions in Malignant Melanoma

    PubMed Central

    Regan, Kelly; Raje, Satyajeet; Saravanamuthu, Cartik; Payne, Philip R.O.

    2016-01-01

    The worldwide incidence of melanoma is rising faster than any other cancer, and prognosis for patients with metastatic disease is poor. Current targeted therapies are limited in their durability and/or effect size in certain patient populations due to acquired mechanisms of resistance. Thus, the development of synergistic combinatorial treatment regimens holds great promise to improve patient outcomes. We have previously shown that a model for in-silico knowledge discovery, Translational Ontology-anchored Knowledge Discovery Engine (TOKEn), is able to generate valid relationships between bimolecular and clinical phenotypes. In this study, we have aggregated observational and canonical knowledge consisting of melanoma-related biomolecular entities and targeted therapeutics in a computationally tractable model. We demonstrate here that the explicit linkage of therapeutic modalities with biomolecular underpinnings of melanoma utilizing the TOKEn pipeline yield a set of informed relationships that have the potential to generate combination therapy strategies. PMID:26262134

  3. Towards personalized therapy for patients with malignant melanoma: molecular insights into the biology of BRAF mutations.

    PubMed

    Bradish, Joshua R; Montironi, Rodolfo; Lopez-Beltran, Antonio; Post, Kristin M; MacLennan, Gregory T; Cheng, Liang

    2013-02-01

    BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. There is a large and continually growing body of evidence regarding the importance of this mutation in targeted therapy for melanoma. In this review, we outline these findings including: molecular pathways used by BRAF, the importance in nonmalignant neoplasms, histologic associations, the relationship of BRAF to KIT and NRAS mutations, and their impact on survival, as well as resistance mechanisms to BRAF inhibitors employed by melanoma. Understanding these topics and how they relate to one another may facilitate the development of new treatments and eventually improve the prognosis for those patients afflicted with this disease.

  4. Melanoma arising in a nevus of Ito: novel genetic mutations and a review of the literature on cutaneous malignant transformation of dermal melanocytosis.

    PubMed

    Tse, Julie Y; Walls, Brooke E; Pomerantz, Hyemin; Yoon, Charles H; Buchbinder, Elizabeth I; Werchniak, Andrew E; Dong, Fei; Lian, Christine G; Granter, Scott R

    2016-01-01

    Dermal melanocytosis refers to a spectrum of benign melanocytic proliferations that includes Mongolian spot, nevus of Ota and nevus of Ito. These lesions most commonly occur in persons of Asian or African descent and are often present at birth or develop during childhood. Very rarely, dermal melanocytoses undergo malignant transformation. There have been only 13 reports in the literature of primary cutaneous melanoma arising in dermal melanocytoses. We report a case of a Chinese woman with melanoma arising in a congenital nevus of Ito. We performed targeted next-generation sequencing of the tumor which revealed mutations of GNAQ and BAP1, suggesting that alterations in these two genes led to malignant transformation of the nevus of Ito. We also provide a summary of reports in the literature regarding primary cutaneous melanoma arising in the context of dermal melanocytosis.

  5. The Pathophysiological Impact of HLA Class Ia and HLA-G Expression and Regulatory T Cells in Malignant Melanoma: A Review

    PubMed Central

    Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

    2016-01-01

    Malignant melanoma, a very common type of cancer, is a rapidly growing cancer of the skin with an increase in incidence among the Caucasian population. The disease is seen through all age groups and is very common in the younger age groups. Several studies have examined the risk factors and pathophysiological mechanisms of malignant melanoma, which have enlightened our understanding of the development of the disease, but we have still to fully understand the complex immunological interactions. The examination of the interaction between the human leucocyte antigen (HLA) system and prognostic outcome has shown interesting results, and a correlation between the down- or upregulation of these antigens and prognosis has been seen through many different types of cancer. In malignant melanoma, HLA class Ia has been seen to influence the effects of pharmaceutical drug treatment as well as the overall prognosis, and the HLA class Ib and regulatory T cells have been correlated with tumor progression. Although there is still no standardized immunological treatment worldwide, the interaction between the human leucocyte antigen (HLA) system and tumor progression seems to be a promising focus in the way of optimizing the treatment of malignant melanoma. PMID:27999823

  6. Efficacy and side effects of dacarbazine in comparison with temozolomide in the treatment of malignant melanoma: a meta-analysis consisting of 1314 patients.

    PubMed

    Teimouri, Fatemeh; Nikfar, Shekoufeh; Abdollahi, Mohammad

    2013-10-01

    The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the palliative treatment of malignant melanoma: intravenous administration of single-agent dacarbazine or oral administration of temozolomide. The aim of this study was to compare the effectiveness and side effects of dacarbazine with those of temozolomide through a meta-analysis. A thorough literature bibliography search was conducted up to 2012 to gather and review all randomized clinical trials comparing the use of dacarbazine with that of temozolomide in the treatment of malignant melanoma. Three head-to-head randomized clinical trials comprising 1314 patients met the criteria and were included. Comparison of temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83 [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control rate. The RR for nonhematologic side effects and hematologic side effects, such as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with dacarbazine in patients with malignant melanoma was nonsignificant in all cases, but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79 (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to administer oral medication, according to the results, there is no significant difference in the efficacy and side effects of these two drugs. Owing to the higher cost of treatment with temozolomide and the increased prevalence of lymphopenia on using temozolomide, use of dacarbazine as the first choice treatment for malignant melanoma is suggested.

  7. Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance

    PubMed Central

    Padrón, Andreina; Garcia-Carbonell, Ricard; Rius, Cristina; González-Perez, Abel; Arumí-Uria, Montserrat; Iglesias, Mar; Nonell, Lara; Bellosillo, Beatriz; Segura, Sonia; Pujol, Ramon Maria; Lopez-Bigas, Nuria; Bertran, Joan

    2015-01-01

    Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene. PMID:25823659

  8. How gender, age, and geography influence the utilization of radiation therapy in the management of malignant melanoma

    SciTech Connect

    French, John . E-mail: jfrench@bccancer.bc.ca; McGahan, Colleen; Duncan, Graeme; Lengoc, Sonca; Soo, Jenny; Cannon, Jerry

    2006-11-15

    Purpose: Comparing radiation therapy utilization rates (RTUR) to those predicted by best evidence is a useful measure of the equity and accessibility of service delivery. In this study the RTUR for melanoma was established for British Columbia, Canada, and compared with the rate suggested by the evidence. Demographic variables, specifically age, gender, and geography that influenced the RTUR were examined with a view to identifying methods of improving underutilization. Methods and Materials: The RTUR in the management of malignant melanoma was taken from British Columbia Cancer registry data for 1986 to 1998. Variations in utilization based on age, gender, health authority, stage of disease, and referral patterns were analyzed. Results: An RTUR of 11% was identified. This was consistent over time. Referral rates decreased between 1986 and 1998. RT is used mostly for later stage disease. Males were more likely to receive RT than females, related to later stage of disease in men. Referral rates decreased, but RTUR for referred cases increased, in health authorities that did not have a cancer center. Conclusions: Use of RT is influenced by age and by stage of disease. Overall RTUR in British Columbia is lower than suggested by best evidence. Referral patterns are influenced by geography. RTUR was higher in males, consistent with a different pattern of disease in males compared with females.

  9. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells.

    PubMed

    Park, Eun-Ji; Lee, Yoon-Mi; Oh, Taek-In; Kim, Byeong Mo; Lim, Beong-Ou; Lim, Ji-Hong

    2017-03-01

    Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR). It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-κB (NF-κB), on HIF1A. Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway.

  10. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells

    PubMed Central

    Park, Eun-Ji; Lee, Yoon-Mi; Oh, Taek-In; Kim, Byeong Mo; Lim, Beong-Ou; Lim, Ji-Hong

    2017-01-01

    Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 (FN1), lysyl oxidase-like 2 (LOXL2), and urokinase plasminogen activator receptor (uPAR). It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-κB (NF-κB), on HIF1A. Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway. PMID:28257048

  11. A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion.

    PubMed

    Suzuki, Shuji; Watanabe, Shoichi; Kato, Hiroshi; Hattori, Hideo; Morita, Akimichi

    2012-12-01

    We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography-computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV) plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam) chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.

  12. Complications after proton beam therapy for uveal malignant melanoma. A clinical and histopathologic study of five cases

    SciTech Connect

    Kincaid, M.C.; Folberg, R.; Torczynski, E.; Zakov, Z.N.; Shore, J.W.; Liu, S.J.; Planchard, T.A.; Weingeist, T.A.

    1988-07-01

    Proton beam therapy for uveal malignant melanoma has been advocated as effective therapy because of documented reduction in tumor size and few clinical complications. However, some eyes have been removed because of adverse effects. The authors report the clinical courses and pathologic findings of five eyes enucleated after proton beam irradiation. Neovascular glaucoma had developed in three eyes, two eyes had vitreous hemorrhage, and two had extraocular extension. The tumors in the radiation treatment field showed continued postirradiation growth clinically in four of the five eyes, and mitotic activity histologically in all five cases. Two and one half years after irradiation, and nearly 2 years after subsequent enucleation, one of those two patients had biopsy-proven liver metastases, and later died. Despite the considerable success rate of proton beam irradiation, the potential for clinical complications and subsequent tumor growth remains.

  13. [Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats].

    PubMed

    Kinzel, Sylvia; Hein, Sven; Stopinski, Thaddeus; Koch, Johannes; Buecker, Arno; Treusacher, Hans-Peter; Schmachtenberg, Axel; Jansen, Thomas; Eble, Michael; Küpper, Wernen

    2003-01-01

    This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.

  14. Meta-Analysis of the Safety and Efficacy of Interferon Combined With Dacarbazine Versus Dacarbazine Alone in Cutaneous Malignant Melanoma

    PubMed Central

    Xin, Yong; Huang, Qian; Zhang, Pei; Yang, Ming; Hou, Xiao-Yang; Tang, Jian-Qin; Zhang, Long Zhen; Jiang, Guan

    2016-01-01

    Abstract The aim of this study was to compare the efficacy and safety of interferon (IFN) combined with dacarbazine (DTIC) (experimental group) versus DTIC alone (control group) in cutaneous malignant melanoma. After searching all available databases, eligible articles were identified and subjected to quality assessment. Meta-analysis was performed using RevMan 5.3; combined relative risk (RR) and 95% confidence intervals (95% CIs) were calculated for survival rates, response rates, and adverse events. Eight randomized controlled trials published between 1990 and 2014 involving 795 patients were included in the meta-analysis. Compared with DTIC alone, IFN combined with DTIC significantly increased the overall response rate (RR = 1.59, 95% CI 1.21–2.08, P = 0.0008),the complete response rate (RR = 3.30, 95% CI 1.89–5.76, P < 0.0001), 2-year survival (RR = 1.59, 95% CI 0.99–2.54, P = 0.050) grade ≥3 hematologic toxicity (RR = 2.30, 95% CI 1.32–4.02, P = 0.003), neurotoxicity (RR = 18.15, 95% CI 5.34–61.74, P < 0.00001), and flu-like symptoms (RR = 6.31, 95% CI 1.95–20.39, P = 0.002). The partial response rate, grade ≥3 nausea and vomiting, treatment-related, and 1- and 3-year survival were not significantly different between IFN combined with DTIC and DTIC alone. IFN combined with DTIC may moderately improve the complete response rate, but increases the incidence of adverse events and has no significant effect on 1- and 3-year survival in cutaneous malignant melanoma. PMID:27100429

  15. Meta-Analysis of the Safety and Efficacy of Interferon Combined With Dacarbazine Versus Dacarbazine Alone in Cutaneous Malignant Melanoma.

    PubMed

    Xin, Yong; Huang, Qian; Zhang, Pei; Yang, Ming; Hou, Xiao-Yang; Tang, Jian-Qin; Zhang, Long Zhen; Jiang, Guan

    2016-04-01

    The aim of this study was to compare the efficacy and safety of interferon (IFN) combined with dacarbazine (DTIC) (experimental group) versus DTIC alone (control group) in cutaneous malignant melanoma. After searching all available databases, eligible articles were identified and subjected to quality assessment. Meta-analysis was performed using RevMan 5.3; combined relative risk (RR) and 95% confidence intervals (95% CIs) were calculated for survival rates, response rates, and adverse events. Eight randomized controlled trials published between 1990 and 2014 involving 795 patients were included in the meta-analysis. Compared with DTIC alone, IFN combined with DTIC significantly increased the overall response rate (RR = 1.59, 95% CI 1.21-2.08, P = 0.0008),the complete response rate (RR = 3.30, 95% CI 1.89-5.76, P < 0.0001), 2-year survival (RR = 1.59, 95% CI 0.99-2.54, P = 0.050) grade ≥3 hematologic toxicity (RR = 2.30, 95% CI 1.32-4.02, P = 0.003), neurotoxicity (RR = 18.15, 95% CI 5.34-61.74, P < 0.00001), and flu-like symptoms (RR = 6.31, 95% CI 1.95-20.39, P = 0.002). The partial response rate, grade ≥3 nausea and vomiting, treatment-related, and 1- and 3-year survival were not significantly different between IFN combined with DTIC and DTIC alone. IFN combined with DTIC may moderately improve the complete response rate, but increases the incidence of adverse events and has no significant effect on 1- and 3-year survival in cutaneous malignant melanoma.

  16. Malignant Melanoma of the Syrinx and Liver in an African Grey Parrot ( Psittacus erithacus erithacus).

    PubMed

    Shrader, Trenton C; Carpenter, James W; Cino-Ozuna, Ada Giselle; Andrews, Gordon A

    2016-06-01

    A 20-year-old, female African grey parrot ( Psittacus erithacus erithacus) was examined because of ataxia and weakness. Radiographs were unremarkable, and results of a complete blood cell count revealed leukocytosis and heterophilia. Because of poor response to therapy with meloxicam, doxycycline, and enrofloxacin; deteriorating condition; and poor prognosis, the parrot was euthanatized. Postmortem examination revealed 2 dark red nodules in the liver. No grossly visible mass was observed in the syrinx. Histologic examination of the liver and syrinx revealed similar foci of round, oval, and polygonal cells exhibiting severe pleomorphism, with poorly demarcated cytoplasmic borders and moderate amounts of eosinophilic cytoplasm containing brown to black granules (melanin). The mitotic index was 15. The presence of melanin pigment is consistent with a diagnosis of melanoma at both sites. The multifocal distribution and intravascular invasion indicate metastasis; however, the site of origin was unknown. To our knowledge, this is the first recorded case of melanoma in an avian syrinx.

  17. Melanoma to the heart

    PubMed Central

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

    2016-01-01

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

  18. Melanoma to the heart.

    PubMed

    Durham, Charis G; Hall, James A; Fidone, Erica J; Mack, Ryan; Metting, Austin L

    2016-10-01

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

  19. Wnt Interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    PubMed Central

    Rappa, Germana; Mercapide, Javier; Anzanello, Fabio; Le, Thuc T.; G, Mary; Johlfs, Ronald R. Fiscus; Wilsch-Bräuninger, Michaela; Corbeil, Denis; Lorico, Aurelio

    2013-01-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤ 40 nm; intermediates ~40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. PMID:23318676

  20. Molecular profiling of ADAM12 and ADAM17 genes in human malignant melanoma.

    PubMed

    Cireap, Natalia; Narita, Diana

    2013-10-01

    ADAM12 and ADAM17 proteins belong to a family of transmembrane disintegrin-containing metalloproteinases (ADAMs) involved in the proteins ectodomain shedding and cell-cell and cell-matrix interactions. However, the specific biological functions of ADAMs are still unclear and, until now, these proteins were not investigated yet in melanoma. The aim of this study was to analyze the splicing variants of ADAM12 (L and S) and ADAM17 gene expression in melanoma at transcriptional and translational level in comparison with control (non-tumor) tissues. Taking in account that ADAM17 sheddase is involved in the modulation of TNF-α (tumor necrosis factor alpha), we analyzed also this cytokine in the plasma of the same patients before any treatment, and we compared the results with healthy controls. Quantitative-RT-PCR and immunohistochemistry were used to analyze ADAM12 and ADAM17 genes expression and the analysis of TNF-α expression was carried out in the plasma using ELISA. We demonstrated that ADAM12L splicing variant together with ADAM17 gene are strongly overexpressed in melanomas, whereas ADAM12S, although up-regulated when compared with the non-tumor controls, the difference was not statistically significant. When we compared the levels of expression for the ADAMs genes according to the tumor stage, we observed that all three investigated genes were significantly overexpressed in advanced stage in comparison with early stage melanomas. In the plasma of the same patients, the expression of TNF-α was up-regulated and significantly correlated with the expression of ADAM17 and respectively, with the advanced tumor stage.

  1. PD-1 Antibody Monotherapy for Malignant Melanoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Lin, Zhijuan; Chen, Xing; Li, Zhifeng; Luo, Yiming; Fang, Zhihong; Xu, Bing; Han, Mingzhe

    2016-01-01

    Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from escaping immune-mediated destruction. We conducted this systematic review and meta-analysis to gain insight into the efficacy of PD-1 antibodies for the treatment of melanoma. Five trials involving 2,828 adult patients were included in this meta-analysis. In patients with previously untreated or refractory melanoma, treatment with PD-1 antibodies significantly improved the six-month progression-free survival (PFS) (HR 0.55, 95% CI 0.50–0.60, P<0.00001) and the overall response rate (OR 3.89, 95% CI 3.12–4.83, P<0.00001). This meta-analysis indicated that anti-PD-1 treatment might provide a significant survival benefit in patients with melanoma. In addition, we found that patients treated with nivolumab reported significantly fewer treatment-related adverse events (OR 0.74, 95% CI 0.57–0.97, P = 0.03) than those treated with other agents, but there was a dose-dependent increase in the frequency of adverse events in patients treated with pembrolizumab. PMID:27483468

  2. Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma

    PubMed Central

    Scheffrahn, Inka; Bartling, Sönke; Weis, Joachim; von Felbert, Verena; Middleton, Mark; Kato, Masahi; Ergün, Süleyman; Augustin, Hellmut G.

    2010-01-01

    Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor β, and the late-stage maturity marker α smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this. PMID:20194633

  3. Biopsychosocial studies on cutaneous malignant melanoma: psychosocial factors associated with prognostic indicators, progression, psychophysiology and tumor-host response.

    PubMed

    Temoshok, L

    1985-01-01

    A series of seven studies investigating biopsychosocial aspects of cutaneous malignant melanoma were conducted by a multidisciplinary group of researchers at the University of California, San Francisco. Two studies investigated the relationship of variables derived from a videotaped psychosocial interview and from self-report measures, and two histopathologic indicators: tumor thickness and level of invasion. Associations of psychosocial variables to prognostic indicators were stronger within the younger vs the older subject group. In a multiple regression analysis, patient delay in seeking medical attention emerged as the most significant variable predicting tumor thickness. A study of factors related to patient delay found longer delays in patients who had lesions on the back, less previous knowledge of melanoma, less understanding of its treatment and less minimization of its seriousness. Another study compared the repressive coping reactions--defined as the discrepancy between reported anxiety and that reflected in electrodermal activity--in melanoma patients, cardiovascular disease patients and disease-free controls. The melanoma group was significantly more 'repressed' on the combined self-report/physiological measure, as well as on other self-report measures of repressiveness. In order to investigate the relationship of psychosocial factors to more disease-relevant physiological variables, the next study focused on two clinical variables significantly predictive of disease outcome:mitotic rate of the tumor and lymphocytes at tumor site. Emotional expression of sadness and anger, rated from the videotaped interviews, was positively correlated with tumor-specific host-response factors and negatively correlated with mitotic rate. In another study, subjects who had died or had disease progression were matched on the basis of tumor and demographic characteristics with subjects who had no evidence of disease by follow-up. The unfavorable outcome group had higher

  4. Optimization of radioimmunotherapy using human malignant melanoma multicell spheroids as a model

    SciTech Connect

    Kwok, C.S.; Crivici, A.; MacGregor, W.D.; Unger, M.W. )

    1989-06-15

    In vitro multicell spheroids from a human melanoma cell line and the human colon cancer cell line HT29, used as control, have been established as a model of poorly vascularized micrometastases in vivo. The antimelanoma monoclonal antibody 96.5 was radiolabeled with 131I at specific radioactivities from 1.85 to 3.96 GBq/mg. Cytotoxicity of 131I-96.5 to the spheroids, at an initial size of 300 microns in diameter, was investigated as a function of concentration of 131I-96.5 in the incubation medium, specific radioactivity, and treatment time. Spheroid growth delay and clonogenic survival of cells disaggregated from the spheroids at various times after treatment were used as end points. Therapeutic effects increased with the concentration of 131I-96.5 within the range 0.2 to 2 mg/liter (0.34 to 3.4 GBq/liter) at a fixed specific radioactivity. The effects increased with specific radioactivity at a fixed concentration of 131I-96.5. Difference in therapeutic effect was also observed between treatment times of 8 and 24 h. Radiation doses to the melanoma spheroids varied from 10 to 16 Gy. Unlabeled 96.5 at 2 mg/liter or 131I-iodide at 1.7 GBq/liter did not affect the growth of the melanoma spheroids. The HT29 spheroids, however, only suffered slight cytotoxicity at 1 or 2 mg/liter of 131I-96.5 and for a treatment time of 24 h despite comparable radiosensitivity of HT29 cells and melanoma cells to high-dose-rate radiation. Similar cytotoxicity was observed in the HT29 group treated with 131I-iodide at 1.7 GBq/liter. Present findings therefore demonstrate preferential and adequate killing of the melanoma spheroids by 131I-96.5 at 0.5 mg/liter and 3.96 GBq/mg in 8 h.

  5. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    SciTech Connect

    Rappa, Germana; Mercapide, Javier; Anzanello, Fabio; Le, Thuc T.; Johlfs, Mary G.; Fiscus, Ronald R.; Wilsch-Bräuninger, Michaela; Corbeil, Denis; Lorico, Aurelio

    2013-04-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  6. A Seven-Marker Signature and Clinical Outcome in Malignant Melanoma: A Large-Scale Tissue-Microarray Study with Two Independent Patient Cohorts

    PubMed Central

    Bosserhoff, Anja K.; Hofstädter, Ferdinand; Pauer, Armin; Roth, Volker; Buhmann, Joachim M.; Moll, Ingrid; Anagnostou, Nikos; Brandner, Johanna M.; Ikenberg, Kristian; Moch, Holger; Landthaler, Michael; Vogt, Thomas; Wild, Peter J.

    2012-01-01

    Background Current staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment. Methods and Findings Using tissue microarrays, we retrospectively analyzed samples from 364 patients with primary MM. We investigated a panel of 70 immunohistochemical (IHC) antibodies for cell cycle, apoptosis, DNA mismatch repair, differentiation, proliferation, cell adhesion, signaling and metabolism. A marker selection procedure based on univariate Cox regression and multiple testing correction was employed to correlate the IHC expression data with the clinical follow-up (overall and recurrence-free survival). The model was thoroughly evaluated with two different cross validation experiments, a permutation test and a multivariate Cox regression analysis. In addition, the predictive power of the identified marker signature was validated on a second independent external test cohort (n = 225). A signature of seven biomarkers (Bax, Bcl-X, PTEN, COX-2, loss of β-Catenin, loss of MTAP, and presence of CD20 positive B-lymphocytes) was found to be an independent negative predictor for overall and recurrence-free survival in patients with MM. The seven-marker signature could also predict a high risk of disease recurrence in patients with localized primary MM stage pT1-2 (tumor thickness ≤2.00 mm). In particular, three of these markers (MTAP, COX-2, Bcl-X) were shown to offer direct therapeutic implications. Conclusions The seven-marker signature might serve as a prognostic tool enabling physicians to selectively triage, at the time of diagnosis, the subset of high recurrence risk stage I–II patients for adjuvant therapy. Selective treatment of those patients that are more likely to develop distant metastatic disease could

  7. Application of new in situ hybridization probes for Ku70 and Ku80 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemical analysis.

    PubMed

    Korabiowska, Monika; Bauer, Hanne; Quentin, Tomas; Stachura, Jerzy; Cordon-Cardo, Carlos; Brinck, Ulrich

    2004-02-01

    Ku70 and Ku80 proteins are responsible for the repair of DNA double-strand breaks and function as a regulatory subunit of the DNA-dependent protein kinase. In this study we analyzed expression of both genes in malignant melanoma tissue arrays applying in situ hybridization probes produced by our research group and using immunohistochemical analysis. Expression of both genes was down-regulated as melanoma progressed. In situ hybridization demonstrated more Ku70- and Ku80-positive cells than immunohistochemical methods, but the correlation between the two methods was highly significant (P <0.01). We conclude that the in situ hybridization assay for the detection of Ku70 and Ku80 expression used in this study is also suitable for tissue microarray analysis of paraffin-embedded melanoma samples. The laboratory procedure is much more complicated than the immunohistochemical method, however.

  8. The anti-proliferative effects of a palm oil-derived product and its mode of actions in human malignant melanoma MeWo cells.

    PubMed

    Komarasamy, Thamil Vaani; Sekaran, Shamala Devi

    2012-01-01

    Melanoma incidence and mortality have risen dramatically in recent years. No effective treatment for metastatic melanoma exists; hence currently, an intense effort for new drug evaluation is being carried out. In this study, we investigated the effects of a palm oil-derived nanopolymer called Bio-12 against human malignant melanoma. The nanopolymers of Bio-12 are lipid esters derived from a range of fatty acids of palm oil. Our study aims to identify the anti-proliferative properties of Bio-12 against human malignant melanoma cell line (MeWo) and to elucidate the mode of actions whereby Bio-12 brings about cell death. Bio-12 significantly inhibited the growth of MeWo cells in a concentration- and time- dependent manner with a median inhibitory concentration (IC₅₀) value of 1/25 dilution after 72 h but was ineffective on human normal skin fibroblasts (CCD-1059sk). We further investigated the mode of actions of Bio-12 on MeWo cells. Cell cycle flow cytometry demonstrated that MeWo cells treated with increasing concentrations of Bio-12 resulted in S-phase arrest, accompanied by the detection of sub-G1 content, indicative of apoptotic cell death. Induction of apoptosis was further confirmed via caspase (substrate) cleavage assay which showed induction of early apoptosis in MeWo cells. In addition, DNA strand breaks which are terminal event in apoptosis were evident through increase of TUNEL positive cells and formation of a characteristic DNA ladder on agarose gel electrophoresis. Moreover, treatment of MeWo cells with Bio-12 induced significant increase in lactate dehydrogenase (LDH) activity. These results show that Bio-12 possesses the ability to suppress proliferation of human malignant melanoma MeWo cells and this suppression is at least partly attributed to the initiation of the S-phase arrest, apoptosis and necrosis, suggesting that it is indeed worth for further investigations.

  9. The Impact of Escitalopram on IL-2-Induced Neuroendocrine, Immune, and Behavioral Changes in Patients with Malignant Melanoma: Preliminary Findings

    PubMed Central

    Musselman, Dominique; Royster, Erica B; Wang, Ming; Long, Qi; Trimble, Lisa M; Mann, Tara K; Graciaa, Daniel S; McNutt, Marcia D; Auyeung, N S Freda; Oliver, Lindsay; Lawson, David H; Miller, Andrew H

    2013-01-01

    Interleukin (IL)-2, a T-cell cytokine used to treat malignant melanoma, can induce profound depression. To determine whether pretreatment with the antidepressant escitalopram could reduce IL-2-induced neuroendocrine, immune, and neurobehavioral changes, 20 patients with Stage IV melanoma were randomized to either placebo or the serotonin reuptake inhibitor, escitalopram (ESC) 10–20 mg/day, 2 weeks before, and during IL-2 treatment (720 000 units/kg Q8 h × 5 days (1 cycle) every 3 weeks × 4 cycles). Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n=9), placebo (n=11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6, and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p=0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1–3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of ∼3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment can prevent IL-2-induced neurobehavioral changes. PMID:23575741

  10. The impact of escitalopram on IL-2-induced neuroendocrine, immune, and behavioral changes in patients with malignant melanoma: preliminary findings.

    PubMed

    Musselman, Dominique; Royster, Erica B; Wang, Ming; Long, Qi; Trimble, Lisa M; Mann, Tara K; Graciaa, Daniel S; McNutt, Marcia D; Auyeung, N S Freda; Oliver, Lindsay; Lawson, David H; Miller, Andrew H

    2013-09-01

    Interleukin (IL)-2, a T-cell cytokine used to treat malignant melanoma, can induce profound depression. To determine whether pretreatment with the antidepressant escitalopram could reduce IL-2-induced neuroendocrine, immune, and neurobehavioral changes, 20 patients with Stage IV melanoma were randomized to either placebo or the serotonin reuptake inhibitor, escitalopram (ESC) 10-20 mg/day, 2 weeks before, and during IL-2 treatment (720 000 units/kg Q8 h × 5 days (1 cycle) every 3 weeks × 4 cycles). Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n=9), placebo (n=11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6, and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p=0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1-3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of ∼3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment can prevent IL-2-induced neurobehavioral changes.

  11. Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

    PubMed Central

    DONG, MENG-HUA; ZHANG, QIAN; WANG, YUAN-YUAN; ZHOU, BAI-SUI; SUN, YU-FEI; FU, QIANG

    2016-01-01

    Euphorbia fischeriana Steud, a traditional Chinese medicine, has been shown to inhibit the growth of various cancers by the induction of apoptosis and cell cycle arrest. The purpose of the present study was to investigate the association between the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and the inhibitory effect of Euphorbia fischeriana Steud on the growth and metastasis of melanoma B16 cells in vitro, and the underlying mechanisms. MTT assay results indicated that Euphorbia fischeriana Steud inhibited the growth of B16 cells in a time- and dose-dependent manner. Flow cytometric analysis revealed that Euphorbia fischeriana Steud markedly induced apoptosis of the B16 cells, with arrest at the G0/G1 phase of the cell cycle. In addition, in a Transwell assay Euphorbia fischeriana Steud significantly suppressed the migration of B16 cells. Western blot analysis revealed that the expression levels of phosphatase and tensin homolog (PTEN) were upregulated, and the phosphorylation of Akt was downregulated, which resulted in inhibition of the PI3K/Akt signaling pathway and the eventual suppression of its downstream targets, such as matrix metalloproteinase-2 mRNA, in B16 cells. The results demonstrated that Euphorbia fischeriana Steud inhibited the growth and migration of B16 cells, possibly via modulation of the PI3K/Akt signaling pathway and upregulation of PTEN expression levels, in addition to downregulation of p-Akt expression. The aforementioned findings suggest that Euphorbia fischeriana Steud may have broad therapeutic applications in the treatment of malignant melanoma. PMID:27073468

  12. Trends in malignant skin melanoma and other skin cancers in Spain, 1975-1983, and their relation to solar radiation intensity.

    PubMed

    Morales Suárez-Varela, M; Llopis-González, A; Lacasaña-Navarro, M; Ferrandiz-Ferragud, J

    1990-01-01

    Epidemiological studies have shown solar exposure to play an important role in the appearance of skin cancer. We investigated the association between mortality standardized by the indirect method for malignant skin melanoma and other skin cancers and the mean intensity of solar radiation during July and August for the different provinces in Spain. A statistically significant relation was observed (p less than .05) for these two months but not upon considering mean annual solar radiation. We thus suggest that intermittent, intense exposure to sunlight constitutes an important risk factor for skin cancer. We observed an 8.5% and 15.72% increase in mortality due to malignant skin melanoma and other skin cancers, respectively, during the period 1975-1983. Mortality was slightly higher among males than females.

  13. Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide

    SciTech Connect

    Howell, J.N.; Greene, M.H.; Corner, R.C.; Maher, V.M.; McCormick, J.J.

    1984-02-01

    Because of a possible etiologic link between mutations and carcinogenesis, the authors compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistant to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killing by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer. 46 references, 3 figures.

  14. F-18-fluoro-2-deoxyglucose positron emission tomography (PET) and PET/computed tomography imaging in primary staging of patients with malignant melanoma: a systematic review

    PubMed Central

    2012-01-01

    Purpose The aim of this systematic review was to systematically assess the potential patient-relevant benefit (primary aim) and diagnostic and prognostic accuracy (secondary aim) of positron emission tomography (PET) and PET/computed tomography (CT) in primary staging of malignant melanoma. This systematic review updates the previous evidence for PET(/CT) in malignant melanoma. Materials and methods For the first aim, randomized controlled trials (RCTs) investigating patient-relevant outcomes and comparing PET and PET(/CT) with each other or with conventional imaging were considered. For the secondary aim, a review of reviews was conducted, which was amended by an update search for primary studies. MEDLINE, EMBASE and four databases of the Cochrane Library were searched. The risk of bias was assessed using a modified QUADAS tool. Results No RCTs investigating the patient-relevant benefit of PET(/CT) and no prognostic accuracy studies were found. Seventeen diagnostic accuracy studies of varying quality were identified. For patients with American Joint Committee on Cancer (AJCC) stages I and II, sensitivity mostly ranged from 0 to 67%. Specificity ranged from 77 to 100%. For AJCC stages III and IV, sensitivity ranged from 68 to 87% and specificity from 92 to 98%. Conclusion There is currently no evidence of a patient-relevant benefit of PET(/CT) in the primary staging of malignant melanoma. RCTs investigating patient-relevant outcomes are therefore required. The diagnostic accuracy of PET(/CT) appears to increase with higher AJCC stages. PMID:23237499

  15. Late-onset bulky naevocytoma of the perineum masquerading as a malignant melanoma.

    PubMed

    Huh, J W; Yoo, J; Kim, M S; Choi, K H; Jue, M S; Park, H J

    2017-03-01

    Bulky naevocytoma of the perineum is a very rare variant of giant congenital melanocytic naevus (GCMN). It presents as a bulky naevocytic tumour in the perineal region with characteristic histological findings, such as extensive areas with a neural appearance called 'lames foliacees', formation of a pseudofollicular structure and extension of naevus cells between collagen bundles in a row called 'Indian-file' pattern. We report a case of late-onset bulky naevocytoma of the perineum in a 13-year-old girl. The patient presented with two bulky, pedunculated, heavily pigmented masses in the vulvar area that developed in a pre-existing GCMN lesion, which began around puberty and caused severe gait disturbance. Given the possibility of malignant transformation, we conducted staged reduction surgery of the tumour masses, which were found to be intradermal naevi without evidence of malignancy. The patient's gait disturbance improved markedly after surgery.

  16. An incidental finding of a nodal recurrence of cutaneous malignant melanoma after a 45-year disease-free period.

    PubMed

    Goodenough, Jenny; Cozon, Caroline Louise; Liew, Se Hwang

    2014-06-03

    We report the case of an 84-year-old woman who had a nodal recurrence of melanoma 45 years after the primary diagnosis of an extremity cutaneous melanoma. It is believed to be the longest disease-free latency period reported between primary melanoma diagnosis and recurrence to date. Late recurrences of melanoma are rare and recurrence after four decades extremely rare. This article suggests melanoma is a disease with a potentially lifelong risk of recurrence and thus clinicians and patients must be vigilant and aware of this risk, particularly if late recurrences are to be recognised early and management optimised.

  17. Cutaneous Melanoma in Asians

    PubMed Central

    Kim, Sang Yub

    2016-01-01

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

  18. Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

    PubMed

    Giannopoulou, Christina; Sideris, Eleftherios; Wade, Ros; Moe-Byrne, Thirimon; Eastwood, Alison; McKenna, Claire

    2015-12-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3

  19. Functional activation of Src family kinase yes protein is essential for the enhanced malignant properties of human melanoma cells expressing ganglioside GD3.

    PubMed

    Hamamura, Kazunori; Tsuji, Momoko; Hotta, Hiroshi; Ohkawa, Yuki; Takahashi, Masataka; Shibuya, Hidenobu; Nakashima, Hideyuki; Yamauchi, Yoshio; Hashimoto, Noboru; Hattori, Hisashi; Ueda, Minoru; Furukawa, Keiko; Furukawa, Koichi

    2011-05-27

    The possible roles of Src family kinases in the enhanced malignant properties of melanomas related to GD3 expression were analyzed. Among Src family kinases only Yes, not Fyn or Src, was functionally involved in the increased cell proliferation and invasion of GD3-expressing transfectant cells (GD3+). Yes was located upstream of p130Cas and paxillin and at an equivalent level to focal adhesion kinase. Yes underwent autophosphorylation even before serum treatment and showed stronger kinase activity in GD3+ cells than in GD3- cells following serum treatment. Coimmunoprecipitation experiments revealed that Yes bound to focal adhesion kinase or p130Cas more strongly in GD3+ cells than in GD3- cells. As a possible mechanism for the enhancing effects of GD3 on cellular phenotypes, it was shown that majority of Yes was localized in glycolipid-enriched microdomain/rafts in GD3+ cells even before serum treatment, whereas it was scarcely detected in glycolipid-enriched microdomain/rafts in GD3- cells. An in vitro kinase assay of Yes revealed that coexistence of GD3 with Yes in membranous environments enhances the kinase activity of GD3- cell-derived Yes toward enolase, p125, and Yes itself. Knockdown of GD3 synthase resulted in the alleviation of tumor phenotypes and reduced activation levels of Yes. Taken together, these results suggest a role of GD3 in the regulation of Src family kinases.

  20. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans

    PubMed Central

    Bauer, Alexander T.; Suckau, Jan; Frank, Kathrin; Desch, Anna; Goertz, Lukas; Wagner, Andreas H.; Hecker, Markus; Goerge, Tobias; Umansky, Ludmila; Beckhove, Philipp; Utikal, Jochen; Gorzelanny, Christian; Diaz-Valdes, Nancy; Umansky, Viktor

    2015-01-01

    Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation. PMID:25977583

  1. Imaging Mass Spectrometry – a new and promising method to differentiate Spitz nevi from Spitzoid malignant melanomas

    PubMed Central

    Lazova, Rossitza; Seeley, Erin H; Keenan, Megan; Gueorguieva, Ralitza; Caprioli, Richard M

    2011-01-01

    Background Differentiating Spitz nevus (SN) from Spitzoid malignant melanoma (SMM) is one the most difficult problems in Dermatopathology. Specific Aim To identify differences on proteomic level between SN and SMM. Methods We performed Imaging Mass Spectrometry (IMS) analysis on formalin-fixed, paraffin embedded tissue samples (FFPE) to identify differences on proteomic level between SN and SMM. The diagnosis of SN and SMM was based on histopathologic criteria, clinical features, and follow up data, which confirmed that none of the lesions diagnosed as SN recurred or metastasized. The melanocytic component (tumor) and tumor microenvironment (dermis) from 114 cases of SN and SMM from the Yale Spitzoid Neoplasm Repository were analyzed. After obtaining mass spectra from each sample, classification models were built using a training set of biopsies from 26 SN and 25 SMM separately for tumor and for dermis. The classification algorithms developed on the training data set were validated on another set of 30 samples from SN and 33 from SMM. Results We found proteomic differences between the melanocytic components of SN and SMM and identified five peptides that were differentially expressed in the two groups. From these data, 29 out of 30 SN and 26 out of 29 SMM were recognized correctly based on tumor analysis in the validation set. This method correctly classified SN with 97% sensitivity and 90% specificity in the validation cohort. Conclusions IMS analysis can reliably differentiate SN from SMM in FFPE tissue based on proteomic differences. PMID:22197864

  2. Uptake of genetic counseling, genetic testing and surveillance in hereditary malignant melanoma (CDKN2A) in Norway.

    PubMed

    Levin, Trine; Mæhle, Lovise

    2016-11-01

    Germline mutations in the CDKN2A gene are associated with an increased risk of malignant melanoma and pancreatic cancer. In order to find out if the behavior pattern in families with a CDKN2A mutation is similar to what we previously have described in families with a BRCA1 mutation, we have studied the uptake of genetic services in probands and their relatives. We describe whether they attend genetic counseling when invited, whether they want a mutation test after being counseled and whether they adhere to recommendations for surveillance. 66 % (95/144) of first-degree relatives to mutation carriers contacted us within the study period. 98 % (126/128) of all relatives who came for genetic counseling decided on genetic testing for their family's mutation, and 93 % (66/71) of all mutation carriers wanted referral to yearly skin examinations. Female relatives had a significantly higher uptake of genetic services compared to males, similar to the findings in families with a BRCA1 mutation. Uptake of genetic services in general in families with a CDKN2A mutation is high. Females seem to have a higher interest in genetic testing than males, regardless of gene mutated.

  3. Esculetin, a Coumarin Derivative, Exhibits Anti-proliferative and Pro-apoptotic Activity in G361 Human Malignant Melanoma

    PubMed Central

    Jeon, Young-Joo; Jang, Jeong-Yun; Shim, Jung-Hyun; Myung, Pyung Keun; Chae, Jung-Il

    2015-01-01

    Background: Although esculetin, a coumarin compound, is known to induce apoptosis in human cancer cells, the effects and molecular mechanisms on the apoptosis in human malignant melanoma (HMM) cells are not well understood yet. In this study, we investigated the anti-proliferative effects of esculetin on the G361 HMM cells. Methods: We analyzed the anti-proliferative effects and molecular mechanisms of esculetin on G361 cells by a 3-(4,5-dimethylthiazol- 2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, 4′,6-diamidino-2-phenylindole staining and Western blotting. Results: Esculetin exhibited significant anti-proliferative effects on the HMM cells in a dose-dependent manner. Interestingly, we found that esculetin induced nuclear shrinkage and fragmentation, typical apoptosis markers, by suppression of Sp1 transcription factor (Sp1). Notably, esculetin modulated Sp1 downstream target genes including p27, p21 and cyclin D1, resulted in activation of apoptosis signaling molecules such as caspase-3 and PARP in G361 HMM cells. Conclusions: Our results clearly demonstrated that esculetin induced apoptosis in the HMM cells by downregulating Sp1 protein levels. Thus, we suggest that esculetin may be a potential anti-proliferative agent that induces apoptotic cell death in G361 HMM cells. PMID:26151043

  4. Intralesional immunotherapy of malignant melanoma with mycobacterium smegmatis cell wall skeleton combined with trehalose dimycolate (P3).

    PubMed

    Vosika, G J; Schmidtke, J R; Goldman, A; Ribi, E; Parker, R; Gray, G R

    1979-08-01

    The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.

  5. Bi-cytopenia possibly induced by anti-PD-1 antibody for primary malignant melanoma of the esophagus

    PubMed Central

    Inadomi, Kyoko; Kumagai, Hozumi; Arita, Shuji; Tsuruta, Nobuhiro; Takayoshi, Kotoe; Mishima, Koji; Ota, Shun-Ichiro; Tanaka, Mamoru; Okumura, Yuta; Sagara, Kosuke; Nio, Kenta; Nakano, Michitaka; Uchi, Hiroshi; Yamamoto, Hidetaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Niiro, Hiroaki; Oda, Yoshinao; Akashi, Koichi; Baba, Eishi

    2016-01-01

    Abstract Background: Anti-programmed cell death 1 antibody nivolumab is a promising agent for various cancers. Immune-related adverse events are recognized; however, bi-cytopenia with nivolumab has not been reported. Case presentation: A 73-year-old man was diagnosed with advanced primary malignant melanoma of the esophagus with liver, lung, and lymph node metastases. Previous therapies including dacarbazine and radiation of 39 Gy to the esophageal region were performed, but the liver metastases deteriorated. The patient was then administered nivolumab (2 mg/kg, every 3 weeks). After 3 cycles, the esophageal tumor and lymph nodes showed marked reductions in size, the lung metastases disappeared, and the liver metastases shrank partially. The treatment continued with 7 cycles for 4 months. However, severe anemia and thrombocytopenia appeared in the 6th cycle, and intermittent blood transfusions were required. The patient received high-dose intravenous methylprednisolone therapy for bi-cytopenia, but it was ineffective. Seven months after the initiation of nivolumab, the patient died of tumor. Although the mechanisms of bi-cytopenia were unclear, it could have been induced by nivolumab. Conclusion: The present case shows a rare but serious life-threatening bi-cytopenia possibly associated with nivolumab and suggests the importance of awareness of hematological adverse events during nivolumab therapy. PMID:27442668

  6. Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

    PubMed Central

    Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2016-01-01

    Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

  7. Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells.

    PubMed

    Lin, Shuw-Yuan; Lai, Wan-Wen; Chou, Chi-Chung; Kuo, Hsiu-Maan; Li, Te-Mao; Chung, Jing-Gung; Yang, Jen-Hung

    2006-12-01

    Vitamin C has been reported to be useful in the treatment and prevention of cancer. Inconsistent effects from growth stimulation to induction of apoptosis of malignant tumor cells, however, have been reported. Melanoma is an increasingly common and potentially lethal malignancy. It was reported that melanoma cells were more susceptible to ascorbate toxicity than any other tumor cells. The mechanisms accounting for ascorbate-induced apoptosis in human melanoma cells, however, have remained unclear. This study was undertaken to investigate the effect of sodium ascorbate on cytotoxicity and apoptosis in human malignant melanoma A375.S2 cells. A375.S2 cells were incubated with a certain range of concentrations of sodium ascorbate for various time periods. In order to examine the effects of sodium ascorbate on cell proliferation, cell cycle, apoptosis and necrosis, we performed 4,6-diamidino-2-phenylindole dihydrochloride assays and flow cytometry analysis. Polymerase chain reaction was used to examine the mRNA levels of p53, p21, p27, cyclin A, cyclin E, CDK2 and CDK4, which are associated with cell cycle S-phase arrest and apoptosis. Flow cytometric analysis showed that sodium ascorbate significantly induced cell cycle arrest and apoptosis in the A375.S2 cell line in a dose-dependent manner. The increased expressions of p53 and p21, and the decreased expressions of cyclin A, cyclin E, CDK2 and CDK4, indicated the cell cycle arrest at G1/S phase after the cells had been treated with sodium ascorbate. Induction of apoptosis involved an increase in the levels of p53, p21 and cellular Ca, and a decrease in mitochondrial membrane potential and activation of caspase 3 before culminating in apoptosis in sodium ascorbate-treated A375.S2 cells.

  8. Melanoma with gastric metastases

    PubMed Central

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

    2016-01-01

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

  9. Second malignancies after Hodgkin's disease: the Munich experience.

    PubMed

    Munker, R; Grützner, S; Hiller, E; Aydemir, U; Enne, W; Dietzfelbinger, H; Busch, M; Haas, R; Emmerich, B; Schmidt, M; Dühmke, E; Hölzel, D; Wilmanns, W

    1999-12-01

    The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic

  10. Noninvasive and label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    NASA Astrophysics Data System (ADS)

    Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Wei, Xunbin

    2015-03-01

    Melanoma is a malignant tumor of melanocytes. Circulating melanoma cell has 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). PAFC 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. In our research, we developed in vitro experiments to prove the ability of PAFC system of detecting PA signals from melanoma cells. For in vivo experiments, we constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells B16F10 with subcutaneous injection. PA signals were detected in the blood vessels of mouse ears in vivo. By counting circulating melanoma cells termly, we obtained 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. Our PAFC system is an efficient tool to monitor melanoma metastases, cancer recurrence and therapeutic efficacy.

  11. Pigmented spindle cell nevus: clues for differentiating it from spindle cell malignant melanoma. A comprehensive survey including clinicopathologic, immunohistochemical, and FISH studies.

    PubMed

    Díaz, Alba; Valera, Alexandra; Carrera, Cristina; Hakim, Sofía; Aguilera, Paula; García, Adriana; Palou, Josep; Puig, Susana; Malvehy, Josep; Alos, Llúcia

    2011-11-01

    Pigmented spindle cell nevus (PSCN), also known as Reed nevus, is a distinctive melanocytic tumor that can show worrisome clinical and histologic features mimicking a malignant melanoma. From a series of 46 pigmented spindle cell melanocytic lesions, including 22 PSCN and 24 spindle cell malignant melanomas (SCMMs), we collected clinical and histopathologic characteristics and evaluated cell cycle and apoptosis regulators by immunohistochemistry. Moreover, fluorescence in situ hybridization (FISH) using probes targeting 6p25 (RREB1), 11q13 (CCND1), 6q23 (MYB), and centromere 6 was performed. PSCN presented in younger people, frequently in women, and were small lesions under 7 mm in diameter affecting the lower limbs, whereas SCMMs arose more frequently in the trunk, upper limbs, and head and neck region. Histologically, symmetry, good lateral demarcation, and uniformity of cellular nests were significantly differential features of PSCN, whereas pagetoid and adnexal spread were frequently seen in both tumors. Immunohistochemical markers that significantly differed from melanomas were Ki-67, cyclin D1, and survivin. FISH was positive in 1 of 15 PSCN and was negative in 4 of 15 SCMMs. These results correlated to a sensitivity of 73% and a specificity of 93%. In conclusion, in the evaluation of pigmented spindle cell melanocytic tumors, the integration of clinical and histologic assessment is essential. However, ancillary techniques such as proliferation antigen Ki-67, cyclin D1, survivin, and FISH can be useful as adjunctive tools.

  12. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    PubMed Central

    Zhang, Ying; Le, Trong Kim; Shaw, James W; Kotapati, Srividya

    2015-01-01

    Background This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment (“observation”) for malignant melanoma following surgery. Methods A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan®) to identify all adjuvant melanoma patients (aged ≥18 years) diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery) and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression. Results Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0%) were treated with IFN and 1,820 (91.0%) were observed. The median duration (days) and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179); significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001). Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and demonstrated the largest difference between IFN-treated and observation patients. Outpatient service costs for IFN-treated patients were $32,414±$2,498, over three times greater than those for observation patients ($10,556±$1,128; P<0.0001). Conclusion The majority of adjuvant melanoma patients in this study was treated with observation versus IFN treatment. Among those who attempted IFN treatment, most could not complete the recommended course of therapy. Health care costs were

  13. The Experience of Melanoma Follow-Up Care: An Online Survey of Patients in Australia

    PubMed Central

    Street, Jackie; Neuhaus, Susan; Bessen, Taryn

    2014-01-01

    Investigating patients' reports on the quality and consistency of melanoma follow-up care in Australia would assist in evaluating if this care is effective and meeting patients' needs. The objective of this study was to obtain and explore the patients' account of the technical and interpersonal aspects of melanoma follow-up care received. An online survey was conducted to acquire details of patients' experience. Participants were patients treated in Australia for primary melanoma. Qualitative and quantitative data about patient perceptions of the nature and quality of their follow-up care were collected, including provision of melanoma specific information, psychosocial support, and imaging tests received. Inconsistencies were reported in the provision and quality of care received. Patient satisfaction was generally low and provision of reassurance from health professionals was construed as an essential element of quality of care. “Gaps” in follow-up care for melanoma patients were identified, particularly provision of adequate psychosocial support and patient education. Focus on strategies for greater consistency in the provision of support, information, and investigations received, may generate a cost dividend which could be reinvested in preventive and supportive care and benefit patient well-being. PMID:25535589

  14. Evaluating the cytotoxic effects of the water extracts of four anticancer herbs against human malignant melanoma cells

    PubMed Central

    Ling, Binbing; Michel, Deborah; Sakharkar, Meena Kishore; Yang, Jian

    2016-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer, killing more than 1,100 people each year in Canada. Prognosis for late stage and recurrent MM is extremely poor due to insensitivity to chemotherapy drugs, and thus many patients seek complementary and alternative medicines. In this study, we examined four commonly used anticancer herbs in traditional Chinese medicine, Hedyotis diffusa, Scutellaria barbata, Lobelia chinensis, and Solanum nigrum, for their in vitro antitumor effects toward human MM cell line A-375. The crude water extract of S. nigrum (1 g of dry herb in 100 mL water) and its 2-fold dilution caused 52.8%±13.0% and 17.3%±2.7% cytotoxicity in A-375 cells, respectively (P<0.01). The crude water extract of H. diffusa caused 11.1%±12.4% cytotoxicity in A-375 cells with no statistical significance (P>0.05). Higher concentrated formulation might be needed for H. diffusa to exert its cytotoxic effect against A-375 cells. No cytotoxicity was observed in A-375 cells treated with crude water extract of S. barbata and L. chinensis. Further high performance liquid chromatography-tandem mass spectroscopy analysis of the herbal extracts implicated that S. nigrum and H. diffusa might have adopted the same bioactive components for their cytotoxic effects in spite of belonging to two different plant families. We also showed that the crude water extract of S. nigrum reduced intracellular reactive oxygen species generation in A-375 cells, which may lead to a cytostatic effect. Furthermore, synergistic effect was achieved when crude water extract of S. nigrum was coadministered with temozolomide, a chemotherapy drug for skin cancer. PMID:27843296

  15. Knockdown of lecithin retinol acyltransferase increases all-trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells.

    PubMed

    Amann, Philipp M; Czaja, Katharina; Bazhin, Alexandr V; Rühl, Ralph; Skazik, Claudia; Heise, Ruth; Marquardt, Yvonne; Eichmüller, Stefan B; Merk, Hans F; Baron, Jens M

    2014-11-01

    Retinoids such as all-trans retinoic acid (ATRA) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid-metabolizing enzyme known as lecithin retinol acyltransferase (LRAT) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all-trans retinol (ATRol). In this study, we show that a stable LRAT knockdown (KD) in the human melanoma cell line SkMel23 leads to significantly increased levels of the substrate ATRol and biologically active ATRA. LRAT KD restored cellular sensitivity to retinoids analysed in cell culture assays and melanoma 3D skin models. Furthermore, ATRA-induced gene regulatory mechanisms drive depletion of added ATRol in LRAT KD cells. PCR analysis revealed a significant upregulation of retinoid-regulated genes such as CYP26A1 and STRA6 in LRAT KD cells, suggesting their possible involvement in mediating retinoid resistance in melanoma cells. In conclusion, LRAT seems to be important for melanoma progression. We propose that reduction in ATRol levels in melanoma cells by LRAT leads to a disturbance in cellular retinoid level. Balanced LRAT expression and activity may provide protection against melanoma development and progression. Pharmacological inhibition of LRAT activity could be a promising strategy for overcoming retinoid insensitivity in human melanoma cells.

  16. Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.

    PubMed

    Chang, Chih-Chao; Chang, Chih-Hsien; Lo, Yi-Hsuan; Lin, Ming-Hsien; Shen, Chih-Chieh; Liu, Ren-Shyan; Wang, Hsin-Ell; Chen, Chuan-Lin

    2016-08-15

    Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel (18)F-labeled NOTA-benzamide conjugate, Al(18)F-NOTA-BZA, which can be synthesized in 30min with a radiochemical yield of 20-35% and a radiochemical purity of >95%. Al(18)F-NOTA-BZA is highly hydrophilic (logP=-1.96) and shows good in vitro stability. Intravenous administration of Al(18)F-NOTA-BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67±0.91 and 1.50±0.26%ID/g at 15 and 120min p.i., respectively), but not in A375 amelanotic melanoma (0.87±0.21 and 0.24±0.09%ID/g at 15 and 120min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al(18)F-NOTA-BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al(18)F-NOTA-BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and thelow projected human dosimetry supported that Al(18)F-NOTA-BZA is a very promising melanin-specific PET probe for melanin-positive melanoma.

  17. Clinical experiences with microwave thermal ablation of lung malignancies.

    PubMed

    Sidoff, Luby; Dupuy, Damian E

    2017-02-01

    Approximately 30% of early stage lung cancer patients are not surgical candidates due to medical co-morbidities, poor cardiopulmonary function and advanced age. These patients are traditionally offered chemotherapy and radiation, which have shown relatively modest improvements in mortality. For over a decade, percutaneous image-guided ablation has emerged as a safe, cost-effective, minimally invasive treatment alternative for patients who would otherwise not qualify for surgery. Although radiofrequency ablation (RFA) is currently the most extensively studied and widely utilised technique in the treatment of lung malignancies, there is a growing body of evidence that microwave ablation (MWA) has several unique benefits over RFA and cryoablation in the lung. This article reviews our institution's clinical experiences in the treatment of lung malignancies with MWA including patient selection, procedural technique, imaging follow-up, treatment outcomes and comparison of ablation techniques.

  18. Cytochrome P450 CYP2D6 genotypes: association with hair colour, Breslow thickness and melanocyte stimulating hormone receptor alleles in patients with malignant melanoma.

    PubMed

    Strange, R C; Ellison, T; Ichii-Jones, F; Bath, J; Hoban, P; Lear, J T; Smith, A G; Hutchinson, P E; Osborne, J; Bowers, B; Jones, P W; Fryer, A A

    1999-06-01

    We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were > or = 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or val92met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in

  19. ORAL AMELANOTIC MELANOMA

    PubMed Central

    Adisa, A.O.; Olawole, W.O.; Sigbeku, O.F.

    2012-01-01

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases are amelanotic. No etiologic factors or risk factors have been recognized for oral melanomas. Some authors have suggested that oral habits and selfmedication may be of etiological significance. Oral melanoma is rare but it is relatively frequent in countries like Japan, Uganda, and India. It is rarely identified under the age of 20 years. In Australia where cutaneous melanomas are relatively common primary melanoma of the oral mucosa is rare. The surface architecture of oral melanomas ranges from macular to ulcerated and nodular. The lesion is said to be asymptomatic in the early stages but may become ulcerated and painful in advanced lesions. The diagnosis of amelanotic melanoma is more difficult than that of pigmented lesions. The neoplasm consists of spindle-shaped cells with many mitotic figures and no cytoplasmic melanin pigmentation. Immunohistochemistry using S-100, HMB-45, Melan-A and MART-1 will help in establishing the correct diagnosis. Radical surgery with ample margins and adjuvant chemotherapy are appropriate management protocol for malignant melanoma. Oral melanoma is associated with poor prognosis but its amelanotic variant has even worse prognosis because it exhibits a more aggressive biology and because of difficulty in diagnosis which leads to delayed treatment. PMID:25161399

  20. Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

    PubMed Central

    Chen, Zhongjian; Zhang, Tianpeng; Wu, Baojian; Zhang, Xingwang

    2016-01-01

    Malignant melanoma (MM) represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs) for hypoxia-inducible factor-1α (HIF-1α) small interfering (siRNA) delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs) were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM. PMID:27042054

  1. MHC Class I Chain-Related Gene A Diversity in Patients with Cutaneous Malignant Melanoma from Southeastern Spain

    PubMed Central

    Campillo, José Antonio; López-Hernández, Ruth; Martínez-Banaclocha, Helios; Bolarín, José Miguel; Gimeno, Lourdes; Mrowiec, Anna; López, Manuela; Heras, Beatriz Las; Minguela, Alfredo; Moya-Quiles, Maria Rosa; Legáz, Isabel; Frías-Iniesta, José Francisco; García-Alonso, Ana María; Álvarez-López, María Rocío; Martínez-Escribano, Jorge Antonio; Muro, Manuel

    2015-01-01

    A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA*009 in melanoma patients compared with controls (P = 0.002, Pc = 0.03). Our results also showed an association between MICA*009 and HLA-B*51 alleles in both patients and controls. This association was stronger in patients than controls (P = 0.015). However, a multivariate logistic regression model showed that neither MICA*009 nor the combination MICA*009/HLA-B*51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis. PMID:25838620

  2. MHC class I chain-related gene a diversity in patients with cutaneous malignant melanoma from southeastern Spain.

    PubMed

    Campillo, José Antonio; López-Hernández, Ruth; Martínez-Banaclocha, Helios; Bolarín, José Miguel; Gimeno, Lourdes; Mrowiec, Anna; López, Manuela; Las Heras, Beatriz; Minguela, Alfredo; Moya-Quiles, Maria Rosa; Legáz, Isabel; Frías-Iniesta, José Francisco; García-Alonso, Ana María; Álvarez-López, María Rocío; Martínez-Escribano, Jorge Antonio; Muro, Manuel

    2015-01-01

    A limited number of studies have been performed so far on the polymorphism in the transmembrane region (exon 5) of the major histocompatibility complex class I chain-related gene A (MICA) in patients with melanoma. However, the influence of MICA polymorphism in extracellular domains (exons 2, 3, and 4) has not been investigated on melanoma disease. This study aims to characterize the influence of extracellular MICA polymorphism, and its previously described linkage disequilibrium with HLA-B locus, on patients with cutaneous melanoma from southeastern Spain. For this purpose, MICA and HLA-B genotyping was performed in 233 patients and 200 ethnically matched controls by luminex technology. Patients were classified according to the presence of methionine or valine at codon 129 of MICA gene. We found a high frequency of MICA(*)009 in melanoma patients compared with controls (P = 0.002, Pc = 0.03). Our results also showed an association between MICA(*)009 and HLA-B(*)51 alleles in both patients and controls. This association was stronger in patients than controls (P = 0.015). However, a multivariate logistic regression model showed that neither MICA(*)009 nor the combination MICA(*)009/HLA-B(*)51 was associated with melanoma susceptibility. No relationship was observed between MICA-129 dimorphism and melanoma nor when MICA polymorphism was evaluated according to clinical findings at diagnosis.

  3. NAD(P)H:Quinone Oxidoreductase-1 Expression Sensitizes Malignant Melanoma Cells to the HSP90 Inhibitor 17-AAG

    PubMed Central

    Kasai, Shuya; Arakawa, Nobuyuki; Okubo, Ayaka; Shigeeda, Wataru; Yasuhira, Shinji; Masuda, Tomoyuki; Akasaka, Toshihide; Shibazaki, Masahiko; Maesawa, Chihaya

    2016-01-01

    The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional induction of genes associated with antioxidant synthesis and detoxification in response to oxidative stress. Previously, we reported that KEAP1 mutation elicits constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine (DTIC) in human melanomas. The present study was conducted to clarify whether an HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma and non-small cell lung carcinoma cell lines with or without KEAP1 mutations, NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines despite the presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2 activation. Because either CDDP or DTIC produces reactive oxygen species that activate NRF2, we determined whether these agents would sensitize NQO1-low melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP combination was detected in four out of five NQO1-low cell lines, but not in the cell line with KEAP1 mutation. These data indicate that 17-AAG could be a potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1 expression. PMID:27045471

  4. Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink

    PubMed Central

    Langan, Sinéad M.; Douglas, Ian J.; Smeeth, Liam; Bhaskaran, Krishnan

    2016-01-01

    Background Laboratory evidence suggests that reduced phosphodiesterase type 5 (PDE5) expression increases the invasiveness of melanoma cells; hence, pharmacological inhibition of PDE5 could affect melanoma risk. Two major epidemiological studies have investigated this and come to differing conclusions. We therefore aimed to investigate whether PDE5 inhibitor use is associated with an increased risk of malignant melanoma, and whether any increase in risk is likely to represent a causal relationship. Methods and Findings We conducted a matched cohort study using primary care data from the UK Clinical Practice Research Datalink. All men initiating a PDE5 inhibitor and with no prior cancer diagnosis were identified and matched on age, diabetes status, and general practice to up to four unexposed controls. Ever use of a PDE5 inhibitor and time-updated cumulative number of PDE5 inhibitor prescriptions were investigated as exposures, and the primary outcome was malignant melanoma. Basal cell carcinoma, solar keratosis, and colorectal cancer were investigated as negative control outcomes to exclude bias. Hazard ratios (HRs) were estimated from Cox models stratified by matched set and adjusted for potential confounders. 145,104 men with ≥1 PDE5 inhibitor prescription, and 560,933 unexposed matched controls were included. In total, 1,315 incident malignant melanoma diagnoses were observed during 3.44 million person-years of follow-up (mean 4.9 y per person). After adjusting for potential confounders, there was weak evidence of a small positive association between PDE5 inhibitor use and melanoma risk (HR = 1.14, 95% CI 1.01–1.29, p = 0.04). A similar increase in risk was seen for the two negative control outcomes related to sun exposure (HR = 1.15, 95% CI 1.11–1.19, p < 0.001, for basal cell carcinoma; HR = 1.21, 95% CI 1.17–1.25, p < 0.001, for solar keratosis), but there was no increased risk for colorectal cancer (HR = 0.91, 95% CI 0.85–0.98, p = 0.01). There was

  5. Effect of inhibition of aloe-emodin on N-acetyltransferase activity and gene expression in human malignant melanoma cells (A375.S2).

    PubMed

    Lin, Shuw-Yuan; Yang, Jen-Hung; Hsia, Te-Chun; Lee, Jau-Hong; Chiu, Tsan-Hung; Wei, Yau-Huei; Chung, Jing-Gung

    2005-12-01

    Arylamine carcinogens and drugs are N-acetylated by cytosolic N-acetyltransferase (NAT), which uses acetyl-coenzyme A as a cofactor. NAT plays an initial role in the metabolism of these arylamine compounds. 2-Aminofluorene is one of the arylamine carcinogens which have been demonstrated to undergo N-acetylation in laboratory animals and humans. Our previous study showed that human cancer cell lines (colon cancer, colo 205; liver cancer, Hep G2; bladder cancer, T24; leukemia, HL-60; prostate cancer, LNCaP; osteogenic sarcoma, U-2 OS; malignant melanoma, A375.S2) displayed NAT activity, which was affected by aloe-emodin in human leukemia cells. The purpose of this study was to determine whether aloe-emodin could affect the enzyme activity and gene expression of NAT at the mRNA and protein levels in malignant human melanoma A375.S2 cells. The results showed that aloe-emodin inhibited NAT1 activity (decreased N-acetylation of 2-aminofluorene) in intact cells in a dose-dependent manner. The effect of aloe-emodin on NAT1 at the protein level was determined by Western blotting and the mRNA levels were examined by polymerase chain reaction (PCR) and cDNA microarray. These results clearly indicate that aloe-emodin inhibits the mRNA expression and enzyme activity of NAT1 in A375.S2 cells.

  6. Differential Inhibition of Ex-Vivo Tumor Kinase Activity by Vemurafenib in BRAF(V600E) and BRAF Wild-Type Metastatic Malignant Melanoma

    PubMed Central

    Tahiri, Andliena; Røe, Kathrine; Ree, Anne H.; de Wijn, Rik; Risberg, Karianne; Busch, Christian; Lønning, Per E.; Kristensen, Vessela; Geisler, Jürgen

    2013-01-01

    Background Treatment of metastatic malignant melanoma patients harboring BRAF(V600E) has improved drastically after the discovery of the BRAF inhibitor, vemurafenib. However, drug resistance is a recurring problem, and prognoses are still very bad for patients harboring BRAF wild-type. Better markers for targeted therapy are therefore urgently needed. Methodology In this study, we assessed the individual kinase activity profiles in 26 tumor samples obtained from patients with metastatic malignant melanoma using peptide arrays with 144 kinase substrates. In addition, we studied the overall ex-vivo inhibitory effects of vemurafenib and sunitinib on kinase activity status. Results Overall kinase activity was significantly higher in lysates from melanoma tumors compared to normal skin tissue. Furthermore, ex-vivo incubation with both vemurafenib and sunitinib caused significant decrease in phosphorylation of kinase substrates, i.e kinase activity. While basal phosphorylation profiles were similar in BRAF wild-type and BRAF(V600E) tumors, analysis with ex-vivo vemurafenib treatment identified a subset of 40 kinase substrates showing stronger inhibition in BRAF(V600E) tumor lysates, distinguishing the BRAF wild-type and BRAF(V600E) tumors. Interestingly, a few BRAF wild-type tumors showed inhibition profiles similar to BRAF(V600E) tumors. The kinase inhibitory effect of vemurafenib was subsequently analyzed in cell lines harboring different BRAF mutational status with various vemurafenib sensitivity in-vitro. Conclusions Our findings suggest that multiplex kinase substrate array analysis give valuable information about overall tumor kinase activity. Furthermore, intra-assay exposure to kinase inhibiting drugs may provide a useful tool to study mechanisms of resistance, as well as to identify predictive markers. PMID:24023633

  7. Uveal Melanoma

    PubMed Central

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

    2011-01-01

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

  8. Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

    SciTech Connect

    Caujolle, Jean-Pierre; Mammar, Hamid; Chamorey, Emmanuel Phar; Pinon, Fabien; Herault, Joel; Gastaud, Pierre

    2010-09-01

    Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital. Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.

  9. Neuroleptic malignant syndrome in Malaysia: a university hospital experience.

    PubMed

    Lee, M K; Ong, S B; Tan, C T; Loh, T G

    1992-09-01

    The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of antipsychotic therapy. A retrospective study of nine patients seen over six years at the University Hospital, Kuala Lumpur (UHKL), is described. The estimated annualised incidence was 1.2 per 1000 in-patients with psychosis. No ethnic difference was detected. Clinical features were similar to experiences elsewhere, with wide variability seen in the severity of illness. The neuroleptic drugs implicated were haloperidol, trifluoperazine, chlorpromazine, fluphenazine and clopenthixol. Treatment consisted of withdrawal of offending drugs and supportive measures. Specific therapy was given to five patients. There was one death. At follow-up no deterioration was detected. A different neuroleptic drug was successfully re-introduced in four patients. In view of the wide usage of major tranquillizers, a high degree of clinical awareness of this serious complication is necessary for early diagnosis to reduce morbidity and mortality.

  10. Optimized Nanosecond Pulsed Electric Field Therapy Can Cause Murine Malignant Melanomas to Self-Destruct with a Single Treatment

    PubMed Central

    Nuccitelli, Richard; Tran, Kevin; Sheikh, Saleh; Athos, Brian; Kreis, Mark; Nuccitelli, Pamela

    2010-01-01

    We have identified a new, nanosecond pulsed electric field (nsPEF) therapy capable of eliminating murine melanomas located in the skin with a single treatment. When these optimized parameters are used, nsPEFs initiate apoptosis without hyperthermia. We have developed new suction electrodes that are compatible with human skin and have applied them to a xenograft nude mouse melanoma model system to identify the optimal field strength, pulse frequency and pulse number for the treatment of murine melanomas. A single treatment using the optimal pulse parameters (2000 pulses, 100 ns in duration, 30 kV/cm in amplitude at a pulse frequency of 5–7 pulses/s) eliminated all 17 melanomas treated with those parameters in 4 mice. This was the highest pulse frequency that we could use without raising the treated skin tumor temperature above 40 °C. We also demonstrate that the effects of nsPEF therapy are highly localized to only cells located between electrodes and results in very little scarring of the nsPEF-treated skin. PMID:20473857

  11. CD147 interacts with NDUFS6 in regulating mitochondrial complex I activity and the mitochondrial apoptotic pathway in human malignant melanoma cells.

    PubMed

    Luo, Z; Zeng, W; Tang, W; Long, T; Zhang, J; Xie, X; Kuang, Y; Chen, M; Su, J; Chen, X

    2014-01-01

    Malignant melanoma (MM) is one of the most lethal tumors and is characterized by high invasiveness, frequent metastasis, and resistance to chemotherapy. The risk of metastatic MM is accompanied by disordered energy metabolism involving the oxidative phosphorylation (OXPHOS) process, which is largely carried out in mitochondrial complexes. Complex I is the first and largest mitochondrial enzyme complex associated with this process. CD147 is a transmembrane glycoprotein mainly expressed on the cell surface, and also appears in the cytoplasm in some tumors. We found that CD147 is often translocated to the cytoplasm in metastatic MM specimens as compared to primary MM. We also demonstrated high expression of CD147 in isolated mitochondrial fractions of A375 cells. The yeast two-hybrid (Y2H) assay identified NDUFS6 (which encodes a subunit of mitochondrial respiratory chain complex I) as a candidate that interacts with CD147 and depletion of CD147 in A375 cells significantly decreased complex I enzyme activity. We also showed that CD147 increased the viability of A375 cells exposed to berberine-induced mitochondrial damage, and protected them from apoptosis through a mitochondrial-dependent pathway. This finding was confirmed by adding exogenous Bcl-2 to A375 cell cultures. In summary, our results identify the existence of CD147 in human melanoma cell mitochondria. They indicate that CD147 appears to regulate complex I activity and apoptosis in MM by interacting with mitochondrial NDUFS6. Our findings provide new insight into the function of CD147 and identify it as a promising therapeutic target in melanoma through disruption of the energy metabolism.

  12. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    SciTech Connect

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed; Corriveau, Christine; Edelstein, Chaim; Deschenes, Jean; Ruo, Russel; Patrocinio, Horacio; Cury, Fabio L.B.; DeBlois, Francois; Shenouda, George

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range, 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.

  13. The role of positron emission tomography with computed tomography in the follow-up of asymptomatic cutaneous malignant melanoma patients with a high risk of disease recurrence.

    PubMed

    Abbott, Rachel Angharad; Acland, Katharine M; Harries, Mark; O'Doherty, Michael

    2011-10-01

    The aim of this study was to evaluate the role of [F] fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) as a surveillance tool in asymptomatic patients with primary cutaneous melanoma with the American Joint Committee on Cancer stage 3 disease. Thirty-four patients with primary cutaneous malignant melanoma with American Joint Committee on Cancer stage 3 disease, who underwent at least one annual surveillance PET/CT scan, were retrospectively identified from our PET Centre Database in May 2008 and their characteristics, PET/CT results and disease course were reviewed. In 20 patients with microscopic stage 3 disease at diagnosis, annual surveillance PET/CT detected two of three recurrences and detected one incidental breast carcinoma. In 14 patients with macroscopic stage 3 disease at, or subsequent to, their initial diagnosis, annual PET/CT detected four of four recurrences, detected metastases in one patient who remains asymptomatic and detected one incidental thyroid carcinoma. PET/CT seems to be a useful surveillance tool in patients with macroscopic stage 3 disease, although the numbers in this study are small. However, the role of PET/CT in patients initially presenting with microscopic stage 3 disease requires further confirmation.

  14. Genital melanocytic nevus arising in a background of lichen sclerosus in a 7-year-old female: the diagnostic pitfall with malignant melanoma. A literature review.

    PubMed

    Pinto, Andre; Mclaren, Son H; Poppas, Dix P; Magro, Cynthia M

    2012-12-01

    Genital melanocytic nevus represents a distinct form of melanocytic proliferation, which can exhibit significant atypia, both clinically and histologically. In a background of lichen sclerosus (LS), the histologic changes could be misconstrued as indicative of malignant melanoma. We present herein a case of the atypical genital nevus of childhood complicated by LS, and a review of the literature is performed. Tissue was available for routine light microscopy and immunohistochemical evaluation to assess the expression of soluble adenylyl cyclase. Fluorescent in situ hybridization studies were conducted to assess for abnormalities in Myb1, CCND1, RREB1 and CEP6. The specimen showed an atypical compound melanocytic proliferation arising in a background of LS. The lesion exhibited significant architectural atypia based on the high-density confluent nature of the junctional melanocytic proliferation with epidermal effacement, rare areas of pagetoid ascent, and the heavily pigmented epithelioid quality of the melanocytes. Fluorescent in situ hybridization studies were normal. The soluble adenylyl cyclase antibody preparation demonstrated a benign nevus-like pattern. The lesion was felt to represent an atypical genital melanocytic nevus, which can resemble a partially regressed melanoma in a background of LS. It is very important for the pathologist to be aware of this entity to avoid misdiagnosis.

  15. Similar efficacy for phase I trials in comparison with DTIC for advanced malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored phase I trials 1995-2011.

    PubMed

    Luke, Jason J; Rubinstein, Lawrence V; Smith, Gary L; Ivy, S Percy; Harris, Pamela J

    2013-04-01

    After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate ∼9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy with lower clinical benefit rate, and chemotherapy with higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone.

  16. Overview of Local Flaps of the Face for Reconstruction of Cutaneous Malignancies: Single Institutional Experience of Seventy Cases

    PubMed Central

    Rao, Jagdeep K; Shende, Kaustubh Sharad

    2016-01-01

    Context: The most common malignant tumours of the face are basal cell carcinoma, squamous cell carcinoma and melanoma. While the results of skin graft are less than satisfactory for large areas to cover, distant flaps are bulky with a poor colour match. Local fasciocutaneous flaps provide reasonable option for reconstruction of facial defects with good colour and texture match and good success rate. Aims: This study aimed to analyse the various modalities of reconstruction after resection of facial malignancies and their advantages and disadvantages. Settings and Design: This was a retrospective study. Materials and Methods: Of 70 patients, 34 were managed with V-Y advancement flap, 24 with nasolabial flap, 8 with median forehead flap and 4 with standard forehead flap cover. The duration of follow-up ranged from 6 months to 2 years. Statistical Analysis Used: Nil. Results: Of 34 V-Y advancement flaps, 2 showed suture dehiscence at the apex of triangle which was allowed to heal secondarily with regular dressings. All the 24 nasolabial flaps were healthy without any complication. All patients had satisfactory functional and cosmetic outcomes. Conclusions: In our experience, local flaps give the best results and are the first choice for reconstruction of the face. Most defects can be best closed by nasolabial, V-Y advancement and forehead flap. Outstanding functional and cosmetic results can be achieved. Proper execution requires considerable technical skill and experience. PMID:28163451

  17. Radiosensitization and downregulation of heterogeneous nuclear ribonucleoprotein K (hnRNP K) upon inhibition of mitogen/extracellular signal-regulated kinase (MEK) in malignant melanoma cells

    PubMed Central

    Eder, Stefan; Lamkowski, Andreas; Priller, Markus; Port, Matthias; Steinestel, Konrad

    2015-01-01

    Background Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is an important cofactor in the p53-mediated DNA damage response pathway upon ionizing radiation (IR) and exerts anti-apoptotic effects also independent of p53 pathway activation. Furthermore, hnRNP K is overexpressed in various neoplasms including malignant melanoma (MM). Here, we investigate the role of hnRNP K in the radioresistance of MM cells. Methods and results Our results show cytoplasmic expression of hnRNP K in human MM surgical specimens, but not in benign nevi, and a quick dose- and time-dependent upregulation in response to IR accompanied by cytoplasmic redistribution of the protein in the IPC-298 cellular tumor model carrying an activating NRAS mutation (p.Q61L). SiRNA-based knockdown of hnRNP K induced a delayed decline in γH2AX/53BP1-positive DNA repair foci upon IR. Pharmacological interference with MAPK signaling abrogated ERK phosphorylation, diminished cellular hnRNP K levels, impaired γH2AX/53BP1-foci repair and proliferative capability and increased apoptosis comparable to the observed hnRNP K knockdown phenotype in IPC-298 cells. Conclusion Our results indicate that pharmacological interference with MAPK signaling increases vulnerability of NRAS-mutant malignant melanoma cells to ionizing radiation along with downregulation of endogenous hnRNP K and point towards a possible use for combined MEK inhibition and localized radiation therapy of MM in the NRAS-mutant setting where BRAF inhibitors offer no clinical benefit. PMID:26136337

  18. Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals.

    PubMed Central

    Offner, F. A.; Wirtz, H. C.; Schiefer, J.; Bigalke, I.; Klosterhalfen, B.; Bittinger, F.; Mittermayer, C.; Kirkpatrick, C. J.

    1992-01-01

    Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical-scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1519667

  19. Detection of cell surface and intracellular antigens by human monoclonal antibodies. Hybrid cell lines derived from lymphocytes of patients with malignant melanoma

    PubMed Central

    1983-01-01

    This study represents an initial attempt to analyze the humoral immune reactions of patients with malignant melanoma by hybridoma methodology. Using lymphocytes from regional lymph nodes, peripheral blood and tumor infiltrates, 158 fusions were performed with SKO-007 (human myeloma line), LICR-LON-HMy2 (LICR-2), GM 4672 (human lymphoblastoid lines), or NS-1 (mouse myeloma line). Fusion of lymph node lymphocytes with NS-1 resulted in a 3-4 times higher frequency of clones than fusion with LICR-2, and a 10 times higher frequency than fusion with SKO-007 or GM 4672. In the case of peripheral blood lymphocytes, fusion with NS-1 gave greater than 25 times higher frequency of clones than fusion with LICR-2 or SKO-007. Production of human mu, gamma, or alpha heavy chains was detected in 50-80% of wells containing growing clones, and the levels of immunoglobulin ranged from 0.3 micrograms to 40 micrograms/ml. NS-1-derived clones could be easily subcultured, while LICR-2 and SKO-007 clones grew more slowly on subculturing. In this study, Ig secretion appeared to be a more stable property of LICR-2- derived clones than NS-1-derived clones. A panel of 20 human cancer cell lines was used to screen 771 Ig-secreting cultures for antibody to cell surface or intracellular antigens. Reactivity with cell surface antigens was found infrequently (6 cultures), whereas reactivity with intracellular antigens was more common (27 cultures). A new cell surface antigen with properties of a glycolipid was defined with an IgM monoclonal antibody secreted by a tetraploid cell derived from a fusion of LICR-2 with lymphocytes from the axillary lymph node of a patient with melanoma. The hybrid cell line has been subcloned four times and secretes 5 micrograms IgM/ml. The antigen detected by this IgM antibody was found on 5 of 23 melanoma cell lines and 12 of 30 epithelial cancer cell lines. No reactions were found with 11 cultures derived from normal cells. Stable cell lines secreting human

  20. Vemurafenib for the treatment of locally advanced or metastatic BRAF V600 mutation-positive malignant melanoma: a NICE single technology appraisal.

    PubMed

    Beale, Sophie; Dickson, Rumona; Bagust, Adrian; Blundell, Michaela; Dundar, Yenal; Boland, Angela; Marshall, Ernie; Plummer, Ruth; Proudlove, Chris

    2013-12-01

    Vemurafenib is an oral BRAF inhibitor licenced for the treatment of locally advanced or metastatic BRAF V600-mutation positive malignant melanoma. The manufacturer of vemurafenib, Roche Products Limited, was invited by the National Institute for Health and Care Excellence (NICE) to submit evidence of the drug's clinical- and cost-effectiveness for its licenced indication, to inform the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. This article summarises the ERG's review of the evidence submitted by the manufacturer and also includes a summary of the NICE Appraisal Committee (AC) decision. The ERG reviewed the clinical- and cost-effectiveness evidence in accordance with the decision problem defined by NICE. The ERG's analysis of the submitted economic model assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. It also included an assessment of the reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to impact substantially on the base-case cost-effectiveness results. The clinical evidence was derived from BRIM 3 (BRAF Inhibitor in Melanoma 3), a well-designed, multi-centre, multi-national, phase III, randomised controlled trial (RCT). Clinical outcome results from the October 2011 data cut showed that median overall survival for patients treated with vemurafenib was 13.2 months compared with 9.6 months for those treated with dacarbazine. The ERG's main concern with the trial was the potential for confounding because of the early introduction of the crossover from the comparator drug to vemurafenib or another BRAF inhibitor. The submitted incremental cost-effectiveness ratio (ICER

  1. Long-term Survival after Metastatic Childhood Melanoma

    PubMed Central

    Jensen, Mette Bybjerg; Krag, Christen

    2014-01-01

    Summary: Malignant melanoma in children is very rare and accounts for only 1–3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant 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 survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma. PMID:25289356

  2. [Vulvar melanoma].

    PubMed

    Chokoeva, A; Tchernev, G; Wollina, U

    2015-01-01

    Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist < 5% of all cases of 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.

  3. Phase II Trial of Combination Thalidomide plus Temozolomide in Patients with Metastatic Malignant Melanoma: Southwest Oncology Group S0508

    PubMed Central

    Clark, Joseph I.; Moon, James; Hutchins, Laura F.; Sosman, Jeffrey A.; Kast, W. Martin; Da Silva, Diane M.; Liu, P.Y.; Thompson, John A.; Flaherty, Lawrence E.; Sondak, Vernon K.

    2009-01-01

    Purpose In limited institution Phase II studies, thalidomide and temozolomide has yielded response rates (RR) up to 32% for advanced melanoma, leading to the use of this combination as “standard” by some. We conducted a multi-center Phase II trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma. Patients and Methods Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0–1, up to 1 prior systemic therapy excluding thalidomide, temozolomide or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200mg/d escalated to 400mg/d for patients <70, or 100mg/d escalated to 250mg/d for patients ≥70) plus temozolomide (75mg/m2/d × 6 weeks then 2 weeks rest). Results Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% CI, 6%–23%); 1-year OS was 35% (95% CI, 24%–47%); RR was 13% (95% CI, 5%–25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other Grade 4 events occurred including pulmonary embolism, neutropenia and CNS ischemia. There was no significant correlation between biomarkers and PFS or OS. Conclusion This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase III trials or for standard community use. PMID:19918923

  4. [Molecular and immunohistochemical diagnostics in melanoma].

    PubMed

    Schilling, B; Griewank, K G

    2016-07-01

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

  5. Reinduction of PD1-inhibitor therapy: first experience in eight patients with metastatic melanoma.

    PubMed

    Blasig, Hanna; Bender, Carolin; Hassel, Jessica C; Eigentler, Thomas K; Sachse, Michael M; Hiernickel, Julia; Koop, Anika; Satzger, Imke; Gutzmer, Ralf

    2017-03-02

    Significant progress has been made in the treatment of metastatic melanoma during the last years. Approval of immune-checkpoint inhibitors and targeted therapies has been achieved recently. The sequencing of these therapies is an important issue. Here, we report our experience with the treatment and retreatment with PD1-inhibitors (PD1i) in eight patients. The patients (two female and seven male with a median age of 70 years, all melanoma stage IV, M1c) underwent a first treatment period with PD1i for a median of 5.5 months. Three (37.5%) patients had a stable disease as best response, two (25%) showed progression, two (25%) showed partial response, and one (12.5%) achieved complete remission. PD1i was discontinued due to disease progression in seven patients and due to side effects (pancreatitis) in one patient. Patients were subsequently treated with ipilimumab (n=2), or chemotherapy (n=4), or no other medical treatment (n=2). All eight patients were subsequently retreated with PD1i for a median of 2.5 months. One (12.5%) developed a partial response, whereas in three patients (37.5%) the disease was stabilized. PD1i have shown a high and durable response rate in the first-line treatment of metastatic melanoma. Our study suggests PD1i retreatment as a reasonable option for selected patients. Further investigations are needed to verify the value of PD1i re-exposure and to identify subgroups of patients who can benefit.

  6. A phase II study of REOLYSIN(®) (pelareorep) in combination with carboplatin and paclitaxel for patients with advanced malignant melanoma.

    PubMed

    Mahalingam, Devalingam; Fountzilas, Christos; Moseley, Jennifer; Noronha, Nicole; Tran, Hue; Chakrabarty, Romit; Selvaggi, Giovanni; Coffey, Matthew; Thompson, Brad; Sarantopoulos, John

    2017-04-01

    REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN(®) in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN(®), including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN(®) combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN(®) with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.

  7. Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies

    PubMed Central

    Fisher, Kevin E.; Zhang, Linsheng; Wang, Jason; Smith, Geoffrey H.; Newman, Scott; Schneider, Thomas M.; Pillai, Rathi N.; Kudchadkar, Ragini R.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Lawson, David H.; Delman, Keith A.; El-Rayes, Bassel F.; Wilson, Malania M.; Sullivan, H. Clifford; Morrison, Annie S.; Balci, Serdar; Adsay, N. Volkan; Gal, Anthony A.; Sica, Gabriel L.; Saxe, Debra F.; Mann, Karen P.; Hill, Charles E.; Khuri, Fadlo R.; Rossi, Michael R.

    2017-01-01

    We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID:26801070

  8. Uveal melanoma: estimating prognosis.

    PubMed

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

    2015-02-01

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

  9. Hsp90 Inhibitor AT13387, Dabrafenib, and Trametinib in Treating Patients With Recurrent Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-03-13

    BRAF V600E Mutation Present; BRAF V600K Mutation Present; Metastatic Malignant Solid Neoplasm; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma; Unresectable Solid Neoplasm

  10. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    SciTech Connect

    Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2013-09-13

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM

  11. CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT.

    PubMed

    Bier, Georg; Hoffmann, Vera; Kloth, Christopher; Othman, Ahmed E; Eigentler, Thomas; Garbe, Claus; La Fougère, Christian; Pfannenberg, Christina; Nikolaou, Konstantin; Klumpp, Bernhard

    2016-04-01

    Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT. Fifty patients (age 61 ± 15.12 years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions. According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05). In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow

  12. Long Noncoding RNA PVT1 Promotes Melanoma Progression Via Endogenous Sponging MiR-26b.

    PubMed

    Wang, Bao-Juan; Ding, Hong-Wei; Ma, Guo-An

    2017-04-12

    Melanoma is an extremely aggressive and high mortality skin malignant tumor, and various long noncoding RNAs (lncRNAs)have been reported to be associated with the oncogenesis of melanoma. The purpose of this study is to investigate the potential roles of lncRNA PVT1 in melanoma progression and to explore the possible mechanisms. A total of 35 patients who were diagnosed as malignant melanoma were enrolled in this study. Expression of PVT1 was significantly up-regulated in melanoma tissue and associated with poor prognosis. Loss-of-function experiments showed that PVT1 knock-down markedly suppressed the proliferation activity, induced cell cycle arrest at G0/G1 phase, and enhanced the apoptosis of melanoma cell lines. Bioinformatics analysis and dual-luciferase reporter assay revealed that PVT1 directly bound to miR-26b, which had been verified as a tumor suppressor in melanoma. Moreover, further functional rescue experiments revealed that PVT1 knock-down could observably reverse the tumor-promoting role of miR-26b inhibitor. Overall, our study demonstrates the oncogenic role of PVT1 as a miR-26b sponge, possibly providing a novel therapeutic target for melanoma.

  13. Thiopurines related malignancies in inflammatory bowel disease: Local experience in Granada, Spain

    PubMed Central

    Gómez-García, María; Cabello-Tapia, Maria José; Sánchez-Capilla, Antonio Damián; De Teresa-Galván, Javier; Redondo-Cerezo, Eduardo

    2013-01-01

    , 27.27% (112 patients) and 11.66% (50 patients) received treatment with Infliximab and Adalimumab respectively, but only 1.83% (7 patients) and 0.78% (3 patients) received these drugs in the group of patients who did not received thiopurines (P < 0.001 and P < 0.001 respectively). Finally, 6.8% (29 patients) among those treated with thiopurines have received other immunesupresants (Methotrexate, Tacrolimus, Cyclosporin), compare to 1% (4 patients) of patients not treated with thiopurines (P < 0.001). Among patients treated with thiopurines, 3.97% developed a malignancy, and among those not treated neoplasms presented in 8.1% (P = 0.013). The most frequent neoplasms were colorectal ones (12 cases in patients not treated with thiopurines but none in treated, P < 0.001) followed by non-melanoma skin cancer (8 patients in treated with thiopurines and 6 in not treated, P > 0.05). CONCLUSION: In our experience, thiopurine therapy did not increase malignancies development in IBD patients, and was an efective and safe treatment for these diseases. PMID:23946592

  14. Defining the Pharmacodynamic Profile and Therapeutic Index of NHS-IL12 Immunocytokine in Dogs with Malignant Melanoma

    PubMed Central

    Paoloni, Melissa; Mazcko, Christina; Selting, Kimberly; Lana, Susan; Barber, Lisa; Phillips, Jeffrey; Skorupski, Katherine; Vail, David; Wilson, Heather; Biller, Barbara; Avery, Anne; Kiupel, Matti; LeBlanc, Amy; Bernhardt, Anna; Brunkhorst, Beatrice; Tighe, Robert; Khanna, Chand

    2015-01-01

    Background Interleukin (IL)-12 is a pro-inflammatory cytokine that mediates T-helper type 1 responses and cytotoxic T-cell activation, contributing to its utility as anti-cancer agent. Systemic administration of IL-12 often results in unacceptable toxicity; therefore, strategies to direct delivery of IL-12 to tumors are under investigation. The objective of this study was to assist the preclinical development of NHS-IL12, an immunocytokine consisting of an antibody, which targets necrotic tumor regions, linked to IL-12. Specifically this study sought to evaluate the safety, serum pharmacokinetics, anti-tumor activity, and immune modulation of NHS-IL12 in dogs with naturally occurring cancers. Methodology/Principal Findings A rapid dose-escalation study of NHS-IL12 administered subcutaneously to dogs with melanoma was conducted through the Comparative Oncology Trials Consortium (COTC). Eleven dogs were enrolled in four dose-escalation cohorts; thereafter, an additional seven dogs were treated at the defined tolerable dose of 0.8 mg/m2. The expanded cohort at this fixed dose (ten dogs in total) was accrued for further pharmacokinetics and pharmacodynamics assessment. NHS-IL12 levels, serum cytokine concentrations, and peripheral blood mononuclear cell characterization (post-treatment) and draining lymph node immune profiling, and tumor biopsies (pre- and post-treatment) were collected. Adverse events included thrombocytopenia, liver enzymopathies, fever, and vasculitis. Correlation between interferon (IFN)-γ induction, adverse events, and NHS-IL12 exposure (maximum concentration and area under the concentration-time curve) were dose-dependent. Serum IL-10 levels and intratumoral CD8+ populations increased after treatment. Partial responses, according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, were observed in two dogs treated with NHS-IL12 0.8 mg/m2 and 1.6 mg/m2. Conclusions/Significance NHS-IL12 was administered safely to dogs with melanoma

  15. [Solar radiation and melanomas--is there any doubt about the connection?].

    PubMed

    Moan, J

    1998-06-10

    Arguments for and against there being a connection between exposure to solar radiation and cutaneous, malignant melanoma are reviewed. Recent experiments with animals and epidemiological observations provide relatively strong arguments that solar radiation causes cutaneous, malignant melanoma. Furthermore, epidemiological data from Norway and Australia support the assumption that UVA-radiation plays a significant role in melanoma induction; this is in agreement with data from experiments with Xiphophorus and Monodelphis domestica. A new hypothesis for melanoma induction is presented: Radiation absorbed by melanin in melanocytes generates free radicals that may activate the carcinogenic process. Radicals produced by light absorption in melanin in the upper layers of the epidermis are not able to diffuse as far down as to the melanocytes. Thus, this melanin may be protective, while that in the melanocytes may be a photocarcinogen. Findings that support this hypothesis are discussed.

  16. Triggering Apoptotic Death of Human Malignant Melanoma A375.S2 Cells by Bufalin: Involvement of Caspase Cascade-Dependent and Independent Mitochondrial Signaling Pathways

    PubMed Central

    Hsiao, Yu-Ping; Yu, Chun-Shu; Yu, Chien-Chih; Yang, Jai-Sing; Chiang, Jo-Hua; Lu, Chi-Cheng; Huang, Hui-Ying; Tang, Nou-Ying; Yang, Jen-Hung; Huang, An-Cheng; Chung, Jing-Gung

    2012-01-01

    Bufalin was obtained from the skin and parotid venom glands of toad and has been shown to induce cytotoxic effects in various types of cancer cell lines, but there is no report to show that whether bufalin affects human skin cancer cells. The aim of this investigation was to study the effects of bufalin on human malignant melanoma A375.S2 cells and to elucidate possible mechanisms involved in induction of apoptosis. A375.S2 cells were treated with different concentrations of bufalin for a specific time period and investigated for effects on apoptotic analyses. Our results indicated that cells after exposure to bufalin significantly decreased cell viability, and induced cell morphological changes and chromatin condensation in a concentration-dependent manner. Flow cytometric assays indicated that bufalin promoted ROS productions, loss of mitochondrial membrane potential (ΔΨm), intracellular Ca2+ release, and nitric oxide (NO) formations in A375.S2 cells. Additionally, the apoptotic induction of bufalin on A375.S2 cells resulted from mitochondrial dysfunction-related responses (disruption of the ΔΨm and releases of cytochrome c, AIF, and Endo G), and activations of caspase-3, caspase-8 and caspase-9 expressions. Based on those observations, we suggest that bufalin-triggered apoptosis in A375.S2 cells is correlated with extrinsic- and mitochondria-mediated multiple signal pathways. PMID:22719785

  17. Functional graphene oxide as a plasmid-based Stat3 siRNA carrier inhibits mouse malignant melanoma growth in vivo

    NASA Astrophysics Data System (ADS)

    Yin, Di; Li, Yang; Lin, Hang; Guo, Baofeng; Du, Yanwei; Li, Xin; Jia, Huijie; Zhao, Xuejian; Tang, Jun; Zhang, Ling

    2013-03-01

    Graphene oxide (GO) has attracted intensive interest in the biomedical field in recent years. We investigate whether the use of functional graphene oxide as an efficient delivery system for delivering specific molecular antitumor therapeutics in vivo could achieve a more excellent antitumor effect. Constitutive activation of signal transducer and activator of transcription 3 (Stat3) promotes survival in a wide spectrum of human cancers. In this paper, we study the in vivo behavior of graphene oxide chemically functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) as a plasmid-based Stat3-specific small interfering RNA (siRNA) carrier in mouse malignant melanoma. The in vivo results indicate significant regression in tumor growth and tumor weight after plasmid-based Stat3 siRNA delivered by GO-PEI-PEG treatment. Moreover, there was no significant side effect from GO-PEI-PEG treatment according to histological examination and blood chemistry analysis in mice. Thus, our work is the first success of using GO-PEI-PEG as a promising carrier for plasmid Stat3 siRNA delivery and down-regulation of Stat3 by a polymer-mediated vehicle and suggests the great promise of graphene in biomedical applications such as cancer treatment.

  18. [The quantitative immunochemical determination of specific antibodies against Candida albicans within the scope of immunological testing in the malignant melanoma (author's transl)].

    PubMed

    Schwartze, G; Friedrich, E; Kühn, G; Lübbe, D

    1980-01-01

    Precipitating antibodies against a polysaccharide antigen from Candida albicans were in the human serum determined quantitatively by the aid of a reversed radial immunodiffusion technique. The gel, therewith, contained the antigens, whilst into the gel's punching holes the serum specimens and the calibrated standards were filled in. Amplifying examinations of the course in patients suffering from malignant melanoma, the findings of the methods used hitherto were compared within the scope of an immunological status (in vivo-skin testing by dinitrochlorobenzene, Candida antigen, trichophytin, and tuberculin, precipitation test after Ouchterlony, immunofluorescence-optical evidence of Candida antibodies as well as determination of the Candida antibodies. In contrast to the hitherto available qualitative or semi-quantitative methods evidencing humoral antibodies, we consider the feasibility of simply workable quantitative determinations of antibodies to be an enrichment of the scale of methods. The reversed Mancini technique, simultaneously, is appropriate to determine specific antibodies against other diagnostically relevant antigens, so far as precipitating antigen/antibody complexes are formed. Therewith, commercially available testing kits could favour the standardization.

  19. Local distribution and concentration of intravenously injected sup 131 I-9. 2. 27 monoclonal antibody in human malignant melanoma

    SciTech Connect

    Del Vecchio, S.; Reynolds, J.C.; Carrasquillo, J.A.; Blasberg, R.G.; Neumann, R.D.; Lotze, M.T.; Bryant, G.J.; Farkas, R.J.; Larson, S.M. )

    1989-05-15

    Regional measurements of {sup 131}I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of {sup 131}I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

  20. Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

    2016-03-01

    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.

  1. Sentinel lymph node biopsy in melanoma: Our 8-year clinical experience in a single French institute (2002–2009)

    PubMed Central

    2012-01-01

    Background Since the introduction of sentinel lymph node biopsy (SLNB), its use as a standard of care for patients with clinically node-negative cutaneous melanoma remains controversial. We wished to evaluate our experience of SLNB for melanoma. Methods A single center observational cohort of 203 melanoma patients with a primary cutaneous melanoma (tumour thickness > 1 mm) and without clinical evidence of metastasis was investigated from 2002 to 2009. Head and neck melanoma were excluded. SLN was identified following preoperative lymphoscintigraphy and intraoperative gamma probe interrogation. Results The SLN identification rate was 97%. The SLN was tumor positive in 44 patients (22%). Positive SLN was significantly associated with primary tumor thickness and microscopic ulceration. The median follow-up was 39.5 (5–97) months. Disease progression was significantly more frequent in SLN positive patients (32% vs 13%, p = 0.002). Five-year DFS and OS of the entire cohort were 79.6% and 84.6%, respectively, with a statistical significant difference between SLN positive (58.7% and 69.7%) and SLN negative (85% and 90.3%) patients (p = 0.0006 and p = 0.0096 respectively). Postoperative complications after SLNB were observed in 12% of patients. Conclusion Our data confirm previous studies and support the clinical usefulness of SLNB as a reliable and accurate staging method in patients with cutaneous melanoma. However, the benefit of additional CLND in patients with positive SLN remains to be demonstrated. PMID:23228015

  2. Malignant intraperitoneal mesothelioma-Başkent University experience

    PubMed Central

    Macuks, Ronalds; Özdemir, Halis; Dursun, Polat; Özen, Özlem Işıksaçan; Haberal, Nihan; Ayhan, Ali

    2011-01-01

    Objective To evaluate diagnostic and treatment results of malignant intraperitoneal mesothelioma in one setting. Materials and Method: 12 patients treated for malignant peritoneal mesothelioma from January 2007 to June 2009 in Başkent University Ankara Hospital, Department of Gynaecology and Obstetrics were evaluated. In a retrospective observational study design tumour stage, grade, differentiation, time from first symptoms, pleural involvement, peritoneal cancer index, surgical cytoreduction, chemotherapeutic regimen, number of cycles, disease free survival and overall survival were evaluated. Disease free survival, overall survival, time until first symptoms were researched. Results The main presenting symptom was abdominal distension. Primary cytoreductive surgery followed by chemotherapy was performed in 9 patients. In 6 patients completeness of cytoreductive score below 2 was achieved. As a first line chemotherapy the most often used was cisplatin in combination with pemetrexed. Themean time from first symptoms until the diagnosis was 1.9 months. Disease free survival of 4.4±1.0 months after completing particular treatment and overall 1-year survival of 85.7 % was observed. No correlations between first symptoms (0.27, p=0.52), time until the diagnosis (−0.29, p=0.44) and overall survival were observed. Similarly, correlations between peritoneal cancer index (0.25, p=0.67), prior surgical score (−.45, p=0.37), completeness of cytoreduction score (0.61, p=0.27) and overall survival were not observed. Conclusions Because of the low number of patients and different treatment approaches data from a particular patient setting are inconclusive, but from the literature there is evidence that patients with malignant intraperitoneal mesothelioma should undergo optimal cytoreduction and receive a combination of cisplatin and pemetrexed as a first line chemotherapy for intravenous or cisplatin in different chemotherapy regimens using the intraperitoneal

  3. Worldwide cutaneous malignant melanoma incidences analyzed by sex, age, and skin type over time (1955–2007): Is HPV infection of androgenic hair follicular melanocytes a risk factor for developing melanoma exclusively in people of European-ancestry?

    PubMed Central

    Merrill, Stephen J.; Subramanian, Madhan; Godar, Dianne E.

    2016-01-01

    ABSTRACT The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies. PMID:27588159

  4. KIR gene variability in cutaneous malignant melanoma: influence of KIR2D/HLA-C pairings on disease susceptibility and prognosis.

    PubMed

    Campillo, José A; Legaz, Isabel; López-Álvarez, M Rocío; Bolarín, José Miguel; Las Heras, Beatriz; Muro, Manuel; Minguela, Alfredo; Moya-Quiles, María R; Blanco-García, Rosa; Martínez-Banaclocha, Helios; García-Alonso, Ana M; Alvarez-López, M Rocío; Martínez-Escribano, Jorge A

    2013-05-01

    Natural killer and CD8(+) T cells are believed to be involved in the immune protection against melanoma. Their function may be regulated by a group of receptors defined as killer immunoglobulin-like receptors (KIRs) and their cognate HLA class I ligands. In this study, we analyzed the influence of KIR genes and KIR/HLA-I combinations on melanoma susceptibility and/or prognosis in a Spanish Caucasian population. For this purpose, KIR genotyping by PCR-SSP and HLA-C genotyping by reverse PCR-SSO were performed in 187 melanoma patients and 200 matched controls. We found a significantly low frequency of KIR2DL3 in nodular melanoma (NM) patients (P = 0.001) and in ulcerated melanoma patients (P < 0.0001). Similarly, the KIR2DL3/C1 combination was significantly decreased in melanoma patients (Pc = 0.008) and in patients with sentinel lymph node (SLN) melanoma metastasis (Pc = 0.002). Multivariate logistic regression models showed that KIR2DL3 behaves as a protective marker for NM and ulcerated melanoma (P = 0.02, odds ratio (OR) = 0.14 and P = 0.04, OR = 0.28, respectively), whereas the KIR2DL3/C1 pair acts as a protective marker for melanoma (P = 0.017, OR = 0.54), particularly superficial spreading melanoma (P = 0.02, OR = 0.52), and SLN metastasis (P = 0.0004, OR = 0.14). In contrast, the KIR2DL3(-)/C1C2 genotype seems to be correlated with NM and ulceration. We also report that the KIR2DL1(+)/S1(-)/C2C2 genotype is associated with susceptibility to melanoma and SLN metastasis. Altogether, the study of KIR2D genes and HLA-C ligands may help in assessing cutaneous melanoma risk and prognosis.

  5. High prevalence of the G101W germline mutation in the CDKN2A (P16(ink4a)) gene in 62 Italian malignant melanoma families.

    PubMed

    Mantelli, Michela; Barile, Monica; Ciotti, Paola; Ghiorzo, Paola; Lantieri, Francesca; Pastorino, Lorenza; Catricalà, Caterina; Torre, Gabriella Della; Folco, Ugo; Grammatico, Paola; Padovani, Laura; Pasini, Barbara; Rovini, Dario; Queirolo, Paola; Rainero, Maria Luisa; Santi, Pier Luigi; Sertoli, Roberto M; Goldstein, Alisa M; Bianchi-Scarrà, Giovanna

    2002-01-22

    CDKN2A germline mutation frequency estimates are commonly based on families with several melanoma cases. When we started counseling in a research setting on gene susceptibility analysis in northern and central Italy, however, we mostly found small families with few cases. Here we briefly characterize those kindred, estimate CDKN2A/CDK4 mutation test yields, and provide indications on the possibility of implementing formal DNA testing for melanoma-prone families in Italy. In September 1995 we started genetic counseling in a research setting at our Medical Genetics Center. Screening for CDKN2A/CDK4 mutations was performed on families with two melanoma patients, one of whom was younger than 50 years at onset, the other complying with one of the following: 1) being a first-degree relative, 2) having an additional relative with pancreatic cancer, or 3) having multiple primary melanomas. Sixty-two of 67 (80%) melanoma cases met our criteria. Four previously described CDKN2A mutations (G101W, R24P, V126D, and N71S) were found in 21 of the 62 families (34%) with a high prevalence of G101W (18/21). The percentage of families with two melanoma cases/family harboring a mutation was low (7%, 2/27), but rose to 45% (9/20) if one of the melanoma patients carried multiple melanomas or if pancreatic cancer was present in that family. In the 15 families with three melanoma cases the presence of a mutation was higher (67%, 10/15) and reached 100% in the 4 families with four or more melanoma cases. Our results suggest that CDKN2A/CDK4 counseling-based mutational analysis may be reasonably efficient also for families with two melanoma cases, if one patient carries multiple melanomas or if pancreatic cancer is present in the family.

  6. Long-term treatment outcome after only popliteal lymph node dissection for nodal metastasis in malignant melanoma of the heel: the only "interval node" dissection can be an adequate surgical treatment.

    PubMed

    Tanaka, Kentaro; Mori, Hiroki; Okazaki, Mutsumi; Nishizawa, Aya; Yokozeki, Hiroo

    2013-01-01

    We present a patient with malignant melanoma on his heel. Wide local excision was performed, along with sentinel lymph node biopsy of the inguinal and popliteal lesions. The primary site was clear of tumor at all margins; the inguinal nodes were negative, but the popliteal node was positive for metastatic melanoma. Only radical popliteal lymph node dissection was performed. The patient went on to receive adjuvant chemoimmunotherapy. There was no recurrence or complication until the long-term followup. Popliteal drainage from below the knee is uncommon, and the rate of popliteal-positive and inguinal-negative cases is estimated to be less than 1% of all melanomas. There is no established evidence about how to treat lymph nodes in these cases. Because we considered popliteal nodes as a regional, not interval, lymph node basin, only popliteal lymph node dissection was performed, and good postoperative course was achieved. The first site of drainage is the sentinel node, and the popliteal node can be a sentinel node. The inguinal node is not a sentinel node in all lower extremity melanomas. This case illustrates the importance of individual detailed investigation of lymphatic drainage patterns from foot to inguinal and popliteal nodes.

  7. Correlation of cell cycle regulatory proteins (p53 and p16(ink)⁴(a)) and bcl-2 oncoprotein with mitotic index and thickness of primary cutaneous malignant melanoma.

    PubMed

    Kostov, Miloš; Mijović, Zaklina; Mihailović, Dragan; Cerović, Snežana; Stojanović, Miroslav; Jelić, Marija

    2010-11-01

    The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl-2 oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51%) male and 26 (49%) female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05), whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.

  8. Management of malignant pleural mesothelioma—The European experience

    PubMed Central

    2014-01-01

    Management of malignant pleural mesothelioma (MPM) remains a clinical challenge and the incidence of the disease will continue to increase worldwide. Several aspects of mesothelioma treatment are discussed controversially, in particular, regarding extent and best type of surgery, radiotherapy, and the role of neoadjuvant or adjuvant treatment. However, best survival data is reported from groups using multimodality treatment including macroscopic complete resection (MCR) achieved by either extrapleural pneumonectomy (EPP) or (extended) pleurectomy/decortication for patients qualifying from the tumor biology, stage, and patient’s performance status and comorbidities. Several aspects have to be considered during surgery but morbidity and mortality have been reduced at experienced centres. The final analysis of extended selection algorithms is pending. PMID:24868442

  9. Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

    PubMed Central

    Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

    2015-01-01

    For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection. PMID:26413188

  10. Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination.

    PubMed

    Piras, L A; Riccardo, F; Iussich, S; Maniscalco, L; Gattino, F; Martano, M; Morello, E; Lorda Mayayo, S; Rolih, V; Garavaglia, F; De Maria, R; Lardone, E; Collivignarelli, F; Mignacca, D; Giacobino, D; Ferrone, S; Cavallo, F; Buracco, P

    2016-05-04

    Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78-1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75-1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non-vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.

  11. Trends in net survival from skin malignant melanoma in six European Latin countries: results from the SUDCAN population-based study.

    PubMed

    Galceran, Jaume; Uhry, Zoé; Marcos-Gragera, Rafael; Borràs, Joan

    2017-01-01

    In Europe as a whole, survival from skin malignant melanoma (SMM) has increased constantly since the 1980s. The aim of the SUDCAN collaborative study was to compare the trends in the 5-year net survival from SMM and in related excess mortality rate between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland). The data were extracted from the EUROCARE-5 database (end of follow-up: 01 January 2009). First, the net survival was studied over the 2000-2004 period using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland and from 2000 to 2004 in Belgium and Portugal. The analyses were carried out using a flexible excess rate modeling. Over the 2000-2004 period, the 5-year net survival from SMM ranged from 79 (Portugal) to 90% (Switzerland). In all countries, net survival was higher in women versus men and in young versus old age groups. From 1992 to 2004, the 5-year net survival increased the most in the countries with the lowest survivals in 1992 (+9% in Italy and Spain vs. +2% in Switzerland or +4% in France). The differences between countries decreased between 1992 and 2004. Although survival increased to a lower or higher extent in all countries during the period studied, significant differences in net survival from SMM persisted among the six countries studied. Health policies should mainly enhance early diagnosis by increasing public awareness and with screening campaigns. Furthermore, new immunotherapies, which will be approved soon hopefully, should also be used to improve the outcomes of SMM treatment.

  12. The melanocortin 1 receptor (Mc1r) variants do not account for the co-occurrence of Parkinson's disease and malignant melanoma.

    PubMed

    Elincx-Benizri, Sandra; Inzelberg, Rivka; Greenbaum, Lior; Cohen, Oren S; Yahalom, Gilad; Laitman, Yael; Djaldetti, Ruth; Orlev, Yael; Scope, Alon; Azizi, Esther; Friedman, Eitan; Hassin-Baer, Sharon

    2014-12-01

    Parkinson's disease (PD) is characterized by loss of melanin-positive dopaminergic neurons in the substantia nigra. Malignant melanoma (MM), a melanocyte-derived neoplasm, occurs with higher than expected frequency among PD patients. Red-haired individuals exhibit a threefold risk for developing MM than dark-haired people; PD risk also increases with lighter hair color. One plausible explanation for the associations between MM, hair color, and PD is the melanocortin-1 receptor (MC1R) gene that plays a key role in hair and skin pigmentation as well as in MM predisposition. We hypothesized that specific MC1R variants may predispose to both MM and PD. Genotyping of the MC1R gene was performed for 16 PD patients with MM (PD+ MM+) and for three sets of age, sex, and ethnically matched controls, including 36 patients with PD (PD+ MM-), 37 with MM (PD- MM+) and 37 with neither diagnosis (PD- MM-). No association was found between MC1R variants and the co-occurrence of PD and MM. The risk for MM was higher in carriers of two MC1R variants versus with no MC1R variant (odds ratio (OR)=5.0, 95% confidence interval (CI) 1.7-14.4, p=0.003). The risk for PD in carriers of two MC1R variants was markedly lower (OR=0.213, 95% CI 0.063-0.725) compared with individuals with no MC1R variant (p=0.013). In this study, MC1R variants were not associated with both MM and PD. Further studies in larger cohorts are necessary to confirm these preliminary results.

  13. An intense and unforgettable experience: the lived experience of malignant wounds from the perspectives of patients, caregivers and nurses.

    PubMed

    Alexander, Susan J

    2010-12-01

    Malignant wounds occur infrequently, but are typically described as devastating and overwhelming. However, there has been little formalised research, and the vast majority of existing malignant wound literature comprises reports of health care professionals from their management of the physical symptoms. Few studies have investigated the lived experience from the perspectives of patients and nurses and none have investigated the experiences of lay caregivers caring for a patient with a malignant wound. As a result, there has been little mention in existing literature of the non physical issues associated with malignant wounds or how they might be addressed. The purpose of this study was to address this gap in knowledge by investigating the lived experience of malignant wounds from the perspectives of those living it. In-depth interviews were conducted with patients, caregivers and nurses. The data were analysed thematically within a hermeneutic phenomenological methodology to show four themes: (i) malodour; (ii) new mode of being-in-the-world; (iii) still room for hope and (iv) enduring memories. Although this study confirmed previous findings that malodour was one of the worst aspects of malignant wounds, it was significant that the other three themes occurred in the previously largely overlooked psychosocial domain.

  14. Absence of germline CDKN2A mutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?

    PubMed Central

    Di Lorenzo, Sara; Fanale, Daniele; Corradino, Bartolo; Caló, Valentina; Rinaldi, Gaetana; Bazan, Viviana; Giordano, Antonio; Cordova, Adriana; Russo, Antonio

    2016-01-01

    ABSTRACT Germline CDKN2A mutations have been described in 25% to 40% of melanoma families from several countries. Sicilian population is genetically different from the people of Europe and Northern Italy because of its historical background, therefore familial melanoma could be due to genes different from high-penetrance CDKN2A gene. Four hundred patients with cutaneous melanoma were observed in a 6-years period at the Plastic Surgery Unit of the University of Palermo. Forty-eight patients have met the criteria of the Italian Society of Human Genetics (SIGU) for the diagnosis of familial melanoma and were screened for CDKN2A and CDK4 mutations. Mutation testing revealed that none of the families carried mutations in CDK4 and only one patient harboured the rare CDKN2A p.R87W mutation. Unlike other studies, we have not found high mutation rate of CDKN2A in patients affected by familial melanoma or multiple melanoma. This difference could be attributed to different factors, including the genetic heterogeneity of the Sicilian population. It is likely that, as in the Australian people, the inheritance of familial melanoma in this island of the Mediterranean Sea is due to intermediate/low-penetrance susceptibility genes, which, together with environmental factors (as latitude and sun exposure), could determine the occurrence of melanoma. PMID:26650572

  15. Absence of germline CDKN2A mutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?

    PubMed

    Di Lorenzo, Sara; Fanale, Daniele; Corradino, Bartolo; Caló, Valentina; Rinaldi, Gaetana; Bazan, Viviana; Giordano, Antonio; Cordova, Adriana; Russo, Antonio

    2016-01-01

    Germline CDKN2A mutations have been described in 25% to 40% of melanoma families from several countries. Sicilian population is genetically different from the people of Europe and Northern Italy because of its historical background, therefore familial melanoma could be due to genes different from high-penetrance CDKN2A gene. Four hundred patients with cutaneous melanoma were observed in a 6-years period at the Plastic Surgery Unit of the University of Palermo. Forty-eight patients have met the criteria of the Italian Society of Human Genetics (SIGU) for the diagnosis of familial melanoma and were screened for CDKN2A and CDK4 mutations. Mutation testing revealed that none of the families carried mutations in CDK4 and only one patient harboured the rare CDKN2A p.R87W mutation. Unlike other studies, we have not found high mutation rate of CDKN2A in patients affected by familial melanoma or multiple melanoma. This difference could be attributed to different factors, including the genetic heterogeneity of the Sicilian population. It is likely that, as in the Australian people, the inheritance of familial melanoma in this island of the Mediterranean Sea is due to intermediate/low-penetrance susceptibility genes, which, together with environmental factors (as latitude and sun exposure), could determine the occurrence of melanoma.

  16. Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience.

    PubMed

    Zilinska, Z; Sersenova, M; Chrastina, M; Sr, J Breza; Bena, L; Baltesova, T; Jurcina, A; Roland, R; Lackova, E; Cellar, M; Laca, L; Dedinska, I

    2017-01-05

    Malignancies are one of the three major causes of renal recipient´s death with a functioning graft after cardiovascular diseases and infections. Among the variety of risk factors, including conventional and specific to transplant recipients, the duration of immunosuppressive therapy, the intensity of therapy, and the type of immunosuppressive agent all have an impact on development of post-transplant malignancy. The aim of our retrospective study was to document the incidence, the type of malignancies, the patient/graft survival in the group of kidney transplant recipients in Slovak Republic, and to identify the factors which influenced the outcome. We analyzed the data of 1421 patients who underwent renal transplantation from deceased or living donors in the period from 2007 to 2015 in the Slovak transplant centers. The incidence of malignant tumors was 6%, the malignancy was diagnosed in 85 patients at the age of 54.1 ± 9.8 years, more frequently in men (68.2 %; P < 0.0001). The mean time of malignancy occurrence was 45 months after transplantation. The most frequent malignancies were skin cancers- basal cell carcinoma (BCC) in 17.6%, squamous cell carcinoma (SCC) in 8.2%, and malignant melanoma (MM) in 2.4% of patients, followed by non-skin tumors such as renal cell carcinoma (RCC) in 16.5%, cancer of colon in 12.9%, prostatic cancer in 9.4%, breast cancer in 9.4%, cancer of lung in 7.1%, post-transplant lymphoproliferative disease (PTLD) in 2.4%, cancer of urine bladder in 2.4%, and cancer of sublingual gland in 1.17% of patients. Surgical treatment was used in 40% of patients, chemotherapy in 7.1%, radiotherapy in 2.4%, treatment with biological agents in 15.3%, combined therapy in 29.4% and palliative treatment in 5.9% of patients. 55.3% of patients underwent conversion from other immunosuppressive agents into mTORi at the time of malignancy occurrence. The remission was achieved in 48.2% of patients, 28.2% of patients were in the oncology treatment in the

  17. [Colorectal melanoma: review of two distinct forms of presentation].

    PubMed

    Díaz-Sánchez, Antonio; Lara, Miguel Ángel; Ortega, Patricia; Aramendi, Teresa; González, Carmen; Alberdi, José M; Del Valle, Emilio; Casado, Isabel; Campos, Rocío; Aldeguer, Mercedes

    2011-02-01

    Malignant melanoma of the colon and rectum is an infrequent disease. Primary anorectal melanoma accounts for 0.1-4.6% of all malignant neoplasms of the anal canal. Melanoma metastatic to the colon is symptomatic only in 4.4% of patients with a primary melanoma at another site and most of these tumors are diagnosed postmortem. We report two cases of colorrectal malignant melanoma. The first case concerned a patient with rectal bleeding who was diagnosed with a rectal lesion compatible with melanoma. Abdominoperineal resection was performed due to positivity of the sentinel lymph node. We discuss the utility of sentinel lymph node detection in this kind of tumor. In the second case, we discovered a polyp compatible with metastatic melanoma in the transverse colon in a patient with a previous diagnosis of melanoma. In both surgical specimens, the diagnosis of melanoma was confirmed by positivity for protein S-100, Melan-A and HMB-45.

  18. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies.

    PubMed

    Höckel, Michael

    2015-03-01

    Gynecologic cancers recurring in the pelvis are generally advanced in malignant progression limiting curative treatment approaches. The cancer field theory links cancer progression to reversed morphogenesis and allows the exact anatomical delineation of the cancer field, i.e., the tissue compartment of potential tumor infiltration related to the tumor's ontogenetic stage. Cancer surgery is redefined with the resection of ontogenetic stage-related cancer fields instead of the mere removal of the malignant tumor with an uninvolved tissue margin. Most gynecologic pelvic malignancies recurring in the pelvis represent ontogenetic stages 3 and 4. (Laterally) extended endopelvic resection ((L)EER) has been designed to resect the cancer fields of gynecologic tumors in these advanced ontogenetic stages. This paper reports long-term experience with (L)EER for relapsed pelvic malignancies strongly supporting the cancer field theory and the principle and practice of cancer field resection.

  19. Etiology of melanoma.

    PubMed

    Koh, H K; Sinks, T H; Geller, A C; Miller, D R; Lew, R A

    1993-01-01

    the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.

  20. Induction of primary cutaneous melanocytic neoplasms in urokinase-type plasminogen activator (uPA)-deficient and wild-type mice: cellular blue nevi invade but do not progress to malignant melanoma in uPA-deficient animals.

    PubMed

    Shapiro, R L; Duquette, J G; Roses, D F; Nunes, I; Harris, M N; Kamino, H; Wilson, E L; Rifkin, D B

    1996-08-01

    Evidence suggests that the plasminogen activators (PAs), in particular urokinase-type PA (uPA), play a pivotal role in tumor invasion and metastasis. We studied the contribution of the PAs to the malignant phenotype through the chemical induction of melanocytic neoplasms in uPA-deficient mice. Primary tumors were induced and promoted concurrently in 35 uPA-/- deficient and 35 uPA+/+ wild-type mice using a single application of 7,12-dimethylbenz(a)anthracene followed by repetitive applications of croton oil. Animals were sacrificed at 60-day intervals for 1 year. At necropsy, the four largest pigmented lesions in each animal were excised, characterized histologically, and evaluated microscopically for evidence of invasion. The regional lymph nodes, lungs, and solid abdominal visceral organs were sectioned and examined microscopically for evidence of metastatic disease. Cellular blue nevi were induced in 100% of uPA-/- and uPA+/+ promoted animals. Although a reduction in the radial and vertical progression of these lesions was noted in the uPA-deficient mice compared with the wild-type group, more than 95% of cellular blue nevi induced in both groups of animals invaded the underlying tissues. These lesions did not metastasize to the regional lymph nodes. Malignant melanoma arose in 5 of 35 (14.3%) of promoted wild-type mice. These tumors were locally aggressive, produced tissue-type PA, but were not metastatic to the regional nodes, lungs, or abdominal viscera. These results indicate that the invasive capability of melanocytic lesions may depend more on tissue-type PA than uPA activity. No melanomas were induced in the uPA-/- mice. The resistance of the uPA -/- strain to melanoma induction suggests that uPA contributes to malignant progression. We propose that the absence of uPA negatively affects tumorigenesis by decreasing the liberation and availability of growth factors such as basic fibroblast growth factor.

  1. Quantitative label-free mass spectrometry analysis of formalin-fixed, paraffin-embedded tissue representing the invasive cutaneous malignant melanoma proteome

    PubMed Central

    Dowling, Paul; Moran, Benvon; McAuley, Edel; Meleady, Paula; Henry, Michael; Clynes, Martin; McMenamin, Mairin; Leonard, Niamh; Monks, Mary; Wynne, Bairbre; Ormond, Patrick; Larkin, Annemarie

    2016-01-01

    Understanding the events at a protein level that govern the progression from melanoma in situ to invasive melanoma are important areas of current research to be developed. Recent advances in the analysis of formalin-fixed, paraffin-embedded tissue by proteomics, particularly using the filter-aided sample preparation protocol, has opened up the possibility of studying vast archives of clinical material and associated medical records. In the present study, quantitative protein profiling was performed using tandem mass spectrometry, and the proteome differences between melanoma in situ and invasive melanoma were compared. Biological pathway analyses revealed several signalling pathways differing between melanoma in situ and invasive melanoma, including metabolic pathways and the phosphoinositide 3-kinase-Akt signalling pathway. Selected proteins of interest (14–3-3ε and fatty acid synthase) were subsequently investigated using immunohistochemical analysis of tissue microarrays. Identifying the key proteins that play significant roles in the establishment of a more invasive phenotype in melanoma may ultimately aid diagnosis and treatment decisions. PMID:27899996

  2. [Skin cancer and sun radiation: peruvian experience in the prevention and early detection of skin cancer and melanoma].

    PubMed

    Sordo, Carlos; Gutiérrez, César

    2013-03-01

    The excessive exposure to sun radiation, especially to ultraviolet radiation (UV), has led to various diseases, in particular to skin cancer. In 1995, the Peruvian Dermatological Association conducted the first "Campaign for Education, Prevention and Early Detection of Skin Cancer and Melanoma" called "Mole's Day". The Ministry of Health has turned it into an official event, and the Health Social Security (EsSalud) also participates. This is a free campaign that takes place every year nationwide. 118,092 people attended from 1995 to 2011 in 76 sites distributed in 18 cities throughout the country. A cutaneous lesion were malignancy was suspected was identified in 2.8% of people attending, out of which 64.9% corresponded to basal cell carcinoma, 26.7% to cutaneous melanoma, and 8.4% to squamous cell carcinoma. These campaigns are highly important not only because of the assistance given, but also because of the educational activities aimed at promoting a prevention culture in favor of the most vulnerable populations. Finally, we believe it is important to continue educating the population on skin cancer prevention, to build awareness among the authorities so that they actively participate in the performance of these activities, and to ask all physicians to coordinately join this initiative, in order to continue growing, and to improve all that has been attained for the benefit of our country.

  3. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    PubMed

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

  4. Debilitating Skin Toxicity Associated with Pembrolizumab Therapy in an 81-Year-Old Female with Malignant Melanoma

    PubMed Central

    Khokhar, Muhammad O.; Kettle, Jacob; Palla, Amruth R.

    2016-01-01

    Frequently described immune-mediated adverse effects of immune therapy include dermatological complications, hepatitis, colitis, pneumonitis, and endocrinopathies. As utilization of pembrolizumab and related agents continues to expand both in the available indications as well as duration of exposure, there remains a significant potential to uncover previously undescribed adverse events. From a dermatological standpoint, 39% of patients receiving pembrolizumab therapy experience some form of skin-related drug toxicity [Naidoo et al.: Ann Oncol 2015;26: 2375–2391]. We describe a case of pembrolizumab-induced disabling autoimmune ectodermal toxicity. PMID:28101032

  5. Prognostic Variables and Surgical Management of Foot Melanoma: Review of a 25-Year Institutional Experience

    PubMed Central

    Rashid, Omar M.; Schaum, Julia C.; Wolfe, Luke G.; Brinster, Nooshin K.; Neifeld, James P.

    2011-01-01

    Introduction. Cutaneous foot melanoma is rare, challenging to manage, and not adequately examined in the literature. This study evaluated the prognostic variables and surgical management of foot melanoma. Materials and Methods. Foot melanoma cases managed at an academic center from 1985 to 2010 were retrospectively reviewed. Results. 46 patients were identified with a broad range of demographic characteristics. Overall recurrence was 32.6%: 19% acral lentiginous, 57% nodular, 66% superficial spreading, 30% melanoma unspecified, 50% severely atypical; 53% ulcerated, 23% nonulcerated; 29% on the dorsum of the foot, 17% heel, 60% ankle, 22% toe, 50% plantar; 0% <1 mm thick, 47% 1–4 mm, 33% >4 mm. 13 had positive nodes, 4 (31%) of whom recurred. Prognostic factors and recurrence did not correlate, and survival was 96% with a median followup of 91 months. Conclusions. Aggressive management of foot melanoma may result in excellent long-term survival even following disease recurrence. PMID:22363851

  6. Melanoma: oncogenic drivers and the immune system

    PubMed Central

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

    2015-01-01

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

  7. Uveal melanoma: Estimating prognosis

    PubMed Central

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

    2015-01-01

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

  8. Adjuvant Treatment of Melanoma

    PubMed Central

    Moreno Nogueira, J. A.; Valero Arbizu, M.; Pérez Temprano, R.

    2013-01-01

    Melanomas represent 4% of all malignant tumors of the skin, yet account for 80% of deaths from skin cancer.While in the early stages patients can be successfully treated with surgical resection, metastatic melanoma prognosis is dismal. Several oncogenes have been identified in melanoma as BRAF, NRAS, c-Kit, and GNA11 GNAQ, each capable of activating MAPK pathway that increases cell proliferation and promotes angiogenesis, although NRAS and c-Kit also activate PI3 kinase pathway, including being more commonly BRAF activated oncogene. The treatment of choice for localised primary cutaneous melanoma is surgery plus lymphadenectomy if regional lymph nodes are involved. The justification for treatment in addition to surgery is based on the poor prognosis for high risk melanomas with a relapse index of 50–80%. Patients included in the high risk group should be assessed for adjuvant treatment with high doses of Interferon-α2b, as it is the only treatment shown to significantly improve disease free and possibly global survival. In the future we will have to analyze all these therapeutic possibilities on specific targets, probably associated with chemotherapy and/or interferon in the adjuvant treatment, if we want to change the natural history of melanomas. PMID:23476798

  9. Malignant Melanoma of the Foot

    MedlinePlus

    ... foot and ankle surgeons. All Fellows of the College are board certified by the American Board of Foot and Ankle Surgery. Copyright © 2017 American College of Foot and Ankle Surgeons (ACFAS), All Rights ...

  10. Genetics of pigmentation and melanoma predisposition.

    PubMed

    Pho, L N; Leachman, S A

    2010-02-01

    About 5-10% of human cutaneous malignant melanoma is hereditary and known to involve rare germline mutations in highly penetrant, autosomal dominant genes. These genes are important in cell cycle control but are not responsible for all familial cases of melanoma. Epidemiologic studies have linked specific phenotypic traits including fair skin, light-colored eyes, and poor tanning ability to melanoma risks. The ability to visually discern and define pigmentary phenotypes in humans and in animal models has permitted elucidation of many genes involved in pigmentation and melanin biosynthesis. Additional genetic epidemiological studies have recently identified a subset of these pigmentation genes that are associated with risk for melanoma and other cutaneous malignancies as well as photosensitivity. Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes. These findings emphasize the contribution of pigmentation pathways to melanoma predisposition and tumorigenesis through gene-environment interactions. Since pigmentation genes in the melanin synthesis pathway also confer risk for cutaneous malignancy, a better understanding of the operative molecular mechanisms involved in this relationship has the potential to impact individual risk assessment for cutaneous malignant melanoma in the future. This paper is an overview of our current understanding of pigmentation gene modifications that have been associated with melanoma risk and how these genes can enrich clinical management, prevention, and early detection of malignant melanoma.

  11. Molecular biology of normal melanocytes and melanoma cells.

    PubMed

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

    2013-08-01

    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.

  12. [Choroidal melanoma - evolution and prognosis].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

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

  13. Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

    PubMed Central

    Montagnani Marelli, Marina; Marzagalli, Monica; Moretti, Roberta M.; Beretta, Giangiacomo; Casati, Lavinia; Comitato, Raffaella; Gravina, Giovanni L.; Festuccia, Claudio; Limonta, Patrizia

    2016-01-01

    Malignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of δ-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. δ-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, δ-TT exerted its antitumor effect through activation of the PERK/p-eIF2α/ATF4/CHOP, IRE1α and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of δ-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that δ-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by δ-TT treatment. In conclusion, δ-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. δ-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma. PMID:27461002

  14. Decline in arylsulfatase B leads to increased invasiveness of melanoma cells.

    PubMed

    Bhattacharyya, Sumit; Feferman, Leo; Terai, Kaoru; Dudek, Arkadiusz Z; Tobacman, Joanne K

    2017-01-17

    Arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase) is reduced in several malignancies, but levels in melanoma have not been investigated previously. Experiments were performed in melanoma cell lines to determine ARSB activity and impact on melanoma invasiveness. ARSB activity was reduced ~50% in melanoma cells compared to normal melanocytes. Silencing ARSB significantly increased the mRNA expression of chondroitin sulfate proteoglycan(CSPG)4 and pro-matrix metalloproteinase(MMP)-2, known mediators of melanoma progression. Also, invasiveness and MMP activity increased when ARSB was reduced, and recombinant ARSB inhibited invasiveness and MMP activity. Since the only known function of ARSB is to remove 4-sulfate groups from the N-acetylgalactosamine 4-sulfate residue at the non-reducing end of chondroitin 4-sulfate (C4S) or dermatan sulfate, experiments were performed to determine the transcriptional mechanisms by which expression of CSPG4 and MMP2 increased. Promoter activation of CSPG4 was mediated by reduced binding of galectin-3 to C4S when ARSB activity declined. In contrast, increased pro-MMP2 expression was mediated by increased binding of the non-receptor tyrosine phosphatase SHP2 to C4S. Increased phospho-ERK1,2 resulted from SHP2 inhibition. Combined effects of increased C4S, CSPG4, and MMP2 increased the invasiveness of the melanoma cells, and therapy with recombinant ARSB may inhibit melanoma progression.

  15. Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells.

    PubMed

    Montagnani Marelli, Marina; Marzagalli, Monica; Moretti, Roberta M; Beretta, Giangiacomo; Casati, Lavinia; Comitato, Raffaella; Gravina, Giovanni L; Festuccia, Claudio; Limonta, Patrizia

    2016-07-27

    Malignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of δ-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. δ-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, δ-TT exerted its antitumor effect through activation of the PERK/p-eIF2α/ATF4/CHOP, IRE1α and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of δ-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that δ-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by δ-TT treatment. In conclusion, δ-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. δ-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma.

  16. Nivolumab for Metastatic Melanoma.

    PubMed

    Gupta, A K; Daigle, D

    2016-03-01

    Melanoma is an aggressive skin cancer with a generally poor prognosis at Stage III-IV disease. Traditionally, metastatic melanoma was treated by surgical resection, when possible, and with systemic chemotherapy. New developments in molecular biology have led to the identification of immune checkpoints which are exploited by malignant cells, allowing them to go undetected by the immune system. Nivolumab (Opdivo®) is a human monoclonal antibody which prevents immune inhibition by interacting with PD-1 on tumor cells; thus, increasing tumor-specific T cell proliferation. Nivolumab has demonstrated efficacy superior to that of standard chemotherapy and relative safety in clinical trials. Indeed, the outcomes for patients with advanced melanoma are being improved by novel biologic agents such as nivolumab.

  17. Dabrafenib in metastatic melanoma: a monocentric ‘real life’ experience

    PubMed Central

    Cocorocchio, E; Gandini, S; Alfieri, S; Battaglia, A; Pennacchioli, E; Tosti, G; Spadola, G; Barberis, M; Leo, M Di; Riviello, C; Pala, L; Intelisano, A; Martinoli, C; Ferrucci, PF

    2016-01-01

    Dabrafenib is a potent BRAF-kinase inhibitor. Its activity was evaluated on 40 consecutive metastatic melanoma patients (pts) harboring the V600BRAF mutations. Dabrafenib was administered orally at the dosage of 150 mg b.i.d. daily. ORR was 82%, with 7% CR, 62% PR, 13% SD and 18% PD. The median PFS and OS were seven and 17 months, respectively (median follow-up: 8.5 months). Increased risk of progression was found in pts with elevated LDH, ECOG PS >1 and more than two metastatic sites. Grade 3–4 adverse events were recorded in 4 pts. In this retrospective analysis, Dabrafenib confirmed its role as the standard clinical option in metastatic melanoma pts. PMID:26981153

  18. The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-{alpha}-induced apoptosis

    SciTech Connect

    Wagley, Yadav; Yoo, Yung-Choon; Seo, Han Geuk; Rhee, Man Hee; Kim, Tae-Hyoung; Kang, Keon Wook; Nah, Seung-Yeol; Oh, Jae-Wook . E-mail: ohjw@mail.chosun.ac.kr

    2007-03-23

    Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-{alpha} in combination with IFN-{gamma} in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-{alpha}-resistant B16/F10.9 melanoma cells. A low dose of TNF-{alpha} or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-{alpha}-resistant F10.9 melanoma cells to TNF-{alpha}-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-{alpha} resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-{alpha} responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-{alpha}-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-{alpha}-resistant melanoma cells to TNF-{alpha}-induced apoptosis, may provide a new target for immunotherapy.

  19. Early experiences of planning stereotactic radiosurgery using 3D printed models of eyes with uveal melanomas

    PubMed Central

    Furdová, Alena; Sramka, Miron; Thurzo, Andrej; Furdová, Adriana

    2017-01-01

    Objective The objective of this study was to determine the use of 3D printed model of an eye with intraocular tumor for linear accelerator-based stereotactic radiosurgery. Methods The software for segmentation (3D Slicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from computed tomography and magnetic resonance imaging data. A virtual model was then processed in the slicing software (Simplify3D®) and printed on 3D printer using fused deposition modeling technology. The material that was used for printing was polylactic acid. Results In 2015, stereotactic planning scheme was optimized with the help of 3D printed model of the patient’s eye with intraocular tumor. In the period 2001–2015, a group of 150 patients with uveal melanoma (139 choroidal melanoma and 11 ciliary body melanoma) were treated. The median tumor volume was 0.5 cm3 (0.2–1.6 cm3). The radiation dose was 35.0 Gy by 99% of dose volume histogram. Conclusion The 3D printed model of eye with tumor was helpful in planning the process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures. PMID:28203052

  20. In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma.

    PubMed

    Nath, Lekshmi R; Kumar, S N; Das, Arya A; Nambisan, Bala; Shabna, A; Mohandas, Chellapan; Anto, Ruby John

    2016-01-01

    3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS

  1. The neurotrophin Neuritin1 (cpg15) is involved in melanoma migration, attachment independent growth, and vascular mimicry

    PubMed Central

    Bosserhoff, Anja Katrin; Schneider, Nadja; Ellmann, Lisa; Heinzerling, Lucie; Kuphal, Silke

    2017-01-01

    The neurotrophin Neuritin1 (NRN1; cpg15) belongs to the candidate plasticity gene (CPG) family and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the brain of human adult. Our newest findings document that NRN1 deregulation could contribute also to disease development and have impact on malignant melanoma. Our analyses displayed the over-expression of NRN1 in melanoma in vitro and in vivo, shown by immunohistochemistry and qRT-PCR on microdissected melanoma tissue; furthermore, soluble NRN1 was detectable in tissue culture supernatant and serum of melanoma patients. To investigate the role of NRN1 in melanoma we performed knockdown, over-expression and recombinant-NRN1-treatment experiments affiliated by functional assays. Our results show that migration, attachment independent growth and vasculogenesis were affected after manipulation of NRN1 on endogenous and extrinsic level. Interestingly, high NRN1 serum levels correlate with low MIA serum levels (< 10ng/ml). Therefore, we speculate that NRN1 could be a marker for early melanoma stages, in particular. In summary, we detected an overexpression of NRN1 in melanoma patient. In functional cell culture experiments we found a correlation between NRN1 expression and the cancerous behavior of melanoma cells. PMID:27901477

  2. Expression of Phosphatase and Tensin Homologue, phospho-Akt, and p53 in Acral Benign and Malignant Melanocytic Neoplasms (Benign Nevi, Dysplastic Nevi, and Acral Melanomas)

    PubMed Central

    Lyu, So Min; Wu, Ju Yeon; Byun, Ji Yeon; Choi, Hae Young; Park, Sang Hee

    2016-01-01

    Background The role of the phosphatidylinositol-3 kinase signaling pathway in the development of acral melanoma has recently gained evidence. Phosphatase and tensin homologue (PTEN), one of the key molecules in the pathway, acts as a tumor suppressor through either an Akt-dependent or Akt-independent pathway. Akt accelerates degradation of p53. Objective We assessed the expression of PTEN, phospho-Akt (p-Akt), and p53 by immunohistochemistry in benign acral nevi, acral dysplastic nevi, and acral melanomas in the radial growth phase and with a vertical growth component. Methods Ten specimens in each group were included. Paraffin-embedded specimens were immunostained with antibodies for PTEN, p-Akt, and p53. We scored both the staining intensity and the proportion of positive cells. The final score was calculated by multiplying the intensity score by the proportion score. Results All specimens of benign acral nevi except one showed some degree of PTEN-negative cells. The numbers of p-Akt and p53-positive cells were higher in acral dysplastic nevi and melanoma than in benign nevi. P-Akt scores were 1.7, 1.8, 2.6, and 4.4, and p53 scores were 2.0, 2.1, 3.8, and 4.1 in each group. PTEN and p-Akt scores in advanced acral melanoma were higher than in the other neoplasms. Conclusion The expression of PTEN was decreased and the expression of p-Akt was increased in acral melanoma, especially in advanced cases. The PTEN-induced pathway appears to affect the late stage of melanomagenesis. Altered expression of p-Akt is thought to be due to secondary changes following the loss of PTEN. PMID:27746632

  3. Optimizing LINAC-based stereotactic radiotherapy of uveal melanomas: 7 years' clinical experience

    SciTech Connect

    Dieckmann, Karin . E-mail: Karin.Dieckmann@akhwien.at; Georg, Dietmar; Bogner, Joachim; Zehetmayer, Martin; Petersch, Bernhard; Chorvat, Martin; Weitmann, Hajo; Poetter, Richard

    2006-11-15

    Purpose: To report on the clinical outcome of LINAC-based stereotactic radiotherapy (SRT) of uveal melanomas. Additionally, a new prototype (hardware and software) for automated eye monitoring and gated SRT using a noninvasive eye fixation technique is described. Patients and Methods: Between June 1997 and March 2004, 158 patients suffering from uveal melanoma were treated at a LINAC with 6 MV (5 x 14 Gy; 5 x 12 Gy prescribed to 80% isodose) photon beams. To guarantee identical patient setup during treatment planning (CT and MRI) and treatment delivery, patients were immobilized with a BrainLAB thermoplastic mask. Eye immobilization was achieved by instructing the patient to fixate on a light source integrated into the mask system. A mini-video camera was used to provide on-line information about the eye and pupil position, respectively. A new CT and magnetic resonance (MR) compatible prototype, based on head-and-neck fixation and the infrared tracking system ExacTrac, has been developed and evaluated since 2002. This system records maximum temporal and angular deviations during treatment and, based on tolerance limits, a feedback signal to the LINAC enables gated SRT. Results: After a median follow-up of 33.4 months (range, 3-85 months), local control was achieved in 98%. Fifteen patients (9.0%) developed metastases. Secondary enucleation was performed in 23 patients (13.8%). Long-term side effects were retinopathy (n = 70; 44%), cataract (n = 30; 23%), optic neuropathy (n = 65; 41%), and secondary neovascular glaucoma (n = 23; 13.8%). Typical situations when preset deviation criteria were exceeded were slow drifts (fatigue), large sudden eye movements (irritation), or eye closing (fatigue). In these cases, radiation was reliably interrupted by the gating system. In our clinical setup, the novel system for computer-controlled gated SRT of uveal melanoma was well tolerated by about 30 of the patients treated with this system so far. Conclusion: LINAC-based SRT of

  4. Current Research and Development of Chemotherapeutic Agents for Melanoma

    PubMed Central

    Hsan, Kyaw Minn; Chen, Chun-Chieh; Shyur, Lie-Fen

    2010-01-01

    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. PMID:24281076

  5. Identification of cells initiating human melanomas

    PubMed Central

    Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M.; Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Sayegh, Mohamed H.; Frank, Markus H.

    2012-01-01

    Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1,2 and solid cancers3–6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5− bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ sub-populations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5− progeny, whereas ABCB5− tumour populations give rise, at lower rates, exclusively to ABCB5− cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. PMID:18202660

  6. Genetics and epigenetics of melanoma

    PubMed Central

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-01-01

    Cancer affects multiple organs in the body Malignant melanoma involves the invasion of skin and occasionally mucosal membrane or eye choroidal tissues. The incidence of cutaneous malignant melanoma is on the increase worldwide and is a major concern in current research. The increase is associated with UV irradiation-induced genetic aberrations that stimulate skin melanocytes to develop unlimited growth. This eventually leads to cell immortality, which in turn causes metastases. The present review examines the genetics and epigenetics of this pathological state together with recent perspectives of the therapeutic management of disease. PMID:27899960

  7. Methods of Melanoma Detection.

    PubMed

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

    2016-01-01

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

  8. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  9. Blue light inhibits proliferation of melanoma cells

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    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.

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

    PubMed Central

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

    2011-01-01

    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 fishes, which were previously found to develop melanomas after acute neonatal UVB irradiation. In two separate tumorigenesis experiments, we exposed adult Xiphophorus hybrids to either acute UVB irradiations (5 consecutive daily treatments) or chronic solar irradiations (continuous UVA/UVB treatment for 9 months). Acute adult UVB irradiation resulted in the significant induction of melanomas, and moreover, this induction rate is equivalent to that of animals exposed to acute neonatal UVB irradiation. This study represents the first evidence that acute adult UVB irradiation, in the absence of any early life exposures, induces CMM. Similar to the findings conducted on other divergent melanoma models, including HGF/SF transgenic mice and Monodelphis domestica, prolonged chronic solar UV was not a factor in melanomagenesis. PMID:21457786

  11. Ipilimumab for advanced melanoma: experience from the Spanish Expanded Access Program

    PubMed Central

    Arance, Ana; Lopez Martin, Jose Antonio; Soriano, Virtudes; Muñoz, Eva; Alonso, Lorenzo; Espinosa, Enrique; Lopez Criado, Pilar; Valdivia, Javier; Martin Algarra, Salvador

    2014-01-01

    Ipilimumab, a fully human, recombinant, monoclonal antibody to cytotoxic T-lymphocyte antigen 4 improves overall survival (OS) in previously treated and untreated metastatic melanoma. This retrospective analysis reports data gathered by a questionnaire on the demographics, outcomes, and toxicity of ipilimumab administered through an Expanded Access Program (EAP). Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for four cycles to adults with metastatic melanoma. Efficacy outcomes included complete response, partial response (PR), progressive disease, stabilized disease, and OS. EAP data were collected from EAP physicians. A subgroup analysis examined efficacy in elderly patients (≥70 years) and factors predictive of survival were identified. Of 355 requests for ipilimumab, resulting in 288 treatments, completed questionnaires were received for 153 ipilimumab recipients (median age 58 years, 57.2% men). Efficacy was evaluated in 144 patients: complete response in 1.3%, PR in 9.6%, PR with previous progression 8.4%, stabilized disease in 14.5%, and progressive disease in 66.2%. The median OS was 6.5 months (199 days); 1-year survival was 32.9%. Predictive survival factors included lymphocytes over 1000/ml (P=0.0008) and lactate dehydrogenase more than 1.5×upper limit of normal (P=0.003). Cutaneous, hepatic, and gastrointestinal toxicities were mild. In 30 patients aged more than 70 years, ipilimumab efficacy and tolerability was similar to that of the overall population. In the clinical practice setting, ipilimumab is effective and well tolerated in patients with advanced melanoma, including elderly patients, when administered at the recommended dosage. Ipilimumab improves treatment options for patients who, until recently, have had little hope of an improved prognosis. PMID:25046550

  12. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation

    SciTech Connect

    Ichihashi, M.; Nakanishi, T.; Mishima, Y.

    1982-03-01

    A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.

  13. Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine.

    PubMed

    Propper, D J; Braybrooke, J P; Levitt, N C; O'Byrne, K; Christodoulos, K; Han, C; Talbot, D C; Ganesan, T S; Harris, A L

    2000-06-01

    This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20-41) and 285 days (range 50-1,240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients.

  14. In Vitro Evaluation of the Antioxidant, 3,5-Dihydroxy-4-ethyl-trans-stilbene (DETS) Isolated from Bacillus cereus as a Potent Candidate against Malignant Melanoma

    PubMed Central

    Nath, Lekshmi R.; Kumar, S. N.; Das, Arya A.; Nambisan, Bala; Shabna, A.; Mohandas, Chellapan; Anto, Ruby John

    2016-01-01

    3,5-dihydroxy Q1 -4-ethyl-trans-stilbene (DETS) is a natural stilbene, which was first identified as bioactive bacterial secondary metabolite isolated from Bacillus cereus associated with a rhabditid entomopathogenic nematode. The present study was intended to investigate the antioxidant and anticancer activity of this compound in vitro. Antioxidant activity was investigated by assaying DPPH free radical scavenging, superoxide radical-(O2..) scavenging, hydroxyl radical scavenging and metal chelating activity, which proved that the compound is a powerful antioxidant. The metal chelating activity of DETS was higher than butylated hydroxyanisol (BHA) and gallic acid, two well-known antioxidants. As the molecule exhibited strong antioxidant potential, it was further evaluated for cytotoxic activity toward five cancer cells of various origins. Since the compound has a strong structural similarity with resveratrol (trans- 3,4,5-trihydroxystilbene), a well-studied chemopreventive polyphenolic antioxidant, its anticancer activity was compared with that of resveratrol. Among the five cancer cells studied, the compound showed maximum cytotoxicity toward the human melanoma cell line, [A375, IC50: 24.01 μM] followed by cervical [HeLa-46.17 μM], colon [SW480- 47.28 μM], liver [HepG2- 69.56 μM] and breast [MCF-7- 84.31 μM] cancer cells. A375 was much more sensitive to DETS compared to the non-melanoma cell line, A431, in which the IC50 of the compound was more than double (49.60 μM). In the present study, the anticancer activity of DETS against melanoma was confirmed by various apoptosis assays. We also observed that DETS, like resveratrol, down-regulates the expression status of major molecules contributing to melanoma progression, such as BRAF, β-catenin and Brn-2, all of which converge in MITF-M, the master regulator of melanoma signaling. The regulatory role of MITF-M in DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity of DETS

  15. Radiotherapy applications of patients with malignant mesothelioma: A single center experience

    PubMed Central

    Akmansu, Muge; Erpolat, Ozge Petek; Goksel, Fatih; Tunc, Evrim; Ozturk, Can

    2012-01-01

    Background In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms. Aim The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma. Materials and methods Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy. Results Prophylactic radiation was applied to 27 patients with 4–15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6–18 MV photon and/or 4–12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases. Conclusion Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes. PMID:24416534

  16. Dermoscopic patterns of cutaneous melanoma metastases.

    PubMed

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

    2014-04-01

    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.

  17. Patients’ experiences of chronic non-malignant musculoskeletal pain: a qualitative systematic review

    PubMed Central

    Toye, Francine; Seers, Kate; Allcock, Nick; Briggs, Michelle; Carr, Eloise; Andrews, JoyAnn; Barker, Karen

    2013-01-01

    Background Musculoskeletal (MSK) pain is one of the most predominant types of pain and accounts for a large portion of the primary care workload. Aim To systematically review and integrate the findings of qualitative research to increase understanding of patients’ experiences of chronic non-malignant MSK pain. Design and setting Synthesis of qualitative research using meta-ethnography using six electronic databases up until February 2012 (Medline, Embase, Cinahl, Psychinfo, Amed and HMIC). Method Databases were searched from their inception until February 2012, supplemented by hand-searching contents lists of specific journals for 2001–2011 and citation tracking. Full published reports of qualitative studies exploring adults’ own experience of chronic non-malignant MSK pain were eligible for inclusion. Results Out of 24 992 titles, 676 abstracts, and 321 full texts were screened, 77 papers reporting 60 individual studies were included. A new concept of pain as an adversarial struggle emerged. This adversarial struggle was to: 1) affirm self; 2) reconstruct self in time; 3) construct an explanation for suffering; 4) negotiate the healthcare system; and 5) prove legitimacy. However, despite this struggle there is also a sense for some patients of 6) moving forward alongside pain. Conclusions This review provides a theoretical underpinning for improving patient experience and facilitating a therapeutic collaborative partnership. A conceptual model is presented, which offers opportunities for improvement by involving patients, showing them their pain is understood, and forming the basis to help patients move forward alongside their pain. PMID:24351499

  18. Genetic testing for melanoma predisposition: current challenges.

    PubMed

    Gerstenblith, Meg R; Goldstein, Alisa M; Tucker, Margaret A; Fraser, Mary C

    2007-01-01

    A complex interaction of genetic, host, and environmental factors results in cutaneous malignant melanoma, the fifth most common cancer among men and the sixth among women in the United States. Mortality rates for cutaneous malignant melanoma depend on stage at diagnosis; thus, efforts are aimed at early detection and identification of risk factors for melanoma to distinguish those individuals requiring close surveillance. Melanoma susceptibility genes CDKN2A and CDK4 play a role in the development of melanoma, especially among some familial melanoma kindreds. The functions of CDKN2A and CDK4 in melanoma development, however, are currently incompletely understood. Therefore, at this time, predictive genetic testing for CDKN2A mutations outside of defined research protocols is not recommended because of the low likelihood of detecting mutations even in high-risk groups, the present inadequacy of interpreting a test result due to variations in penetrance and unclear associations with other cancers, and the minimal influence knowledge of mutation status currently has on medical management. Oncology nurses have an important role in identifying individuals at high risk for melanoma regardless of CDKN2A mutation status, encouraging enrollment in skin surveillance programs, and providing patient education regarding sun protection, prevention and early detection of melanoma.

  19. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    SciTech Connect

    Carpano, Marina; Perona, Marina; Rodriguez, Carla; Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A.; Brandizzi, Daniel; Cabrini, Romulo; Pisarev, Mario; Juvenal, Guillermo Juan; Dagrosa, Maria Alejandra

    2015-10-01

    Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT

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

    PubMed

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

    2010-07-01

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

  1. Melanoma immunotherapy dominates the field

    PubMed Central

    Diamantopoulos, Panagiotis

    2016-01-01

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

  2. Recent discoveries in the genetics of melanoma and their therapeutic implications.

    PubMed

    Marquette, Amélie; Bagot, Martine; Bensussan, Armand; Dumaz, Nicolas

    2007-01-01

    The incidence of cutaneous malignant melanoma, tumors arising from melanocytes, has increased markedly over the past few years in many countries. Although early melanoma is curable through surgical excision, the prognosis of advanced melanoma is very poor, this tumor being resistant to current therapies. Thus there is a need for new therapies to improve the treatment of advanced melanoma. This review provides an overview of recent discoveries in the genetics of melanoma which could offer new therapeutic opportunities.

  3. Melanoma thickness measurement in two-layer tissue phantoms using pulsed photothermal radiometry (PPTR)

    NASA Astrophysics Data System (ADS)

    Wang, Tianyi; Qiu, Jinze; Paranjape, Amit; Milner, Thomas E.

    2009-02-01

    Melanoma is a malignant tumor of melanocytes which are found predominantly in skin. Melanoma is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths. The staging of malignant melanoma using Breslow thickness is important because of the relationship to survival rate after five years. Pulsed photothermal radiometry (PPTR) is based on the time-resolved acquisition of infrared (IR) emission from a sample after pulsed laser exposure. PPTR can be used to investigate the relationship between melanoma thickness and detected radiometric temperature using two-layer tissue phantoms. We used a Monte Carlo simulation to mimic light transport in melanoma and employed a three-dimensional heat transfer model to obtain simulated radiometric temperature increase and, in comparison, we also conducted PPTR experiments to confirm our simulation results. Simulation and experimental results show similar trends: thicker absorbing layers corresponding to deeper lesions produce slower radiometric temperature decays. A quantitative relationship exists between PPTR radiometric temperature decay time and thickness of the absorbing layer in tissue phantoms.

  4. Choroidal melanoma clinically simulating a retinal angioma.

    PubMed

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

    1978-01-01

    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.

  5. Oncogenes in melanoma: an update.

    PubMed

    Kunz, Manfred

    2014-01-01

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

  6. Surgery for massive malignant tumors of the left atrium – one center’s experience

    PubMed Central

    Andrushchuk, Uladzimir; Ostrovsky, Youry; Zharkov, Vladimir; Krutau, Valery; Yudina, Olga; Ilyina, Tatsiana; Grinchuk, Irina

    2016-01-01

    Introduction Surgery for primary non-resectable malignant tumors of the left atrium is controversial. Today heart autotransplantation as a method of surgical treatment for patients suffering primary massive malignant tumors of the left atrium is still not sufficiently studied. Material and methods We provide information on our single-center 5-year experience in performing surgical interventions for massive malignant tumors of the left atrium and including cases of 5 patients (3 males – 60%, 2 females – 40%). One case (1/5, 20%) involved debulking surgery with partial resection of the left atrial (LA) wall and its reconstruction using a xenopericardium patch. Orthotopic heart transplantation was performed in 1 patient (1/5, 20%) and heart autotransplantation (HA) in the 3 other cases (3/5, 60%). Results Mean myocardial ischemia duration was 165.6 ±12.0 minutes (range: 137–198), cardiopulmonary bypass (CPB) duration was 248.6 ±36.6 minutes (range: 188–392), and intervention duration was 498.0 ±77.4 minutes (range: 330–780). Mean total blood loss was estimated to be 2432 ±616.5 ml (range: 1610–4880). Major in-hospital complications were registered in 4 patients (4/5, 80%). In-hospital mortality was registered in 3 patients (3/5, 60%). Survival time in 2 (2/5, 40%) patients discharged from the hospital was 29 and 9 months, respectively. Both died because of disease progression. Conclusions Surgery in patients with massive resectable primary malignant tumor of the left atrium is associated with high incidence of major hospital complications and mortality. Heart autotransplantation with radical tumor resection is the treatment of choice for these cases. The surgical approach implies thorough primary hemostasis and selection of a proper surgical approach, allowing revision of all the regions of intervention during each step. The possibility of excessive tension and bleeding in the area of bicaval anastomosis should be considered when performing heart

  7. Photodynamic Therapy in Gynecologic Malignancies: A Review of the Roswell Park Cancer Institute Experience

    PubMed Central

    Mayor, Paul C.; Lele, Shashikant

    2016-01-01

    Photodynamic therapy (PDT) is a treatment modality used in the management of solid tumor malignancies that employs the use of a photosensitizing agent, a light source and oxygen in order to illicit a direct cytotoxic effect. Its use in gynecologic malignancies is somewhat novel and has been used for palliative and curative intent. At the Roswell Park Cancer Institute, the use of PDT in the management of gynecologic cancers began in the mid 1980s and since that time 35 patients have received PDT as a treatment for recurrent or metastatic cutaneous and vulvar, vaginal, anal, and cervical recurrences. In our experience, 85% patients with metastatic cutaneous lesions had a complete response. Twenty-seven percent of patients with metastatic vaginal, cervical or anal recurrences had a complete response to therapy with a median response time of 28 months. Side effects from the treatment included moderate to severe burning sensation, pain and edema at the treatment site requiring narcotic pain medication for symptom management in patients who underwent treatment to cutaneous lesions as well as lower genital tract recurrences. PDT should be considered an option in patients who are too frail to undergo the standard of care or decline the standard of care in lieu of a less invasive treatment modality. PMID:27669307

  8. Metabolic rewiring in melanoma

    PubMed Central

    Ratnikov, Boris I.; Scott, David A.; Osterman, Andrei L.; Smith, Jeffrey W.; Ronai, Ze’ev A.

    2016-01-01

    Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the MAPK pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1α, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy. PMID:27270434

  9. Multiple primary melanoma in a Thai male: a case report.

    PubMed

    Payapvipapong, Kittisak; Kanechorn-Na-Ayuthaya, Pinyapat

    2014-02-01

    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.

  10. Multiple cutaneous melanomas associated with gastric and brain metastases*

    PubMed Central

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

    2016-01-01

    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. PMID:28300909

  11. CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma

    PubMed Central

    Su, Juan; Gao, Tianyuan; Jiang, Minghao; Wu, Lisha; Zeng, Weiqi; Zhao, Shuang; Peng, Cong; Chen, Xiang

    2016-01-01

    Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma. PMID:27556188

  12. Mast cells promote melanoma colonization of lungs.

    PubMed

    Öhrvik, Helena; Grujic, Mirjana; Waern, Ida; Gustafson, Ann-Marie; Ernst, Nancy; Roers, Axel; Hartmann, Karin; Pejler, Gunnar

    2016-10-18

    Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre+ R-DTA+ mice, in which the deficiency of mast cells is independent of c-kit defects. Melanoma cells (B16.F10) were administered either subcutaneously or intravenously into Mcpt5-Cre+ R-DTA+ mice or Mcpt5-Cre- R-DTA+ littermate controls, followed by the assessment of formed tumors. In the subcutaneous model, mast cells were abundant in the tumor stroma of control mice but were absent in Mcpt5-Cre+ R-DTA+ mice. However, the absence of mast cells did not affect tumor size. In contrast, after intravenous administration of B16.F10 cells, melanoma colonization of the lungs was markedly reduced in Mcpt5-Cre+ R-DTA+ vs. Mcpt5-Cre- R-DTA+ animals. Decreased melanoma colonization of the lungs in Mcpt5-Cre+ R-DTA+ animals was accompanied by increased inflammatory cell recruitment into the bronchoalveolar lavage fluid, suggesting that mast cells suppress inflammation in this setting. Further, qPCR analysis revealed significant alterations in the expression of Twist and E-cadherin in lungs of Mcpt5-Cre+ R-DTA+ vs. control Mcpt5-Cre- R-DTA+ animals, suggesting an impact of mast cells on epithelial-mesenchymal transition. In conclusion, this study reveals that mast cells promote melanoma colonization of the lung.

  13. Downregulation of sphingosine kinase-1 induces protective tumor immunity by promoting M1 macrophage response in melanoma

    PubMed Central

    Mrad, Marguerite; Imbert, Caroline; Garcia, Virginie; Rambow, Florian; Therville, Nicole; Carpentier, Stéphane; Ségui, Bruno; Levade, Thierry; Azar, Rania; Marine, Jean-Christophe; Diab-Assaf, Mona; Colacios, Céline; Andrieu-Abadie, Nathalie

    2016-01-01

    The infiltration of melanoma tumors by macrophages is often correlated with poor prognosis. However, the molecular signals that regulate the dialogue between malignant cells and the inflammatory microenvironment remain poorly understood. We previously reported an increased expression of sphingosine kinase-1 (SK1), which produces the bioactive lipid sphingosine 1-phosphate (S1P), in melanoma. The present study aimed at defining the role of tumor SK1 in the recruitment and differentiation of macrophages in melanoma. Herein, we show that downregulation of SK1 in melanoma cells causes a reduction in the percentage of CD206highMHCIIlow M2 macrophages in favor of an increased proportion of CD206lowMHCIIhigh M1 macrophages into the tumor. This macrophage differentiation orchestrates T lymphocyte recruitment as well as tumor rejection through the expression of Th1 cytokines and chemokines. In vitro experiments indicated that macrophage migration is triggered by the binding of tumor S1P to S1PR1 receptors present on macrophages whereas macrophage differentiation is stimulated by SK1-induced secretion of TGF-β1. Finally, RNA-seq analysis of human melanoma tumors revealed a positive correlation between SK1 and TGF-β1 expression. Altogether, our findings demonstrate that melanoma SK1 plays a key role in the recruitment and phenotypic shift of the tumor macrophages that promote melanoma growth. PMID:27708249

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

  16. An approach to unsupervised hair removal from skin melanoma image

    NASA Astrophysics Data System (ADS)

    Xie, Feng-Ying; Qin, Shi-Yin; Jiang, Zhi-Guo; Meng, Ru-Song; Xu, Bin

    2008-10-01

    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.

  17. Cyclin D1 expression in acral melanoma: a case control study in Sarawak.

    PubMed

    Ibrahim, Zainal Abidin; Narihan, M Zulkarnaen A; Ojep, Dk Norlida A; Soosay, Ashley Edward Roy; Pan, Kok Long

    2012-12-01

    Acral melanoma has been reported to have distinctive clinical presentation and ethnic distribution compared to other histological types of malignant melanoma. Acral melanoma also exhibits distinctive focused gene amplifications, including cyclin D1 overexpression. We reviewed archived histological material of malignant melanoma in the Sarawak General Hospital from year 2004 to 2010. 43 tumours, comprising 28 acral melanoma and 15 non-acral melanoma, had sufficient material to be included in the study. The majority (36%) of acral melanoma tumours occurred in the heel. The tumours were analyzed for cyclin D1 expression by immunohistochemistry. 68% of acral melanoma were cyclin D1 positive compared to a positivity of 33% in non-acral tumours. This difference was statistically significant (p < 0.05). This finding may improve the histological diagnosis of acral melanoma and detection of positive resection margins.

  18. Tumoral Melanosis Associated with Pembrolizumab-Treated Metastatic Melanoma

    PubMed Central

    Cohen, Philip R

    2017-01-01

    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

  19. Melanoma and pregnancy.

    PubMed

    Morton, Sarah Kym; Morton, Adam Park

    2017-02-10

    Melanoma is the most common cancer in women during their reproductive years and kills more young Australians than any other single cancer. Care of women whose pregnancy is complicated by a diagnosis of malignancy is complex. The risk of delaying treatment to the mother, the short-term and long-term risks of premature delivery to the child, and the immediate risks to the foetus and long-term risks to the child of maternal treatment with surgery, radiotherapy or medical therapies must be considered.

  20. [Choroidal melanoma].

    PubMed

    Desjardins, Laurence

    2016-03-01

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

  1. DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo

    PubMed Central

    Wang, Jeffrey; Xie, Chen; Huang, Xuan; Zhan, Shuyu; Zheng, Yongxia; Huang, Yueyan; Xu, Ningyin; Ding, Xueying; Gao, Shen

    2016-01-01

    We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment. PMID:27494835

  2. DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo.

    PubMed

    Ding, Baoyue; Zhang, Wei; Wu, Xin; Wang, Jeffrey; Xie, Chen; Huang, Xuan; Zhan, Shuyu; Zheng, Yongxia; Huang, Yueyan; Xu, Ningyin; Ding, Xueying; Gao, Shen

    2016-08-30

    We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment.

  3. In vivo evidences of nanosecond pulsed electric fields for melanoma malignancy treatment on tumor-bearing BALB/c nude mice.

    PubMed

    Guo, F; Yao, C; Li, C; Mi, Y; Peng, Q; Tang, J

    2014-08-01

    In order to get in vivo evidences of nanosecond pulsed electric fields (nsPEF) for skin tumor treatment, tumor models in 10 female BALB/c nude mice were established by inoculating them with human melanoma cells A375. These mice were randomly divided into treated group (exposed to nsPEF with intensity of 20 kV/cm and duration of 300 ns) and control group equally. Five days post-nsPEF treatment, tumor growth in the treated group was effectively inhibited (P < 0.01 compared with that in control group), typical apoptotic characteristics (DNA damage and fragmentation) were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and significant increases in Bax and decreases in Bcl-2, micro-vessel density (MVD), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) were observed by immunohistochemistry (P < 0.01). These experimental results indicate that in vivo tumor growth can be effectively inhibited by nsPEF, which activate two targets, apoptosis initiation and angiogenesis inhibition.

  4. [2008 Update of Standards, Options: recommendations for management of patients with salivary gland malignant tumours (excluding lymphoma, sarcoma and melanoma), summary report].

    PubMed

    Bensadoun, René-Jean; Dassonville, Olivier; Rousmans, Sophie

    2008-01-01

    The < Standards, Options : Recommendations > (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. This paper is a summary version of the full clinical practice guideline presenting the updated recommendations for management of patients with salivary gland malignant tumours. Recommendations on radiotherapy have been updated to underline new Options on more and more accessible emerging techniques including intensity-modulated radiotherapy, 3D conformational radiotherapy, Cyberknife, tomotherapy, protontherapy and particle accelerators producing carbon ions (e.g. last generation hadrontherapy).

  5. Extracorporeal Life Support in Patients with Hematologic Malignancies: A Single Center Experience

    PubMed Central

    Choi, Kuk Bin; Kim, Hwan Wook; Jo, Keon Hyon; Kim, Do Yeon; Choi, Hang Jun; Hong, Seok Beom

    2016-01-01

    Background Extracorporeal life support (ECLS) in patients with hematologic malignancies is considered to have a poor prognosis. However, to date, there is only one case series reported in the literature. In this study, we compared the in-hospital survival of ECLS in patients with and without hematologic malignancies. Methods We reviewed a total of 66 patients who underwent ECLS for treatment of acute respiratory failure from January 2012 to December 2014. Of these patients, 22 (32%) were diagnosed with hematologic malignancies, and 13 (59%) underwent stem cell transplantation before ECLS. Results The in-hospital survival rate of patients with hematologic malignancies was 5% (1/22), while that of patients without malignancies was 26% (12/46). The number of platelet transfusions was significantly higher in patients with hematologic malignancies (9.69±7.55 vs. 3.12±3.42 units/day). Multivariate analysis showed that the presence of hematologic malignancies was a significant negative predictor of survival to discharge (odds ratio, 0.07; 95% confidence interval, 0.01–0.79); p=0.031). Conclusion ECLS in patients with hematologic malignancies had a lower in-hospital survival rate, compared to patients without hematologic malignancies. PMID:27525237

  6. The Psychosocial Experience of Adolescents with Haematological Malignancies in Jordan: An Interpretive Phenomenological Analysis Study

    PubMed Central

    2014-01-01

    The qualitative research method of interpretive phenomenological analysis was used to explore the lived experience of 14 Jordanian adolescents with haematological malignancies. They were admitted to two hospitals in Jordan and were interviewed for this study twice during the first six months after receiving their diagnosis. The results of this study revealed three themes: (1) Being in hospital, (2) The changing self, and (3) Fearing the unknown. When the participants were hospitalised due to their illness they were removed from their families and friends and prevented from engaging in their normal daily routine. Participants also reported receiving limited emotional and psychological support from health team members during hospitalisation. From the onset of cancer treatments, the bio-psychosocial side effects of the chemothera