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Sample records for advanced malignant melanoma

  1. New therapeutic options for advanced non-resectable malignant melanoma.

    Science.gov (United States)

    Stadler, Simone; Weina, Kasia; Gebhardt, Christoffer; Utikal, Jochen

    2015-03-01

    Melanoma is a malignant tumor which is inclined to metastasize promptly into the lymphatic system and other organs such as lung, liver, brain or bone. Therefore early diagnosis remains crucial for improving clinical outcome for melanoma patients. Current chemotherapy and chemo-immunotherapy regimes have shown little clinical benefit with no improvement in overall survival. However, new advances in melanoma biology such as the discovery of predisposed gene signatures and key somatic events have changed clinical practice. New therapeutic approaches are being tested or have been approved by the FDA/EMA recently including targeted therapies, such as BRAF- and MEK-inhibitors, and novel immunotherapies, such as anti-CTLA4 or anti-PD1 therapies. For these therapies an improvement of progression-free and overall survival has been seen in patients with advanced non-resectable melanoma. The following review summarizes recent therapeutic options after the ASCO and ESMO annual meetings 2014 for the treatment of malignant melanoma. PMID:25596540

  2. Malignant Melanoma

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    Eshini Perera

    2013-12-01

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

  3. Malignant melanoma of nose

    OpenAIRE

    Kundu, I. N.; Haldar, B.; Saha, A. K.

    2001-01-01

    Malignant melanoma (MM) is one of the uncommon malignancies of the nose. We present an unusually big proliferative like MM in the vestibule of the nose. Malignancy of nose constitutes less than 1% of all malignancies (3% of head & neck tumour). MM however contributes only 2% of all malignant neoplasms of the nose (Moore & Martin. 1955).

  4. Familial malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-10-10

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

  5. [Malignant melanoma coexisting with pregnancy].

    Science.gov (United States)

    Krasomski, G; Broniarczyk, D; Gładysiak, A

    1992-09-01

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

  6. Current management and novel agents for malignant melanoma

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    Lee Byung

    2012-02-01

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

  7. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

    Science.gov (United States)

    Theurich, Sebastian; Rothschild, Sacha I; Hoffmann, Michael; Fabri, Mario; Sommer, Andrea; Garcia-Marquez, Maria; Thelen, Martin; Schill, Catherine; Merki, Ramona; Schmid, Thomas; Koeberle, Dieter; Zippelius, Alfred; Baues, Christian; Mauch, Cornelia; Tigges, Christian; Kreuter, Alexander; Borggrefe, Jan; von Bergwelt-Baildon, Michael; Schlaak, Max

    2016-09-01

    Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR. PMID:27466265

  8. Giant melanoacanthoma mimicking malignant melanoma

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    Vikas Shankar

    2011-01-01

    Full Text Available Melanoacanthoma denotes a rare variant of pigmented seborrheic keratosis. A 65-year-old male farmer had pigmented, verrucous, itchy, highly painful, progressively growing irregularly oval plaque on left side of lower back for the past five years. The indurated lesion, measuring maximum diameter 10 cm Χ 5 cm, had no discharge, bleeding, ulceration, or associated lymphadenopathy. Dermoscopy showed regular pigmentary network and cribiform pattern of ridges without any feature of malignant melanoma. Histopathology showed well-defined islands of basaloid cells interspersed with large and richly dendritic melanocytes. The lesion was totally excised followed by skin grafting. Our patient was unique in its massive size and clinical resemblance with malignant melanoma. The diagnosis was confirmed by dermoscopy and skin biopsy.

  9. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  10. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  11. Mistletoe in the treatment of malignant melanoma

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    Esin Sakallı Çetin

    2014-03-01

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

  12. Technique and outcomes of isolated limb infusion for locally advanced malignant melanoma - A radiological perspective

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    Chun, J.-Y., E-mail: drjyc78@gmail.com [Department of Radiology, St George' s Hospital, London (United Kingdom); Hussain, M.; Powell, B. [Plastic Surgery, St George' s Hospital, London (United Kingdom); Belli, A.-M. [Department of Radiology, St George' s Hospital, London (United Kingdom)

    2011-12-15

    Aim: Isolated limb infusion (ILI) is a novel, minimally invasive technique for delivering high-dose regional chemotherapy in patients with recurrent and in-transit melanoma. The aim of this study was to review our single-centre experience in treating eleven patients. We emphasize the role of radiologists in setting up this service, including pre-treatment workup and placement of vascular catheters. Materials and methods: A retrospective analysis of 11 patients who underwent 12 procedures between 2005 and 2009 was performed. Pre-procedural staging computed tomography (CT), CT angiography, and duplex studies were performed. All patients received a cytotoxic combination of melphalan and actinomycin-D via radiologically placed arterial and venous catheters in the affected limb under mild hyperthermic conditions. The outcome measures include response rates, limb toxicity, complications, and survival. Results: All patients were female with a mean age of 72 years. Three patients had American Joint Committee on Cancer (AJCC) stage IIIB melanoma, seven had stage IIIC melanoma, and one had a stage IIIB Merkel cell tumour. Complete response was seen in five patients (46%), partial response in four (36%), and progressive disease in two (18%). One patient developed grade 4 toxicity requiring a fasciotomy and another experienced systemic toxicity. Conclusion: These outcomes are comparable to previous studies and shows that ILI is effective in locoregional control of unresectable melanoma. It is a relatively safe procedure but not without risk. Our experience shows the importance of radiological input to ensure safe and effective delivery of services.

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

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    Anita Munde

    2014-01-01

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

  14. Unusual thoracic manifestation of metastatic malignant melanoma

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    Mohan K

    2010-01-01

    Full Text Available Massive pleural effusion due to metastatic malignant melanoma is rare. We report a case of bilateral (massive on left side pleural effusion as a metastatic manifestation of cutaneous malignant melanoma. In our case, successful outcome of pleurodesis with vincristine is significant as this agent is rarely used.

  15. Primary malignant melanoma of the esophagus

    International Nuclear Information System (INIS)

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography

  16. Malignant rectal melanoma. Case report.

    Science.gov (United States)

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

    2015-03-26

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

  17. 恶性黑素瘤的治疗新进展%New Advances in Treatment of Malignant Melanoma

    Institute of Scientific and Technical Information of China (English)

    陈文静

    2013-01-01

    In recent years the incidence of malignant melanoma has a clear upward trend, it is not sensitive to radiotherapy or chemotherapy. However,malignant melanoma is a tumor with higher immunogenicity. Current biological treatments for malignant melanoma include immune therapy, gene therapy and anti-angio-genic treatment etc. , among which the clinical application of adoptive immune therapy is in the rapid development in recent years;meanwhile,the clinical research of regulatory monoclonal antibody drugs and therapy targeted at BRAF V600E and C-KIT mutations have drawn the most attention. The studies have provided new ideas for malignant melanoma immune and gene therapy,which have become the hotspot for the time being.%近年来恶性黑素瘤发病率有明显上升趋势,其对单纯放疗及化疗均不敏感,它是一种免疫原性较高的肿瘤.目前用于恶性黑素瘤的生物治疗方法包括免疫治疗、基因治疗及抗血管生成治疗等,其中过继性免疫治疗的临床应用研究近年来得到快速发展,同时免疫调节性单克隆抗体药物以及针对BRAF基因V600E突变和C-KIT基因突变为靶点的临床研究最引人关注.这些研究为恶性黑素瘤的免疫及基因治疗提供了新思路,成为目前的研究热点.

  18. Thigmotropism of Malignant Melanoma Cells

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    Pascale Quatresooz

    2012-01-01

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

  19. Thigmotropism of malignant melanoma cells.

    Science.gov (United States)

    Quatresooz, Pascale; Piérard-Franchimont, Claudine; Noël, Fanchon; Piérard, Gérald E

    2012-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called "accretive" growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread. PMID:22203839

  20. Angiogenic and Metastatic Determinants of Malignant Melanoma

    NARCIS (Netherlands)

    A. Mooppilmadham Das (Asha)

    2015-01-01

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

  1. MALIGNANT MELANOMA OF THE ORAL CAVITY

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    Vishnu Prasad

    2016-02-01

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

  2. Vaginal Primary Malignant Melanoma: A Rare and Aggressive Tumor

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    Georgios Androutsopoulos

    2013-01-01

    Full Text Available Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient is an 80-year-old, postmenopausal Greek woman presented with a complaint of abnormal vaginal bleeding. On gynecologic examination there was a pigmented, raised, ulcerated, and irregular lesion  cm in the upper third of anterior vaginal wall. She underwent a wide local excision of the lesion. The histopathology revealed vaginal primary malignant melanoma with ulceration and no clear surgical margins. She denied any additional surgical interventions and underwent to postoperative adjuvant radiotherapy. Follow up 5 months after initial diagnosis revealed no evidence of local recurrence or distant metastasis. The prognosis of vaginal primary malignant melanoma is very poor despite treatment modality, because most of the cases are diagnosed at advanced stage. Particularly patients with no clear surgical margins and tumor size >3 cm needed postoperative adjuvant radiotherapy.

  3. Malignant melanoma of the oral cavity

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    Ebenezer Jagadish

    2006-01-01

    Full Text Available Oral malignant melanoma is a rare disease. The common sites of its occurrence are the palate and gingiva with the maxillary arch being affected 80% of the time. Because of their presence at relatively obscure areas in the oral cavity, most of the malignant melanomas of the oral cavity are diagnosed at a late stage. These lesions are associated with poor prognosis. The dental clinician must therefore carefully examine the head, neck, and oral cavity, and any pigmented lesion that may exhibit growth potential must be biopsied. This article describes a case of malignant melanoma that was present in the oral cavity and briefly reviews the relevant literature that explains the nature of this lesion.

  4. Screening for metastatic malignant melanoma of the uvea revisited

    DEFF Research Database (Denmark)

    Eskelin, Sebastian; Pyrhönen, Seppo; Summanen, Paula;

    1999-01-01

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

  5. MALIGNANT MELANOMA OF THE HEAD SKIN

    OpenAIRE

    Camelia Tamas; Doinita Radulescu; Lucian Popa; C. Tarasi; Cristina Stanescu; R. Nita

    2006-01-01

    Malignant melanoma (MM) is known as a tumor with high malignancy. The development of a melanoma on the head skin is even more severe, as prognosis, because of the limitted possibilities for large excision and high potential of diffusion in the wide vascular network. We treated 11 cases with MM head localisation in a period of 10 years. The rate of survival is very poor (6 months – 4 years after surgery). We used skin graft or fasciocutaneous flap for the regional reconstruction after exc...

  6. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

    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

  7. Adjuvant therapy of malignant melanoma.

    Science.gov (United States)

    Molife, R; Hancock, B W

    2002-10-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  9. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...... to elaborate the care to these patients. Method: In 2007 the nurses from our ward gained experience from the psychosocial care to these patients. These experiences are a starting point to the study of literature the group has made. A group of five nurses have from this literature study, substantiated...... the psychosocial perspective. Results: After the literature review, the psychosocial aspects have been divided into five main areas: 1. Diagnosis, hospitalisation, and treatment 2. The body with cancer 3. Psychological 4. Social 5. Existential/spiritual Primary results show that patients with MM in general respond...

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

    Directory of Open Access Journals (Sweden)

    John C Morris

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

  11. Metastatic Malignant Melanoma Presenting as an Appendiceal Mucocele

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    A. A. Alduaij

    2011-01-01

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

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

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    Mohamed Alsharedi

    2016-10-01

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

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

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    Sanjeev Bhagat

    2010-04-01

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

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

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    Caglayan Geredeli

    2015-01-01

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

  15. Parotid Cystic Lesion in Amelanotic Malignant Melanoma.

    Science.gov (United States)

    Santos, Vitorino Modesto Dos; Gondim Neto, Manoel da Costa; de Melo, Tereza Rodrigues de Carvalho Vieira; Motta, Iara Machado

    2016-09-01

    A 60-year Brazilian woman, presented with an enlarged lymph node in the neck for one year, and a superficial nonulcerated lesion was observed in the scalp. Fine needle aspiration and biopsy of the lymph node revealed amelanocytic metastasis, and immunohistochemistry study showed Melan-A/ Mart-1 antigen (clone A103 and S-100 protein). The entire suspected area of the scalp was further resected and an amelanotic melanoma without angiolymphatic invasion was diagnosed. Ultrasonography and PET-computed tomography showed hypermetabolic cystic area in the right parotid. Furthermore, aspiration biopsy and surgical samples from parotid cyst confirmed the malignant amelanotic melanoma. Cystic metastases are scarcely reported in parotid gland, and can pose diagnostic challenges. PMID:27671185

  16. Malignant melanoma arising in mature cystic teratoma of the ovary

    OpenAIRE

    Heidi E Godoy; Kesterson, Joshua P.; Kasznica, John M.; Lele, Shashikant

    2011-01-01

    ► Teratomas are composed of elements of all three germ layers, all potentially capable of undergoing malignant transformation. ► A case of malignant melanoma arising in a mature teratoma is presented.

  17. Established and Emerging Biomarkers in Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Stamatina Verykiou

    2014-01-01

    Full Text Available In an era of personalized medicine, disease specific biomarkers play an increasing role in the stratification of high-risk patient groups. Cutaneous malignant melanoma is the most deadly form of skin cancer with an ever-increasing global incidence, especially in patients under 35-years of age. Despite the excellent prognosis for patients diagnosed with early stage disease, metastatic disease still carries significant overall mortality. Biomarkers aim not only to identify high-risk patients, but also to provide potential therapeutic targets for differing patient subgroups. Furthermore, accessibility to tissue samples from a range of disease stages in malignant melanoma, unlike most other solid tissue tumours, provides the unique opportunity to explore the biology of tumour progression that may be relevant in the biology of cancer as a whole. Over the past decade, there have been major advances in targeted therapies, providing new avenues and hope to patients with this devastating disease. This review will focus on most up to date histological, serological and molecular biomarkers in malignant melanoma.

  18. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  19. A CASE OF LIMBAL MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Hansa H

    2015-05-01

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

  20. Oral malignant melanoma: a rare case with unusual clinical presentation

    OpenAIRE

    Ali, Elneel Ahmed Mohamed; Karrar, Musadak Ali; El-Siddig, Abeer Abdalla; Zulfu, Azza

    2015-01-01

    Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested.

  1. Primary malignant melanoma of cervix and vagina

    Science.gov (United States)

    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

  2. Primary Spindle Cell Malignant Melanoma of Esophagus: An Unusual Finding.

    Science.gov (United States)

    Rawandale, Nirmalkumar A; Suryawanshi, Kishor H

    2016-02-01

    Malignant melanoma of esophagus is usually a metastatic tumour rather than a primary tumour. Primary malignant melanoma accounts for less than 0.2% of all esophageal neoplasm. We report a case of primary spindle cell malignant melanoma of esophagus in a 69-year-old male who presented with history of dysphagia since 1 month. Radiological examinations revealed polypoidal growth at lateral aspect of esophagus. Biopsy was reported as grade III squamous cell carcinoma. Video assisted thoracoscopic esophagectomy was performed. Histopathological examination along with immunohistochemistry gave confirmed diagnosis of primary spindle cell malignant melanoma of esophagus. Though a rare entity, due to its aggressive nature and poor prognosis primary malignant melanoma should be one of the differential diagnoses in a patient with polypoidal esophageal mass lesion. Despite radical surgical treatment prognosis is extremely poor. PMID:27042502

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

    Directory of Open Access Journals (Sweden)

    Swati Singh

    2013-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    高玉平; 朱建善; 林维; 郑文钧

    2003-01-01

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

  5. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  6. Genetic determinants of cutaneous malignant melanoma in Sinclair swine.

    OpenAIRE

    Blangero, J; Tissot, R. G.; Beattie, C W; Amoss, M S

    1996-01-01

    The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine ...

  7. Primary malignant melanoma in the pineal region treated without chemotherapy

    OpenAIRE

    SHINSATO, Yoshinari; Hanada, Tomoko; Kisanuki, Takao; Yonezawa, Hajime; Yunoue, Shunji; Yoshioka, Takako; Hanaya, Ryosuke; Tokimura, Hiroshi; Hirano, Hirofumi; ARITA, Kazunori

    2012-01-01

    Background: Primary pineal malignant melanomas are uncommon intracranial tumor. Here we discuss and review a case of primary pineal malignant melanoma over its feature of imaging studies, pathological findings, and management. Case Description: A 49-year-old woman receiving renal dialysis underwent computed tomography due to a 4-month history of tinnitus and hearing disturbance. A high-density 35-mm diameter tumor was detected in the pineal region; there was obstructive hydrocephalus. The tum...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis...... patients tested. TIL cultures contained specificity towards tumor cells as well as peptides derived from tumor-associated antigens (TAAs) during expansion procedures....

  9. Epidemiological aspects of cutaneous malignant melanoma (review).

    Science.gov (United States)

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

    1998-01-01

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

  10. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dianne E. Godar

    2011-01-01

    Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  11. Primary malignant melanoma of the vagina: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Young; Kim, Do Kang; Lee, Eun Hee [College of Medicine, Catholic Univ., Seoul (Korea, Republic of); Kim, Jun Sang [College of Medicine, Chungnam National Univ., Daejeon (Korea, Republic of)

    2003-09-01

    A primary malignant melanoma of the vagina is a very rare gynecological malignant tumor. Its clinical behavior is more aggressive than that of cutaneous and vulvar melanomas. We present a case of a large sized primary melanoma of the lower third of the vagina, with a cervical lesion, in a 58-year-old postmenopausal woman. The patient was treated with conventional external radiation therapy and intracavitary radiotherapy (lCR), without surgical treatment. Although the primary lesion showed a partial response, the patient died of extensive metastases, which were found 4.5 months after the initial diagnosis. We suggest that shortening the treatment period, such as hypofractionated radiation therapy and surgical removal, and various systemic therapies for preventing early distant metastasis, are appropriate treatments for a primary malignant melanoma of the vagina, with a large tumor size.

  12. Malignant melanoma-The cradle of anti-neoplastic immunotherapy.

    Science.gov (United States)

    Koller, Kristian M; Wang, Wenge; Schell, Todd D; Cozza, Eugene M; Kokolus, Kathleen M; Neves, Rogerio I; Mackley, Heath B; Pameijer, Colette; Leung, Anna; Anderson, Bryan; Mallon, Carol A; Robertson, Gavin; Drabick, Joseph J

    2016-10-01

    One of the defining characteristics of the malignant phenotype is the ability to evade the host immune system. Immunotherapy as a treatment modality represents a new dawn in the way we think about the treatment of a variety of malignancies. The story of immunotherapy traces its roots to its relationship with malignant melanoma. In this article, we review the intertwined history of immunotherapy and melanoma, including the early significant history, a discussion on immune mechanisms, resistance, local and systemic immunotherapeutic modalities, and speculate on possible novel future treatment options. PMID:27637351

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity...... of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes...

  14. Cutaneous malignant melanoma in association with mycosis fungoides.

    Science.gov (United States)

    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.

  15. Rhabdomyosarcoma and late malignant melanoma of the orbit

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Rhabdomyosarcoma and late malignant melanoma of the orbit

    International Nuclear Information System (INIS)

    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

  17. Malignant melanoma metastatic to the larynx: treatment and functional outcome

    OpenAIRE

    Lanson, B.G.; Sanfilippo, N.; Wang, B; Grew, D.; DeLacure, M.D.

    2010-01-01

    The review considers management strategies for malignant melanoma metastatic to the larynx. This rare clinical entity lacks clear treatment recommendations because extirpative surgery can often result in severe functional debilitation in patients with limited life expectancy. Here, we report a case of melanoma metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma. The patient was treated with partial laryngectomy and local radiation therapy. The rationale for treatmen...

  18. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin;

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; this...... report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence of...... therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional...

  19. MALIGNANT MELANOMA WITH MULTIPLE METASTASES ON THE SMALL BOWEL - CASE REPORT

    OpenAIRE

    V.T. Grigorean; M.A. Iacobini; Popescu, M.; C.M. Neacşu; A-R. Stoian; Corina Roxana Buf; Violeta Elena Radu; Aurelia Mihaela Sandu

    2010-01-01

    BACKGROUND: Malignant melanomas often cause intestinal metastasis.Metastases of malignant melanoma are the most common secondary tumors of the gastrointestinal tract.The incidence of intestinal metastasis of malignant melanomas is 1.5-4.4% in clinical studies, reaching upto 35.6-58% in necroptic studies. AIM: We present a clinical case of multiple metastases to the smallbowel with point of departure right retroauricular malignant melanoma. METHODS: Patient T.I., 76years old, is admitted in ou...

  20. Malignant melanoma of the cerebello-pontine angle region

    Directory of Open Access Journals (Sweden)

    F. Menezes Braga

    1989-12-01

    Full Text Available A case of malignant melanoma in the cerebello-pontine angle region is presented in a 72 years old female patient, who had neurological examination and CT scan suggestive of acoustic neuroma. The surgical finding and the histological examination provided the diagnosis. As a primary focus was not found on clinical examination and although autopsy was not carried out, there is a possibility of the diagnosis being a primary malignant melanoma in CNS. This specific location for this kind of tumor was found to be rare when literature is looked up.

  1. Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report.

    Science.gov (United States)

    Ozgun, Alpaslan; Tuncel, Tolga; Emirzeoglu, Levent; Celik, Serkan; Bilgi, Oguz; Haholu, Abdullah; Urhan, Muammer; Karagoz, Bulent

    2015-01-01

    Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously. PMID:25436010

  2. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options.

    Science.gov (United States)

    Metcalfe, Lucy Va; O'Brien, Peter J; Papakonstantinou, Stratos; Cahalan, Stephen D; McAllister, Hester; Duggan, Vivienne E

    2013-01-01

    A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thoracic radiography, cytological examination of the pleural fluid and a fine needle aspirate of a thoracic mass led to a presumptive diagnosis of malignant melanoma and this was confirmed at post mortem examination. Further metastatic spread to the central nervous system and right guttural pouch was also identified. In conclusion this case manifests the potential malignant behaviour of equine melanomas, and a review of proposed therapies for melanoma treatment highlights the therapeutic options and current areas of research. PMID:24196087

  3. Malignant melanoma transformation within a nevus of Ito.

    Science.gov (United States)

    Wise, Sean R; Capra, Gregory; Martin, Peter; Wallace, Donna; Miller, Charles

    2010-05-01

    The mongolian spot, nevus of Ota, and nevus of Ito are the most common morphologic forms of the dermal melanocytoses, a group of benign pigmented lesions histologically characterized by the presence of melanocytes within the dermis. Nevus of Ito is clinically distinct, presenting with unilateral, bluish gray, patchy discolorations in the skin within the distributions of the posterior supraclavicular and lateral cutaneous brachial nerves. Although all dermal melanocytoses are generally considered benign, rare cases of malignant transformation associated with nevus of Ota have been described. Only one case of malignant melanoma transformation in association with nevus of Ito has previously been reported. We present the second description of malignant melanoma transformation within a nevus of Ito and provide comment on the malignant potential of the dermal melanocytoses.

  4. Malignant cutaneous melanoma in patients from Las Tunas province

    Directory of Open Access Journals (Sweden)

    Alicia María Yabor Palomo

    2015-11-01

    Full Text Available Background: malignant melanoma is a highly aggressive skin neoplasia, whose incidence shows a constant and rapid increase.Objective: to characterize variables in patients diagnosed with cutaneous melanoma, whose biopsies were analyzed in the pathologic anatomy department of "Dr. Ernesto Guevara de la Serna" General Teaching Hospital from January, 2008 to December, 2014.Methods: a descriptive and cross-sectional study was performed in 31 patients treated in the place and period of time mentioned above. The official form of biopsy was used as a secondary source of collecting information and it was processed using descriptive statistics.Results: the 10,6 % of the biopsies analyzed corresponded with cutaneous melanoma, its frequency prevailed in 2011 and 2010, with a 25,8 % and 19,3 % respectively. It was evident a higher percentage in males (67,7 % and in the age group between 60 and 69 years old, with a 35,4 %. Caucasian patients were the most affected ones, with a 90,3 % and the predominant location was in the lower limbs in 45,1 % of the cases. The prevailing Clark invasion level was IV, evident by the 32,2 % of the sample, and the most frequent histological variety was the malignant nodular melanoma in 19 patients, for a 61,2 %.Conclusions: cutaneous melanoma prevailed in lower extremities in males and it had a belated diagnosis, since there was prevalence of IV Clark invasion level and nodular melanoma as the most frequent histological type.

  5. MR imaging of mucocutaneous malignant melanoma in head and neck

    International Nuclear Information System (INIS)

    MR imaging was performed in three patients with mucocutaneous malignant melanoma of the head and neck, and surgical specimens were investigated in MR-pathological correlation. Two of 3 cases were revealed to be melanotic melanoma; one arised in the maxillary sinus, and another in the bulbar conjunctiva. The remaining one was amelanotic melanoma originated in the nasal cavity. Two cases of melanotic melanoma showed different intensity on T1WI according to the melanin concentration; the more the melanin-producing process existed, the higher intensity in the tumor was shown. On T2WI there were also some differences in signal intensity; the case having more concentration of melanin changed lower partially in the areas where very high intensity was noted on T1WI, while another case remained unchanged. These findings are based on the inherent paramagnetic effect mostly compatible with the previous reports. On the other hand, the amelanotic melanoma was demonstrated as an intermediate intensity both on T1- and T2WI. Because of the higher incidence of hemorrhage in/around the tumor, it is an important diagnostic clue to this tumor, as in our case of amelanotic type. On reviewing the three cases, we consider that MR imaging offers a useful adjunct in the diagnosis of malignant melanoma. (author)

  6. CT of malignant choroidal melanoma - morphology and perfusion characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Heller, M.; Hagemann, J.; Jend, H.H.; Guthoff, R.

    1982-03-01

    The computed tomographic morphology of malignant choroidal melanoma and its perfusion characteristics are described. Thirty-three static and serial CT examinations made on 29 patients with choroidal melanoma, three with pseudotumors of the macula and one with choroidal metastasis revealed the choroidal melanoma to be usually a hyperdense, markedly perfused tumor, while the non-contrast, diagnostically undifferentiable pseudotumors and the choroidal metastasis, revealed no significant change in density after the administration of contrast material. Density values or perfusion characteristics of choroidal melanoma that are outside of the normal range are a result of secondary changes within the immediate surroundings of the tumor, such as detachment of the retina, tumor-induced glaucoma, or tumor necrosis.

  7. Malignant melanoma of the vagina: a report of 2 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Bae; Kim, Jin Hee; Jung, Young Yeon; Cho, Chi Heum; Choi, Tae Jin [Dongsan Medical Center, School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    2005-06-15

    Primary malignant melanoma of the vagina is an extremely rare genital neoplasm occurring mainly in postmenopausal women. It has a worse prognosis than cutaneous melanomas, because of the high rate of locoregional recurrences and rapid systemic dissemination. In the past, radical surgical extirpation as the primary management had been recommended to improve loco-regional control, and possibly overall survival. However, the prognosis was poor in spite of such a radical approach. Recently, more conservative treatment such as wide local excision combined with adjuvant high-dose fraction radiotherapy seems to have promising results. Primary radiation therapy could be served as an alternative to surgery for patients with lesion less than 3 cm in diameter. We report 2 cases of primary vaginal malignant melanoma treated with radiotherapy.

  8. Malignant melanoma in an area of chronic radiodermatitis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Shono, Yoshitaka [Matsuyama Red Cross Hospital (Japan); Nakanishi, Hideki; Hashimoto, Ichiro

    2000-02-01

    This is a case report of malignant melanoma that occurred in an area of chronic radiodermatitis on the sole of the foot. A 55-year-old woman was irradiated for corns on the soles of both feet in 1967. Dermatoplasty was performed for hyperkeratosis of the sole of the right foot in 1988, but a tumor developed on the right heel in 1998, and grew larger. The histological findings suggested malignant melanoma, and the tumor including the periosteum, was removed. The patient was treated with four cycles of adjuvant chemotherapy (dacarbazine, nimustine hydrochloride, and vincristine), and no signs of recurrence one year after surgery. Based on a review of the literature, there appears to be little relation between melanoma and irradiation, and this is only the second case ever reported in Japan. (K.H.)

  9. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R

    2013-01-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical......-RAF-MEK-ERK pathway, the p16(INK4A) -CDK4-RB pathway, the PIK3-AKT pathway and the MITF pathway....... to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...

  10. Subungual malignant melanoma – re-learning the lesson

    OpenAIRE

    Amin, Kavit; Edmonds, Katy; Fleming, Andrew; Powell, Barry

    2011-01-01

    The authors present two patients referred by colleagues after traumatic hand injury. However, upon closer inspection, both patients had pigmented lesions under the nail bed, which upon biopsy showed proven subungual malignant melanoma. The authors wish to emphasise the importance of this diagnosis, especially in emergency care.

  11. Primary pulmonary malignant melanoma: a clinicopathologic study of two cases

    Directory of Open Access Journals (Sweden)

    Gong Li

    2012-09-01

    Full Text Available Abstract Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  12. Malignant melanoma revealed by testicular metastasi.

    Directory of Open Access Journals (Sweden)

    Marie Dusaud

    2015-01-01

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

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

    Science.gov (United States)

    Jaworek-Korjakowska, Joanna

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Joanna Jaworek-Korjakowska

    2016-01-01

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

  15. MicroRNAs in the pathogenesis of malignant melanoma.

    Science.gov (United States)

    Glud, M; Gniadecki, R

    2013-02-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS-RAF-MEK-ERK pathway, the p16(INK4A) -CDK4-RB pathway, the PIK3-AKT pathway and the MITF pathway. PMID:22621697

  16. Nivolumab-Based Treatments for Advanced Melanoma

    Science.gov (United States)

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  17. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  18. Metastatic malignant melanoma of the uterus diagnosed by colposcopy

    Directory of Open Access Journals (Sweden)

    Živadinović Radomir

    2016-01-01

    Full Text Available Introduction. Primary and metastatic malignant melanomas represent a rare diagnosis with a small number of described cases. The aggressive nature of the tumor, non-specific symptoms, difficult diagnosis, and no official protocol about the treatment result in poor disease prognosis. Case Outline. The authors presented a 41-year-old multigravida patient. She had an operation of malignant melanoma in the occipital area of the head. She went to her gynecologist because of increased pale pink vaginal secretion. Gynecological examination didn’t show any significant abnormalities apart from a slightly enlarged uterus. Papanicolaou test and vaginal secretion examination were normal. Colposcopically, a significant dark brown hyperpigmented area around 1 cm in size was observed on the posterior lip of the cervix, near the orifice and cervical canal, suspicious of melanoma, which was proven on targeted biopsy of the hyperpigmented change on the cervix, and by magnetic resonance imaging of the lesser pelvis. Classic hysterectomy with adnexectomy and regional pelvic lymphadenectomy were performed. Conclusion. This case report pointed out the significance of applying colposcopy in diagnosing suspected metastatic melanoma of the uterine cervix, along with other diagnostic methods and anamnestic data.

  19. Symptomatic malignant melanoma presenting as multiple gastrointestinal polyps.

    Science.gov (United States)

    Casey, Shauna; Dvorkin, Lee; Alsanjari, Nazar; Dezso, Balazs

    2011-01-01

    We report on a 66-year-old man with a past medical history of gout who presented to his general practitioner (GP) in July 2009 with a history of nausea and intermittent diarrhoea. He had lost 6 kg in weight over 6 months. His GP found he was anaemic and referred him to a gastrointestinal outpatient clinic. He went on to have a gastroscopy and colonoscopy, which revealed multiple polyps in the stomach, duodenum and colon. Histology revealed that all the polyps were malignant melanoma. He had no known history of malignant melanoma. A staging CT scan revealed multiple lung metastases and he was referred for palliative care. The patient died 4 months after diagnosis. PMID:22715248

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

    Energy Technology Data Exchange (ETDEWEB)

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. (Texas Retina Associates, Dallas (USA))

    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.

  1. Updates in Therapy for Advanced Melanoma.

    Science.gov (United States)

    Singh, Bhavana P; Salama, April K S

    2016-01-15

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

  2. Sun exposure before and after a diagnosis of cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Philipsen, P A; Wulf, H C

    2011-01-01

    Previous studies on ultraviolet radiation (UVR) exposure before and after a diagnosis of cutaneous malignant melanoma (CMM) have been based primarily on questionnaires. Objective measures are needed....

  3. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  4. Primary gastric melanoma: case report of a rare malignancy

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-03-01

    Full Text Available We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.

  5. A PRELIMARY APPROACH FOR THE AUTOMATED RECOGNITION OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Ezzeddine Zagrouba

    2011-05-01

    Full Text Available In this work, we are motivated by the desire to classify skin lesions as malignants or benigns from color photographic slides of the lesions. Thus, we use color images of skin lesions, image processing techniques and artificial neural network classifier to distinguish melanoma from benign pigmented lesions. As the first step of the data set analysis, a preprocessing sequence is implemented to remove noise and undesired structures from the color image. Second, an automated segmentation approach localizes suspicious lesion regions by region growing after a preliminary step based on fuzzy sets. Then, we rely on quantitative image analysis to measure a series of candidate attributes hoped to contain enough information to differentiate melanomas from benign lesions. At last, the selected features are supplied to an artificial neural network for classification of tumor lesion as malignant or benign. For a preliminary balanced training/testing set, our approach is able to obtain 79.1% of correct classification of malignant and benign lesions on real skin lesion images.

  6. Desmoplastic malignant melanoma presenting as large lung mass.

    LENUS (Irish Health Repository)

    Al-Alao, Bassel Suffian

    2010-08-01

    We describe a case of successful minimally invasive thoracoscopic surgical resection of metastatic desmoplastic malignant melanoma replacing the entire right lower lobe of the lung, presenting 4 years after the initial complete resection of the primary scalp lesion. An 89-year-old man presented with a 6-month history of right-sided chest pain. A computed tomographic scan showed a large paravertebral mass with possibility of chest wall invasion. Core biopsy initially raised the suspicion of a schwannoma. We also discussed the atypical delayed presentation and misleading radiologic and histologic findings.

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

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

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

  8. Recurrence and massive extraocular extension of choroidal malignant melanoma after vitrectomy and endoresection

    Directory of Open Access Journals (Sweden)

    Mehdi Modarres

    2014-01-01

    Full Text Available Vitrectomy and endoresection is an alternative to enucleation for the treatment of large malignant choroidal melanoma. We report a rare case of extensive recurrence of choroidal malignant melanoma with extraocular extension 11 years after surgical endoresection without adjuvant treatment.

  9. Primary malignant melanoma of the lung in the elderly: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    PAN Xu-dong; ZHANG Bin; GUO Ling-chuan; GU Dong-mei; MAO Yan-qing; LI Jie; XIE Yan; WANG Ling

    2010-01-01

    @@ Malignant melanoma involving the respiratory tract, which is predominantly found in the skin, is nearly metastatic and true primary tumours are very rare.1 To date, only 32 cases have been reported in English literature and 22 cases of primary malignant melanoma of the lung have been reported in Chinese literature.

  10. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2012-02-01

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  11. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2009-03-05

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  12. Orbital malignant melanoma associated with nevus of Ota.

    Science.gov (United States)

    Radhadevi, Cherungottil V; Charles, Kakkuzhiyil S; Lathika, Vasu K

    2013-06-01

    Nevus of Ota (oculodermal melanosis) is a dermal melanocytic hamartoma with bluish hyperpigmentation along the first and second branches of the trigeminal nerve. Extracutaneous involvement, especially ocular, has been reported. A 45-year-old male presented with malignant melanoma of the left orbit in association with nevus of Ota. Being locally invasive, a modified exenteration with frontal flap repair was done on left eye. Adjuvant chemotherapy was given after wound healing. All pigmented lesions of the eye require close monitoring to help in the early diagnosis. Since malignant transformation has been reported in oculodermal melanosis, close follow-up and patient education will facilitate early diagnosis and prompt management. This case is reported for its rarity and unusual presentation.

  13. Orbital malignant melanoma associated with nevus of Ota

    Directory of Open Access Journals (Sweden)

    Cherungottil V Radhadevi

    2013-01-01

    Full Text Available Nevus of Ota (oculodermal melanosis is a dermal melanocytic hamartoma with bluish hyperpigmentation along the first and second branches of the trigeminal nerve. Extracutaneous involvement, especially ocular, has been reported. A 45-year-old male presented with malignant melanoma of the left orbit in association with nevus of Ota. Being locally invasive, a modified exenteration with frontal flap repair was done on left eye. Adjuvant chemotherapy was given after wound healing. All pigmented lesions of the eye require close monitoring to help in the early diagnosis. Since malignant transformation has been reported in oculodermal melanosis, close follow-up and patient education will facilitate early diagnosis and prompt management. This case is reported for its rarity and unusual presentation.

  14. Recurrent malignant melanoma of the palate successfully treated by gamma knife radiosurgery

    OpenAIRE

    YAMADA, SHIN-ICHI; Yanamoto, Souichi; Kawakita, Akiko; Kawasaki, Goro; Fujita, Shuichi; Ikeda, Tohru; Matsuo, Takemitsu; UMEDA, MASAHIRO

    2013-01-01

    The prognosis of oral malignant melanoma is reported to be extremely poor. In this report, a patient with recurrent oral melanoma in the skull base that was successfully treated by gamma knife radiosurgery (GKS) is described. A 53-year-old man was referred with a chief complaint of a mass of the hard palate. The histological diagnosis of a biopsy specimen was malignant melanoma. He underwent a wide local resection with bilateral neck dissection, followed by immunochemotherapy with DAV-Feron. ...

  15. Adoptive immunotherapy of advanced melanoma.

    Science.gov (United States)

    Shapira-Frommer, Ronnie; Schachter, Jacob

    2012-09-01

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

  16. Nevus of the Eyelid Margin Mimicking a Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    A. Echchaoui

    2016-06-01

    Full Text Available Nevi are a benign skin lesions commonly found on the eyelid margin, these tumors are usually pigmented and have thickness. Nevi are not typically visible at birth; they appear during childhood and often exhibit a more rapid increase in pigmentation about the time of puberty. Most eyelid nevi can be diagnosed by clinical examination; suspicious lesions should be biopsied when rapid growth, loss of eyelashes or discoloration of the nevus is noted. Eyelid nevi require treatment if malignant transformation and/or cosmetically bothersome to the patient. We report a case of a 37-year-old female patient exhibited a single cutaneous tumor at the free margin of the lower left eyelid, she noticed a dark spot on their eyelid since childhood. It was a brown, fleshy, thickened, and nodular well-circumscribed exophytic mass, measuring 6 mm in diameter; its clinical appearance argued for a possible nodular melanoma. Excisional-biopsy was performed using a full-thickness pentagonal wedge excision technique. Histopathology showed that the lesion was a benign melanocytic nevocellular nevus. The post-operative courses were uneventful with excellent cosmetic and functional result. Preventive measures (cap, sunglasses... and regular monitoring of the lesion by assessing ABCDE criteria (asymmetry, irregular borders, multiple colors, diameter ≥ 6 mm, and enlargement remain necessary to detect and rule out a possible risk of malignant melanoma.

  17. Amelanotic Esophageal Malignant Melanoma: Case Report and Short Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michael Kranzfelder

    2008-07-01

    Full Text Available Malignant melanoma in the esophagus is a rare condition which has been described only occasionally in case reports or in larger series of patients with esophageal disease. We describe here the very rare case of a patient who presented initially with a 2-month history of dysphagia and weight loss which led to the endoscopic diagnosis of an unclear lesion in the distal esophagus. Biopsies were taken revealing positive immunohistochemical staining against HMB-45. As there were no signs of skin melanoma and there was an absence of pigmentation, a diagnosis of primary amelanotic malignant melanoma was made. Primary staging of the lesion was completed with computed tomography (CT, which revealed a locally advanced tumor with lymph node metastases at the lesser curvature of the stomach and celiac trunk. As there is still a lack of potential protocols for multimodal neoadjuvant treatment for this rare tumor entity, a palliative abdominothoracic esophagectomy with systemic lymphadenectomy and intrathoracic anastomosis was carried out. Due to an intraoperative R2 situation, clip marking was performed to allow postoperative radiotherapy. Two months postoperatively, the planning CT scan for radiotherapy revealed progression of the retroperitoneal tumor mass, which was enclosing the celiac trunk, renal vein, and superior mesenteric artery. Multiple new liver and lung metastases were also found. During the following weeks, the patient developed acute renal failure and was admitted for dialysis, and the planned radiotherapy was deferred. At the end of May 2007, 4 months after the primary diagnosis, the patient died due to acute renal failure.

  18. The dysplastic naevus syndrome in patients with cutaneous malignant melanoma in Western Australia.

    Science.gov (United States)

    English, D R; Menz, J; Heenan, P J; Elder, D E; Watt, J D; Armstrong, B K

    1986-09-01

    One hundred and three patients with cutaneous malignant melanoma responded to an invitation to attend a dermatology outpatient clinic. All patients with a family history of melanoma, a history of multiple melanomas, or histological evidence of a dysplastic naevus that was associated with their melanoma were invited. A random sample of other patients with cutaneous malignant melanoma was also invited to attend. First-degree relatives of patients with the dysplastic naevus syndrome (DNS) were invited for a similar examination. DNS was found in 27% of the patients with a family history of melanoma, multiple melanomas, or histological evidence of a dysplastic naevus in association with their melanoma, and in 6% of the remaining patients who were selected at random. DNS was estimated to be present in 12.8% of 17- to 55-year-old patients with cutaneous malignant melanoma in the Perth region, while familial DNS was present in 4.5%. Patients with melanomas with DNS were more likely to be young men and to have numerous naevi, particularly on the lateral surfaces of the arms, shoulders and trunk, than were patients with melanomas without the syndrome. PMID:3747894

  19. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Hölmich, Lisbet Rosenkrantz

    2012-01-01

    Malignant melanoma is one of the most rapidly increasing cancer types globally, and it is by far the most serious skin cancer. Patients with a melanoma ≥ 1 mm in Breslow thickness are offered sentinel node (SN) biopsy and subsequent radical lymph node dissection if the biopsy is positive. The obj...

  20. PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS: REPORT OF FOUR CASES AND REVIEW OF THE LITERATURES

    Institute of Scientific and Technical Information of China (English)

    张辉; 汪良骏; 赵峻

    2002-01-01

    Objective: To investigate the clinical features and prognosis of the primary malignant melanoma of esophagus, to try to find out a rational therapy and to evaluate the value of surgical resection. Methods: Retrospective study was conducted for four cases with Primary malignant melanoma of esophagus hospitalized from May 1975 to April 1999. The relevant literatures of primary malignant melanoma of esophagus in recent years were also reviewed. Results: Four patients received multimodality therapy including surgical resection. The survival time is 16 years, 53 months, 5 months and 6 months, respectively. Conclusion: Primary malignant melanoma of the esophagus has a poor prognosis. Surgical resection plays an important role and is indispensable. The patterns of combination treatment modality need further investigation. Preoperative therapy combined with surgical resection and post-operative therapy may be a better management.

  1. Linear accelerator-based stereotactic radiosurgery in 140 brain metastases from malignant melanoma

    OpenAIRE

    Hauswald, Henrik; Stenke, Alina; Debus, Jürgen; Combs, Stephanie E

    2015-01-01

    Background: To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma. Methods: Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diamete...

  2. Correlations between cutaneous malignant melanoma and other cancers: An ecological study in forty European countries

    OpenAIRE

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

    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 datab...

  3. A distinct histopathological variant of a malignant melanoma with perivascular pseudorosettes: A case report.

    Science.gov (United States)

    Ishida, Mitsuaki; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi

    2013-09-01

    Although a rare condition, rosette formation in malignant melanoma has been previously documented. The present study describes the second documented case of malignant melanoma with perivascular pseudorosettes. A 38-year-old male presented with a black nodule on his back. Histopathological study revealed diffuse proliferation of neoplastic cells in the dermis and subcutis. A section of the tumor (~30%) was composed of a conventional malignant melanoma component. The remaining area was comprised of medium-sized polygonal cells with slightly eosinophilic cytoplasm and small-to-medium, round nuclei. Melanin pigment was rarely observed. A noteworthy observation was the presence of perivascular pseudorosette formations, which were characterized by their radial arrangement around the blood vessels, with a perivascular, anuclear zone. Immunohistochemically, the neoplastic cells were diffusely positive for S-100 protein and Melan-A and focally positive for HMB-45. Clinicopathological analyses of cases of malignant melanoma with rosette formations revealed that the types of rosette included the Homer-Wright type (two cases), perivascular pseudorosettes (two cases) and an unclassifiable type (one case). Immunohistochemical analysis is a useful method for forming a diagnosis as Melan-A or HMB-45 are generally expressed in all cases. Rosette formation in malignant melanoma is a distinct histopathological variant and may be an under-recognized phenomenon. Therefore, its recognition is significant for obtaining an accurate diagnosis of malignant melanoma.

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer;

    2010-01-01

    This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma...... melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved...

  5. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

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

  6. Malignant melanoma: A retrospective series from a regional cancer center in India

    Directory of Open Access Journals (Sweden)

    Sharma Kuldeep

    2009-01-01

    Full Text Available Purpose : To present our experience in treating malignant melanoma patients. Methods and Materials : All melanoma patients treated at the Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India, from 1995 to 2007 were studied retrospectively. The endpoints were loco-regional recurrence, distant recurrence, recurrence-free survival (RFS, and duration of follow-up (DOFU. RFS and DOFU were analyzed with respect to the factors like age, sex, tissue of origin, site of disease, number of nodes, lymphadenopathy, ulceration, stage, and operability to find out any association. Results : Seventy-two patients were found evaluable with 40 males and 32 females (median age 46.5 years. Eye was the commonest primary site with visual disturbance as the commonest symptom. Overall, 87% of the lesions were single, with most of the nonocular lesions presenting in the advanced stage. During the disease course, regional lymphadenopathy and distant metastases were seen in 33% and 32% of cases, respectively. Highest incidence of lymphadenopathy was seen in skin lesions and in primaries from trunk and extremities. Of all treated patients, 47% achieved complete response, 18% partial response, and others had either stable or progressive disease. The median DOFU was 6.2 months. RFS was studied only in curatively treated cases with a median of 10 months. Operability at presentation was the only prognostic factor influencing DOFU. Conclusion : Malignant melanoma is an uncommon disease in India carrying a lot of morbidity due to late presentation. Its management is still not clear regarding the optimum use and schedule of treatment modalities. More prospective studies in the future are required to come to a definite conclusion.

  7. Pembrolizumab: A Review in Advanced Melanoma.

    Science.gov (United States)

    Deeks, Emma D

    2016-03-01

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

  8. Ovarian metastasis of malignant melanoma: The first pediatric case

    Directory of Open Access Journals (Sweden)

    Yuko Araki

    2014-10-01

    Full Text Available We report a case of an 8-year-old girl with metastasis of malignant melanoma (MM to the ovary. She was initially diagnosed with cutaneous MM on the left buttock for which she underwent wide local excision, left inguinal/pelvic lymph node dissection, and subcutaneous injection of interferon beta. In spite of the treatment, she developed dissemination of MM to the liver, the bone, and the right ovary. All the lesions responded well to systemic chemotherapy (intravenous dacarbazine, except for the right ovarian tumor. She underwent an elective right salpingo-oophorectomy to avoid torsion or rupture of the tumor. However, she developed metastases to the contralateral ovary with peritoneal dissemination in 4 months. She received home palliative care and died at home 14 months after the last surgery. Ovarian metastasis of MM is a rare form of dissemination, and only 15 adult cases have ever been reported. Our patient is the first pediatric case. Since there is no standard of surgical indication for metastatic MM to the ovary, palliative resection can be an option for improving quality of life of a patient with this rare condition.

  9. Priapism in a stallion with generalized malignant melanoma.

    Science.gov (United States)

    Blanchard, T L; Schumacher, J; Edwards, J F; Varner, D D; Lewis, R D; Everett, K; Joyce, J R

    1991-03-15

    A Thoroughbred stallion developed priapism that was unresponsive to medical treatment and lavage of the corpus cavernosum penis with heparinized 0.9% NaCl solution. Three weeks after onset of priapism, the penis was firm and noncompliant, and penile pain sensation and ability to retract the penis were lost. Ultrasonography confirmed thrombosis of the corpus cavernosum penis. The stallion was euthanatized because of poor prognosis for return to breeding soundness. Necropsy revealed enlargement of numerous lymph nodes. The dorsal penile nerves were demyelinated distal to the crura of the penis. A diagnosis of generalized malignant melanoma was made; however, neither metastasis to the vertebral canal nor compression of spinal nerve roots as they exited the vertebral foramen was found. Priapism is a persistent erection without sexual arousal and is initially unassociated with penile paralysis, but if prolonged, leads to irreversible venous occlusion where collecting veins join the cavernous spaces. Damage to the dorsal penile nerves may explain the long-term penile paralysis and loss of sensation that accompanied priapism in this stallion. Priapism unassociated with the use of phenothiazine-derivative tranquilizers is uncommon in horses. PMID:2032912

  10. Brain metastases of malignant melanoma in Chinese:report of 23 cases

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-chou; LEE Shih-tseng

    2007-01-01

    Background Patients with melanoma metastasized to the central nervous system have a poor prognosis. Because the incidence of malignant melanoma in the Oriental is lower than that in the Caucasian population, brain metastases of malignant melanoma are rarely reported in Asia. Here we present our experience of brain metastasis of melanoma in an Asian perspective.Methods From 1990 to 2003, 369 patients with melanoma were treated in our hospital, 26 of them were diagnosed as having central nervous system involvement. Of the 26 cases, the clinical history, image, and pathologic findings of 23 patients were analyzed; the other 3 were excluded because of incomplete clinical data.Results Among the 369 patients with melanoma, 45% (167/369) developed lower extremity melanoma, and 27.1%(100/369) had acral lentiginous melanoma (ALM); while in the 23 patients with brain metastases, 34.7% (8/23) had lower extremity melanoma, and 34.7% (8/23) had ALM. Among the 23 patients, 17 had acute hemorrhage into the tumor,8 initially presented with a single cerebral metastatic lesion, and 15 had multiple brain lesions. Ten of them received surgery, 3 underwent stereotactic radiosurgery, and 16 received whole brain radiation. During follow-up, only 2 patients survived for more than 1 year, the median survival period was 5 months. The longest follow-up period was 11 years.Conclusions Compared with the Caucasian, Chinese patients with melanoma have a different proportion of melanoma subtype and higher incidence rates of lower extremities melanoma and ALM. However, their clinical presentation and prognosis are similar. The patients, who have excisable single or multiple brain lesions or limited extracranial disease and who are actively treated, may survive longer.

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

    Directory of Open Access Journals (Sweden)

    Priscilla A. Melville

    2003-01-01

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

  12. MALIGNANT MELANOMA WITH MULTIPLE METASTASES ON THE SMALL BOWEL - CASE REPORT

    Directory of Open Access Journals (Sweden)

    V.T. Grigorean

    2010-08-01

    Full Text Available BACKGROUND: Malignant melanomas often cause intestinal metastasis.Metastases of malignant melanoma are the most common secondary tumors of the gastrointestinal tract.The incidence of intestinal metastasis of malignant melanomas is 1.5-4.4% in clinical studies, reaching upto 35.6-58% in necroptic studies. AIM: We present a clinical case of multiple metastases to the smallbowel with point of departure right retroauricular malignant melanoma. METHODS: Patient T.I., 76years old, is admitted in our clinic with occlusion clinical features installed by approximately 2-3 days.From anamnesis we retain a subocclusion clinical feature installed by approximately 1-2 months, withgradual overheating. On clinical examination a right supraclavicular tumoral formation is found, sizing2.5-3cm, suggestive for malignant melanoma. The abdominal CT shows multiple tumoral formations inthe small bowel, with no other secondary determinations in the other organs. RESULTS: Intraoperatorywe have found six secondary lesions on the jejunum, two on the ileum and two mesenteric metastases. Itwas done partial enterectomy on the jejunal segment with latero-lateral jejuno-jejunal anastomoses andpartial enterectomy on the ileum segment with ileostoma. Postoperatory short-term outcome, at six andtwelve months was favorable. CONCLUSIONS: Small bowel metastases of malignant melanoma is thefirst suspected diagnosis in a patient with oclusive/suboclusive intestinal manifestations and clinicallesions suggestive of malignant melanoma. The patient presentes for acute complications (occlusion,intestinal perforation or chronic complications (chronic digestive bleeding, anemic syndrome. Oftennon-specific symptoms are present, which delay the diagnosis. Surgical treatment is the first therapeuticoption, even in case of multiple secondary determinations.

  13. Oral malignant melanoma: A case report of an unusual clinical and histologic presentation

    Directory of Open Access Journals (Sweden)

    Uzma Iqbal Belgaumi

    2013-01-01

    Full Text Available Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. The present case occurred in a 60-year-old female patient, as a pedunculated growth involving the palate and alveolar ridge and histologically showing a desmoplastic differentiation. The article discusses the distinct clinico-pathologic presentation of this case and emphasizes on the need to identify and report such cases for further understanding of their biologic behavior.

  14. Clear Cell Sarcoma of Gluteal Region Malignant Melanoma of Soft Parts

    Directory of Open Access Journals (Sweden)

    Haren V. Oza

    2013-04-01

    Full Text Available Clear cell sarcoma (CCS is described as variant of sarcoma characterized by prominent clear cells showing features similar to malignant melanoma of soft parts. This neoplasm was first described by Dr. Franz m. Enzinger. Primary CCS usually arises in deeper soft tissues, in association with fascia, tendons, or aponeuroses. Clear cell sarcoma (CCS is a rare malignant tumor with a propensity for slow progressive invasion. It is a tumor derived from Melanoblast like cell. They occur most commonly in the extremities, with a predilection for young females. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultra structural level. The tumor is very rare and can pose clinical challenges in early diagnosis. This case report demonstrates an unusual site of occurrence for clear cell sarcoma. [Natl J Med Res 2013; 3(2.000: 193-195

  15. Metastatic malignant melanoma representing a multiple mesenteric cystic tumor: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Lim; Woo, Ji Young [Kangnam Sacred Heart, College of Medicine, Hallym University, Seoul (Korea, Republic of)

    2008-05-15

    A metastatic malignant melanoma is a malignant tumor which can involve virtually every organ system. It has variable radiographic findings which mostly indicate solid masses in the mesentery. We report here on a case of a metastatic malignant melanoma, which is made up of multiple mesenteric cystic tumors that need to differentiate from the mesenteric cystic tumor. These include the cystic spindle cell tumor, cystic teratoma, cystic mesothelioma as well as the mesenteric cystic and the solid tumor, which in turn comprises the gastrointestinal stromal tumor, lymphoma and metastatic lesion. The metastatic malignant melanoma can offer a differential diagnosis when the image findings indicate multiple mesenteric cystic masses, multiple organic metastases, and subcutaneous nodules.

  16. Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

    International Nuclear Information System (INIS)

    Purpose/Objective: This course will (a) review the epidemiology, clinical presentation, staging, radiobiology, and radiation treatment of malignant melanoma and (b) review the epidemiology, clinical presentation, staging, and therapy of cutaneous T-cell lymphoma with an emphasis on radiotherapy based studies. I. Malignant Melanoma (MM): The incidence of MM has one of the fastest growth rates in the world. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for stage I-II cutaneous MM. Five-year survival rates depend on (a) sex: female-63%, male-40%; (b) tumor thickness: t 4mm-25%; (c) location: extremity-60%, trunk-41%; and (d) regional lymph node status: negative-77%, positive-31%. Despite adequate surgery, 45%-50% of MM patients will develop metastatic disease. Both the multi-target model and the linear quadratic model predict a possible benefit for high dose per fraction (> 400 cGy) radiation therapy for some MM cell lines. Other radiobiologic factors (repair of potentially lethal damage, hypoxia, reoxygenation, and repopulation) predict a wide variety of clinical responses to different time-dose prescriptions including high dose per fraction (> 400 cGy), low dose per fraction (200-300 cGy), or b.i.d. therapy. Based on a review of the radiobiology of MM, no single therapeutic strategy emerges which could be expected to be successful for all tumors. A review of all of the clinical trials evaluating various time-dose prescriptions for MM reveals that MM is a radiosensitive tumor over a very wide range of time-dose prescriptions. RT is the single most effective therapy for local palliation of metastatic disease. Complete response (CR) rates range from 24%-75% and overall response (OR) rates are 59%-98% with RT compared with CR rates of 3%-10% and OR rates of only 15%-36% with either chemotherapy or immunotherapy. In addition, postoperative RT for residual microscopic/macroscopic disease produces long term

  17. Correlations between cutaneous malignant melanoma and other cancers: An ecological study in forty European countries

    Directory of Open Access Journals (Sweden)

    Pablo Fernandez-Crehuet Serrano

    2016-01-01

    Full Text Available 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.

  18. Metastatic Malignant Melanoma of the Inguinal Lymph Node with Unknown Primary Lesion

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available Background. Malignant melanoma could present with metastasis with unknown primary (MUP and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy. Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

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

  2. The Molecular Biology and Treatment of Malignant Melanoma with BRAFV600 Mutations

    Directory of Open Access Journals (Sweden)

    Michael P. Mullane

    2014-01-01

    Full Text Available Since 2011, the treatment options for metastatic malignant melanoma have significantly changed. In that year, ipilimumab, an anti-CTLA4 monoclonal antibody, and vemurafenib, a potent inhibitor of mutated-BRAF (V600E and V600K, were approved by the U.S. Food and Drug Administration (FDA. In 2013, dabrafenib, another inhibitor of mutated-BRAF, and trametinib, a MEK inhibitor, were approved by the FDA. Most recently, combination therapy with dabrafenib and trametinib was approved. This article will describe a patient with metastatic malignant melanoma with BRAFV600E who has responded very well to vemurafenib monotherapy. We will then explore the molecular basis, pharmacologic development and clinical outcomes of inhibition of the mitogen-activated protein (MAP kinase pathway in patients with metastatic malignant melanoma with oncogenic BRAF (V600E and V600K.

  3. Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study.

    Science.gov (United States)

    Gallagher, R P; Elwood, J M; Threlfall, W J; Spinelli, J J; Fincham, S; Hill, G B

    1987-10-01

    In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure. PMID:3116308

  4. O6-methylguanine-DNA-methyltransferase and DNA mismatch repair in relation to drug resistance in malignant melanoma

    OpenAIRE

    Ma, Shuhua

    2004-01-01

    Although the survival rate of patients with malignant melanoma has improved, treatment of the disease poses large problems since disseminated melanoma frequently shows primary resistance to chemotherapy. Resistance to chemotherapy is thus a major clinical problem and a cause of failure in the treatment of metastatic malignant melanoma. The primary aim of this thesis was to investigate whether the DNA repair protein 06-methylguanineDNA-metbyltransferase (MGMT) and the post...

  5. PATHOLOGICAL FRACTURE TIBIA DUE TO METASTATIC LESION FROM MALIGNANT MELANOMA OF FOOT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Kunal R

    2016-03-01

    Full Text Available There is considerable variation in the reported incidence of skeletal metastasis from malignant melanoma. Metastasis to axial skeleton is almost four times more common than to appendicular skeleton.1 In long bones, the metastasis is usually located symmetrically at diaphysis.1 Patients with skeletal metastasis have grave prognosis with mean survival of 3.6 months.2 We report a case of malignant melanoma of foot with symmetrical metastasis to tibial diaphysis and pathological fracture on one side with 18 months’ survival.

  6. Imaging Finding of Malignant Melanoma of Eustachian Tube with Extension to Middle Ear Cavity: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Km Hong Chul [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of); Jang, Han Won [Daekyung Radiologic Clinics, Daegu (Korea, Republic of); Lee, Hui Joong [Dept. of Radiology, Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2012-11-15

    We report a case of malignant melanoma of Eustachian tube with extension to the middle ear cavity and nasopharynx in a 51-year-old woman who presented with right ear fullness. Computed tomography showed a soft tissue mass in the middle ear cavity and caused the widening and eroding of the bony eustachian tube. Magnetic resonance imaging showed well enhancing mass in eustachian tube extending nasopharynx to middle ear cavity. A biopsy of the middle ear cavity mass revealed a malignant amelanotic melanoma.

  7. Imaging Finding of Malignant Melanoma of Eustachian Tube with Extension to Middle Ear Cavity: Case Report

    Science.gov (United States)

    Kim, Hong Chul; Jang, Han Won

    2012-01-01

    We report a case of malignant melanoma of Eustachian tube with extension to the middle ear cavity and nasopharynx in a 51-year-old woman who presented with right ear fullness. Computed tomography showed a soft tissue mass in the middle ear cavity and causedthe widening and eroding of the bony eustachian tube. Magnetic resonance imaging showed well enhancing mass in eustachian tube extending nasopharynx to middle ear cavity. A biopsy of the middle ear cavity mass revealed a malignant amelanotic melanoma. PMID:23118582

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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. PMID:25046141

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

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

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

  11. A clinicopathological study of malignant melanoma with special reference to atypical presentation

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Subhalakshmi

    2008-10-01

    Full Text Available Malignant melanoma is a tumor of melanocytic origin. Lymphatic and hematogenous metastases are common in this condition. Retrospective analysis was performed in 16 consecutive cases diagnosed histopathologically as malignant melanoma at the pathology department of a medial college in eastern India. 75% of the patients were male; majority of them was in their sixth decade. All (100% the lesions were pigmented. The primary site was known in all cases, except two (12.5%. Out of the 14 cases with known primary site 11 (78.57% were cutaneous melanomas, including one arising in labia minora, two (14.29% were ocular and one (7.14% was vaginal in origin. Among cutaneous melanomas, superficial spreading type was the commonest variety and mixed population of epithelioid and spindle cell was the commonest histopathological pattern. The commonest grade of invasion was grade III (Clark′s. The clinical presentation of the case of vaginal melanoma and the two cases of secondary melanomas, including the one with obscure primary tumor, were bewildering and hence are discussed separately.

  12. Redox effects and cytotoxic profiles of MJ25 and auranofin towards malignant melanoma cells

    Science.gov (United States)

    Drummond, Catherine J.; McCarthy, Anna R.; Higgins, Maureen; Campbell, Johanna; Brodin, Bertha; Arnér, Elias S.J.; Laín, Sonia

    2015-01-01

    Malignant melanoma is the most dangerous type of skin cancer. Although recent progress in treatment has been achieved, lack of response, drug resistance and relapse remain major problems. The tumor suppressor p53 is rarely mutated in melanoma, yet it is inactive in the majority of cases due to dysregulation of upstream pathways. Thus, we screened for compounds that can activate p53 in melanoma cells. Here we describe effects of the small molecule MJ25 (2-{[2-(1,3-benzothiazol-2-ylsulfonyl)ethyl]thio}-1,3-benzoxazole), which increased the level of p53-dependent transactivation both as a single agent and in combination with nutlin-3. Furthermore, MJ25 showed potent cytotoxicity towards melanoma cell lines, whilst having weaker effects against human normal cells. MJ25 was also identified in an independent screen as an inhibitor of thioredoxin reductase 1 (TrxR1), an important selenoenzyme in the control of oxidative stress and redox regulation. The well-characterized TrxR inhibitor auranofin, which is FDA-approved and currently in clinical trials against leukemia and a number of solid cancers, displayed effects comparable with MJ25 on cells and led to eradication of cultured melanoma cells at low micromolar concentrations. In conclusion, auranofin, MJ25 or other inhibitors of TrxR1 should be evaluated as candidate compounds or leads for targeted therapy of malignant melanoma. PMID:26029997

  13. Malignant melanoma of the stomach presenting in a woman: a case report

    Directory of Open Access Journals (Sweden)

    Aslan İlknur

    2011-03-01

    Full Text Available Abstract Introduction Malignant melanoma is reported to metastasize to all organs of the human body. Although it is common for it to metastasize to the gastrointestinal tract, a melanoma located primarily in the gastric mucosa is an uncommon tumor. Gastrointestinal metastases are rarely diagnosed before death with radiological and endoscopic techniques. Case presentation In this case report the clinical course and treatment of a woman with melanoma of the stomach, without any other detectable primary lesion, is presented and discussed. A 55-year-old Turkish woman presented to our clinic with complaints of muscle pain and bone pain in the left side of her chest. During an upper gastrointestinal system endoscopy, dark cherry-colored, light elevated, round-shaped lesions were taken from her gastric fundus and from the first part of her duodenum. Biopsies from these samples were determined to be malignant melanoma by the pathologist. Conclusion Metastatic malignant melanoma cases should be examined through endoscopy for gastrointestinal metastases.

  14. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

    Directory of Open Access Journals (Sweden)

    Barry Richard D

    2011-01-01

    Full Text Available Abstract Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21 possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13, Coxsackievirus A15 (CVA15 and Coxsackievirus A18 (CVA18, also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM-1 and intratumoral injection of preformed subcutaneous SK-Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction. As preexisting immunity could potentially hinder oncolytic virotherapy, sera from stage IV melanoma patients and normal controls were tested for levels of protective antibody against the panel of oncolytic Coxsackieviruses. Serum neutralization assays revealed that 3 of 21 subjects possessed low levels of anti-CVA21 antibodies, while protective antibodies for CVA13, CVA15 and CVA18 were not detected in any sample. Serum from individuals who were seropositive for CVA21 failed to exhibit cross-neutralization of CVA13, CVA15 and CVA18. From these studies it can be concluded that the administration of CVA13, CVA15 or CVA18 could be employed as a potential multivalent oncolytic therapy against malignant melanoma.

  15. Delayed presentation of tattoo lymphadenopathy mimicking malignant melanoma lymphadenopathy.

    Science.gov (United States)

    Bordea, C; Latifaj, B; Jaffe, W

    2009-08-01

    Tattooing is a popular cosmetic practice and the technique has been adopted in breast reconstruction. Pigment injected intradermally is transported to lymph nodes leading to permanent pigmentation. Differential diagnosis between melanoma and tattoo pigmentation of lymph nodes is done microscopically. We present the case study of a patient who presented with palpable and pigmented axillary lymph nodes, 2 years after excision of melanoma and 20 years after tattooing. Intraoperative finding of enlarged, pigmented lymph nodes is not a certain sign of metastasis, as causes other then melanoma can lead to pigmented lymphadenopathy. The diagnostic and investigation process should start with history (including history of previous tattooing) and fine needle aspiration (FNA) of enlarged lymph node. If FNA is negative an open biopsy should be performed for confirmation of diagnosis before proceeding to completion lymphadenectomy. PMID:18249051

  16. PET of Malignant Melanoma Using 18F-Labeled Metallopeptides

    OpenAIRE

    Ren, Gang; Liu, Zhe; Miao, Zheng; Liu, Hongguang; Subbarayan, Murugesan; Chin, Frederick T.; Zhang, Lan; Sanjiv S Gambhir; CHENG Zhen

    2009-01-01

    Melanocortin type 1 receptor (MC1R), also known as α-melanocyte–stimulating hormone (α-MSH) receptor, is an attractive molecular target for melanoma imaging and therapy. An 18F-labeled linear α-MSH peptide (18F-FB-Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 [NAPamide]) shows promising melanoma imaging properties but with only moderate tumor uptake and retention. A transition metal rhenium-cyclized α-MSH peptide, ReO[Cys3,4,10,D-Phe7,Arg11] α-MSH3–13 (ReCCMSH(Arg11)), has shown high in vitro bind...

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

    Science.gov (United States)

    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. Establishment of optimal thermal neutron capture therapy for 5 types of human malignant melanoma

    International Nuclear Information System (INIS)

    A series of boron neutron capture therapy (BNCT) studies has already germinated in 1972, with a view to establishing the BNCT particularly suited for the treatment of various types of malignant melanoma, and has been succeeded by research teams comprised of multi-disciplinary members. Twelve patients (7 men and 5 women, aged from 50 to 85 years) with malignant melanoma have been treated with BNCT; among them, six patients were completely cured, four had extremely reduced tumors, and two were still in the clinical process. The present Progress Report is a compilation of 39 research presentations for the recent two years. In this report, three patients are described. Of these, one patient had deep-seated lesions in right and left lymph nodes. These lesions were cured by the use of D2O that allowed neutron beams to reach them. Application of positron emission tomography to the diagnosis of melanoma is a highlight in this Report. (N.K.)

  19. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    International Nuclear Information System (INIS)

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy

  20. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

  1. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dirk Schadendorf

    2012-04-01

    Full Text Available Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA tyrosinase, tyrosinase related protein (TRP-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

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

    Science.gov (United States)

    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) Pxxx)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.

  3. Epidemiological and clinical characteristics of malignant melanoma in Southeast Anatolia in Turkey

    Science.gov (United States)

    Sula, Bilal; Uçmak, Feyzullah; Kaplan, Mehmet Ali; Urakçi, Zuhat; Arica, Mustafa; Isikdogan, Abdurrahman

    2016-01-01

    Introduction The present study aimed to establish the epidemiological and clinical characteristics of patients who were histopathologically diagnosed with malignant melanoma (MM). Methods The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM in Dicle University Medical Faculty, Dermatology and Medical Oncology departments between 2005 and 2014. Results The study included 78 patients in total with 44 (56.4%) male and 34 (43.6%) female. Median age of the patients was 62.50 years (range: 27 - 84 years). Of the patients, 78.2% (n = 61) had cutaneous melanoma, 8.9% had solid organ melanoma, and 2.5% had ocular and mucosal melanoma. The most common tumor localization among the patients was the lower extremities with 29.4% (n = 23). The most common histopathological type was nodular malignant melanoma with 35.8% (n = 28). Based on TNM, Clark and Breslow classifications, 26.9% (n = 21) of the patients were stage 4, 26.9% (n = 21) were Clark stage 4, and 37.1% (n = 29) were Breslow stage 4. Median overall survival in all patients was 14.9 months (95% CI 10.9 - 18.8 months). In the multivariate Cox analysis, only stage statistically significantly affecting survival [odds ratio (OR): 0.54; (95% CI 0.16-1.82, p = 0.02)]. Conclusion Malignant melanoma data are also important for the optimal utilization of effective methods and healthcare resources to prevent the disease. In order to minimize MM mortality and morbidity, not only the society but also physicians from primary and secondary care hospitals should become familiar with melanoma.

  4. Successful non-typical radiotherapy of a recurrent and metastasizing malignant melanoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Dietz, W.; Dietz, R.

    1982-02-01

    A report is given about the successful, ambulatory, non-typical radiotherapy of a malignant vulvar melanoma producing recurrences and metastases after surgery. The problems of radiotherapy are discussed under special consideration of this case. With regard to the communications found in literature, the author underlines the efficiency of radiotherapy, especially if it is fractionated into high individual doses.

  5. Successful non-typical radiotherapy of a recurrent and metastasizing malignant melanoma of the vulva

    International Nuclear Information System (INIS)

    A report is given about the successful, ambulatory, non-typical radiotherapy of a malignant vulvar melanoma producing recurrences and metastases after surgery. The problems of radiotherapy are discussed under special consideration of this case. With regard to the communications found in literature, the author underlines the efficiency of radiotherapy, especially if it is fractionated into high individual doses. (orig.)

  6. CHEK2*1100delC and risk of malignant melanoma

    DEFF Research Database (Denmark)

    Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E;

    2012-01-01

    It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated...

  7. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Rasmussen, Helle; Breiting, Line;

    2012-01-01

    A 73-year-old woman was referred to the hospital due to a pigmented, asymptomatic nevus on her right arm that had changed in size and color. The histopathological examination showed a superficial spreading malignant melanoma, Clark level III, 2.26 mm in thickness. Two years later, the patient pre...

  8. Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

    2013-01-01

    The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) perform...

  9. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

  10. Amelanotic Malignant Melanoma Mimicking Hemangioma of the Hand: One Case Report and Literature Review

    Institute of Scientific and Technical Information of China (English)

    Lei Ma; Xinghua Gao

    2009-01-01

    @@ Introduction Malignant melanoma (MM) is one of the most deadly cancers[1]. Although the disease accounts for only about 4% of skin cancer related cases, it is responsible for about 79% of skin cancer deaths[2]. Early diagnosis of MM is, therefore, essential for appropriate treatment decision and, in turn, may give patients the best chance for prolonged survival[3-5].

  11. Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

    Science.gov (United States)

    Kubecek, Ondrej; Trojanova, Petronela; Molnarova, Veronika; Kopecky, Jindrich

    2016-08-01

    Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. PMID:27372860

  12. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T;

    2013-01-01

    The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast-enhance...

  13. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin;

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; thi...

  14. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    Science.gov (United States)

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  15. Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

    Directory of Open Access Journals (Sweden)

    Tajahuerce Marcos

    2011-08-01

    Full Text Available Abstract Background Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Case Presentation Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A mutation was detected in exon 15 of the BRAF gene. Conclusion Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.

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

    Science.gov (United States)

    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

    Science.gov (United States)

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

  20. A phase II study of thalidomide in patients with brain metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Vestermark, Lene; Larsen, Susanne; Lindeløv, Birgit;

    2008-01-01

    Introduction. Brain metastases develop in nearly half of the patients with advanced melanoma and in 15 to 20% of these patients CNS is the first site of relapse. Overall median survival is short, ranging from 2 to 4 months. Thalidomide has antiangiogenic and immunomodulatory effects. Results...... obtained in prior trials indicate that Thalidomide acts as a cytostatic agent in metastatic melanoma. We evaluated single agent antitumour activity and toxicity of Thalidomide in a phase II setting in patients with brain metastases associated with metastatic melanoma. Material and methods. Patients...

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

    Directory of Open Access Journals (Sweden)

    Asmar R

    2016-02-01

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

  2. [The humoral immunity indices of patients with malignant skin melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Heisele, O G; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of a viral immunomodulator rigvir on humoral immunity was studied in patients with skin malignant melanoma. Peripheral blood levels of B-lymphocytes, IgA, G and M and circulating immune complexes were assayed and immunoglobulin/B-cell ratio (Ig/B) calculated. Preoperative treatment with rigvir brought the indexes of humoral immunity to normal. Response of melanoma patients to rigvir treatment was different from that seen in healthy subjects and was determined by the course of disease. PMID:1300751

  3. Malignant melanoma and Charcot-Marie-Tooth disease: A further case

    Energy Technology Data Exchange (ETDEWEB)

    Manoukian, S.; Briscioli, V.; Lalatta, F. [Instituti Clinici di Perfezionamento, Milan (Italy)

    1997-01-20

    In a previous issue of this journal, Greene et al. described 2 patients with Charcot-Marie-Tooth (CMT) disease who later developed cutaneous malignant melanoma. Although the development of the two diseases in the same patient may have occurred by chance, the authors raised the possibility of a shared neural crest defect or a genetic linkage. Among the patients reported by Greene et al., one had a dominant form of CMT. The patient`s mother and brother were similarly affected. A paternal aunt died of melanoma. The second patient had a neuronal type of CMT. His brother showed the same disease, but the parents were not examined. 7 refs.

  4. DNA-index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Kristensen, I B; Grymer, F;

    1990-01-01

    determined by flow cytometry in adjacent sections from the same paraffin-embedded tumours. Only a poor correlation was found between nuclear vv and DI (Kendall's tau = +0.21). The variability of nuclear vv among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values...... obtained objectively by point-sampled intercepts. Using this approach, the volume-weighted mean nuclear volume, nuclear vv, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA-indices (DI) were...

  5. Nectin like-5 overexpression correlates with the malignant phenotype in cutaneous melanoma

    Science.gov (United States)

    Bevelacqua, Valentina; Bevelacqua, Ylenia; Candido, Saverio; Skarmoutsou, Evangelia; Amoroso, Alfredo; Guarneri, Claudio; Strazzanti, Angela; Gangemi, Pietro; Mazzarino, Maria C.; D'Amico, Fabio; McCubrey, James A.

    2012-01-01

    NECL-5 is involved in regulating cell–cell junctions, in cooperation with cadherins, integrins and platelet-derived growth factor receptor, that are essential for intercellular communication. Its role in malignant transformation was previously described. It has been reported that transformation of melanocytes is associated with altered expression of adhesion molecules suggesting the potential involment of NECL-5 in melanoma development and prognosis. To shed light on this issue, the expression and the role of NECL-5 in melanoma tissues was investigated by bioinformatic and molecular approaches. NECL-5 was up-regulated both at the mRNA and the protein levels in WM35, M14 and A375 cell lines compared with normal melanocytes. A subsequent analysis in primary and metastatic melanoma specimens confirmed “in vitro” findings. NECL-5 overexpression was observed in 53 of 59 (89.8%) and 12 of 12 (100%), primary melanoma and melanoma metastasis, respectively; while, low expression of NECL-5 was detected in 12 of 20 (60%) benign nevi. A significant correlation of NECL-5 overexpression was observed with most of known negative melanoma prognostic factors, including lymph-node involvement (P = 0.009) and thickness (P = 0.004). Intriguingly, by analyzing the large series of melanoma samples in the Xu dataset, we identified the transcription factor YY1 among genes positively correlated with NECL-5 (r = 0.5). The concordant computational and experimental data of the present study indicate that the extent of NECL-5 expression correlates with melanoma progression. PMID:22929570

  6. Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xiang; Pham, Tien Q.; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc' h, Christian [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia); Katsifis, Andrew [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia)], E-mail: akx@ansto.gov.au

    2008-10-15

    Introduction: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods: [{sup 123}I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results: The iodonicotinamides displayed low-affinity binding for {sigma}{sub 1}-{sigma}{sub 2} receptors (K{sub i}>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[{sup 123}I]iodonicotinamide ([{sup 123}I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ({approx}8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [{sup 123}I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [{sup 123}I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [{sup 123}I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion: These findings suggest that [{sup 123}I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

  7. Testing Adjuvant Ipilimumab in Advanced Melanoma

    Science.gov (United States)

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

  8. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Anna Niezgoda

    2015-01-01

    Full Text Available The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013, MEK-inhibitors (trametinib 2013, anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014, anti-CTLA-4 antibody (ipilimumab 2011, or peginterferon-alfa-2b (2011 intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015.

  9. Primary cerebral malignant melanoma: an unusual cause of dyspraxia.

    Science.gov (United States)

    Farnsworth, T A

    1998-09-01

    Primary intracranial melanomas are rare and occur mainly in young adults. Originating from leptomeningeal melanoblasts and extending into the parenchyma, the tumours closely resemble meningiomas, from which they are radiologically difficult to distinguish despite progress in neuroimaging. Definitive diagnosis is usually made on histopathological examination, though confirmed only after post-mortem examination in some cases. Prolonged disease-free periods, and in rare cases long-term survival, are possible following successful total surgical excision. This case presented with typical clinical features but, at 79 years old, an unusual age. PMID:9894390

  10. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

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

    Science.gov (United States)

    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.

  12. Uveal and conjunctival malignant melanoma in denmark 1943-97: observed and relative survival of patients followed through 2002

    DEFF Research Database (Denmark)

    Isager, Peter; Engholm, G.; Overgaard, Jens;

    2006-01-01

    PURPOSE: To evaluate the observed and relative survival of patients diagnosed with a malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The study included 2,504 patients (1,292 men and 1,212 women) diagnosed with a melanoma in the ocular region, of which 2,434 ...

  13. Preliminary studies of radiolabeled monoclonal antibody lymphoscintigraphy in malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Eary, R.F.; Jones, R.; Kishore, R.; Krohn, K.A.; Beaumier, P.; Hellstrom, I.; Hellstrom, K.E.

    1985-05-01

    Studies have been initiated to examine the ability of I-131 anti-melanoma antibody (Fab) to delineate metastases in regional lymp nodes. 500 ..mu..gm of I-131 Fab (48.7) directed against HMW antigen of melanoma and I-125 non-specific Fab were injected subcutaneously distal to sites of node resection in 5 patients 20 hours prior to surgery. 3 additional injections were made distal to non-diseased inguinal nodes. 3 pts had no palpable nodes (class 1) and 2 did (class II). Gamma imaging of nodes at 3 and 18 hrs was negative in non-diseased areas and was positive in Pts 1-3; Pt 1 had only micrometastases occupying less than 1% of node volume. In-vitro counting of nodes showed concentrations of I-131 of % .0015 dose/gm of whole node and presumably much higher on tumor cells per se. Autoradiography of I-131 specific Fab in tumored nodes showed high discrete concentration on tumor compared to normal areas. Autoradiography of non-specific I-125 is currently underrway. The authors conclude these preliminary data show considerable promise for pre-surgical delineation of metastatic disease by radiommuno- lymphoscintigraphy.

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

    OpenAIRE

    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 fish...

  15. The role of radiation therapy in the treatment of malignant melanoma in the nasal cavity and nasopharynx-case report

    International Nuclear Information System (INIS)

    Purpose: Primary mucosal malignant melanoma of the nasal cavity, paranasal sinuses, and nasopharynx (hereinafter referred to collectively as the sinonasal tract, i.e., sinonasal tract mucosal malignant melanomas [SNMMs]) is rare, accounting for between 0.3% and 2% of all malignant melanomas and about 4% of head and neck melanomas. Surgery is the treatment of choice for sinonasal mucosal malignant melanomas, especially complete resection of the tumor with sufficient free margins. Radiotherapy has controversial role in the treatment. Melanoma cells are traditionally considered as radioresistant because they have a high capacity for repair of sublethal damages, in particular when we used a conventional fractionation. Therefore, hypo fractionation considered as a reasonable treatment regimen for this disease. Case: In this paper, we have reported the patient with intranasal cavity malignant melanoma. Functional endoscopic sinus surgery was performed to excise the nasal cavity tumor. However, using positron emission tomography/computed tomography scan with fluorodeoxyglucose was diagnosed residual nasopharyngeal tumor. Then, intracavitary brachytherapy for nasopharynx was further administered. Solitary metastatic cervical nodal involvement which was completely removed has been occurred 6 months after the end of brachytherapy. Even with the regional disease progression, we used external radiation therapy, as a modality of treatment. Conclusion: We decided to show this case report because of its rarity and the possible use of radiotherapy. (author)

  16. [The reaction of the T-immunity system in patients with malignant skin melanoma and stomach cancer to active nonspecific immunotherapy].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh

    1992-01-01

    Changes in E-receptor-bearing T-lymphocyte level (total and that of active T-lymphocytes) were studied in peripheral blood and resected material obtained from skin malignant melanoma and gastric cancer patients treated with rigvir, an original immunomodulator of the viral origin. Injection of rigvir into peripheral blood was followed by an increase in active T-lymphocyte level and stimulated their migration into tumor. The latter was determined by stage and rate of tumor advancement. PMID:1300766

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

    Science.gov (United States)

    Huang, Sharon K; Hoon, Dave S B

    2016-03-01

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

  18. Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    Recent developments in stereology have made it possible to obtain unbiased, objective estimates of the volume weighted mean nuclear volume (vV) from ordinary histological sections, without any assumptions concerning nuclear shape. The aim of this study was to gather baseline data of nuclear v......V in melanocytic cutaneous tumors and to compare these with estimates of nuclear volume fraction and with traditional two-dimensional morphometric estimates of nuclear profile area, nuclear density, and mitotic index. Routinely processed, paraffin embedded tissue specimens from 47 malignant melanomas and 76...... noninvasive melanocytic cutaneous tumors were investigated retrospectively. vV clearly distinguished between noninvasive (average vV = 122 microns 3) and invasive lesions (average vV = 246 microns 3). Most of the patients with malignant melanomas showing an overlap of nuclear vV with benign lesions had...

  19. Selective Expression of Progesterone Receptor in Malignant Melanoma Was Inversely Correlated with PCNA

    Institute of Scientific and Technical Information of China (English)

    Jiawen LI; Xianfeng FANG; Xu'e CHEN; Jing CHEN

    2008-01-01

    To investigate the role of progesterone receptor (PR) expression in malignant melanoma (MM), PR and proliferative cell nuclear antigen (PCNA) expression were immunohistochemistri- tally evaluated in a series of 35 specimens of MM, and the correlation between the immunohisto- chemistrical findings and clinicopathological data was also analyzed. PR expression was detected in 25.7% (9/35) of the patients with MM. No PR expression was observed in nevi. PR expression was inversely correlated with PCNA expression (r=-0.353, P=0.026). PR expression was slightly in- creased in females, subjects aged under 55 y, those with ulceration, non-acral subtype and diagnosis delay longer than 1 y, but the difference was not statistically significant. Selective expression of pro- gesterone receptor in malignant melanoma might be correlated with inhibited tumor growth.

  20. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  1. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  2. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options

    OpenAIRE

    Metcalfe, Lucy VA; O’Brien, Peter J; Papakonstantinou, Stratos; Cahalan, Stephen D; McAllister, Hester; Duggan, Vivienne E

    2013-01-01

    A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thor...

  3. Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma.

    Science.gov (United States)

    Szegezdi, Eva; Leverkus, Martin

    2016-02-01

    Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug-resistant melanoma remains a challenge. Agents designed to activate the cell death machinery directly, for example by activating the death receptors expressed by melanoma cells, could break drug resistance, and they may achieve long-lasting therapeutic success. He et al. report their studies of an MCSPxDR5 bispecific, tetravalent antibody that can simultaneously target death receptor 5 (DR5, TRAIL-R2) and melanoma-associated chondroitin sulfate proteoglycan (MCSP). This antibody can exert strong and selective DR5-dependent cytotoxic activity against MCSP-expressing melanoma cells. Crosslinking of the antibody with Fcγ-receptors increased the cytotoxic potential further, without compromising its selectivity. This approach offers a novel immunotherapeutic tool via coupling of three cooperating processes: delivering the death receptor agonist to the malignant cell population, potent activation of DR5-mediated cell death signaling, and recruitment of Fcγ-receptor-carrying immune cells that can mount an immune response against the tumor cells. PMID:26802233

  4. Carborane compounds for neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    The possibility of using thiouracil as a vehicle for stable nuclei such as 10B for neutron capture therapy (NCT) of melanoma was first discussed by Fairchild and co-workers in 1982. The author's research has been directed towards the design and synthesis of a number of o-carboranyl-thiouracils, the ten boron atoms of the carborane cage having a clear advantage for NCT. The first step was the preparation, previously reported, of thiouracils bearing an alkyl group continuing a triple bond for later elaboration to a carborane. The present paper describes the continuation of this work with the preparation of the carboranes of this series and its extension to the synthesis of a thiouracil in which a carboranylalkyl group is attached to the nitrogen in the 3-position

  5. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

    Directory of Open Access Journals (Sweden)

    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  6. Regressing thin cutaneous malignant melanomas (< or = 1.0 mm) are associated with angiogenesis.

    OpenAIRE

    Barnhill, R. L.; Levy, M. A.

    1993-01-01

    In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the...

  7. Malignant melanomas of the nasal cavity after occupational exposure to formaldehyde.

    OpenAIRE

    Holmstrom, M.; Lund, V J

    1991-01-01

    Formaldehyde is a well known nasal carcinogen in rodents, but so far there has been no convincing evidence that workers occupationally exposed to formaldehyde have an increased risk of nasal cancer. In this study three cases of malignant melanoma of the nasal mucosa in persons occupationally exposed to formaldehyde for a long time are presented. The occurrence of such a rare tumour in patients with significant exposure to a known carcinogen warrants further investigation.

  8. A 60-Year-Old Man with Cerebral Metastasis of Malignant Melanoma of Left Sole

    OpenAIRE

    Abhisak Bhattacharjee; Nabir Hossain

    2016-01-01

    A 60-year-old man was diagnosed as a case of malignant melanoma on the left sole and received three cycles of neoadjuvant chemotherapy. Then local excision of the lesion was done. During preoperative diagnostic work-up, there were no features of metastases in lung, liver and bones. On the 3rd postoperative day he presented with right sided hemiparesis. After appearance of neurological features, computed tomography was done and it showed multiple cerebral metastases surrounded by brain edema i...

  9. Pigmented Bowen’s Disease of the Genitalia Masquerading as Malignant Melanoma

    OpenAIRE

    Emel Öztürk Durmaz; Işın Doğan Ekici; Ferda Özkan; Sedef Şahin

    2015-01-01

    Abstract Pigmented Bowen’s disease is a rare subtype of in situ squamous cell carcinoma of the skin and mucosa, with a potential risk of invasion and metastasis. It is universally accepted that human papillomavirus (HPV) is the cause of genital Bowen’s disease. Herein we report an unusual case of pigmented Bowen’s disease of the genital area that clinically simulated malignant melanoma. Accurate diagnosis could only be established after histological examination. Polymerase chain reaction (PCR...

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

    Science.gov (United States)

    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. PMID:27154314

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

    Directory of Open Access Journals (Sweden)

    Martha M. Motomo Chojniak

    2001-04-01

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

  12. Management of a patient with advanced BRAF-mutant melanoma.

    Science.gov (United States)

    Ashworth, Michelle T; Daud, Adil

    2014-03-01

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

  13. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

    Full Text Available Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated median survival of 40 to 90 months and 5-year survival of 30% to 60% after the combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This improvement in survival has prompted new searches into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

  14. Treatment side effects and follow-up of malignant melanoma; Therapienebenwirkungen und Nachsorge bei malignem Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, T. [Klinikum der Stadt Ludwigshafen gGmbH, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany); Loquai, C. [Universitaetsmedizin der Johannes-Gutenberg Universitaet Mainz, Hautklinik und Poliklinik, Mainz (Germany)

    2015-01-30

    Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (> 50 %) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20 %) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20 %) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17 %), thyroiditis (0.8 %), myositis (1.7 %), fasciitis and sarcoid-like lymph node alterations (6.8 %). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists. (orig.) [German] Nebenwirkungen der Therapie des malignen Melanoms sind fuer den Radiologen primaer in fortgeschrittenen Tumorstadien von Bedeutung. Die zur Verfuegung stehenden Therapieoptionen und ihre jeweiligen Nebenwirkungsprofile haben sich in den letzten Jahren nach Einfuehrung moderner onkologischer Therapieoptionen, die sich zunehmend an der individuellen Tumorbiologie orientieren (zielgerichtete Therapie, Immuntherapie), einem

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report

    Directory of Open Access Journals (Sweden)

    Gogakos AS

    2016-01-01

    Full Text Available Apostolos S Gogakos,1 Dimitrios Paliouras,1 Christos Asteriou,1 Thomas Rallis,1 Achilleas Lazopoulos,1 Fotios Chatzinikolaou,2 Athanassios Zissimopoulos,3 Drosos Tsavlis,4 Katerina Tsirgogianni,4 Konstantinos Zarogoulidis,4 Konstantinos Porpodis,4 Kosmas Tsakiridis,5 Georgia Pitsiou,4 Ioannis Kioumis,4 Ilias Karapantzos,6 Chrysanthi Karapantzou,6 Nikos Sachpekidis,5 Paul Zarogoulidis,4 Nikolaos Barbetakis1 1Thoracic Surgery Department, 2Department of Pathology, Theagenio Cancer Hospital, Thessaloniki, 3Nuclear Medicine Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 4Pulmonary Department – Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, 5Cardiothoracic Surgery Department, 6Ear, Nose and Throat Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, Greece Abstract: Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient’s history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival. Keywords: melanoma, metastasis, chest wall, sternum

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

    Science.gov (United States)

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

    2016-03-01

    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

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

    Directory of Open Access Journals (Sweden)

    Alfredo Addeo

    2013-05-01

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

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

    Science.gov (United States)

    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. PMID:26825038

  20. An uncommon presentation and course of metastatic malignant melanoma: a case report

    Directory of Open Access Journals (Sweden)

    Dalhaug Astrid

    2007-11-01

    Full Text Available Abstract Most patients with brain metastases from malignant melanoma are diagnosed after treatment for known extracranial metastases and have a poor outcome despite various local and systemic therapeutic approaches. Here we discuss an unusual case where a 45-year old patient presented with a brain metastasis as the first symptom of disease and where the presumed primary lesion later was found in the gastro-intestinal tract. Treatment consisted of sequential surgical removal of a total of 4 tumor sites (2 extracranially, whole-brain radiotherapy and two radiosurgery procedures within 13 months. Following her last treatment, the patient has now been in remission for 20 months. This case illustrates that some patients with multi-organ melanoma manifestations may benefit from the repeated use of effective local therapeutic approaches and may experience a quite favourable prognosis.

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

    DEFF Research Database (Denmark)

    Nyholm, Anne Marie; Lerche, Catharina M; Manfé, Valentina;

    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...

  2. c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.

    Directory of Open Access Journals (Sweden)

    Yuichiro Ohshima

    Full Text Available 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.

  3. Differentiation of Human Malignant Melanoma Cells that Escape Apoptosis After Treatment with 9-Nitrocamptothecin In Vitro

    Directory of Open Access Journals (Sweden)

    Panayotis Pantazis

    1999-08-01

    Full Text Available After in-vitro exposure to 0.05 μmol/L 9-nitrocamptothecin (9NC for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1 B cells die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G2 exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G1-arrested, but downregulated in density G1-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells.

  4. N-isopropyl-p-I-123-Iodoamphetamine is a sensitive test for detecting malignant melanoma

    International Nuclear Information System (INIS)

    N-isopropyl-p-I-123-Iodoamphetamine (I-123-IMP) was originally developed for the measurement of the brain blood flow. I-123-IMP is known to be incorporated into melanin-producing cells suggesting that I-123-IMP is incorporated in malignant melnoma. We tested both I-123-IMP and Ga-67 citrate in 36 cases with malignant melanoma in order to compare their clinical utility in the same patients. Of the 22 primary lesions, 11 (50%) were detected by I-123-IMP scan, but only 6 (22.7%) were detected by Ga-67 citrate scan. Of the 28 metastatic lesions, 15 (53.6%) were detected by I-123-IMP scan, but only 13 (46.4%) were detected by Ga-67 citrate scan. Among the I-123-IMP scans, there were no false positive cases, but Ga-67 citrate detected post operative lesions. In conclusion, I-123 IMP has advantages in the detection of malignant melanoma in terms of sensitivity and specificity. (author)

  5. Involvement of ANXA5 and ILKAP in susceptibility to malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Yoana Arroyo-Berdugo

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Courtney Nicholas

    Full Text Available 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.

  7. Radiation therapy of malignant melanoma: Experience with high individual treatment doses

    International Nuclear Information System (INIS)

    Melanoma is a complex tumor, metastasizes early both by lymphatic and blood vessels, and which may invoke a significant host ''immune,'' response. One can imagine a number of potentially useful roles for an effective radiation therapy regimen: 1. Treatment of the primary lesion. For small lesions located on the extremities, surgery may be simpler and obviate the risk of radiation failure. In other areas, e.g., head and neck, which may require more cosmetically or functionally debilitating surgery, a trial of radiation therapy may be worthwhile. 2. Preoperative radiation to the primary lesion before surgical resection in the hope of preventing tumor dissemination. 3. Prophylactic, local and regional lymph node radiation therapy. It has been popular in the past to remove malignant melanoma with wide local excision and dissection of adjacent node areas. It is still an open question whether some or any additional patients will be cured by the more vigorous local and extended treatment. Generally, those procedures have fallen into disfavor because of the associated morbidity. Presumably subclinical amounts of malignant melanoma could be sterilized with doses of radiation smaller than those necessary for bulk tumor. Wide field irradiation to the areas surrounding the primary lesion and the adjacent lymph nodes, to doses causing little morbidity, may well be worth clinical trial. 4. In combination with other forms of therapy, e.g., chemotherapy, immunotherapy, hyperthermia, to reduce the number of malignant cells in localized areas known to contain diseases. This may be particularly important prior to initiation of immunotherapy which may be much more effective in the absence of gross disease

  8. RAS/RAF/MEK/ERK and PI3K/PTEN/AKT Signaling in Malignant Melanoma Progression and Therapy

    Directory of Open Access Journals (Sweden)

    Ichiro Yajima

    2012-01-01

    Full Text Available Cutaneous malignant melanoma is one of the most serious skin cancers and is highly invasive and markedly resistant to conventional therapy. Melanomagenesis is initially triggered by environmental agents including ultraviolet (UV, which induces genetic/epigenetic alterations in the chromosomes of melanocytes. In human melanomas, the RAS/RAF/MEK/ERK (MAPK and the PI3K/PTEN/AKT (AKT signaling pathways are two major signaling pathways and are constitutively activated through genetic alterations. Mutations of RAF, RAS, and PTEN contribute to antiapoptosis, abnormal proliferation, angiogenesis, and invasion for melanoma development and progression. To find better approaches to therapies for patients, understanding these MAPK and AKT signaling mechanisms of melanoma development and progression is important. Here, we review MAPK and AKT signaling networks associated with melanoma development and progression.

  9. 〈Case Reports〉Pigmented Bowen's disease of the palm mimicking malignant melanoma: report of a case

    OpenAIRE

    Yoshida, Masuki; Kawada, Akira

    2013-01-01

    [Abstract] A variety of cutaneous lesions may clinically simulate malignant melanoma, including Bowen's disease, which is a squamous cell carcinoma in situ that typically presents as a scaly pink to erythematous patch or plaque. On rare occasions, the lesion is pigmented and may resemble seborrheic keratosis, actinic keratosis, basal cell carcinoma, atypical nevus, or melanoma, and the correct diagnosis is suggested by dermatoscopy. We report an unusual case of pigmented Bowen's disease of th...

  10. [The cellular immunity indices of patients with malignant melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh; Venskus, D R; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of rigvir, an immunomodulator of the viral origin, on cell-mediated immunity was studied in patients with skin malignant melanoma. Rosette formation and monoclonal antibody techniques were used to measure blood immunocompetent cell levels in patients with the above pathology, cases of benign skin tumors and healthy subjects. Rigvir was shown to influence natural resistance by raising blood monocyte and large granule-containing lymphocyte levels. It potentiated recruitment of pre-T-lymphocytes and young active T-lymphocytes to the peripheral blood. PMID:1300752

  11. Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells.

    Science.gov (United States)

    Morita, Hiroshi; Murata, Taku; Shimizu, Kasumi; Okumura, Kenya; Inui, Madoka; Tagawa, Toshiro

    2013-04-01

    The prognosis for malignant melanoma is poor; therefore, new diagnostic methods and treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of 21 phosphodiesterases, which are divided into 11 families (PDE1-PDE11). PDE2 hydrolyzes cyclic AMP (cAMP) and cyclic GMP (cGMP), and its binding to cGMP enhances the hydrolysis of cAMP. We previously reported the expression of PDE1, PDE3 and PDE5 in human malignant melanoma cells. However, the expression of PDE2 in these cells has not been investigated. Herein, we examined the expression of PDE2A and its role in human oral malignant melanoma PMP cells. Sequencing of RT-PCR products revealed that PDE2A2 was the only variant expressed in PMP cells. Four point mutations were detected; one missense mutation at nucleotide position 734 (from C to T) resulted in the substitution of threonine with isoleucine at amino acid position 214. The other three were silent mutations. An in vitro migration assay and a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay revealed that suppressing PDE2 activity with its specific inhibitor, erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA), had no impact on cell motility or apoptosis. Furthermore, the cytotoxicity of EHNA, assessed using a trypan blue exclusion assay, was negligible. On the other hand, assessment of cell proliferation by BrdU incorporation and cell cycle analysis by flow cytometry revealed that EHNA treatment inhibited DNA synthesis and increased the percentage of G2/M-arrested cells. Furthermore, cyclin A mRNA expression was downregulated, while cyclin E mRNA expression was upregulated in EHNA-treated cells. Our results demonstrated that the PDE2A2 variant carrying point mutations is expressed in PMP cells and may affect cell cycle progression by modulating cyclin A expression. Thus, PDE2A2 is a possible new molecular target for the treatment of malignant melanoma.

  12. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs

    Directory of Open Access Journals (Sweden)

    Carbone Michele

    2012-08-01

    Full Text Available Abstract Background BRCA1–associated protein 1 (BAP1 is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W with germline BAP1 mutations and increased risk of malignant mesothelioma. Methods Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ2 test or two-tailed Fisher’s exact test. Results Melanocytic tumors: of the five members of the L family studied, four (80% carried a germline BAP1 mutation (p.Gln684* and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48 and four of them (57% presented one or more atypical melanocytic tumors, that we propose to call “melanocytic BAP1-mutated atypical intradermal tumors” (MBAITs. Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001. Conclusions Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a

  13. Effects of Progesterone on the Growth Regulation in Classical Progesterone Receptor-negative Malignant Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    方险峰; 张序心; 周萌; 李家文

    2010-01-01

    This study investigated the growth-regulating effects of progesterone(Prog) on nPR-negative malignant melanoma cells and the possible mechanisms.A375 and A875 cells were cultured and treated with Prog of different concentrations.For signal transduction pathway studies,the cells were pretreated with Prog receptor antagonist(RU486,1×10-7 mol/L) or MAPK inhibitor(U0126,5×10-6 mol/L) for 1 h and then co-incubated with prog(10-9 mol/L) for another 24 h.Indirect immunofluorescence assay,MTT,flow cytometry and Wes...

  14. Melanoma-specific mortality and competing mortality in patients with non-metastatic malignant melanoma: a population-based analysis

    OpenAIRE

    Shen, Weidong; Sakamoto, Naoko; Yang, Limin

    2016-01-01

    Background The objectives of this study were to evaluate and model the probability of melanoma-specific death and competing causes of death for patients with melanoma by competing risk analysis, and to build competing risk nomograms to provide individualized and accurate predictive tools. Methods Melanoma data were obtained from the Surveillance Epidemiology and End Results program. All patients diagnosed with primary non-metastatic melanoma during the years 2004–2007 were potentially eligibl...

  15. The Non-Coding RNA Llme23 Drives the Malignant Property of Human Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    Chuan-Fang Wu; Guang-Hong Tan; Cheng-Chuan Ma; Ling Li

    2013-01-01

    Several lines of evidence support the notion that increased RNA-binding ability of polypyrimidine tract-binding (PTB) proteinassociated splicing factor (PSF) and aberrant expression of long non-coding RNAs (lncRNAs) are associated with mouse and human tumors.To identify the PSF-binding IncRNA involved in human oncogenesis,we screened a nuclear RNA repertoire of human melanoma cell line,YUSAC,through RNA-SELEX affinity chromatography.A previously unreported lncRNA,termed as Lime23,was found to bind immobilized PSF resin.The specific binding of Llme23 to both recombinant and native PSF protein was confirmed in vitro and in vivo.The expression of PSF-binding Llme23 is exclusively detected in human melanoma lines.Knocking down Lime23 remarkably suppressed the malignant property of YUSAC cells,accompanied by the repressed expression of proto-oncogene Rab23.These results may indicate that Llme23 can function as an oncogenic RNA and directly associate the PSF-binding IncRNA with human melanoma.

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

    LENUS (Irish Health Repository)

    Field, S

    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.

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

    LENUS (Irish Health Repository)

    Field, S

    2012-02-01

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

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

  20. Chemokine Receptor CXCR4 Is a Novel Marker for the Progression of Cutaneous Malignant Melanomas

    International Nuclear Information System (INIS)

    The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis

  1. Study on docetaxel-loaded nanoparticles with high antitumor efficacy against malignant melanoma

    Institute of Scientific and Technical Information of China (English)

    Donghui Zheng; Xiaolin Li; Huae Xu; Xiaowei Lu; Yong Hu; Weixin Fan

    2009-01-01

    Docetaxel (Doc) has extraordinary activities against a variety of solid tumors.However,the clinical efficacy of Doc is limited due to its poor solubility,low selective dis-tribution,fast elimination in vivo,etc.In the present study,Doc was incorporated into the core-shell structure of nanoparticles prepared based on our previous work.The obtained docetaxel-loaded nanoparticles (DOCNP) were characterized with various biophysical method-ologies,and its antitumor efficacy against malignant mel-anoma was evaluated both in vitro and in vivo.Our results indicated that Doc could be incorporated into the nanoparticles with high encapsulation efficiency (>90%).The incorporated Doc can be released from DOCNP in a sustained manner.In vitro cytotoxicity studies indicated that DOCNP could effectively kill B16 cells and show a dose- and time-dependent efficacy.Furthermore,intratu-moral administration revealed that DOCNP has signifi-cantly higher antitumor effect and lower toxicity to normal cells and tissues than free Doc.These results suggest that DOCNP may be a promising drug delivery system in therapy for malignant melanoma.

  2. Apoptotic effect and mechanisms of AHPN on human skin malignant melanoma cell A375

    Institute of Scientific and Technical Information of China (English)

    Min Pan; Zhenhui Peng; Shengxiang Xiao; Jianwen Ren; Yan Liu; Xiaoli Li; Zhengxiao Li

    2008-01-01

    Objective: To study apoptotic effects of synthetic retinoic acid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid(AHPN) on human skin malignant melanoma A375 cells in comparison with the natural iigand all-trans-retinoic acid(ATRA) in vitro and the mechanisms related to the actions of AHPN. Methods:MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results:Firstly, AHPN promoted apoptosis and G1 arrest in A375 cells compared with ATRA. Secondly, the activity of NF-kB in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conelusion:AHPN,in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-kB.

  3. Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells.

    Science.gov (United States)

    Halder, Babli; Singh, Shruti; Thakur, Suman S

    2015-01-01

    In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.

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

    Directory of Open Access Journals (Sweden)

    Bausch Birke

    2006-09-01

    Full Text Available Abstract 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.

  5. Photodynamic therapy of advanced malignant tumors

    Science.gov (United States)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  6. Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

    Directory of Open Access Journals (Sweden)

    Louise J. Smith

    2012-04-01

    Full Text Available Although malignant melanoma (MM and both basal cell carcinoma (BCC and actinic keratosis (AK are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS. In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV.

  7. Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro

    Science.gov (United States)

    Li, Bo; Guo, Bo; Fan, Hongsong; Zhang, Xingdong

    2008-11-01

    To investigate the effects of nano-hydroxyapatite (HA) particles with different morphology on highly malignant melanoma cells, three kinds of HA particles with different morphology were synthesized and co-cultured with highly malignant melanoma cells using phosphate-buffered saline (PBS) as control. A precipitation method with or without citric acid addition as surfactant was used to produce rod-like hydroxyapatite (HA) particles with nano- and micron size, respectively, and a novel oil-in-water emulsion method was employed to prepare ellipse-like nano-HA particles. Particle morphology and size distribution of the as prepared HA powders were characterized by transmission electron microscope (TEM) and dynamic light scattering technique. The nano- and micron HA particles with different morphology were co-cultured with highly malignant melanoma cells. Immunofluorescence analysis and MTT assay were employed to evaluate morphological change of nucleolus and proliferation of tumour cells, respectively. To compare the effects of HA particles on cell response, the PBS without HA particles was used as control. The experiment results indicated that particle nanoscale effect rather than particle morphology of HA was more effective for the inhibition on highly malignant melanoma cells proliferation.

  8. Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Li Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); Guo Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); West China Eye Center of Huaxi Hospital, Sichuan University, Chengdu 610064 (China); Fan Hongsong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)], E-mail: leewave@126.com; Zhang Xingdong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)

    2008-11-15

    To investigate the effects of nano-hydroxyapatite (HA) particles with different morphology on highly malignant melanoma cells, three kinds of HA particles with different morphology were synthesized and co-cultured with highly malignant melanoma cells using phosphate-buffered saline (PBS) as control. A precipitation method with or without citric acid addition as surfactant was used to produce rod-like hydroxyapatite (HA) particles with nano- and micron size, respectively, and a novel oil-in-water emulsion method was employed to prepare ellipse-like nano-HA particles. Particle morphology and size distribution of the as prepared HA powders were characterized by transmission electron microscope (TEM) and dynamic light scattering technique. The nano- and micron HA particles with different morphology were co-cultured with highly malignant melanoma cells. Immunofluorescence analysis and MTT assay were employed to evaluate morphological change of nucleolus and proliferation of tumour cells, respectively. To compare the effects of HA particles on cell response, the PBS without HA particles was used as control. The experiment results indicated that particle nanoscale effect rather than particle morphology of HA was more effective for the inhibition on highly malignant melanoma cells proliferation.

  9. Changes of proliferation kinetics after X-irradiation of a human malignant melanoma grown in nude mice

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Vindeløv, L L

    1984-01-01

    A human malignant melanoma grown in nude mice was exposed to single-dose X-irradiation and the effect on the proliferation kinetics was investigated by two methods. Flow cytometric DNA analysis was performed on tumour tissue obtained by sequential fine-needle aspirations after the treatment to mo......-related increasing proportion of radiation-inactivated tumour cells....

  10. Clinical evaluation of metastases of malignant melanoma imaging with 99Tcm-glutathione and 99Tcm-anti-melanoma antibody: a comparative study.

    Science.gov (United States)

    Duman, Y; Burak, Z; Ercan, M T; Dirlik, A; Bilkay, B C; Akin, Y; Taner, M; Bekdik, C F

    1995-11-01

    The aim of this investigation was to test for the scintigraphic detection of metastases of malignant melanoma with a new radiopharmaceutical, 99Tcm-glutathione (99Tcm-GSH), in comparison with 99Tcm-anti-melanoma antibody (99Tcm-AMAb). Glutathione was labelled with 99Tcm by a Sn2+ reduction method with an efficiency of > 99% as determined by instant thin layer chromatography (ITLC). Anti-melanoma antibody was obtained as a kit from SORIN (Italy) and labelled with 99TcmO-4. Forty-three patients with a total of 55 biopsy-proven metastatic melanoma foci, 1 ocular melanoma and 20 benign pathologic foci, also confirmed by ultrasound, computed tomography and magnetic resonance imaging, were included in the study after giving their informed consent. Following the intravenous (i.v.) injection of 500 MBq 99Tcm-AMAb, scintigraphic images of the involved areas were obtained 6 h post-injection. Three days later, the same patients were given 500 MBq 99Tcm-GSH i.v. and images were obtained 6 and 24 h post-injection. The images were classified as positive (focal abnormal accumulation) or negative. Quantitative evaluation was also applied. Regions of interest were drawn over the involved areas and nearby soft tissues and the target-to-nontarget (T/NT) ratios obtained with 99Tcm-AMAb (T/NT: 1.92 +/- 0.2) and 99Tcm-GSH (T/NT: 1.84 +/- 0.2) were compared (0.1 < P < or = 0.3). The sensitivity (and specificity) of 99Tcm-AMAb and 99Tcm-GSH in the detection of malignant melanoma metastases were 91% (95%) and 84% (90%), respectively. Compared with 99Tcm-AMAb, the advantages of 99Tcm-GSH are lower levels of blood radioactivity, lower costs and easy in-house preparation. In conclusion, our results show that 99Tcm-GSH is a potentially useful radiopharmaceutical for the detection of metastases of malignant melanoma.

  11. In vitro incorporation of boronophenylalanine by amelanotic and melanotic murine and human malignant melanoma cell lines

    International Nuclear Information System (INIS)

    Pelleted cells were irradiated as previously described, following a 20 h incubation in RPM1 1640 medium, in the presence or absence of 10μg/ml D,L-paraboronophenylalanine hydrochloride (10B1-BPA.HCl). Thermal neutrons were derived from Moata, a 100-kW Argonaut-type light water reactor. The neutron flux was 2.6 x 109 n/cm2/s, dose rate 3.7 Gy/h (n+γ) and the dose range 0.6 - 0.8 Gy. Cells were plated onto X-irradiated feeder layers in triplicate in 25cm2 Falcon flasks and colonies counted after 11-12 days. No differences in thermal neutron radiosensitivity were observed for two amelanotic cell lines. A small but significant difference was observed for the melanotic cell line (418) grown in the presence or absence of BPA. Subsequent experiments showed that the uptake of boron was low in the B16 murine malignant melanoma cell line cultured in the presence of BPA. It was therefore necessary to investigate the boron uptake and incorporation in melanoma cells by increasing the BPA concentration, increasing melanization using different variants of the B16 cell lines, and alternative methods of cell layer detachment

  12. A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Datta, Pameli; Heydenreich, Jakob;

    2014-01-01

    IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes in sun behavior from the first until the third summer after the diagnosis of CMM using matched controls as a reference. DESIGN, SETTING......, AND PARTICIPANTS Three-year follow-up, observational, case-control study performed from May 7 to September 22, 2009, April 17 to September 15, 2010, and May 6 to July 31, 2011, at a university hospital in Denmark of 21 patients with CMM and 21 controls matched to patients by sex, age, occupation, and constitutive...... that measured time-related UVR in standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per participant each participation year). RESULTS Patients' daily UVR dose and UVR dose in connection with various behaviors increased during follow-up (quantified as an increase in daily UVR dose each...

  13. HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuying; Li Huiling; Zheng Tianrong; Lin Xiangsong

    1998-01-01

    Objective:To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM). Methods: From 1984-1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6--8 Gy/fraction)with the total dose ranged from 40 to 60 Gy. Results: The minimum follow-up was 2 years (ranged 2-7 years). The overall 3- and 5-year survival rate was 45.7% and 24%,respectively. Conclusion: High dose fraction radiotherapy is effective for local control of HNMM.

  14. HER4 and its cytoplasmic isoforms are associated with progression-free survival of malignant melanoma

    DEFF Research Database (Denmark)

    Nielsen, Trine O; Poulsen, Steen Seier; Journe, Fabrice;

    2014-01-01

    RNA quantification was carried out of all four EGF receptors (EGFR, HER2, HER3, and HER4) and the HER4 cytoplasmic isoforms in lymph node metastases from patients with malignant melanoma. We related their expression to progression of the disease. HER4 expression was found to be an indicator of short progression......-free survival (P=0.0340). Interestingly, of the two cytoplasmic splice variants of HER4, the association of CYT1 (P=0.0176) with progression-free survival was more pronounced than that for CYT2 (P=0.0458). Also, HER3 was associated with progression-free survival (P=0.0169), whereas no association was found for...

  15. Molecular pathology of malignant melanoma: changing the clinical practice paradigm toward a personalized approach.

    Science.gov (United States)

    Bradish, Joshua R; Cheng, Liang

    2014-07-01

    Melanocytic proliferations are notoriously difficult lesions to evaluate histologically, even among experts, as there is a lack of objective, highly reproducible criteria, which can be broadly applied to the wide range of melanocytic lesions encountered in daily practice. These difficult diagnoses are undeniably further compounded by the substantial medicolegal risks of an "erroneous" diagnosis. Molecular information and classification of melanocytic lesions is already vast and constantly expanding. The application of molecular techniques for the diagnosis of benignity or malignancy is, at times, confusing and limits its utility if not used properly. In addition, current and future therapies will necessitate molecular classification of melanoma into one of several distinct subtypes for appropriate patient-specific therapy. An understanding of what different molecular markers can and cannot predict is of the utmost importance. We discuss both mutational analysis and chromosomal gains/losses to help clarify this continually developing and confusing facet of pathology.

  16. Intratumoral injection of Propionibacterium acnes suppresses malignant melanoma by enhancing Th1 immune responses.

    Directory of Open Access Journals (Sweden)

    Kenshiro Tsuda

    Full Text Available Malignant melanoma (MM is an aggressive cutaneous malignancy associated with poor prognosis; many putatively therapeutic agents have been administered, but with mostly unsuccessful results. Propionibacterium acnes (P. acnes is an aerotolerant anaerobic gram-positive bacteria that causes acne and inflammation. After being engulfed and processed by phagocytes, P. acnes induces a strong Th1-type cytokine immune response by producing cytokines such as IL-12, IFN-γ and TNF-α. The characteristic Th2-mediated allergic response can be counteracted by Th1 cytokines induced by P. acnes injection. This inflammatory response induced by P. acnes has been suggested to have antitumor activity, but its effect on MM has not been fully evaluated.We analyzed the anti-tumor activity of P. acnes vaccination in a mouse model of MM. Intratumoral administration of P. acnes successfully protected the host against melanoma progression in vivo by inducing both cutaneous and systemic Th1 type cytokine expression, including TNF-α and IFN-γ, which are associated with subcutaneous granuloma formation. P. acnes-treated tumor lesions were infiltrated with TNF-α and IFN-γ positive T cells. In the spleen, TNF-α as well as IFN-γ producing CD8(+T cells were increased, and interestingly, the number of monocytes was also increased following P. acnes administration. These observations suggest that P. acnes vaccination induces both systemic and local antitumor responses. In conclusion, this study shows that P. acnes vaccination may be a potent therapeutic alternative in MM.

  17. Radiosensitivity of human malignant melanomas evaluated by cytokinesis- block micronucleus assay

    International Nuclear Information System (INIS)

    Cytokinesis-block micronucleus assay (CB-MNA) was applied for comparison of radiation sensitivity of 25 human malignant melanomas in primary culture. Cells obtained from tumor specimens were irradiated (0-4 Gy) in dishes, incubated with cytochalasin B (2 μg . cm-3) to block cytokinesis, stained in situ and micronuclei (MN) scored in bi-nucleate cells (BNC). Proportions of BNC in nonirradiated controls after fixed time of incubation (96 h) ranged from (2.3 to 38% indicating great differences (C.V. = 74%) in proliferative activity among tumors evaluated. No correlation was observed between proliferative activity and susceptibility of cells to induction of MN by radiation. The great inter-tumor heterogeneity was observed in repeat in respect of radiation sensitivity expressed either as normalized (Net) frequency (Fq) of BNC with MN or as number of MN per BNC. Both endpoints differed widely at 2 Gy and 4 Gy as well (NetFqBNC with MN = 0.28-25.4% or 1.5-45% and MN/BNC = 0.004-0.309 or 0.013-0.593 respectively at 2 Gy and 4 Gy) with coefficients of ranging from 44 to 57%. Extreme difference in MN frequency was also observed between one primary tumor and its metastasis indicating intra-tumor heterogeneity. Our results suggest that CB-MNA may contribute some clinically useful information for discriminating tumors that will eventually respond to radiotherapy and those that will probably not. However, studies aimed at comparison of MN induction in vitro with clinical radio-responsiveness of malignant melanomas are urgently required. (author)

  18. Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the Skin, but Uncommon in Nevus Cell Nevi

    Energy Technology Data Exchange (ETDEWEB)

    Walesch, Sara K.; Richter, Antje M. [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Helmbold, Peter [Department of Dermatology, University of Heidelberg, D-69120 Heidelberg (Germany); Dammann, Reinhard H., E-mail: reinhard.dammann@gen.bio.uni-giessen.de [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)

    2015-07-07

    Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and nevus cell nevi.

  19. The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas

    Directory of Open Access Journals (Sweden)

    Bhattacharya Chitralekha

    2012-11-01

    Full Text Available Abstract Background Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Methods Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. Result The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. Conclusion To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome

  20. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

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    Ludovica Ciuffreda

    2009-08-01

    Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1 and apoptosis (Bcl-2 and survivin regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

  1. Melanoma

    Science.gov (United States)

    ... may be melanoma is the ABCDE checklist: A – Asymmetry: One half of the mole does not look ... 276. PMID: 16050450. Last Updated: 12 Feb 2009 Information for other ages: Table of Contents: Overview Who's ...

  2. Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and enhance docetaxel chemotherapy against malignant melanoma in vivo.

    Science.gov (United States)

    Yang, Yong-Jing; Xu, Han-Mei; Suo, You-Rui

    2015-09-01

    It has been reported previously that the systemic efficacy of chemotherapeutic agents is substantially restricted for some cancer types, including malignant melanoma. Therefore, the development of more effective treatment modalities remains a critical, albeit elusive, goal in anticancer therapy. The study presented here evaluates the antitumor activity of raspberry pulp polysaccharides (RPPs) against malignant melanoma using a murine tumor-bearing model. Furthermore, the underlying mechanism of this antitumor activity has also been investigated. The results show that while RPP exhibits no direct cytotoxic effect on HT-29, MGC-803, HeLa, Bel-7402, L02 and B16F10 cells in vitro, it does demonstrate a dose-dependent growth inhibition of melanoma in vivo with an inhibition ratio of 59.95% at a dose of 400 mg kg(-1). Besides this, the body weight and spleen index in tumor-bearing mice have also been improved in RPP-treated groups. RPP is also found to induce splenocyte proliferation and is able to upregulate the activity of immune-related enzymes, including acid phosphatase (ACP), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the spleen of tumor-bearing mice. The levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and interleukin 2 (IL-2) in the serum of tumor-bearing mice show to be effectively increased upon RPP treatment. Histopathological analyses show that RPP induces tumor tissue necrosis by increasing inflammatory cell infiltration and causes no lesions to liver and kidney tissues. Remarkably, RPP further enhances the antitumor effect of the chemotherapeutic drug docetaxel and alleviates docetaxel-induced liver and kidney lesions in tumor-bearing mice. These findings indicate that RPP exhibits antitumor activity in vivo against malignant melanoma, partly by enhancing the cellular immune response of the host organism. In summary, RPP features critical properties to potentially find use as an

  3. Management of intestinal obstruction in advanced malignancy

    Directory of Open Access Journals (Sweden)

    Henry John Murray Ferguson

    2015-09-01

    Full Text Available Patients with incurable, advanced abdominal or pelvic malignancy often present to acute surgical departments with symptoms and signs of intestinal obstruction. It is rare for bowel strangulation to occur in these presentations, and spontaneous resolution often occurs, so the luxury of time should be afforded while decisions are made regarding surgery. Cross-sectional imaging is valuable in determining the underlying mechanism and pathology. The majority of these patients will not be suitable for an operation, and will be best managed in conjunction with a palliative medicine team. Surgeons require a good working knowledge of the mechanisms of action of anti-emetics, anti-secretories and analgesics to tailor early management to individual patients, while decisions regarding potential surgery are made. Deciding if and when to perform operative intervention in this group is complex, and fraught with both technical and emotional challenges. Surgery in this group is highly morbid, with no current evidence available concerning quality of life following surgery. The limited evidence concerning operative strategy suggests that resection and primary anastomosis results in improved survival, over bypass or stoma formation. Realistic prognostication and involvement of the patient, care-givers and the multidisciplinary team in treatment decisions is mandatory if optimum outcomes are to be achieved.

  4. Mode of c-myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas.

    Science.gov (United States)

    Bergman, R; Lurie, M; Kerner, H; Kilim, S; Friedman-Birnbaum, R

    1997-04-01

    The expression of c-myc protein was studied in formalin-fixed, paraffin-embedded sections of 16 compound Spitz nevi (SNs), 20 ordinary compound melanocytic nevi (MNs) and 30 malignant melanomas (MMs), using monoclonal antibody 9E10 and an immunoperoxidase technique. Nine (56%) SNs, 16 (80%) MNs and 23 (77%) MMs showed positive reactions in some of the tumor cells (P = non-significant). The staining reactions were mostly cytoplasmic, and moderate to strong in intensity. The frequencies of positively stained cells were higher in the MN and SN groups. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Therefore, the mode of expression of c-myc in routinely processed specimens does not differentiate between SNs, MNs and MMs. One possible reason is that the increased expression of the c-myc protein is not sufficient alone to promote proliferation and malignant transformation in these types of tumors. PMID:9138112

  5. Selective growth inhibition of a human malignant melanoma cell line by sesame oil in vitro.

    Science.gov (United States)

    Smith, D E; Salerno, J W

    1992-06-01

    Ayurveda, an ancient and comprehensive system of natural medicine, recommends regular topical application to the skin of sesame oil, above all other oils, as a health-promoting procedure. We examined the effect of sesame oil and several other vegetable oils and their major component fatty acids on the proliferation rate of human normal and malignant melanocytes growing at similar rates in serum-free media. We found that sesame and safflower oils, both of which contain large amounts of linoleate in triglyceride form, selectively inhibited malignant melanoma growth over normal melanocytes whereas coconut, olive and mineral oils, which contain little or no linoleate as triglyceride, did not. These oils were tested at a range of 10-300 micrograms/ml. We found that of the fatty acids tested, only linoleic acid was selectively inhibitory while palmitic and oleic were not. These fatty acids were tested in the range of 3-100 micrograms/ml. These results suggest that certain vegetable oils rich in linoleic acid, such as the sesame oil, recommended for topical use by Ayurveda, may contain selective antineoplastic properties which are similar to those demonstrated for essential polyunsaturated fatty acids and their metabolites. This suggests that whole vegetable oils may have potential clinical usefulness.

  6. Telomere length and the risk of cutaneous malignant melanoma in melanoma-prone families with and without CDKN2A mutations.

    Directory of Open Access Journals (Sweden)

    Laura S Burke

    Full Text Available INTRODUCTION: Recent evidence suggests a link between constitutional telomere length (TL and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. MATERIALS AND METHODS: We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. RESULTS: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02-7.72, P = 0.04. The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002. One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002 after Bonferroni correction. DISCUSSION: Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.

  7. MGMT gene promoter methylation in malignant melanoma patients%恶性黑色素瘤患者MGMT基因启动子甲基化研究

    Institute of Scientific and Technical Information of China (English)

    于玮玮; 俎明; 李强; 郭军; 孔燕; 代杰; 迟志宏; 斯璐; 崔传亮; 盛锡楠; 李思明; 毛丽丽

    2011-01-01

    Objective This study was designed to investigate the association of MGMT promoter methylation and MGMT protein expression in Chinese malignant melanoma patients.Methods We analyzed the MGMT promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and protein expression by immunohistochemistry (IHC) in 44 malignant melanoma cases.Results We found that MGMT promoter hypermethylation occurred in 18 of 44 (40.9% ) cases, MGMT protein expression rate of MGMT promoter methylation patients was 27.8% (5/18) and MGMT protein expression rate of MGMT promoter unmethylation patients was 65.4% (17/26).The presence of hypermethylation was associated with loss of MGMT protein (P = 0.014).Conclusion In the advanced malignant melanoma MGMT promoter methylation may reduce MGMT protein expression;the examination of MGMT promoter methylation status in melanoma may be useful for stratefying patients with melanoma into suitable chemotherapy such as alkylating agents, and offer theoretical and practical basis to personalized treatments.%目的 分析中国恶性黑色素瘤患者MGMT启动子甲基化水平和蛋白表达的关系.方法 通过MS-PCR方法检测44例恶性黑色素瘤患者MGMT启动子甲基化水平,免疫组化法检测MGMT蛋白的表达.结果 44例恶性黑色素瘤患者的MGMT启动子甲基化率为40.9%(18/44),MGMT启动子甲基化患者的MGMT蛋白表达率为27.8%(5/18),非甲基化患者的MGMT蛋白表达率为65.4%(17/26),MGMT启动子甲基化与MGMT蛋白的低表达有相关性(P=0.014).结论 在晚期恶性黑色素瘤中MGMT启动子甲基化可能降低MGMT蛋白的表达,提示可以通过分析晚期黑色素瘤患者MGMT基因启动子甲基化状态,预测患者对烷化剂类药物的敏感性,为实现个体化治疗提供理论和实践依据.

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

    International Nuclear Information System (INIS)

    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. 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. 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. Our results provide information on shared environmental and genetic risk factors for first and later cancers and may help to identify

  9. Cyclic patterns of incidence rate for skin malignant melanoma:association with heliogeophysical activity

    Institute of Scientific and Technical Information of China (English)

    Borislav D. DIMITROV; Mariana I. RACHKOVA; Penka A. ATANASSOVA

    2008-01-01

    Background: Our previous studies revealed cyclicity in the incidence rate of skin malignant melanoma (SMM; ICD9, Dx: 172) in the Czech Republic (period T=7.50~7.63 years), UK (T=11.00 years) and Bulgaria (T=12.20 years). Incidences com-pared with the sunspot index Rz (lag-period dT=+2, +4, +6, +10 or +12 years) have indicated that maximal rates are most likely to appear on descending slopes of the 11-year solar cycle, i.e., out of phase. We summarized and explored more deeply these cyclic variations and discussed their possible associations with heliogeophysical activity (HGA) components exhibiting similar cyclicity. Methods: Annual incidences of SMM from 5 countries (Czech Republic, UK, Bulgaria, USA and Canada) over various time spans during the years 1964~1992 were analyzed and their correlations with cyclic Rz (sunspot number) and aa (planetary geomagnetic activity) indices were summarized. Periodogram regression analysis with trigonometric approximation and phase-correlation analysis were applied. Results: Previous findings on SMM for the Czech Republic, UK and Bulgaria have been validated, and cyclic patterns have been revealed for USA (T=8.63 years, P<0.05) and Canada (Ontario, T=9.91 years, P<0.10). Also, various 'hypercycles' were established (T=45.5, 42.0, 48.25, 34.5 and 26.5 years, respectively) describing long-term cyclic incidence patterns. The association of SMM for USA and Canada with Rz (dT=+6 and +7 years, respectively) and aa (dT=-10 and +9 years, respectively) was described. Possible interactions of cyclic non-photic influences (UV irradiation, Schumann resonance signal, low-frequency geomagnetic fluctuations) with brain waves absorbance, neuronal calcium dynamics, neuro-endocrine axis modulation, melatonin/serotonin disbalance and skin neuro-immunity impairment as likely causal pathways in melanoma appearance, were also discussed. Conclusion: The above findings on cyclicity and temporal association of SMM with cyclic environmental factors

  10. Miliary pattern of brain metastases – a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days. We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology. This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma

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

    International Nuclear Information System (INIS)

    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

  12. Animal-type malignant melanoma associated with nevus of Ota in the orbit of a Japanese woman: a case report.

    Science.gov (United States)

    Nitta, Keisuke; Kashima, Tomoyuki; Mayuzumi, Hideyasu; Akiyama, Hideo; Miyanaga, Tomomi; Hirato, Junko; Kishi, Shoji

    2014-06-01

    We present a patient with an animal-type malignant melanoma associated with the nevus of Ota in the orbit who showed a good prognosis after a combination of orbital extirpation, chemotherapy, stereotactic radiotherapy, and gamma knife. A 42-year-old Japanese woman presented with two tumors, one pathologically diagnosed as right-sided intraconal animal-type malignant melanoma and the other intracranially, presumed to be of the same pathogenesis and both were considered to have arisen from the nevus of Ota. She underwent an extirpation of the orbit, chemotherapy (DAV therapy, which is a combination of dacarbazine, nimustine, and vincristine), stereotactic radiotherapy (54 Gy in 27 fractions), and gamma knife (marginal dose was 17 Gy, target volume was 0.2 ml). She has been alive for 33 months since the extirpation, with no sign of local recurrence, new metastasis, nor enlargement of the intracranial tumor. Not just combination therapy but also the low malignancy of animal-type melanoma may have contributed toward the good prognosis.

  13. A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β

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    Masaru Arima

    2014-03-01

    Full Text Available A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

  14. Cerebral MR imaging of malignant melanoma; Zerebrale MR-Bildgebung beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Breckwoldt, M.; Bendszus, M. [Universitaetsklinikum Heidelberg, Abteilung Neuroradiologie, Neurologische Klinik, Heidelberg (Germany)

    2015-01-16

    Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5 % of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur. Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings. Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66 % of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain imaging. Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification). CNS metastases are common in melanoma. MRI screening starting in stage IIc should be considered

  15. A new look at drugs targeting malignant melanoma--an application for mass spectrometry imaging.

    Science.gov (United States)

    Sugihara, Yutaka; Végvári, Akos; Welinder, Charlotte; Jönsson, Göran; Ingvar, Christian; Lundgren, Lotta; Olsson, Håkan; Breslin, Thomas; Wieslander, Elisabet; Laurell, Thomas; Rezeli, Melinda; Jansson, Bo; Nishimura, Toshihide; Fehniger, Thomas E; Baldetorp, Bo; Marko-Varga, György

    2014-09-01

    Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor targeting BRAF-mutated protein, has shown significant efficacy in slowing disease progression. In this paper, we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using MS fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment. PMID:25044963

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

    Science.gov (United States)

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

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation. PMID:27484276

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-01-01

    Unlike breast and prostate cancers, the nature and sequence of critical genetic and epigenetic events involved in the initiation and progression of melanoma are 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.

  19. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

    Directory of Open Access Journals (Sweden)

    Xiong W

    2015-04-01

    Full Text Available Wei Xiong,1,2 Lixia Peng,1,2 Hongbo Chen,3 Qin Li1,2 1Southern Medical University, Guangzhou, 2Department of Plastic Surgery, General Hospital of Guangzhou Military Command of PLA, Guangzhou, People’s Republic of China; 3Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People’s Republic of China Abstract: To enhance the therapeutic effects of chemotherapy on malignant melanoma, paclitaxel (PTX-loaded methoxy poly(ethylene glycol-b-poly(ε-caprolactone nanoparticles (MPEG-b-PCL NPs that had their surfaces modified with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA were prepared as drug vehicles. The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded NPs were prepared by a modified nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were characterized in terms of size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and in vivo by a xenograft tumor model. The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to Taxol® and precursor PTX-loaded NPs. All the results suggested that the PTX-loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising nanocarriers for malignant melanoma therapy. Keywords: cancer nanotechnology, drug delivery, surface modification, polydopamine, malignant melanoma

  20. Amelanotic malignant melanoma of the esophagus: Report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada

    2009-01-01

    The author reports herein two cases of amelanotic malignant melanoma of the esophagus. Case 1 is an 87-year-old woman who was admitted to our hospital because of nausea and vomiting. Endoscopic examination revealed an ulcerated tumor of the distal esophagus,and a biopsy was taken. The biopsy showed malignant polygonal and spindle cells. No melanin pigment was recognized. Immunohistochemically, the tumor cells were positive for melanosome (HMB45), S100 protein,KIT and Platelet derived growth factor receptor-α (PDGFRA).The patient was treated by chemotherapy and radiation, but died of systemic metastasis 12 mo after the presentation. Case 2 is a 56-year-old man presenting with dysphagia. Endoscopic examination revealed a polypoid tumor in the middle esophagus, and a biopsy was obtained. The biopsy showed malignant spindle cells without melanin pigment. Immunohistochemically,the tumor cells were positively labeled for melanosome,S100 protein, KIT and PDGFRA. The patient refused operation,and was treated by palliative chemotherapy and radiation. He died of metastasis 7 mo after the admission. In both cases, molecular genetic analyses of KIT gene (exons 9, 11, 13 and 17) and PDGFRA gene (exons 12 and 18) were performed by the PCR direct sequencing method, which showed no mutations of KIT and PDGFRA genes. This is the first report of esophageal malignant melanoma with an examination of the expression of KIT and PDGFRA and the mutational status of KIT and PDGFRA genes.

  1. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hansen, Troels Holz; Andersen, Mads Hald;

    2009-01-01

    During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been targeted including malignant melanoma w...

  2. High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.

    Directory of Open Access Journals (Sweden)

    Gry Irene Magnussen

    Full Text Available Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15. Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001, Ki67 (p<0.0001, Cyclin D3 (p = 0.001, p21(Cip1/WAF1 (p = 0.003, p53 (p = 0.025. Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001, ulceration (p = 0.005 and poor disease-free survival (p = 0.008. Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53, WM45.1(MUTp53 and LOX(WTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.

  3. Epidemiology of malignant melanoma in the province of Palermo (2003-2005

    Directory of Open Access Journals (Sweden)

    Maria Antonietta Cascio

    2011-12-01

    Full Text Available

    Background: The incidence of melanoma has steadily increased worldwide and shows geographical variability according to latitude. The aim of this study was to describe the incidence of cutaneous malignant melanoma (CMM cases in the Province of Palermo during the period 2003-2005.

    Methods: 231 incident cases of CMM, registered by the Cancer Registry of Palermo, were analysed. Anatomic localization, histological type, thickness, ulceration, margins, any lymph node involvement and metastases were evaluated. A statistical analysis of survival rates was performed.

    Results: Distribution by sex and stage of diagnosis showed a slight, but not significant, difference between females and males diagnosed both in early and late stage CMM. Age incidence rates were higher in women before the age of 40 and in men over the age of 50. No statistically significant difference in stage was observed between residents in Palermo and of its Province.
    148 cases (64% were found in people living in Palermo, with an incidence rate (EU of 7.2 over 100,000 in males and 6.1 in females, while in the province the incidence rate was lower (4.7 vs 3.9 . Univariate analysis by gender showed better survival in females than in males and a better survival for age <49 and for stage I-II at diagnosis (p<0.05. Multivariate analysis including gender, age and cancer stage showed that survival is significantly positively related to earlier stage (p<0.05 and younger age (p=0.01 but not to sex (p=0.19.

    Conclusions: Diagnosis of CMM is mainly performed in the early stages, in both sexes and regardless of residence, suggesting no difference in early diagnosis and access to care between city and province. The incidence of CMM appears to be higher in the city compared to the province. Survival following diagnosis was strongly, and independently, related to age and stage of CMM, while gender did not

  4. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy.

    Science.gov (United States)

    Xiong, Wei; Peng, Lixia; Chen, Hongbo; Li, Qin

    2015-01-01

    To enhance the therapeutic effects of chemotherapy on malignant melanoma, paclitaxel (PTX)-loaded methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles (MPEG-b-PCL NPs) that had their surfaces modified with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA) were prepared as drug vehicles. The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded NPs were prepared by a modified nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were characterized in terms of size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to Taxol(®) and precursor PTX-loaded NPs. All the results suggested that the PTX-loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising nanocarriers for malignant melanoma therapy. PMID:25945046

  5. Effects of different doses of 2-methoxy-estradiol on the proliferation, apoptosis and angiogenesis genes in malignant melanoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Bo Tong

    2016-01-01

    Objective:To study the inhibitory effect of different doses of 2-methoxy-estradiol on the growth of malignant melanoma cells in vitro.Methods:First, melanoma B16 cells were cultured, and then 0μmol / L, 10 μmol / L, 20 μmol / L, 30umol / L and 40 umol / L of 2-ME were added. Last, cell viability was detected MTS kit, and the contents of proliferation gene, apoptosis gene and angiogenesis gene in both cells and culture medium were determined by Elisa.Results:2-ME reduced cell viability in a dose-dependent and time-dependent way. After 40 umol/L of 2-ME treatment, Mcl-1 and CYR61 contents in cells decreased significantly, while Fas and Caspase14 contents increased significantly. HIF-1α, VEGF, SDF-1 and CXCR4 decreased significantly in both cells and culture medium.Conclusions:Different doses of 2-ME can inhibit the growth of malignant melanoma cells in vitro by reducing the cell viability and inhibiting cell proliferation and angiogenesis.

  6. Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival

    Directory of Open Access Journals (Sweden)

    Slipicevic Ana

    2012-02-01

    Full Text Available Abstract Background/aims Breast cancer metastasis suppressor 1 (BRMS1 blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Methods Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. Results A significantly higher percentage of nevi (87%, compared to primary melanomas (20% and metastases (48%, expressed BRMS1 in the nucelus (p Waf1/Cip1 (p = 0.009. Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013 and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033. Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016 and decreased relapse-free period (p = 0.043. Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011, a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Conclusion Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. Please see related article: http://www.biomedcentral.com/1741-7015/10/19

  7. Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

    Science.gov (United States)

    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

  8. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

    International Nuclear Information System (INIS)

    To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM). Results of 87 patients (median age 58 years; 35 female, 52 male) treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56) or 40 Gy in 20 fractions (n = 31). All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Mean follow-up was 8 months (range, 0–57 months), the 6- and 12-months overall-(OS) survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11) patients showed a complete (partial) remission, while 11 (17) patients had stable disease (intra-cerebral tumor progression). In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months). Furthermore, DS-GPA score (p < 0.001) as well as RPA class (p < 0.001) influenced significantly on OS and patients had a significantly longer OS after surgical resection (p = 0.001, median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral metastases didn't significantly impact on OS (p = 0.21). Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted

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

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available 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.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.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.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.

  10. Seven Novel and Stable Translocations Associated with Oncogenic Gene Expression in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ichiro Okamoto

    2005-04-01

    Full Text Available Cytogenetics has not only precipitated the discovery of several oncogenes, but has also led to the molecular classification of numerous malignancies. The correct identification of aberrations in many tumors has, however, been hindered by extensive tumor complexity and the limitations of molecular cytogenetic techniques. In this study, we have investigated five malignant melanoma (MM cell lines from at least three different passages using high-resolution R-banding and the recently developed methods of comparative genomic hybridization and multicolor or multiplex fluorescence in situ hybridization. We subsequently detected nine consistent translocations, seven of which were novel: dic(1;11(p10;q14, der(9t(3;9(p12;p11, der(4t(9;4;7(q33::p15-q23::q21, der(14t(5;14 (q12;q32, der(9t(9;22(p21;q11, der(19t(19;20(p13.3;p11, der(10t(2;12;7;10(q31::p12→pter::q11.2→q31::q21,der(19t(10;19(q23;q13, and der(20t(Y;20(q11.23;q13.3. Furthermore, using the human HG-U133A Gene-Chip, positive expression levels of oncogenes or tumor-related genes located at the regions of chromosomal breakpoints were identified, including AKT1, BMI1, CDK6, CTNNB1, E2F1, GPNMB, GPRK7, KBRAS2, LDB2, LIMK1, MAPK1, MEL, MP1, MUC18, NRCAM, PBX3, RAB22A, RAB38, SNK, and STK4, indicating an association between chromosomal breakpoints and altered gene expression. Moreover, we also show that growth of all five cell lines can be significantly reduced by downregulating CDK6 gene expression with small interfering RNA (siRNA. Because the majority of these breakpoints have been reported previously in MM, our results support the idea of commonmechanisms in this disease.

  11. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

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

  12. Spotlight on pembrolizumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Rajakulendran T

    2015-06-01

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

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

    Science.gov (United States)

    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

    2016-01-01

    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. PMID:27313729

  14. Distinct host cell fates for human malignant melanoma targeted by oncolytic rodent parvoviruses.

    Science.gov (United States)

    Vollmers, Ellen M; Tattersall, Peter

    2013-11-01

    The rodent parvoviruses are known to be oncoselective, and lytically infect many transformed human cells. Because current therapeutic regimens for metastatic melanoma have low response rates and have little effect on improving survival, this disease is a prime candidate for novel approaches to therapy, including oncolytic parvoviruses. Screening of low-passage, patient-derived melanoma cell lines for multiplicity-dependent killing by a panel of five rodent parvoviruses identified LuIII as the most melanoma-lytic. This property was mapped to the LuIII capsid gene, and an efficiently melanoma tropic chimeric virus shown to undergo three types of interaction with primary human melanoma cells: (1) complete lysis of cultures infected at very low multiplicities; (2) acute killing resulting from viral protein synthesis and DNA replication, without concomitant expansion of the infection, due to failure to export progeny virions efficiently; or (3) complete resistance that operates at an intracellular step following virion uptake, but preceding viral transcription.

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

    OpenAIRE

    GUTMAN, HAIM; BEN-AMI, EYTAN; SHAPIRA-FROMMER, RONI; Schachter, Jacob

    2012-01-01

    Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3–307) mon...

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

    Science.gov (United States)

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

    2015-12-01

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

  17. Increased tartrate-resistant acid phosphatase (TRAP expression in malignant breast, ovarian and melanoma tissue: an investigational study

    Directory of Open Access Journals (Sweden)

    Eck M

    2006-07-01

    Full Text Available Abstract Background Tartrate-resistant acid phosphatase (TRAP is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. Methods TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. Results A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Conclusion Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

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

    Institute of Scientific and Technical Information of China (English)

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

    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:250,1000,1750,2500 V/cm;50 μs by5 impulses for every case. The viability of cells after EP was estimated byMTT assay. The ultrastructural analysis was observed by transmission electron microscope (ZeissEM900). Results:In the current study we observed the intracellular effect followingEP 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 byEP. Conversely, we showed thatEP in some conditions can stimulate cells to proliferation. Some changes induced byEP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters ofEP (250 and1000 V/cm). After applying higher electric field intensities (2500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications afterEP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters ofEP.Conclusions:We can claim thatEP 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 thatEP 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.

  19. Influence of having a home garden on personal UVR exposure behavior and risk of cutaneous malignant melanoma in Denmark

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Thieden, Elisabeth; Philipsen, Peter Alshede;

    2013-01-01

    There is a need for more knowledge concerning the association of higher socioeconomic status (SES) with cutaneous malignant melanoma (CMM). Having a home garden is associated with a higher SES. We aimed to study the influence of having a home garden on UVR exposure behavior and risk of CMM....... Register study: We collected information from Danish national registers about gender, age, type of home and CMM among persons aged 16-75 in 2002-2006. A total of 5,118 CMM cases were identified. Risk of CMM of the trunk was increased by 46% (p

  20. Three-Dimensional Image Fusion of SPECT and CT Scans for Locating Sentinel Lymph Nodes in Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Michiko Akiyama

    2011-03-01

    Full Text Available Image fusion software can derive a fusion image from single photon emission computed tomography and computed tomography scans. We applied a three-dimensional fusion image to detect sentinel lymph nodes (SLNs in 3 patients with malignant melanomas of the lumbar, vulvar and head region, respectively. During each operation, we detected SLNs at the expected site, as indicated by the fusion images. The three-dimensional image fusion could thus be confirmed as a simple and helpful method for precisely localizing SLNs in these patients.

  1. Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas.

    Directory of Open Access Journals (Sweden)

    Adriana Cordova

    Full Text Available T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1(+ and Vδ2(+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.

  2. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth

    Institute of Scientific and Technical Information of China (English)

    Julia Schultz; Peter Lorenz; Gerd Gross; Saleh Ibrahim; Manfred Kunz

    2008-01-01

    A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n=10) and primary malignant melanomas (n=10),using quantitative real-time PCR.Differential expression was found for 72 microRNAs.Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi,suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma.Interestingly,similar findings had been described for lung and colon cancer.Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1,D3,and A,and cyclin-dependent kinase (Cdk) 4,all of which had been described to play a role in melanoma development.The effect oflet-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs,as exemplified by reporter gene analyses for cyclin DI.In line with its downmodulating effects on cell cycle regulators,let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells.Taken together,these findings not only point to new regulatory mechanisms of early melanoma development,but also may open avenues for future targeted therapies of this tumor.

  3. Cancer Malignancy Is Enhanced by Glyceraldehyde-Derived Advanced Glycation End-Products

    Directory of Open Access Journals (Sweden)

    Jun-Ichi Takino

    2010-01-01

    Full Text Available The receptor for advanced glycation end-products (RAGEs is associated with the malignancy of cancer. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs enhanced the malignancy of melanoma cells, but glucose-derived AGEs did not. However, the effects of Glycer-AGEs on other cancer cells remain poorly understood, and the molecular mechanisms behind the above-mentioned effect have not been clarified. The present paper aimed to examine the effect of Glycer-AGEs on cultured lung cancer A549 cells. RAGE was expressed in A549 cells. Glycer-AGEs significantly attenuated cell proliferation. Furthermore, Glycer-AGEs enhanced the migration capacity of the cells by activating Rac1 via ROS and also increased their invasion capacity. We demonstrated that Glycer-AGEs enhanced the migration and invasion of A549 cells rather than their proliferation. These results suggest that Glycer-AGEs play a critical role in the malignancy of cancer rather than its proliferation and are potential targets for therapeutic intervention.

  4. Craniofacial resection of advanced oral and maxillofacial malignant tumors

    Institute of Scientific and Technical Information of China (English)

    张志愿; 邱蔚六

    2003-01-01

    Objective To evaluate the clinical outcome of craniofacial resection for advanced malignant tumors in oral and maxillofacial regions.Methods Forty-six patients who underwent craniofacial resection for malignancies involving the anterior and middle cranial fossa over a 20-year period between June 1978 and December 1997 at our department were evaluated. Twenty patients received radiation therapy and an adjuvant therapy after the operation. Eleven patients received chemotherapy of various types as an adjuvant therapy.Results The 3- and 5-year survival rates were 48.8% (20/41) and 35.1% (13/37), respectively, while the 10-year survival rate was 20% (4/20).Conclusions Our results revealed good prospects of using craniofacial resection on patients with advanced malignancies in the oral and maxillofacial regions.

  5. Estudo comparativo da flarefotometria em pacientes com melanoma maligno e nevo de coróide Comparative study of flare photometry in patients with choroidal malignant melanoma and choroidal nevus

    Directory of Open Access Journals (Sweden)

    Priscilla Luppi Ballalai

    2002-01-01

    Full Text Available Introdução: Os tumores malignos intra-oculares estão associados com um aumento do "flare" na câmara anterior, causado por uma quebra na barreira hemato-aquosa, que pode ocorrer por vários mecanismos. Estudos utilizando a flarefotometria confirmam o aumento do "flare" em olhos com tumores intra-oculares malignos e benignos. Objetivo: Avaliar a flarefotometria como auxiliar no diagnóstico diferencial de melanoma maligno e nevo de coróide, comparando-se com olhos contralaterais normais. Métodos: Foram avaliados olhos com melanoma maligno e olhos com nevo de coróide diagnosticados por meio de oftalmoscopia indireta e/ou ultra-sonografia. Os olhos normais contralaterais foram utilizados como controles. A flarefotometria foi realizada em todos os pacientes, sob midríase bilateral, utilizando equipamento Laser Flare Meter (FC 500, Kowa. Foram aplicados os testes de Wilcoxon, Mann-Whitney, e Spearman para análise estatística. Resultados: A média da flarefotometria nos olhos com melanoma maligno de coróide foi 17,1 ph/ms e nos olhos normais contralaterais foi 4,06 ph/ms. Nos olhos com nevo de coróide o valor da flarefotometria foi 6,12 ph/ms e nos olhos contralaterais normais foi 4,47 ph/ms. O valor da flarefotometria foi maior nos olhos com melanoma maligno e nevo quando comparado com os olhos contralaterais normais (pIntroduction: Malignant intraocular tumors are associated with an increase in the aqueous flare, caused by alterations of the blood-ocular barriers through various mechanisms. Several studies have demonstrated an ocular flare increase using flare photometry in eyes with benign and malignant tumors. Purpose: To evaluate flare photometry as an adjunct method in the differential diagnosis of choroidal malignant melanoma and choroidal nevus comparing to normal control eyes. Methods: Eyes with melanoma and nevus were diagnosed by indirect binocular ophthalmoscopy and/or ultrasound were evaluated. The fellow normal eyes were used

  6. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies.

    Science.gov (United States)

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D'Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma.

  7. Tumor Vascularity Is Not a Prognostic Factor for Malignant Melanoma of the Skin

    OpenAIRE

    Busam, Klaus J.; Berwick, Marianne; Blessing, Karen; Fandrey, Katrin; Kang, Sewon; Karaoli, Themis; Fine, Judy; Cochran, Alistair J.; White, Wain L.; Rivers, Jason; Elder, David E; Po Wen, Duan-Ren; Heyman, Bradley H.; Barnhill, Raymond L.

    1995-01-01

    Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic ...

  8. Selective thermal neutron capture therapy of malignant melanoma using melanogenesis-seeking 10B-compounds

    International Nuclear Information System (INIS)

    This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

  9. Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma.

    Science.gov (United States)

    Damodaran, Senthil; Mrozek, Ewa; Liebner, David; Kendra, Kari

    2014-12-01

    High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma. PMID:25505207

  10. Microincisional vitrectomy for retinal detachment in I-125 brachytherapy-treated patients with posterior uveal malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lonngi M

    2013-02-01

    Full Text Available Marcela Lonngi,1 Samuel K Houston,1 Timothy G Murray,1–3 Robert A Sisk,4 Christina L Decatur,1 Milena Cavalcante,1 Arnold M Markoe31Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USA; 2Murray Ocular Oncology and Retina, Miami, FL, USA; 3Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA; 4Department of Ophthalmology, Cincinnati Eye Institute, Cincinnati, OH, USAPurpose: To analyze functional and anatomical outcomes following 23/25+ gauge microincisional pars plana vitrectomy surgery (MIVS in patients with radiation-related retinal detachment after successful 125-iodine (I-125 brachytherapy treatment for malignant uveal melanoma.Patients and methods: Retrospective case series of 102 consecutive eyes of 102 patients with history of uveal melanoma treated with I-125 brachytherapy that underwent MIVS at the Bascom Palmer Eye Institute. All cases were evaluated for surgical complications and local tumor control. Extended follow-up included Snellen’s best-corrected visual acuity, intraocular pressure evaluation, quantitative echography, indirect ophthalmoscopy, and fundus imaging with optical coherence tomography/wide-field photography.Results: All patients had radiation-related complications, including retinal detachment (102 eyes, vasculopathy (91 eyes, optic neuropathy (32 eyes, and/or vitreous hemorrhage (8 eyes. Sixty-seven patients had vitreoretinal traction. Average follow-up after MIVS was 19.5 months, and from plaque removal was 57.7 months. Interval from plaque to MIVS was 38.1 months. Initial visual acuity was 20/258, which improved to 20/101 at 1 month, 20/110 at 3 months, 20/116 at 6 months, and 20/113 at 12 months (P < 0.05. No eyes required enucleation. Melanoma-related mortality was 0.9% (1/102. There was no intra- or extraocular tumor dissemination, and no tumor recurrence.Conclusion: MIVS was effective in improving

  11. Clinical value of FDG-PET in cutaneous malignant melanoma: First experience in Estonia

    International Nuclear Information System (INIS)

    Full text: In November 2002 first 18F-FDG-PET was performed in Estonia using a mobile truck-mounted scanning technology (Accel, Siemens) provided by the International Healthcare Group (IHG, Amersfoort, Netherlands). The FDG was provided by MAP Medical Technologies, Schering, (Helsinki, Finland). In 2003 this scheme was repeated for further scanning sessions. Evaluation of cutaneous malignant melanoma (CMM) using nuclear technique is of particular interest in Estonia as its incidence is on the rise. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in CMM has a well-documented high diagnostic accuracy, especially in staging of the disease. The aim of the current study was to assess the impact of 18F-FDG-PET on detailed staging and clinical management in CMM. 30 patients of CMM, 16 males and 14 females, all non-diabetic, in the age range of 26 to 69 years were studied. Of these 30 patients, 12 were of high risk primary CMM, 7 had regional lymph node metastases and 11 had distant metastases. Patients were asked to consume a low-carbohydrate diet 3 days prior to the FDG-PET scan. 194 to 410 MBq (average 335 MBq) 18F-FDG was administered to the patients who were asked to come fasting for a minimum of 6 hours. Whole body scan was performed 40 to 65 minutes after the administration of FDG on the mobile PET. In 13 of the 30 patients (43%) 18F-FDG-PET changed the staging. In remaining 17 patients (57%) 18F-FDG-PET increased confidence level for the chosen treatment. Lymphadenectomy was planned in 2 patients showing lymph node involvement on FDG-PET. In other 2 patients, one with small pulmonary and other with a liver lesions found on PET but negative on radiological examination 'wait-and-watch' strategy was chosen. An unexpected hypermetabolic lesion seen in 1 case turned out to be a benign focus of connective tissue. One patient shown to have multiple distant metastases was started on chemotherapy. Finally in 8 of the 30 (27%) patients an immediate positive

  12. Objective histopathologic grading of cutaneous malignant melanomas by stereologic estimation of nuclear volume. Prediction of survival and disease-free period

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    independent prognostic significance, which may be due to attributes of the small data base. It is concluded that Vv may be a powerful prognostic indicator in cutaneous melanomas, suitable for objective malignancy grading. The clinical and prognostic value of nuclear Vv needs further investigation in a larger......Modern stereologic techniques enable unbiased and shape-independent estimation of the three-dimensional nuclear volume (Vv). This study investigates the prognostic impact of Vv in 47 patients with malignant melanomas (10 years of follow-up) and compares Vv to traditional prognostic parameters...

  13. Combination Therapies for the Treatment of Advanced Melanoma: A Review of Current Evidence

    Directory of Open Access Journals (Sweden)

    Mark Voskoboynik

    2014-01-01

    Full Text Available The treatment of advanced melanoma has been revolutionised in recent years with the advent of a range of new therapies. BRAF inhibitors, such as vemurafenib, have demonstrated improvements in the overall survival of patients with advanced melanoma that harbour a BRAF V600 mutation. Alongside these targeted therapies, novel immune-checkpoint inhibitors, such as ipilimumab, have also been developed and have produced similarly improved outcomes for patients. For the first time in the history of melanoma, monotherapy with each of these drugs has produced improvements in the overall survival of patients with advanced disease. Building on this initial success, there has been intense interest in developing combination therapies predominantly with either dual blockade of the MAPK oncogenic pathway or dual immune-checkpoint blockade. The current evidence for the use of these combination therapies will be presented here.

  14. VON RECKLINGHAUSEN’S DISEASE ASSOCIATED WITH PAPILARY THYROID CARCINOMA AND MALIGNANT MELANOMA WITH MULTIPLE METASTASIS – CASE REPORT

    Directory of Open Access Journals (Sweden)

    D. Niculescu

    2006-04-01

    Full Text Available We present the case of a 56 years old, women, known with Recklinghausen’s Disease (RD since 15 years old. She was in the evidence of Iasi Endocrynology Clinic with nodulary goitre since ’97, being treated with Euthyrox until 2005. Due to symptomatology worsening (asphyxia feeling, agitation, palpitations, insomnia, irritability, dizziness and to thyroid increase the surgical procedure was recommended. A right lobeisthmectomy was performed in 2005, but the Histopathology Exam revealed an occult Papillary Thyroid Carcinoma (PTC pT1NxMxG1 (sclerous infiltrative 3 mm node on joint nodular goitre with metaplasia, hemorrhage, sclero hyalinisation and lymphomatous thyroiditis aspects. She was treated with L Thyroxin, chemotherapy (Cisplatinum, Dacarbazin and radioactive iodine therapy. After oncological evaluation she was addressed to the First Surgery Clinic for thyroidectomy totalisation and the treatment of an umbilical tumour occurred after the fourth cure (June-July 2005. The patient was evaluated by physical exam, ultrasonography and computed tomography (cervical and abdominal which revealed tumours in the cervical region and in the liver. Thyroidectomy totalisation with limphadenectomy and an abdominal laparoscopy and biopsy were performed. The pathologic exam diagnosed multiple metastasis of malignant melanoma (MM localized in the cervical region, in the liver, great omentum and cervical limphatic nodes. The postoperative follow-up revealed multiple bone mestastasis from the malignanat melanoma. The case particularities were: association of RD with 2 primitive malignant tumours (occult PTC and MM, both diagnosed histopathologically and the multiple bone metastasis developed in a short time.

  15. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography

    International Nuclear Information System (INIS)

    Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma. Material and methods: Thirty-five patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up >6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined. Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content. Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET

  16. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Nadir [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)]. E-mail: gha@mrs1.ukl.uni-freiburg.de; Altehoefer, Carsten [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Hoegerle, Stefan [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Nitzsche, Egbert [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Lohrmann, Christian [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Schaefer, Oliver [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Kotter, Elmar [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Langer, Mathias [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)

    2005-05-01

    Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma. Material and methods: Thirty-five patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up >6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined. Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content. Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET.

  17. Advances in diagnosis and treatment of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Giorgio Vittorio Scagliotti

    2011-12-01

    Full Text Available Malignant pleural mesothelioma (MPM is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease.The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

  18. Surgical palliation of gastric outlet obstruction in advanced malignancy

    Science.gov (United States)

    Potz, Brittany A; Miner, Thomas J

    2016-01-01

    Gastric outlet obstruction (GOO) is a common problem associated with advanced malignancies of the upper gastrointestinal tract. Palliative treatment of patients’ symptoms who present with GOO is an important aspect of their care. Surgical palliation of malignancy is defined as a procedure performed with the intention of relieving symptoms caused by an advanced malignancy or improving quality of life. Palliative treatment for GOO includes operative (open and laparoscopic gastrojejunostomy) and non-operative (endoscopic stenting) options. The performance status and medical condition of the patient, the extent of the cancer, the patients prognosis, the availability of a curative procedure, the natural history of symptoms of the disease (primary and secondary), the durability of the procedure, and the quality of life and life expectancy of the patient should always be considered when choosing treatment for any patient with advanced malignancy. Gastrojejunostomy appears to be associated with better long term symptom relief while stenting appears to be associated with lower immediate procedure related morbidity. PMID:27648158

  19. Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

    Directory of Open Access Journals (Sweden)

    Kristensen Annemarie T

    2009-12-01

    Full Text Available Abstract Background Head and neck cancers (HNC are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Methods Canine cases entered in the Danish Veterinary Cancer Registry (DVCR from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC. Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. Results A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128. Of these, 64 (50% were malignant and 44 (34% benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant, OMM (13; 20% of malignant, soft tissue sarcoma (11; 17% of malignant and adenocarcinoma (5; 11% of malignant. The most common types of benign neoplasms were adenoma (7; 16% of benign, polyps (6; 14% of benign and fibroma (5; 11% of benign. Conclusions In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans. Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and

  20. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies

    Directory of Open Access Journals (Sweden)

    La Greca M

    2014-06-01

    Full Text Available Michele La Greca,1 Giuseppe Grasso,2 Giovanna Antonelli,1 Alessia Erika Russo,1 Salvatore Bartolotta,3 Alessandro D’Angelo,1 Felice Vito Vitale,1 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina, Messina, Italy; 2Pathology Department, San Vincenzo Hospital, Taormina, Messina, Italy; 3Surgical Unit, Casa di Cura Gretter-Lucina, Catania, Catania, Italy Abstract: Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1] and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK] the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma. Keywords: neoadjuvant setting, biologic, targeted therapy, vemurafenib, advanced melanoma

  1. Future of radiation therapy for malignant melanoma in an era of newer, more effective biological agents

    Directory of Open Access Journals (Sweden)

    Khan MK

    2011-08-01

    Full Text Available Mohammad K Khan1, Niloufer Khan2, Alex Almasan1,2, Roger Macklis11Taussig Cancer Institute, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA; 2Case Western Reserve University School of Medicine, Cleveland, OH, USAAbstract: The incidence of melanoma is rising. The primary initial treatment for melanoma continues to be wide local excision of the primary tumor and affected lymph nodes. Exceptions to wide local excision include cases where surgical excision may be cosmetically disfiguring or associated with increased morbidity and mortality. The role of definitive or adjuvant radiotherapy has largely been relegated to palliative measures because melanoma has been viewed as a prototypical radiotherapy-resistant cancer. However, the emerging clinical and radiobiological data summarized here suggests that many types of effective radiation therapy, such as radiosurgery for melanoma brain metastases, plaque brachytherapy for uveal melanoma, intensity modulated radiotherapy for melanoma of the head and neck, and adjuvant radiotherapy for selected high-risk, node-positive patients can improve outcomes. Similarly, although certain chemotherapeutic agents and biologics have shown limited responses, long-term control for unresectable tumors or disseminated metastatic disease has been rather disappointing. Recently, several powerful new biologics and treatment combinations have yielded new hope for this patient group. The recent identification of several clinically linked melanoma gene mutations involved in mitogen-activated protein kinase (MAPK pathway such as BRAF, NRAS, and cKIT has breathed new life into the drive to develop more effective therapies. Some of these new therapeutic approaches relate to DNA damage repair inhibitors, cellular immune system activation, and pharmacological cell cycle checkpoint manipulation. Others relate to the investigation of more effective targeting and dosing schedules for underutilized therapeutics, such as

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

    Science.gov (United States)

    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.

  3. Ultrasound-mediated interferon β gene transfection inhibits growth of malignant melanoma

    International Nuclear Information System (INIS)

    Highlights: → Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-β genes both in vitro and in vivo. → Ultrasound-mediated IFN-β transfection inhibited proliferation of melanoma cells in vitro. → Ultrasound-mediated IFN-β transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon β (IFN-β) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-β in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-β genes mixed with microbubbles. Successful sonotransfection with IFN-β gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-β 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.

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

    Science.gov (United States)

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

    2015-01-01

    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.

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

    Science.gov (United States)

    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

  6. DNA hydroxymethylation in malignant melanoma%DNA羟甲基化在恶性黑素瘤的进展

    Institute of Scientific and Technical Information of China (English)

    王丹; 杨盛波; 黄进华

    2016-01-01

    DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) protein family.This conversion is an important intermediate step in active DNA demethylation,which can influence gene expressions by dynamically regulating DNA methylation levels.DNA hydroxymethylation can be modulated by TET proteins,the Krebs cycle-related enzymes,vitamin C,miRNAs,etc.Like patients with hematological malignancies or other solid cancers,those with cutaneous malignant melanoma have been reported to have decreased 5-hydroxymethylcytosine levels and abnormal DNA hydroxymethylation,hinting that DNA hydroxymethylation is related to the occurrence,development and prognosis of cutaneous malignant melanoma.%DNA羟甲基化指在TET蛋白酶家族催化下,将5甲基胞嘧啶氧化成5羟甲基胞嘧啶的过程,是DNA主动去甲基化的关键中间步骤,主要通过动态调节DNA甲基化水平,影响基因表达.DNA羟甲基化过程可被TET蛋白、三羧酸循环相关酶、维生素C、微小RNA等多种因素调控.研究发现,和血液系统恶性肿瘤及多种实体肿瘤类似,恶性黑素瘤中同样存在5羟甲基胞嘧啶含量降低,DNA羟甲基化调控因素异常等现象,提示DNA羟甲基化可能与恶性黑素瘤的发生发展及预后等相关.

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer;

    2010-01-01

    cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous...... melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved...

  8. Spotlight on pembrolizumab in the treatment of advanced melanoma

    OpenAIRE

    Rajakulendran T; Adam DN

    2015-01-01

    Thanashan Rajakulendran,1 David N Adam2 1Department of Medicine, Division of Dermatology, Postgraduate Medical Education, 2Department of Medicine, Division of Dermatology, St Michael’s Hospital, University of Toronto, Toronto, ON, Canada Abstract: Metastatic melanoma is an aggressive cancer with a poor prognosis. Many approved therapies often do not achieve durable responses in patients. This underscores the need for novel therapeutic strategies. Recruiting a robust immun...

  9. Evaluation of microphthalmia associated transcription factor (MITF expression in peripheral blood of a population with malign melanoma and control population and cell lines

    Directory of Open Access Journals (Sweden)

    Nelson Rangel

    2009-03-01

    Full Text Available Background: The incidence of malign melanoma tumours has increased more rapidly than any other type of cancer; this has intensified the searching for tools that facilitate early detection of melanoma. Microphthalmia associated transcription factor (MITF is currently known as being a master melanocyte regulator. The article analyses MITF gene expression in peripheral blood of individuals suffering from melanoma, compared to people without any type of cancer and some cell lines.Materials and methods: Thirty one samples of peripheral blood were used: 19 from patients having melanoma and 12 from healthy people. Then RNA was extracted from these samples. MITF and housekeeping genes (b2M and GAPDH expression levels were then quantified by real-time PCR. Five cell lines were also used to determine the MITF expression.Results: MITF gene expression could be observed in all individuals, though no statistical significant differences were found among expression levels in the groups studied (p=0.09. Even so, MITF expression in the group of patients suffering from melanoma was much more variable than that observed in the group of cancer-free people. Expression was detected in the cell line AGS (gastric adenocarcinoma, not yet described.Conclusions: MITF gene expression levels were detected in the peripheral blood from both people suffering from melanoma and people without any type of cancer. However, variability in the number of molecules in MITF gene expression was observed in people with melanoma, this suggests the presence of tumour cells in circulation.

  10. The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1998-01-01

    In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients and...

  11. Tattoo pigment in an axillary lymph node simulating metastatic malignant melanoma

    OpenAIRE

    Jack, CM; Adwani, A; Krishnan, H

    2005-01-01

    We report a case of axillary lymphadenopathy thirty years after a decorative tattoo clinically mimicking metastatic melanoma. The importance of relying on histological confirmation of metastatic disease before altering extent of surgery is discussed. The importance of recording presence of decorative tattoos is stressed.

  12. A Web-based data warehouse on gene expression in human malignant melanoma.

    Science.gov (United States)

    Györffy, Balazs; Lage, Hermann

    2007-02-01

    The identification of melanoma-specific dysregulated genes could identify new molecular markers. By applying bioinformatic tools for screening of biomedical databases, a melanoma-specific gene expression profile "data warehouse" was constructed. Utilizable data sets of global gene expression analyses were available from nine studies that applied different technology platforms. A single study used cell lines, five investigations analyzed cell lines and tissues obtained from patients, two studies used exclusively specimens obtained from patients, and one study analyzed blood cells prepared from patients. The total number of investigated patients was 116. From 815 differential-regulated genes, 772 (95%) were identified merely in a single study, 37 in at least two studies, five (RAB33A, ERBB3, ADRB2, MERTK, SNF1LK, and ITPKB) in at least three studies, and a single gene, RAB33A, in four studies. These data show that the accuracy, reproducibility, and comparability among different gene expression profile studies are low in melanoma. In conclusion, the study demonstrates the high diversity of gene expression profiles associated with melanoma, the necessity to include a sufficient number of samples regarding clinical standards, for the design of standardized sample collecting and preparation, for the development of common standards for microarray data processing, and for developing standardized bioinformatic tools.

  13. Polymorphisms in the CD28/CTLA4/ICOS genes: Role in malignant melanoma susceptibility and prognosis?

    NARCIS (Netherlands)

    M.G. Bouwhuis (Marna); A. Gast (Andreas); A. Figl (Adina); A.M.M. Eggermont (Alexander); K. Hemminki (Kari); D. Schadendorf (Dirk); R. Kumar (Rajiv)

    2010-01-01

    textabstractThe appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic T lymphocyte antigen 4 (CTLA4) and

  14. Frozen section investigation of the sentinel node in malignant melanoma and breast cancer

    NARCIS (Netherlands)

    Tanis, PJ; Boom, RPA; Faneyte, IF; Peterse, JL; Nieweg, OE; Rutgers, EJT; Tiebosch, ATMG; Kroon, BBR; Schraffordt Koops, H.

    2001-01-01

    Background: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients. Methods:

  15. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Directory of Open Access Journals (Sweden)

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

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

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

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

  17. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup;

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably......, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that V600EBRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to V......600EBRAF. Finally, the senescence response associated with inhibition of V600EBRAF is rescued by overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), providing direct evidence that oncogene addiction rests on a metabolic foundation....

  18. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E)BRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup;

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to (V600E)BRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS......). Notably, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that (V600E)BRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes...... an addiction to (V600E)BRAF. Finally, the senescence response associated with inhibition of (V600E)BRAF is rescued by overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), providing direct evidence that oncogene addiction rests on a metabolic foundation....

  19. MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy

    Science.gov (United States)

    Tran, Khiem A; Cheng, Michelle Y; Mitra, Anupam; Ogawa, Hiromi; Shi, Vivian Y; Olney, Laura P; Kloxin, April M; Maverakis, Emanual

    2016-01-01

    The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. PMID:26730180

  20. Having children with multiple partners is associated with reduced risk of malignant melanoma: an observation seeking a plausible explanation

    Directory of Open Access Journals (Sweden)

    Anne V Olesen

    2010-10-01

    Full Text Available Anne V Olesen1,2,3, Erik T Parner4, Preben B Mortensen5, Cecilia H Ramlau-Hansen6, Jørn Olsen71Institute of Public Health, Department of Epidemiology, University of Aarhus; 2Unit for Psychiatric Research, Aalborg Psychiatric Hospital; 3Department of Clinical Epidemiology, Aarhus University Hospital; 4Institute of Public Health, Department of Biostatistics; 5National Centre for Register-based Research; 6Department of Occupational Medicine, Aarhus University Hospital, Denmark; 7Department of Epidemiology, School of Public Health, University of California, Los Angeles, USAObjective: We examined the association between the number of partners that mothers and fathers have children with and occurrence of cutaneous malignant melanoma (CMM.Methods: We conducted a complete registry-based follow-up of all Danish mothers born after 1935 from the birth of their second child until CMM, death, emigration, or end of study in 2002. We conducted a similar follow-up of the corresponding fathers. Incidence rate ratios (IRR and confidence intervals (CI were estimated by Poisson regression.Results: This study corroborates that women having children with three or more men are half as likely to have CMM as women who have children with one man: incidence rate ratio (IRR = 0.51, 95% CI: 0.29, 0.91; having children by two fathers reduces risk among women by 20%: IRR = 0.80, 95% CI: 0.70, 0.91. Fathers with multiple partners tend to face a similar risk reduction.Conclusion: The similar patterns of mothers and fathers challenge us to consider and propose likely mechanisms common to both sexes. The patterns of reduced risk have now been reported in two large independent complete population-based studies in Sweden and Denmark.Keywords: malignant melanoma, epidemiology, children with multiple partners

  1. Molecular Therapeutic Advances in Personalized Therapy of Melanoma and Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Fergal C. Kelleher

    2012-04-01

    Full Text Available The incorporation of individualized molecular therapeutics into routine clinical practice for both non-small cell lung cancer (NSCLC and melanoma are amongst the most significant advances of the last decades in medical oncology. In NSCLC activating somatic mutations in exons encoding the tyrosine kinase domain of the Epidermal Growth Factor Receptor (EGFR gene have been found to be predictive of a response to treatment with tyrosine kinase inhibitors (TKI, erlotinib or gefitinib. More recently the EML4-ALK fusion gene which occurs in 3–5% of NSCLC has been found to predict sensitivity to crizotinib an inhibitor of the anaplastic lymphoma kinase (ALK receptor tyrosine kinase. Similarly in melanoma, 50% of cases have BRAF mutations in exon 15 mostly V600E and these cases are sensitive to the BRAF inhibitors vemurafenib or dabrafenib. In a Phase III study of advanced melanoma cases with this mutation vemurafenib improved survival from 64% to 84% at 6 months, when compared with dacarbazine. In both NSCLC and melanoma clinical benefit is not obtained in patients without these genomic changes, and moreover in the case of vemurafenib the therapy may theoretically induce proliferation of cases of melanoma without BRAF mutations. An emerging clinical challenge is that of acquired resistance after initial responses to targeted therapeutics. Resistance to the TKI’s in NSCLC is most frequently due to acquisition of secondary mutations within the tyrosine kinase of the EGFR or alternatively activation of alternative tyrosine kinases such as C-MET. Mechanisms of drug resistance in melanoma to vemurafenib do not involve mutations in BRAF itself but are associated with a variety of molecular changes including RAF1 or COT gene over expression, activating mutations in RAS or increased activation of the receptor tyrosine kinase PDGFRβ. Importantly these data support introducing re-biopsy of tumors at progression to continue to personalize the choice of

  2. Research progress of cell death and therapy in malignant melanoma%恶性黑色素瘤细胞死亡与治疗研究进展

    Institute of Scientific and Technical Information of China (English)

    王馨苑

    2015-01-01

    恶性黑色素瘤是一种恶性程度高且目前临床常规治疗极为不敏感的皮肤癌.目前已知的细胞死亡方式有凋亡、坏死、自噬作用、老化及有丝分裂崩溃.化疗药物最终通过诱导细胞凋亡这一信号通路来杀伤肿瘤细胞,因而恶性黑色素瘤治疗失败的主要原因是细胞内产生了凋亡抵抗机制.文章探讨了恶性黑色素瘤细胞死亡的方式,并针对恶性黑色素瘤小分子靶向药物治疗进行综述.%Malignant melanoma is the most aggressive form of skin cancer and insensitive to almost all clinical cancer therapies.Apoptosis,necrosis,autophagy,senescence and mitotic catastrophe,all of these different manners constitute cell death way.Chemotherapy induces cell death at last by the signal pathway of apoptosis,so the reason for treatment failure of melanoma is the establishment of the mechanism of apoptotic resistance in melanoma cells.This article reviews the death style of melanoma cells and the progress of targeting small molecule drug therapy for malignant melanoma.

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

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Folkvaljon, Yasin; Garmo, Hans;

    2016-01-01

    .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...

  4. Melanoma immunotherapy dominates the field.

    Science.gov (United States)

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

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

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

    OpenAIRE

    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...

  6. Malignant melanoma of the nasal cavity: a case report with examination of KIT and platelet derived growth factor receptor-α (PDGFRA

    Directory of Open Access Journals (Sweden)

    Tadashi Terada

    2011-10-01

    Full Text Available Although several clinicopathological studies of malignant melanoma of the nasal cavity have been reported, there are no studies of the expression and gene mutation of KIT and platelet derived growth factor receptor-α (PDGFRA in melanoma of the nasal cavity. A 92-year-old Japanese woman consulted to our hospital because of right nasal obstruction and epistaxis. Physical examination and imaging modalities showed a tumor of the right nasal cavity. A biopsy was taken, and it showed malignant epithelioid cells with melanin deposition. Immunohistochemically, the tumor was positive for S100 protein, HMB45, p53, Ki-67 (labeling=20%, KIT and PDGFRA. The tumor was negative for cytokeratins (AE1/3 and CAM5.2. A genetic analysis using PCR-direct sequencing revealed no mutation of KIT gene (exons 9, 11, 13, and 17 or the PDGFRA gene (exons 12 and 18. The pathological diagnosis was primary malignant melanoma of the nasal cavity. The tumor was reduced in size by local resection and chemotherapy (Darthmose regimen: dacarbazine, carmustine, cisplatine, and tamoxifen, and the patient is now alive and free from metastasis 9 months after the first manifestation. In conclusion, the author reported a case of melanoma of the nasal cavity expressing KIT and PDGFRA without gene mutations of KIT and PDGFRA.

  7. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations12

    Science.gov (United States)

    Ciuffreda, Ludovica; Del Bufalo, Donatella; Desideri, Marianna; Di Sanza, Cristina; Stoppacciaro, Antonella; Ricciardi, Maria Rosaria; Chiaretti, Sabina; Tavolaro, Simona; Benassi, Barbara; Bellacosa, Alfonso; Foà, Robin; Tafuri, Agostino; Cognetti, Francesco; Anichini, Andrea; Zupi, Gabriella; Milella, Michele

    2009-01-01

    The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma. PMID:19649202

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Rappa, Germana [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Mercapide, Javier; Anzanello, Fabio [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Le, Thuc T. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Johlfs, Mary G. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Fiscus, Ronald R. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Wilsch-Bräuninger, Michaela [Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany); Corbeil, Denis [Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany); Lorico, Aurelio, E-mail: alorico@roseman.edu [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States)

    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

  10. Múltiplos melanomas malignos em área de cicatriz de queimadura: relato de caso e revisão da literatura Multiple malignant melanomas at burn scar: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Victor Hugo Maion

    2008-08-01

    Full Text Available Alterações neoplásicas malignas podem ocorrer em aproximadamente 2% dos casos de cicatrizes de queimaduras. As lesões neoplásicas se apresentam mais freqüentemente como carcinoma espinocelular. Neste artigo descreve-se o caso de uma paciente do sexo feminino, na sexta década de vida, com melanomas malignos múltiplos que se desenvolveram em uma antiga área de cicatriz de queimadura no tronco. Melanomas malignos múltiplos que se desenvolvem em região de cicatriz de queimadura são extremamente raros, e apenas quatro casos foram descritos na literatura até o presente momento.Malignant changes in burn scars can develop in approximately 2% of patients. The majority of these lesions are squamous cell carcinomas. In this article we present the case of a female patient, in the sixth decade, with multiple melanomas arising in the setting of an extensive old truncal burn scar. Multiple malignant melanomas arising in a burn scar are extremely uncommon and only four previous cases have been described in literature.

  11. Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi

    Science.gov (United States)

    Xia, Jianxin; Wang, Yanlong; Li, Fuqiu; Wang, Jinfeng; Mu, Yan; Mei, Xianglin; Li, Xue; Zhu, Wenjing; Jin, Xianhua; Yu, Kai

    2016-01-01

    Malignant melanoma (MM) is a type of malignant tumor, which originates from neural crest melanocytes. MM progresses rapidly and results in a high mortality rate. The present study aims to investigate the expression of microphthalmia transcription factor (MITF), the S100 protein, and HMB-45 in MM and pigmented nevi. A total of 32 MM samples (including three skin metastasis, three lymph node metastasis and two spindle cell MM samples), two Spitz nevus samples, four pigmented nevus samples and two blue nevus samples were collected. The expression levels of S100 protein, HMB-45, and MITF were observed via immunostaining. The S100 protein exhibited high positive rates in MM and pigment disorders (96.7 and 100%, respectively), but with low specificity. The S100 protein was also expressed in fibroblasts, myoepithelial cells, histocytes and Langerhans cells in normal skin samples. HMB-45 had high specificity. Its positive expression was only confined to MM cells and junctional nevus cells. Furthermore, HMB-45 was not expressed in melanocytes in the normal tissue samples around the tumor or in the benign intradermal nevus cells. MITF exhibited high specificity and high sensitivity. It was expressed in the nuclei of melanocytes, MM cells and nevus cells. It was observed to be strongly expressed in metastatic MM and spindle cell MMs. Thus, MITF may present as a specific immunomarker for the diagnosis and differential diagnosis of MM. PMID:27602212

  12. Therapeutic ureteral occlusion in advanced pelvic malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kinn, A.C.; Ohlsen, H.; Brehmer-Andersson, E.; Brundin, J.

    1986-01-01

    A technique for ureteral occlusion, combining insertion of nylon plugs with injection of polidocanol, is described. The method was used in 15 patients with vesicovaginal fistulas after operation and irradiation for advanced gynecological malignancy, or with severe malfunction and fibrosis of the bladder after radiotherapy for bladder carcinoma. The urinary leakage ceased in 11 patients, was greatly diminished in 2 and was unchanged in 2. Migration of plugs to the renal pelvis was the most serious complication and may have been the cause of pyelonephritis in 1 case. The technique is recommended for patients with a short life expectancy and uncontrolled, distressing leakage of urine.

  13. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

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

  14. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  15. An Unusual Case of Metastatic Malignant Melanoma Presenting as Pseudomesothelioma with Intense Diffuse Pleural FDG Uptake Demonstrated on FDG PET/CT

    Directory of Open Access Journals (Sweden)

    Rosamma Bency

    2015-06-01

    Full Text Available A 75-year-old male, non-smoker with history of asbestos exposure, and excision of 2 mm Clark IV cutaneous malignant melanoma 15 months earlier, presented with rapidly progressive dyspnea, left pleuritic chest pain, and weight loss. CT Pulmonary Angiography (CTPA demonstrated bilateral pulmonary emboli and findings suspicious of mesothelioma. There was no evidence of infection or malignancy in the hemorrhagic pleural fluid aspirate. FDG PET-CT revealed extensive intense FDG uptake throughout the pleura of left hemi-thorax, bilateral hilar and mediastinal lymph nodes, bilateral adrenals and left gluteal musculature. Subsequent pleural biopsy was consistent with metastatic melanoma. The patient was referred for palliative therapy but died 10 days later

  16. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  17. New developments in the management of advanced melanoma – role of pembrolizumab

    Directory of Open Access Journals (Sweden)

    Improta G

    2015-09-01

    Full Text Available Giuseppina Improta,1 Isabella Leone,1 Marco Donia,2 Stefania Gieri,3 Giuseppe Pelosi,4,5 Filippo Fraggetta6 1Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Rionero in Vulture, Potenza, Italy; 2Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; 3Laboratory of Oncologic Technologies, IBFM-CNR, Cefalù, Potenza, 4Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 5Department of Biomedical and Clinical Sciences “Luigi Sacco”, Università degli Studi di Milano, Milan, 6Department of Pathology, Cannizzaro Hospital, Catania, Italy Abstract: Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma. Keywords: advanced melanoma, immunotherapy, PD-1 inhibitor, pembrolizumab

  18. A comparison of high dose Ga-67 SPECT and FDG PET imaging in malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kaliff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1998-06-01

    Full text: Ga-67 imaging for tumour localisation lost favour in the 1970`s. With improvement in technology and use of higher doses, it has now found an important role in lymphoma. A similar phenomenon may be possible in the staging of melanoma. This study therefore compares high dose (370 MBq) Ga-67 imaging using a day 5 and 7 whole-body and comprehensive SPECT protocol, with (100 MBq) F-18 fluorodeoxyglucose (FDG) imaging using positron emission tomography (PET): a technique recently shown to be highly accurate in this condition. 85 patients; 46 males, mean age 52+17 yrs: range 22-83 yrs, underwent both studies within 9{+-}16 days (max-91 days). Scans were judged as positive (+ve), negative (-ve) or equivocal (EQ) for local, regional and distant disease. Clinical follow-up resolved discordant scan findings. PET and Ga-67 results were concordant in 61 (70%) patients (19 with +ve, 37 -ve and 5 EQ scans). None of the 9 ps with one EQ and one eye scan had disease on follow-up. Follow-up was available in 4/5 patients with discordantly +ve (3 patients) or more extensive Ga-67 abnormality: 3 patients had disease confirmed, 1 patient false +ve (asymmetric lung hilum). Follow-up was available in 9/10 patients with discordantly +ve (3 patients) or more extensive PET abnormality: 4 patients had confirmed disease, l pt false +ve (bladder diverticulum). A further 4 patients had second primaries (2 rectal carcinomas, 1 plasmacytoma, 1 basal cell carcinoma). High dose Ga-67 scanning incorporating SPECT appears to be a reasonable alternative to FDG PET for screening patients with melanoma. In this series PET`s main advantages were in the detection of other occult tumours, greater patient convenience and lower radiation dosimetry.

  19. Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition

    Institute of Scientific and Technical Information of China (English)

    Jun-shan RUAN; Yin LU; Yu-ping LIU; Lei ZHANG; Ling-geng YAN; Fang-tian FAN; Cun-si SHEN; Ai-yun WANG; Shi-zhong ZHENG; Shao-ming WANG

    2012-01-01

    Aim:To investigate whether luteolin,a highly prevalent flavonoid,reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal.Methods:Murine malignant melanoma B16F10 cells were exposed to 1% O2 for 24 h.Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay,respectively.EMT-related proteins,such as E-cadherin and N-cad-herin,were examined using Western blotting.Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×106 cells in 0.2 mL per mouse) via the lateral tail vein.The mice were treated with luteolin (10 or 20 mg/kg,ip) daily for 23 d.On the 23rd day after tumor injection,the mice were sacrificed,and the lungs were collected,and metastatic foci in the lung surfaces were photographed.Tissue sections were analyzed with immunohistochemistry and HE staining.Results:Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips,which was accompanied by increased cellular adhesion and invasion.Luteolin (5-50 μmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner.Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation),which was reversed by luteolin (5 μmol/L).In B16F10 cells,luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway.In experimental metastasis model mice,treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%.Furthermore,the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues.Conclusion:Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3integrin,suggesting that luteolin may be

  20. A disguised Melanoma

    Directory of Open Access Journals (Sweden)

    Cláudia Sofia Rego

    2012-02-01

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

  1. Cutaneous Melanoma in Asians.

    Science.gov (United States)

    Kim, Sang Yub; Yun, Sook Jung

    2016-09-01

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

  2. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

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

  3. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2015-01-01

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

  5. New developments in the management of advanced melanoma – role of pembrolizumab

    Science.gov (United States)

    Improta, Giuseppina; Leone, Isabella; Donia, Marco; Gieri, Stefania; Pelosi, Giuseppe; Fraggetta, Filippo

    2015-01-01

    Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma. PMID:26396529

  6. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

    Science.gov (United States)

    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; Schneider, Stefan W

    2015-05-14

    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

  7. Systemic chemotherapy of advanced head and neck malignancies.

    Science.gov (United States)

    Dowell, K E; Armstrong, D M; Aust, J B; Cruz, A B

    1975-04-01

    Several Phase II chemotherapy protocols were evaluated in patients with advanced malignancies; 158 were evaluable head and neck cases. The protocols were as follows: five-drug combination (COMFP), four-drug (COMF), (CCNU, Adriamycin, DTIC, and cytosine arabinoside. Insufficient numbers and data were received to adequately evaluate Yoshi 864, 5 Azacytidine, porfiromycin, BCNU, and Azaserine. Significant responses to therapy were noted in the four and five-drug combinations in which 30-44% of the patients had 50% or greater regression, with an average duration of 2.2 months. Adriamycin and CCNU demonstrated lesser antitumor effects, while DTIC and cytosine arabinoside did not demonstrate significant antitumor activity in the head and neck areas. Usual toxicity consisted largely of nausea and vomiting, leukopenia, and thrombocytopenia. Alopecia was not pronouced in Adriamycin-treated patients. It appears that combination chemotherapy had a higher response rate compared to single agents used in the different cooperative protocols. PMID:1116105

  8. High-dose proton beam therapy for sinonasal mucosal malignant melanoma

    International Nuclear Information System (INIS)

    The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is sill controvertial. This study was to evaluate the role of high-dose proton beam therapy (PBT) in patients with SMM. The cases of 20 patients with SMM localized to the primary site who were treated by PBT between 2006 and 2012 were retrospectively analyzed. The patterns of overall survival and morbidity were assessed. The median follow-up time was 35 months (range, 6–77 months). The 5-year overall and disease-free survival rates were 51% and 38%, respectively. Four patients showed local failure, 2 showed regrowth of the primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5-year local control rate after PBT was 62%. Nodal and distant failure was seen in 7 patients. Three grade 4 late toxicities were observed in tumor-involved optic nerve. Our findings suggested that high-dose PBT is an effective local treatment that is less invasive than surgery but with comparable outcomes

  9. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available ≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: 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

  10. MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy

    Directory of Open Access Journals (Sweden)

    Tran KA

    2015-12-01

    Full Text Available Khiem A Tran,1,* Michelle Y Cheng,1,* Anupam Mitra,1 Hiromi Ogawa,1 Vivian Y Shi,1 Laura P Olney,1 April M Kloxin,2 Emanual Maverakis1 1Department of Dermatology, University of California, Davis, Sacramento, CA, USA; 2Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA *These authors contributed equally to this work Abstract: The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib, which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. Keywords: cobimetinib, trametinib, vemurafenib, dabrafenib, BRAF inhibitor, MAPK pathway

  11. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case

    OpenAIRE

    D’Andrea, Mark A; Reddy, G. Kesava

    2015-01-01

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metast...

  12. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

    OpenAIRE

    Ludovica Ciuffreda; Donatella Del Bufalo; Marianna Desideri; Cristina Di Sanza; Antonella Stoppacciaro; Maria Rosaria Ricciardi; Sabina Chiaretti; Simona Tavolaro; Barbara Benassi; Alfonso Bellacosa; Robin Foà; Agostino Tafuri; Francesco Cognetti; Andrea Anichini; Gabriella Zupi

    2009-01-01

    The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the leas...

  13. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients

    DEFF Research Database (Denmark)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette;

    2016-01-01

    ), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.......1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. Conclusion CuSCC and non-cuSCC were rare events among metastatic melanoma patients....

  14. The research advances in molecular mechanism of curcumin against melanoma%姜黄素抗黑色素瘤分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    谢婉莹; 欧阳鑫; 江冠民; 张秋桂

    2015-01-01

    Melanoma is a kind of malignant tumor that derived from the melanocytes which often located in skin,mu-cous membrane,eye and pigmentation area of the central nervous system. Although the incidence of malignant melano-ma is not high,it is characterized by high malignant degree because of its early invasion and metastasis which lead to patients have poor prognosis. At present,the comprehensive treatment strategy for malignant melanoma including sur-gery,radiotherapy,chemotherapy and Chinese traditional medicine,however,surgical treatment still remains the first choice for early stage patient,however,studies related to Chinese medicine treatment of melanoma is still in its infan-cy. In recent research,they demonstrate that curcumin which is the active ingredient of zingiberaceae plants,turmeric, rhizoma zedoariae,etc,has extensive pharmacological properties of anti - cancer,anti - inflammatory and antioxidant, especially the potential utility in tumor prevention and treatment. Curcumin can inhibit the proliferation and promote the apoptosis of melanoma cells. In this paper,we will review the research advances in molecular mechanism of curcu-min against melanoma.%黑色素瘤是源于皮肤,粘膜,眼和中枢神经系统色素沉着区域的黑色素细胞的恶性肿瘤,虽然其发病率不高,但恶性程度极高,并且瘤细胞很早就能发生侵袭与转移,从而使患者预后很差。目前黑色素瘤的治疗方式仍以外科手术治疗为主,联合放疗、化疗、中药的综合治疗方案,然而有关黑色素瘤的中医中药治疗方面的研究尚处于起步阶段。最新研究表明,姜科植物属姜黄、郁金、莪术等的活性成分之一姜黄素具有广泛的抗癌、抗炎、抗氧化等药理特性,特别是姜黄素在黑色瘤的预防和治疗中起到不容忽视的作用,姜黄素主要通过抑制黑色素瘤细胞的增殖,促进其凋亡等途径参与黑色素瘤细胞的消亡。本文主要针

  15. Comparison of 2 monoclonal antibodies for immunohistochemical detection of BRAF V600E mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas.

    Science.gov (United States)

    Routhier, Caitlin Ann; Mochel, Mark C; Lynch, Kerry; Dias-Santagata, Dora; Louis, David N; Hoang, Mai P

    2013-11-01

    BRAF mutation is seen in a variety of human neoplasms including cutaneous malignant melanoma, papillary thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, pleomorphic xanthoastrocytoma, and others. Currently, there are 2 commercially available monoclonal antibodies for the detection of BRAF V600E mutation; however, a full and practical comparison of their performance in various tumor types on an automated staining platform has not been done. We investigated their sensitivity and specificity in detecting the BRAF V600E mutation in a series of 152 tumors including 31 malignant melanomas, 25 lung carcinomas, 32 gastrointestinal carcinomas, 23 thyroid carcinomas, 35 gliomas, and 6 other malignancies. In this series, the concordance rate between immunohistochemistry (IHC) and mutational analyses was 97% (148/152) for VE1 and 88% (131/149) for anti-B-Raf. The sensitivity and specificity were 98% (60/61) and 97% (88/91) for monoclonal VE1 and 95% (58/61) and 83% (73/88) for anti-B-Raf, respectively. There were 4 cases with discordant IHC and mutational results for monoclonal VE1 in contrast to 18 cases for anti-B-Raf. Our studies showed that IHC with monoclonal VE1 has a better performance compared with anti-B-Raf in an automated staining platform and confirmed that clone VE1 provides excellent sensitivity and specificity for detecting the BRAF V600E mutation in a variety of tumor types in a clinical setting.

  16. Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.

    Science.gov (United States)

    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. PMID:27445169

  17. Novel approaches in melanoma prevention and therapy.

    Science.gov (United States)

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

    2014-01-01

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

  18. Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling.

    Science.gov (United States)

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

    2016-03-01

    Recent advances in cancer genomics have enabled the discovery of many cancer-predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of (and be able to recognize) the clinical signs in high-risk patients in different contexts. Personal and family histories of cancer should always be sought in patients with multiple nevi or a positive history for melanoma, and should be updated annually. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors in cases of BAP1 melanoma syndrome, should also be recognized early. These patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if a risk for internal malignancy is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages; a multidisciplinary approach to their cancer screening and treatment is ideal. PMID:26892651

  19. Pembrolizumab for the treatment of melanoma.

    Science.gov (United States)

    Kumar, Sanjeev Srinivas; McNeil, Catriona Mairi

    2015-01-01

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

  20. Survival after Resection of a Primary Malignant Melanoma of the Small Intestine in a Young Patient: Report of a Case

    Directory of Open Access Journals (Sweden)

    T.K. Timmers

    2013-05-01

    Full Text Available The occurrence of primary melanoma of the small intestine is rare. We describe the case of a 25-year-old man found to have a primary melanoma of the ileum. The patient presented with gradual onset of abdominal pain, fever, diarrhea, weight loss and fatigue. A preoperative diagnosis of a small intestinal tumor was based on the findings of computed tomography scanning. This diagnosis was confirmed at laparotomy and a partial small bowel resection was performed. Histopathological examination of the resected specimen clarified the exact nature of the lesion, confirming the diagnosis of melanoma. Thorough postoperative investigation did not reveal a primary lesion in the skin, gastrointestinal tract, oculus or brain. Thus, we diagnosed this tumor as a primary lesion. One year after his operation, the patient remains well without any evidence of recurrence. Thus, we diagnosed this small bowel tumor as a primary melanoma of the small intestine.

  1. Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Stoffels, Ingo; Leyh, Julia; Schadendorf, Dirk; Klode, Joachim [University of Duisburg-Essen, Department of Dermatology, Venerology and Allergology, University-Hospital Essen, Essen (Germany); Mueller, Markus [University of Duisburg-Essen, Department of Medical controlling, University-Hospital Essen, Essen (Germany); Geisel, Marie Henrike [University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University-Hospital Essen, Essen (Germany); Poeppel, Thorsten [University of Duisburg-Essen, Department of Nuclear Medicine, University-Hospital Essen, Essen (Germany)

    2014-09-15

    Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified. Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of EUR 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was EUR 1,619.7 (Q1;Q3 EUR 1,317.0;2,603.4) and of SLNE without SPECT/CT was EUR 2,330.2 (EUR 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared

  2. Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink.

    Directory of Open Access Journals (Sweden)

    Anthony Matthews

    2016-06-01

    Full Text Available 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.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 no evidence that risk

  3. Advance of Therapeutic Methods for Malignant Pleural Effusion

    Institute of Scientific and Technical Information of China (English)

    XU Tao-tao

    2016-01-01

    Malignant pleural effusion (MPE) is a condition caused by primary malignant tumors in the pleura or other malignant tumors metastasis to the pleura. It is also one of common serious complications of middle-late malignant tumor, which has severe impact on the quality of life, even threatening the life of the patients. The selection of treatments for MPE depends on many factors, including the symptoms, performance status, primary tumor types, response to systemic therapy, and degree of lung recruitment maneuvers (LRM) after drainage of pleural effusion. Generally, the treatment methods include thoracentesis, indwelling pleural catheter, pleurodesis, intrapleural injection of drugs, chemotherapy, radiotherapy, anti-angiogenesis therapy, surgery, and thermotherapy. With the in-depth study on pathogenesis of MPE, the treatments of MPE have continuous improvements. This study mainly reviewed the treatment methods for MPE so as to provide the basis for clinical practice in the future.

  4. Advance of Therapeutic Methods for Malignant Pleural Effusion

    Directory of Open Access Journals (Sweden)

    Tao-tao XU

    2016-06-01

    Full Text Available Malignant pleural effusion (MPE is a condition caused by primary malignant tumors in the pleura or other malignant tumors metastasis to the pleura. It is also one of common serious complications of middle-late malignant tumor, which has severe impact on the quality of life, even threatening the life of the patients. The selection of treatments for MPE depends on many factors, including the symptoms, performance status, primary tumor types, response to systemic therapy, and degree of lung recruitment maneuvers (LRM after drainage of pleural effusion. Generally, the treatment methods include thoracentesis, indwelling pleural catheter, pleurodesis, intrapleural injection of drugs, chemotherapy, radiotherapy, anti-angiogenesis therapy, surgery, and thermotherapy. With the in-depth study on pathogenesis of MPE, the treatments of MPE have continuous improvements. This study mainly reviewed the treatment methods for MPE so as to provide the basis for clinical practice in the future.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...

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

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

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

  7. The role of sentinel node mapping in malignant melanoma: experience with {sup 99m}Tc-phytate and a review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Sapienza, Marcelo T.; Soares Junior, Jose; Marone, Marilia M.S.; Tavares, Marcia G.M.; Endo, Irene S.; Campos Neto, Guilherme C.; Lewin, Shlomo [Hospital Samaritano de Sao Paulo, SP (Brazil). Unidade de Diagnostico e Densitometria Ossea (UDDO)]. E-mail: mtsapienza@hotmail.com; Lopes, Margarida M.M. F.; Nakagawa, Sergio; Belfort, Francisco A. [Instituto Brasileiro de Controle do Cancer (IBCC), Sao Paulo, SP (Brazil)

    2004-04-01

    Sentinel lymph node (SLN), corresponding to the first lymph node draining the tumor, is usually the first one to receive its metastasis, and its biopsy is used to define the status of the whole lymphatic basin. The aim of this paper is to describe the use {sup 99m} Tc-phytate in SLN localization in malignant melanoma patients, and to review the main indications and information provided by SLN biopsy. A total of 92 patients with malignant melanoma was studied. Lymph node scintigraphy was carried out after the sub dermal injection of {sup 99m} Tc-Phytate. After 18-24 hours, intra-operative SLN localization was carried out using the gamma-probe and lymph node dissection was then performed. Lymphoscintigraphy identified the sentinel node in all studies and intra-operative detection using gamma-probe was reached in 98.8% of the cases. The SLN was involved in 23 patients (26%). The method's negative predictive value was 100%, and there were no side effects related to {sup 99m} Tc-Phytate. Scintigraphic and intra-operative sentinel node detection was satisfactorily performed using {sup 99m} Tc- Phytate, an easily available and low cost radiopharmaceutical. SLN mapping allows the use of more accurate tumor staging techniques and reduces surgical morbidity. (author)

  8. Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in BRAF(V600E and BRAF wild-type metastatic malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Andliena Tahiri

    Full Text Available 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.

  9. Multi-center evaluation of the novel fully-automated PCR-based Idylla™ BRAF Mutation Test on formalin-fixed paraffin-embedded tissue of malignant melanoma.

    Science.gov (United States)

    Melchior, Linea; Grauslund, Morten; Bellosillo, Beatriz; Montagut, Clara; Torres, Erica; Moragón, Ester; Micalessi, Isabel; Frans, Johan; Noten, Veerle; Bourgain, Claire; Vriesema, Renske; van der Geize, Robert; Cokelaere, Kristof; Vercooren, Nancy; Crul, Katrien; Rüdiger, Thomas; Buchmüller, Diana; Reijans, Martin; Jans, Caroline

    2015-12-01

    The advent of BRAF-targeted therapies led to increased survival in patients with metastatic melanomas harboring a BRAF V600 mutation (implicated in 46-48% of malignant melanomas). The Idylla(™) System (Idylla(™)), i.e., the real-time-PCR-based Idylla(™) BRAF Mutation Test performed on the fully-automated Idylla(™) platform, enables detection of the most frequent BRAF V600 mutations (V600E/E2/D, V600K/R/M) in tumor material within approximately 90 min and with 1% detection limit. Idylla(™) performance was determined in a multi-center study by analyzing BRAF mutational status of 148 archival formalin-fixed paraffin-embedded (FFPE) tumor samples from malignant melanoma patients, and comparing Idylla(™) results with assessments made by commercial or in-house routine diagnostic methods. Of the 148 samples analyzed, Idylla(™) initially recorded 7 insufficient DNA input calls and 15 results discordant with routine method results. Further analysis learned that the quality of 8 samples was insufficient for Idylla(™) testing, 1 sample had an invalid routine test result, and Idylla(™) results were confirmed in 10 samples. Hence, Idylla(™) identified all mutations present, including 7 not identified by routine methods. Idylla(™) enables fully automated BRAF V600 testing directly on FFPE tumor tissue with increased sensitivity, ease-of-use, and much shorter turnaround time compared to existing diagnostic tests, making it a tool for rapid, simple and highly reliable analysis of therapeutically relevant BRAF mutations, in particular for diagnostic units without molecular expertise and infrastructure.

  10. Real-world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study.

    Science.gov (United States)

    Middleton, Mark R; Dalle, Stéphane; Claveau, Joel; Mut, Pilar; Hallmeyer, Sigrun; Plantin, Patrice; Highley, Martin; Kotapati, Srividya; Le, Trong Kim; Brokaw, Jane; Abernethy, Amy P

    2016-07-01

    The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had ≥1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies. PMID:27118102

  11. Real-world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study.

    Science.gov (United States)

    Middleton, Mark R; Dalle, Stéphane; Claveau, Joel; Mut, Pilar; Hallmeyer, Sigrun; Plantin, Patrice; Highley, Martin; Kotapati, Srividya; Le, Trong Kim; Brokaw, Jane; Abernethy, Amy P

    2016-07-01

    The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had ≥1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies.

  12. Electric pulses used in electrochemotherapy and electrogene therapy do not significantly change the expression profile of genes involved in the development of cancer in malignant melanoma cells

    International Nuclear Information System (INIS)

    Electroporation is a versatile method for in vitro or in vivo delivery of different molecules into cells. However, no study so far has analysed the effects of electric pulses used in electrochemotherapy (ECT pulses) or electric pulses used in electrogene therapy (EGT pulses) on malignant cells. We studied the effect of ECT and EGT pulses on human malignant melanoma cells in vitro in order to understand and predict the possible effect of electric pulses on gene expression and their possible effect on cell behaviour. We used microarrays with 2698 different oligonucleotides to obtain the expression profile of genes involved in apoptosis and cancer development in a malignant melanoma cell line (SK-MEL28) exposed to ECT pulses and EGT pulses. Cells exposed to ECT pulses showed a 68.8% average survival rate, while cells exposed to EGT pulses showed a 31.4% average survival rate. Only seven common genes were found differentially expressed in cells 16 h after exposure to ECT and EGT pulses. We found that ECT and EGT pulses induce an HSP70 stress response mechanism, repress histone protein H4, a major protein involved in chromatin assembly, and down-regulate components involved in protein synthesis. Our results show that electroporation does not significantly change the expression profile of major tumour suppressor genes or oncogenes of the cell cycle. Moreover, electroporation also does not changes the expression of genes involved in the stability of DNA, supporting current evidence that electroporation is a safe method that does not promote tumorigenesis. However, in spite of being considered an isothermal method, it does to some extent induce stress, which resulted in the expression of the environmental stress response mechanism, HSP70

  13. Radiobiology of malignant melanoma. Melanin behavior in gamma radiation induced oxidadative strees and genotoxicity: implications for radiotherapy

    OpenAIRE

    Fonseca, Sérgio Manuel Lopes da

    2009-01-01

    Os objectivos do presente trabalho são: avaliar o efeito sensibilizante ou protector da molécula de melanina na citotoxicidade e genotoxicidade da radiação ionizante, investigar a modulação do stress oxidativo radioinduzido em células de melanoma maligno na presença e ausência de melanina e interpretar os resultados na perspectiva da radioterapia do melanoma ou outras neoplasias malignas. É ainda apresentada uma revisão bibliográfica acerca dos cancros cutâneos com especial atenção para o ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaosong [Department of Oncology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing (China); Hode, Tomas; Guerra, Maria C [Immunophotonics Inc., 1601 South Providence Road, Columbia, Missouri 65211 (United States); Ferrel, Gabriela L [Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490 - Jesus Maria, Lima (Peru); Nordquist, Robert E [Wound Healing of Oklahoma, Inc., Oklahoma City, Oklahoma (United States); Chen, Wei R, E-mail: wchen@uco.edu [Department of Engineering and Physics, University of Central Oklahoma, Edmond, Oklahoma (United States)

    2011-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    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

  17. Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP in Patients with Malignant Melanoma.

    Directory of Open Access Journals (Sweden)

    Ruth Heise

    Full Text Available Interferon alpha (IFNα is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1 is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in 'silent' metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic

  18. Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis.

    Science.gov (United States)

    Heppt, Markus V; Eigentler, Thomas K; Kähler, Katharina C; Herbst, Rudolf A; Göppner, Daniela; Gambichler, Thilo; Ulrich, Jens; Dippel, Edgar; Loquai, Carmen; Schell, Beatrice; Schilling, Bastian; Schäd, Susanne G; Schultz, Erwin S; Matheis, Fanny; Tietze, Julia K; Berking, Carola

    2016-08-01

    Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks. Clinical and laboratory data were collected and analyzed with respect to safety and efficacy. A total of 33 patients from 13 centers were identified with a median follow-up time of 9 months. Twenty-eight patients received ipilimumab, while five patients were treated with a PD-1 inhibitor (pembrolizumab n = 3, nivolumab n = 2). The local overall response rate (ORR) was 66.7 %. The systemic ORR was 19.2 and 40.0 % in the ipilimumab and PD-1 cohort, respectively. The median duration of response was not reached in either group. The median time to disease progression was 2.5 months for the entire population with 2 months for ipilimumab and 5 months for PD-1 blockade. The median overall survival was not reached in patients with ipilimumab and 15 months in the PD-1 group. Severe systemic adverse events were detected in 25.0 % in the ipilimumab group. No treatment-related deaths were observed. This is the first reported evaluation of ECT and simultaneous PD-1 inhibition and the largest published dataset on ECT with concurrent ipilimumab. The local response was lower than reported for ECT only. Ipilimumab combined with ECT was feasible, tolerable and showed a high systemic response rate. PMID:27294607

  19. Pharmacodynamic Characterization of the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    William D. Tap

    2010-08-01

    Full Text Available PURPOSE: About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF that causes the steady-state activation of extracellular signal-regulated kinase (ERK. We sought to investigate the efficacy of PLX4032 (BRAF inhibitor to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma. EXPERIMENTAL DESIGN: Well-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling, cell cycle, apoptosis, and gene expression analyses were performed before and after exposure to drug. RESULTS: Using a growth-adjusted inhibitory concentration of 50% cutoff of 1 µM, 13 of 35 cell lines were sensitive to PLX4032, 16 resistant, and 6 intermediate (37%, 46%, and 17% respectively. PLX4032 caused growth inhibition, G0/G1 arrest, and restored apoptosis in the sensitive cell lines. A BRAF mutation predicted for but did not guarantee a response, whereas a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ line variants and/or a more differentiated melanocyte genotype had a preferential response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a nonmelanocytic genotype, and is associated with an increase in the gene expression of certain metallothioneins and mediators of angiogenesis. CONCLUSIONS: PLX4032 has robust activity in BRAF mutated melanoma. The preclinical use of this molecule identifies criteria for its proper clinical application, describes patterns of and reasons for response/resistance, and affords insight into the role of a BRAF mutation in melanoma.

  20. Dermoscopy on subungual melanoma 

    Directory of Open Access Journals (Sweden)

    Grażyna Kamińska-Winciorek

    2013-05-01

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

  1. Autophagy- An emerging target for melanoma therapy

    Science.gov (United States)

    Ndoye, Abibatou; Weeraratna, Ashani T.

    2016-01-01

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

  2. Autophagy- An emerging target for melanoma therapy.

    Science.gov (United States)

    Ndoye, Abibatou; Weeraratna, Ashani T

    2016-01-01

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

  3. Melanoma maligno cutâneo: sistema de pontos (scoring system para auxílio no diagnóstico histopatológico Cutaneous malignant melanoma: scoring system to assist in the histopathologic diagnosis

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Veronese

    2006-10-01

    . A total of 101 cases of extensive-superficial melanoma less than 2mm thick were comparatively analysed with 33 benign melanocytic lesions (thirteen Spitz nevi, six Reed nevi, six dysplastic nevi, three congenital nevi, three acquired nevi, one combined nevus and one recurrent nevus. RESULTS: The total amount of values obtained on histopathological criteria (scores pointed out significant statistical differences between benign and malignant lesions, what makes this method useful for surgical pathologist in daily routines. CONCLUSION: The objective and systematic application of histopathological criteria by means of the scoring system may be helpful in the differential diagnosis between benign and malignant melanocytic neoplasms, but the approach was not able to distinguish melanocytic lesions of unknown biological behavior.

  4. Cutaneous melanoma.

    Science.gov (United States)

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

    2014-03-01

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

  5. Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation

    DEFF Research Database (Denmark)

    Philipsen, P A; Knudsen, L; Gniadecka, M;

    2013-01-01

    There is a general need for methods to obtain fast in vivo diagnosis of skin tumours. Raman spectroscopy measures molecular structure and may thus have potential as a tool for skin tumour diagnosis. The purpose of this study was to investigate how skin pigmentation influenced the Raman spectra...... and skin tumour diagnostics in vivo. We obtained Raman spectra in vivo from the normal skin of 55 healthy persons with different skin pigmentation (Fitzpatrick skin type I-VI) and in vivo from 25 basal cell carcinomas, 41 pigmented nevi and 15 malignant melanomas. Increased skin pigmentation resulted...... in a higher spectral background caused by fluorescence, which could be removed by background correction. After background correction, we found only a negligible effect of pigmentation on the major spectral bands, and the comparison of the intensity of these bands allowed us to differentiate between normal...

  6. The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1998-01-01

    In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients...... by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different...... between BCC patients and controls except that women patients had higher pigmentation at the lateral side of the upper arm. For CMM, men patients had higher pigmentation at the lateral side of the upper arm. Self-estimations of sun exposure did not show differences between patients and controls...

  7. CD45/CD8 myeloid histioid antigen and plasma cell antibody immune response in a case of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu-Velez

    2012-01-01

    Full Text Available The immune response in metastatic melanoma is not well established and therefore is of particular interest to test for recruitment of immune cells to the tumor. A 46-year-old Caucasian female was evaluated for an asymptomatic right forearm mass. The lesion had been present for at least 4 years and had become painful 4 months ago. Biopsies for hematoxylin and eosin (H and E staining, as well as immunohistochemical analysis were performed on the primary tumor and on sentinel lymph nodes. The H and E staining was consistent with metastatic melanoma. Positive staining was noted on the tumor cells with S-100, Mart-1/Melan A/CD63, PNL2, HMB45, and tyrosinase. Peritumoral and intratumoral inflammatory cells stained positive for CD8, CD45, PCNA, myeloid histoid antigen, antihuman plasma cell antibody, and focal BRCA1. The staining patterns of CD8/CD45, myeloid histoid antigen and plasma cell antibody on inflammatory cells around the melanoma cells suggest an unusual type of immune response.

  8. A phase I/II study of lomustine and temozolomide in patients with cerebral metastases from malignant melanoma.

    Science.gov (United States)

    Larkin, J M G; Hughes, S A; Beirne, D A; Patel, P M; Gibbens, I M; Bate, S C; Thomas, K; Eisen, T G; Gore, M E

    2007-01-15

    Temozolomide is an alkylating agent with activity in the treatment of melanoma metastatic to the brain. Lomustine is a nitrosurea that crosses the blood brain barrier and there is evidence to suggest that temozolomide may reverse resistance to lomustine. A multicentre phase I/II study was conducted to assess the maximum-tolerated dose (MTD), safety and efficacy of the combination of temozolomide and lomustine in melanoma metastatic to the brain. Increasing doses of temozolomide and lomustine were administered in phase I of the study to determine the MTD. Patients were treated at the MTD in phase II of the study to six cycles, disease progression or unacceptable toxicity. Twenty-six patients were enrolled in the study. In phase I of the study, the MTD was defined as temozolomide 150 mg m(-2) days 1-5 every 28 days and lomustine 60 mg m(-2) on day 5 every 56 days. Dose-limiting neutropaenia and thrombocytopaenia were observed at higher doses. Twenty patients were treated at this dose in phase II of the study. No responses to therapy were observed. Median survival from starting chemotherapy was 2 months. The combination of temozolomide and lomustine in patients with brain metastases from melanoma does not demonstrate activity. The further evaluation of this combination therefore is not warranted. PMID:17146474

  9. Patient derived cell culture and isolation of CD133⁺ putative cancer stem cells from melanoma.

    Science.gov (United States)

    Welte, Yvonne; Davies, Cathrin; Schäfer, Reinhold; Regenbrecht, Christian R A

    2013-01-01

    Despite improved treatments options for melanoma available today, patients with advanced malignant melanoma still have a poor prognosis for progression-free and overall survival. Therefore, translational research needs to provide further molecular evidence to improve targeted therapies for malignant melanomas. In the past, oncogenic mechanisms related to melanoma were extensively studied in established cell lines. On the way to more personalized treatment regimens based on individual genetic profiles, we propose to use patient-derived cell lines instead of generic cell lines. Together with high quality clinical data, especially on patient follow-up, these cells will be instrumental to better understand the molecular mechanisms behind melanoma progression. Here, we report the establishment of primary melanoma cultures from dissected fresh tumor tissue. This procedure includes mincing and dissociation of the tissue into single cells, removal of contaminations with erythrocytes and fibroblasts as well as primary culture and reliable verification of the cells' melanoma origin. Recent reports revealed that melanomas, like the majority of tumors, harbor a small subpopulation of cancer stem cells (CSCs), which seem to exclusively fuel tumor initiation and progression towards the metastatic state. One of the key markers for CSC identification and isolation in melanoma is CD133. To isolate CD133(+) CSCs from primary melanoma cultures, we have modified and optimized the Magnetic-Activated Cell Sorting (MACS) procedure from Miltenyi resulting in high sorting purity and viability of CD133(+) CSCs and CD133(-) bulk, which can be cultivated and functionally analyzed thereafter. PMID:23525090

  10. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E;

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  11. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-30

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

  12. Radiopharmacological characterization of ⁶⁴Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma.

    Science.gov (United States)

    Gao, Feng; Sihver, Wiebke; Jurischka, Christoph; Bergmann, Ralf; Haase-Kohn, Cathleen; Mosch, Birgit; Steinbach, Jörg; Carta, Davide; Bolzati, Cristina; Calderan, Andrea; Pietzsch, Jens; Pietzsch, Hans-Jürgen

    2016-03-01

    The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with εAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with εAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-εAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging. PMID:26643502

  13. Primary rectal melanoma - a case report

    Directory of Open Access Journals (Sweden)

    Somak Das

    2015-01-01

    Full Text Available The most common site for malignant melanoma is skin, then eye and third is anorectal region. Primary anorectal malignant melanoma is still very uncommon. It is usually very aggressive and presents with altered bowel habit and rectal bleeding. Proctoscopy shows non-pigmented or lightly pigmented polypoid lesion. Histopathology is confirmatory. Early radical excision is mandatory. A 56 year-old female was presented with malignant melanoma of the lower third of rectum. We report this case for its rarity.

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

    Directory of Open Access Journals (Sweden)

    Elias Ribeiro

    2012-08-01

    difícil diagnóstico, como se puede ver en este caso en que una úlcera en la planta del pie fue diagnosticada muy tarde, atrasando el diagnóstico de una neoplasia grave y de elevada tasa de mortalidad. Melanoma is a tumor that develops as a result of the malignant transformation of the melanocytes. There is a worldwide estimate of 132,000 new cases per year. This case study presents a 70-year-old male person with history of Diabetes Mellitus type 2 for 10 years and extensive psoriasis vulgaris for 6 years. The patient developed an ulcerated lesion in the plantar region of the right foot in one-year time period. The histological examination revealed an ulcerated malignant melanoma, Clark level V, 5.6 mm thick (Breslow. The lesion was surgically removed and the sentinel lymph node biopsy was negative. Initial conclusions revealed an advanced state of evolution of the primary tumor (TNM IIC. CAT scan detected gastric metastasis, reclassifying the illness as a TNM IV stage. Malignant melanoma may be difficult to diagnose, as it was possible to observe in this case study, where a foot ulcer was late diagnosed, delaying the diagnosis of a severe neoplasia with high mortality rate.

  15. The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma.

    Science.gov (United States)

    Pelak, Maciej J; Śnietura, Mirosław; Lange, Dariusz; Nikiel, Barbara; Pecka, Katarzyna M

    2015-12-01

    We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-βR1) and interferon gamma (IFN-γR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-βR1 and IFN-γR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-βR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-βR1 and IFN-γR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together. PMID:27003769

  16. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

  17. Establishment and characterization of a transplantable tumor line (RMM) and cell line (RMM-C) from a malignant amelanotic melanoma in the F344 rat, with particular reference to galectin-3 expression in vivo and in vitro.

    Science.gov (United States)

    Bondoc, Alexandra; Katou-Ichikawa, Chisa; Golbar, Hossain M; Tanaka, Miyuu; Izawa, Takeshi; Kuwamura, Mitsuru; Yamate, Jyoji

    2016-11-01

    To investigate characteristics of malignant melanomas with various pathobiological features, a homotransplantable tumor line (RMM) was established from a spontaneous amelanotic melanoma found in the pinna of an aged F344 rat. RMM tumors were transplanted in syngeneic rats by serial subcutaneous implantation with 100% intake. The original and RMM tumors consisted of spindle-shaped cells arranged mainly in interlacing bundles. Immunohistochemically, the neoplastic cells were positive to PNL-2 (melanocytes), nestin (neuroectodermal stem cells), S-100 (neurogenic cells) and vimentin (mesenchymal cells). Electron microscopically, tumor cells possessed single membrane-bound pre-melanosomes. Further, a cell line (RMM-C) was induced from an RMM tumor. RMM-C cells and the induced tumors in syngeneic rats showed immunohistochemical reactions similar to the original and RMM tumors. Interestingly, serum level of galectin-3 expression was increased with growing RMM tumors, and the expression was influenced by TNF-α (increase) or TGF-β1 (decrease), indicating a possible biomarker of amelanotic melanomas. The RMM tumors and RMM-C cell line could become useful tools for studies on the pathobiology, including tumor immunity, and development of therapeutic strategies against this malignancy. These tools are the first tumor lines of amelanotic melanomas in the rat. PMID:26949998

  18. The impact of surgery and mild hyperthermia on tumor response and angioneogenesis of malignant melanoma in a rat perfusion model

    International Nuclear Information System (INIS)

    The aim of this experimental study was to determine the effect of mild hyperthermia on tumor response and angioneogenesis in an isolated limb perfusion model with a human melanoma xenograft. A human melanoma xenograft was implanted into the hindlimbs of 30 athymic nude rats. The animals were randomized into five groups: group I: control, group II: sham group, group III: external hyperthermia with a tissue temperature of 41.5°C for 30 minutes without ILP, group IV: normothermic ILP (tissue temperature 37°C for 30 minutes, group V: hyperthermic ILP (tissue temperature 41.5°C for 30 minutes). Tumor response was evaluated by tumor size determination and immunohistochemical analysis 6 weeks postoperatively. Tissue sections were investigated for expression of CD34 and basic fibroblast growth factor (bFGF). Average tumor volumes of the controls (I) increased from 105 mm3 to 1388 mm3. In the sham operated group (II) tumor volumes were significantly larger than in group I. Tumor volumes in group IV were significantly smaller than in group I and lowest in group V. There were no significant differences in size between group I and group III after six weeks. In group III and IV each, 5 animals showed tumor progression and one had a partial tumor response. In group V only 2 animals showed tumor progression. Immunhistochemical analysis of the tissue sections demonstrated that angioneogenesis was more pronounced in group II than in group I and less pronounced in group IV and V compared with group I. Our results suggest that even a surgical manipulation such as a skin incision promotes tumor growth, probably by induction of growth factors like bFGF. External hyperthermia of 41.5°C tissue temperature for 30 minutes only has no impact on tumor growth and angioneogenesis in vivo

  19. CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT.

    Science.gov (United States)

    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

  20. Malignant melanoma with vitiligo-like depigmentation: a case report%恶性黑素瘤伴有白癜风样色素减退斑

    Institute of Scientific and Technical Information of China (English)

    廖晖; 李明; 王利红; 樊静

    2013-01-01

    A case of malignant melanoma with vitiligo-like depigmentation is reported. A 58-year-old man presented vitili-go-like depigmentation on his hands and feet for 1 year, and a painful mass on the right heel for 6 months. Physical examination revealed large piece of depigmented patch with sharp margin on the plantar region and medial side of the feet. Light white depigmented macules were seen on the lateral side skin of distal end of the fingers of both hands with blurred margins. The affected skin revealed brilliant white light under Wood's lamp examination. A semi-globular dark red mass of about 3 cm × 2.5 cm × 1 cm in size on the right heel was observed with erosive and exudative surface. Histopathologic examination demonstrated that the subepidermal tumor cells were in patchy distribution, and the muscle tissue focally infiltrated. A closer view revealed that the tumor was composed of atypical cells with hyperchromatic and pleomorphic nuclei of various sizes. The tumor cells stained positive for S-100, HMB-45 and vimentin with a Ki-67(+) >50%, definite diagnosis of malignant melanoma with vitiligo-like depigmentation was made.%报告1例恶性黑素瘤伴有白癜风样色素减退斑.患者男,58岁.双手、足色素脱色斑1年余,右足跟肿块伴疼痛6个月.皮肤科检查:两足底及足内侧见境界清楚的大块色素减退斑,双手指末节侧缘见淡白色色素减退斑,边缘模糊不清,Wood灯下色素脱色斑区呈亮白色荧光.右足跟有一3 cm × 2.5 cm × 1 cm半圆形暗红色肿块,表面糜烂、渗出.皮损组织病理检查示表皮下瘤细胞呈片、块状分布,细胞核大小不一,深染,异形明显,局部向肌组织内浸润.免疫组化染色示S-100蛋白(+)、HMB45E(+)、波形蛋白(+)、Ki-67(+)>50%.诊断为恶性黑素瘤伴有白癜风样色素减退斑.

  1. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Shinya; Hanazono, Kiwamu [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi [Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Iwano, Hidetomo [Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Uchide, Tsuyoshi, E-mail: uchide@rakuno.ac.jp [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan)

    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

  2. Advances in haploidentical stem cell transplantation for hematologic malignancies.

    Science.gov (United States)

    Montoro, Juan; Sanz, Jaime; Sanz, Guillermo F; Sanz, Miguel A

    2016-08-01

    One of the most important advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the use of alternative donors and cell sources, such as haploidentical transplants (haplo-HSCT) from family donors. Several approaches have been developed to overcome the challenging bidirectional alloreactivity. We discuss these approaches, including ex vivo T-cell-depleted grafts with megadose of CD34(+) cells, not requiring immunosuppression after allogeneic transplantation for graft-versus-host disease (GVHD) prophylaxis, and other strategies using unmanipulated T-cell-replete grafts with intensive immunosuppression or post-transplantation cyclophosphamide to minimize the GVHD. We also address the role of other strategies developed in the context of the haplo-HSCT platforms, such as ex vivo selective depletion of alloreactive donor T-cell subpopulations, infusion of antigen-specific T-cells against several pathogens, and infusion of regulatory T-cells, among other experimental approaches. Finally, some considerations about the selection of the most suitable donor, when more than one family member is available, are also addressed.

  3. Main roads to melanoma

    Directory of Open Access Journals (Sweden)

    Sini Maria

    2009-10-01

    Full Text Available Abstract The characterization of the molecular mechanisms involved in development and progression of melanoma could be helpful to identify the molecular profiles underlying aggressiveness, clinical behavior, and response to therapy as well as to better classify the subsets of melanoma patients with different prognosis and/or clinical outcome. Actually, some aspects regarding the main molecular changes responsible for the onset as well as the progression of melanoma toward a more aggressive phenotype have been described. Genes and molecules which control either cell proliferation, apoptosis, or cell senescence have been implicated. Here we provided an overview of the main molecular changes underlying the pathogenesis of melanoma. All evidence clearly indicates the existence of a complex molecular machinery that provides checks and balances in normal melanocytes. Progression from normal melanocytes to malignant metastatic cells in melanoma patients is the result of a combination of down- or up-regulation of various effectors acting on different molecular pathways.

  4. Influence of {sup 18}F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Schuele, Susann-Cathrin; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Eigentler, Thomas Kurt; Garbe, Claus [Eberhard-Karls-University Tuebingen, Skin Cancer Programme, Department of Dermatology, Tuebingen (Germany); Fougere, Christian la [Eberhard-Karls-University Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2016-03-15

    To evaluate the influence of {sup 18}F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data. Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent {sup 18}F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as ''major'' (e.g. change from metastasectomy to systemic therapy) or ''minor'' (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated. In the 52 patients in the primary staging group, the results of {sup 18}F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. {sup 18}F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of {sup 18}F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom {sup 18}F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %). Primary staging of patients with stage III/IV melanoma should be performed with {sup 18}F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients

  5. Influence of 18F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

    International Nuclear Information System (INIS)

    To evaluate the influence of 18F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data. Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent 18F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as ''major'' (e.g. change from metastasectomy to systemic therapy) or ''minor'' (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated. In the 52 patients in the primary staging group, the results of 18F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. 18F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of 18F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom 18F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %). Primary staging of patients with stage III/IV melanoma should be performed with 18F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease. (orig.)

  6. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  7. Melanoma immunotherapy.

    Science.gov (United States)

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

    2010-01-01

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

  8. 肛管直肠恶性黑色素瘤临床研究进展%Clinical research progression of anorectal malignant melanoma

    Institute of Scientific and Technical Information of China (English)

    杨雯靖; 李耀平

    2013-01-01

    Anorectal malignant melanoma is a rare disease with atypical clinical symptoms and has a high misdiagnosis rate.Combined with rectal touch,endoscopy,ultrasonic inspection,CT,MRI,PET-CT,electron microscopy and the result of immunohistochemistry could help improve the diagnosis rate.This tumor tends to relapse and metastasis with poor prognosis,and there is no effective treatment.We should be on the alert for it,and the main point is early discovery,correct diagnosis,multi-disciplinary comprehensive treatment,in order to improve the survival rate of patients.%肛管直肠恶性黑色素瘤临床罕见,临床症状不典型,误诊率高,结合指诊、内镜、超声、CT、MRI、PET-CT、电镜及免疫组织化学结果有助于提高诊断率.本病易复发转移,预后极差,尚无有效的治疗手段,应提高对肛管直肠恶性黑色素瘤的警惕,重点在于早期发现、正确诊断、多学科合理综合治疗,以提高患者生存率.

  9. Translational research in melanoma.

    Science.gov (United States)

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

    2013-10-01

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

  10. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg;

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND M...

  11. Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Bilgen Gençler

    2016-01-01

    Full Text Available The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40–60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA. Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.

  12. Biliary stenting in advanced malignancy: an analysis of predictive factors for survival

    OpenAIRE

    Afshar M; Khanom K; Ma YT; Punia P

    2014-01-01

    Mehran Afshar,1 Koudeza Khanom,2 Yuk Ting Ma,1,3 Pankaj Punia1 1Cancer Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK; 2St James Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 3School of Cancer Sciences, University of Birmingham, Birmingham, UK Purpose: Stenting of the biliary tree is a common palliative procedure to relieve obstructive jaundice in advanced malignancy. Although effective in relief of biliary obstr...

  13. Prognostic relevance of circulating CK19 mRNA in advanced malignant biliary tract diseases

    Institute of Scientific and Technical Information of China (English)

    Kawin Leelawat; Siriluck Narong; Wandee Udomchaiprasertkul; Jerasak Wannaprasert; Sa-ard Treepongkaruna; Somboon Subwongcharoen; Tawee Ratanashu-ek

    2012-01-01

    AIM: To determine the role of circulating tumor cells (CTCs) in prediction of the overall survival of patients with advanced malignant biliary tract obstruction. METHODS: We investigated the prognostic value of CTCs by examining two markers, cytokeratin (CK) 19 and human telomerase reverse transcriptase (hTERT) mRNA, in 40 patients diagnosed with advanced malignant biliary tract diseases. Quantitative real-time reverse transcription polymerase chain reaction was used to detect CK19 and hTERT mRNA in the peripheral blood of these patients. Overall survival was analyzed using the Kaplan-Meier method and Cox regression modeling. RESULTS: Positive CK19 and hTERT mRNA expression was detected in 45% and 60%, respectively, of the 40 patients. Univariable analysis indicated that positive CK19 mRNA expression was significantly associated with worse overall survival (P = 0.009). Multivariable analysis determined that positive CK19 mRNA expression, patient's age and serum bilirubin were each independently associated with overall survival. CONCLUSION: CK19 mRNA expression levels in peripheral blood appear to provide a valuable marker to predict the overall survival of patients with advanced malignant biliary tract obstruction.

  14. 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?

    Science.gov (United States)

    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

  15. 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?

    Science.gov (United States)

    Merrill, Stephen J; Subramanian, Madhan; Godar, Dianne E

    2016-01-01

    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

  16. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells.

    Science.gov (United States)

    Liu, Hao; Zhang, Yikai; Zheng, Shanyuan; Weng, Zeping; Ma, Jun; Li, Yangqiu; Xie, Xinyuan; Zheng, Wenjie

    2016-09-01

    Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to "copper" cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper.

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

    International Nuclear Information System (INIS)

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

  18. Donor Transmission of Melanoma Following Renal Transplant

    Directory of Open Access Journals (Sweden)

    Kathryn T. Chen

    2012-01-01

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

  19. Donor transmission of melanoma following renal transplant.

    Science.gov (United States)

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

    2012-01-01

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

  20. Update on benefit of immunotherapy and targeted therapy in melanoma: the changing landscape

    Directory of Open Access Journals (Sweden)

    Srivastava N

    2014-06-01

    Full Text Available Neeharika Srivastava, David McDermott Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Malignant melanoma is on the rise. There have been recent advances in targeted agents and immunotherapies that have improved the management and treatment of patients with advanced melanoma. This review discusses the clinical efficacy and unique side effects of targeted immunotherapy and the role of predictive biomarkers in better selection of patients who would derive most benefit from specific treatments. Additionally, this review addresses concerns about the best sequencing algorithms for the currently available targeted agents. By thoroughly and extensively researching through PubMed and the American Society of Clinical Oncology, 69 published articles and abstracts were identified as addressing topics related to malignant melanoma and immunotherapy. The research was divided into subcategories discussing cytokine-based therapy, immunotherapy, molecularly targeted agents, other novel targeted agents, and combination regimens for malignant melanoma. New immune checkpoint inhibitors and targeted agents are able to improve immune-mediated regulatory effects against tumors and, specifically in advanced melanoma, are associated with improvement in overall survival. These new agents have distinct side effects that are often controlled and reversed with dose reductions and/or use of corticosteroids. Currently, there are clinical trials underway to assess the role of combination therapy, whereas other trials are focusing on devising algorithms to delineate how best to sequentially administer these drugs. Although there has been tremendous progress in the management of advanced melanoma with immunotherapy and targeted agents, there is still much to be learned about clinically useful predictive biomarkers and combination therapies as well as how to administer these agents safely. Keywords: melanoma, immunotherapy

  1. Choroidal melanoma

    International Nuclear Information System (INIS)

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

  2. Advanced head and neck cancer: Long-term results of chemo-radiotherapy, complications and induction of second malignancies

    OpenAIRE

    Munker, Reinhold; Purmale, L.; Aydemir, Ü.; Reitmeier, M.; Pohlmann, H.; Schorer, H.; Hartenstein, R.

    2001-01-01

    Background: Chemo-radiotherapy is superior to radiotherapy alone in the treatment of advanced, inoperable head and neck cancer. The long-term treatment results, the induction of second malignant tumors, and other long-term toxicities are not well defined. Patients and Methods: 100 consecutive patients with advanced head and neck cancer who were treated at our center were studied. Treatment results, survival, the occurrence of late complications, and second malignant tumors (SMT) were investig...

  3. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

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

  4. Radiosensitization by fullerene-C60 dissolved in squalene on human malignant melanoma through lipid peroxidation and enhanced mitochondrial membrane potential

    Science.gov (United States)

    Kato, Shinya; Kimura, Masatsugu; Miwa, Nobuhiko

    2014-04-01

    We examined fullerene-C60 dissolved in squalene (C60/Sqe) for the ability to potentiate the radiosensitization under X-ray irradiation on human malignant melanoma HMV-II cells, which were treated with C60/Sqe and thereafter irradiated with X-ray. The cell proliferation for C60/Sqe was inhibited more markedly than for Sqe alone. Meanwhile, cell proliferation was almost unaltered for C60/squalane (Sqa) or Sqa, a hydrogenated form of Sqe, as compared to no-additive control. Thus radiosensitization of C60/Sqe is attributed to peroxidation of unsaturated bonds of squalene by X-ray-excited C60 in contrast to squalane. The fluorescence images of HMV-II cells stained with Rhodamine123, an indicator for mitochondrial membrane potential, were monitored for 6 h after X-ray irradiation. C60/Sqe obviously exhibited more augmented fluorescence intensity on perinuclear region of HMV-II cells than Sqe alone. TBARS assay showed that the lipid peroxidation level as malondialdehyde-equivalent increased by combination of C60/Sqe and X-ray dose-dependently on X-ray doses. C60/Sqe exhibited lipid peroxidation more markedly by 1.2-fold than Sqe alone. Thus the level of lipid peroxidation of squalene was sufficiently higher in C60/Sqe than in Sqe in the absence of C60 under X-ray irradiation, suggesting the combination of C60/Sqe and X-ray irradiation induced radiosensitization on HMV-II cells by peroxidation of absorbed Sqe in mitochondrial membrane via oxidative stress mediated by fullerene-C60.

  5. The melanocortin 1 receptor (Mc1r) variants do not account for the co-occurrence of Parkinson's disease and malignant melanoma.

    Science.gov (United States)

    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. PMID:25284244

  6. Cheek-neck advancement-rotation flaps following Mohs excision of skin malignancies.

    Science.gov (United States)

    Katz, A E; Grande, D J

    1986-09-01

    The cheek-neck advancement-rotation flap has proved extremely useful for delayed reconstruction of the face following the microscopically controlled surgical excision (MCSE) of skin malignancies. We have recently used these flaps successfully to repair combined defects of the cheek and nose in eight patients, isolated cheek defects in six patients, combined defects of the cheek and lips in two patients, and isolated defects of the nose, temple, and an antral cutaneous fistula in each of three patients. Defects as large as 6.0 X 10.0 cm have been closed in one stage with this flap. This flap is extremely hearty and its scars can be well concealed. It is especially valuable in the elderly patient and should always be considered as one of the options for reconstruction of the face following MCSE of skin malignancies. PMID:3745621

  7. Retrospective US database analysis of drug utilization patterns, health care resource use, and costs associated with adjuvant interferon alfa-2b therapy for treatment of malignant melanoma following surgery

    Directory of Open Access Journals (Sweden)

    Krishna A

    2012-06-01

    Full Text Available Michelle D Hackshaw,1 Arun Krishna,2 David J Mauro31,2Global Health Outcomes, Merck, Sharpe and Dohme Corporation, Whitehouse Station, NJ, USA; 3Clinical Research, Merck Research Laboratories, Upper Gwynedd, PA, USABackground: The purpose of this study was to identify a real-world US population having undergone surgery for malignant melanoma and describe treatment patterns, health care resource utilization, and costs for patients who subsequently received interferon alfa-2b (IFN therapy or other standard of care chemotherapies.Methods: A retrospective cohort study was conducted using administrative claims from MarketScan® databases among melanoma patients diagnosed between 2004 and 2008 who had surgery and were subsequently treated with IFN or other chemotherapies. Health care resource utilization and costs of services (converted to 2009 dollars were evaluated. Cost refers to the amount paid to providers associated with the health service.Results: Of 18,075 subjects with melanoma surgery claims, 1525 (8.4% were treated with IFN and 1194 (6.6% with other chemotherapies. Median duration (days and number of doses of IFN therapy were 29 and 20, respectively. Approximately half of patients who received IFN discontinued therapy within or after the one-month induction phase. For IFN therapy patients, average total cost per patient for the last melanoma-related surgery prior to start of therapy, including costs of the surgery itself, pathology, anesthesia, and hospital care, was $2219. The average total cost per patient related to IFN therapy was $1188; this included costs for drug, office visits, blood work, and infusions. Other chemotherapy costs ranged from $146 to $2678.Conclusion: There is an unmet treatment need, considering that this study observed that melanoma patients on IFN therapy post-surgery do not complete the recommended one-year course of treatment which may compromise its full therapeutic benefits. Further study to investigate reasons

  8. Cholangiocarcinoma and malignant bile duct obstruction: Areview of last decades advances in therapeutic endoscopy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In the last decades many advances have been achievedin endoscopy, in the diagnosis and therapy ofcholangiocarcinoma,however blood test, magneticresonance imaging, computed tomography scan mayfail to detect neoplastic disease at early stage, thus thediagnosis of cholangiocarcinoma is achieved usuallyat unresectable stage. In the last decades the roleof endoscopy has moved from a diagnostic role toan invaluable therapeutic tool for patients affectedby malignant bile duct obstruction. One of the majorissues for cholangiocarcinoma is bile ducts occlusion,leading to jaundice, cholangitis and hepatic failure.Currently, endoscopy has a key role in the work upof cholangiocarcinoma, both in patients amenable tosurgical intervention as well as in those unfit for surgeryor not amenable to immediate surgical curative resectionowing to locally advanced or advanced disease, withpalliative intention. Endoscopy allows successful biliarydrainage and stenting in more than 90% of patientswith malignant bile duct obstruction, and allows rapidreduction of jaundice decreasing the risk of biliary sepsis.When biliary drainage and stenting cannot be achievedwith endoscopy alone, endoscopic ultrasound-guidedbiliary drainage represents an effective alternativemethod affording successful biliary drainage in morethan 80% of cases. The purpose of this review is tofocus on the currently available endoscopic managementoptions in patients with cholangiocarcinoma.

  9. Loss of S100 antigenicity in metastatic melanoma

    OpenAIRE

    Aisner, Dara L.; Maker, Ajay; Rosenberg, Steven A.; Berman, David M.

    2005-01-01

    Melanoma is a highly malignant disease that may initially present as a poorly differentiated metastatic tumor. Therefore, the S100 immunostain, immunoreactive in 96% to 99% of melanoma, is used to evaluate poorly differentiated malignant tumors. To develop criteria for correctly diagnosing S100-negative melanomas, we studied the immunohistochemical profile of 1553 patients enrolled in ongoing National Cancer Institute clinical trials for melanoma. Seventeen patients (1%) had metastatic melano...

  10. Herpetic viruses and spontaneous recovery in melanoma.

    Science.gov (United States)

    Motofei, I G

    1996-08-01

    The malignant melanoma may display extremely variable forms of development, from clinical forms with a lethal course to the unforeseeable situations of spontaneous cures. The basic immunotherapeutic procedures, as well as hypotheses regarding the mechanisms involved in courses towards spontaneous regressions, are presented. Since viruses of the herpes genus are involved in the mechanisms assumed to be at the basis of spontaneous regressions, it is suggested that these viruses (selected strains) be used in the clinic, in order to check the advanced hypothesis, an opportunity which could permit to study also the very probable therapeutic alternative offered by this virus, namely the association of the well-known immunotherapeutic methods. PMID:8869920

  11. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    Directory of Open Access Journals (Sweden)

    Ahmed R

    2014-03-01

    Full Text Available Rafay Ahmed,1 Matthew J Oborski,2 Misun Hwang,1 Frank S Lieberman,3 James M Mountz11Department of Radiology, 2Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; 3Department of Neurology and Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USAAbstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies

  12. Combined low-dose ipilimumab and pembrolizumab after sequential ipilimumab and pembrolizumab failure in advanced melanoma.

    Science.gov (United States)

    Kirchberger, Michael C; Hauschild, Axel; Schuler, Gerold; Heinzerling, Lucie

    2016-09-01

    With the wide use of anti-PD-1 therapy, an increasing number of patients progress under treatment. Combined immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies induces higher response rates as first-line treatment in comparison to single-agent therapy, however, with substantial toxicity since the combination of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) induced 55% grade 3/4 treatment-related adverse events and treatment discontinuation rates of 39%. In this case series, we investigated the efficacy and toxicity of the combined immunotherapy with low-dose ipilimumab (1 mg/kg) plus pembrolizumab (2 mg/kg) in patients with metastatic melanoma with progressive disease under sequential monotherapy with both agents. All patients had received at least three lines of treatment, 78% of patients were M1c, and 67% had brain metastases. Stable disease was observed in 3 out of 9 patients with a median overall survival of 8 months after double checkpoint inhibition. No treatment-related grade 3/4 adverse events occurred, and none of the patients needed to discontinue the treatment due to toxicity. Further trials are needed to investigate combined immunotherapy as rescue treatment in heavily pretreated melanoma patients to find optimal dosage in regard to outcome and toxicity.

  13. THE MALIGNANT OBSTRUCTION OF THE ESOPHOGAS BY ADVANCED CANCER AND RELIEVED BY ENDOSCOPIC TREATMENT

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ji-chang; ZHANG Li-jian; ZHANG Xiao-dong; WANG Yan-meng; LI Wei

    1999-01-01

    Objective: To study the effect of endoscopic treatment on malignant obstructions of the esophagus. Methods: 64 cases of advanced esophageal cancer patients had obstructions of the esophagus, 7 cases could not be operated on, 57 cases had recurred lesions after operation and radiation therapies. The obstructions were all dilated with esophageal dilators, and then were treated using local chemotherapy, or local administration of elemene emulsion injection and a stent was placed in the esophageal lumen.Results: The obstructions were relieved with dilation for only about one week, but the obstructions, using relieved for more than three months after dilation using other treatments. After dilation, the PR of carcinoma was about 80% in local chemotherapy group, however, CR was about 8% and PR was about 92% in the group of elemene emulsion injection. Conclusion: Endoscopic treatment is an effective palliative method for advanced esophageal cancer.

  14. Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

    Institute of Scientific and Technical Information of China (English)

    MING Shu-hong; SUN Tie-ying

    2007-01-01

    Objective: To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods: Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores(NRS), Corrected serum calcium(CSC) and CSC effective rate. The vital signs, biochemical and hematological parameters were determined. Results: Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion(5.92 vs 3.25,P<0.01;6.13 vs 4.38, P<0.01, respectively). The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion: Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

  15. Inverse expression of hyaluronidase 2 and hyaluronan synthases 1–3 is associated with reduced hyaluronan content in malignant cutaneous melanoma

    OpenAIRE

    Hanna, Siiskonen; Mari, Poukka; Kristiina, Tyynelä-Korhonen; Reijo, Sironen; Sanna, Pasonen-Seppänen

    2013-01-01

    Background Hyaluronan is an extracellular matrix glycosaminoglycan involved in invasion, proliferation and metastasis of various types of carcinomas. In many cancers, aberrant hyaluronan expression implicates disease progression and metastatic potential. Melanoma is an aggressive skin cancer. The role of hyaluronan in melanoma progression including benign nevi and lymph node metastases has not been investigated earlier, nor the details of its synthesis and degradation. Methods The melanocytic...

  16. 反射式共聚焦显微镜在皮肤恶性黑素瘤中的应用进展%The application of relfectance confocal microscopy in malignant melanoma

    Institute of Scientific and Technical Information of China (English)

    吴冬梅; 李青; 戴耕武

    2015-01-01

    Relfectance confocal microscopy is a new auxiliary diagnosis technology after the application of dermoscopy and skin ultrasound. The application of reflectance confocal microscopy in the malignant melanoma is a research hotspot at present. The features of invivo, non-invasi, high resolution make it suitable to be used in the diagnosis, auxiliary treatment and follow-up process. This article summarizes the use of relfectance confocal microscopy in malignant melanoma.%反射式共聚焦显微镜是继皮肤镜、皮肤超声等仪器后新出现应用于皮肤科的辅助诊断技术。该项技术在皮肤恶性黑素瘤诊断中的应用是目前研究热点。在体、无创、高分辨率的特点使其适用于皮肤恶性黑素瘤的诊断、辅助治疗及随访中。该文对反射式共聚焦显微镜在皮肤恶性黑素瘤的应用进行综述。

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

    Directory of Open Access Journals (Sweden)

    Nunes, Ana Teresa

    2012-07-01

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

  18. Melanoma genetics

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  19. Primary malignant melanoma of vulva and vagina:a report of 16 cases%原发性外阴阴道恶性黑色素瘤16例临床分析

    Institute of Scientific and Technical Information of China (English)

    姚玲女; 孔繁斗

    2014-01-01

    Objective To investigate the clinical characteristics, treatment and the prognostic factors in patients with the primary malignant melanoma of vulva and vagina.MethodsThe clinical data of 16 patients with primary malignant melanoma of vulva and vagina, admitted to the first affiliated hospital of Dalian Medical University from 1995.6 to 2010.2 were analyzed retrospectively.Results Of the 16 cases, there were 12 cases of primary malignant melanoma of vulva(75%), 4 cases of primary malignant melanoma of vagina(25%).The rate of surgery was 81%, radical vulvectomy and extended resection were the main forms of the operations, and 8 cases was received the secondary treatment methods (immunotherapy, radiotherapy, chemotherapy). The flow-up time was from 1 to 98 months, 2 cases were out of flow-up, and the flow-up rate was 87.5%.During the flow-up time, 9 patients died of recrudescence or metastasis, and the death rate was 56.7%.The mean survival period of the patients with the primary malignant melanoma of the vulva was 37.1 months, and the survival rate in 3 years was 55.5%(not including the patients who were out of flow-up and whose flow-up time were less than three years), and only 3 cases were alive without tumor. Among patients with the primary malignant melanoma of the vagina, the survival period of 1 patient was 17 months, 2 patients had been alive with tumor for 26-42monthes, the mean period was 34 months; and the other 1 patient was out of flow-up.ConclusionMalignant melanoma of the female genital tract is an high malignancy tumor, the therapy should be based on operation, supplemented by immunotherapy, radiotherapy, chemotherapy. Early diagnose, equitable staging, early therapy and flow-up in time are very important for improving prognosis.%目的:探讨原发性外阴阴道恶性黑色素瘤的临床特点、治疗及预后。方法回顾性分析大连医科大学附属第一医院自1995年6月~2010年2月期间收治的16例外阴阴道恶黑

  20. 原发性外阴阴道恶性黑色素瘤16例临床分析%Primary malignant melanoma of vulva and vagina:a report of 16 cases

    Institute of Scientific and Technical Information of China (English)

    姚玲女; 孔繁斗

    2014-01-01

    目的:探讨原发性外阴阴道恶性黑色素瘤的临床特点、治疗及预后。方法回顾性分析大连医科大学附属第一医院自1995年6月~2010年2月期间收治的16例外阴阴道恶黑的临床资料。结果本组16例病例中,外阴恶黑12例(75.00%),阴道恶黑4例(25.00%)。手术率81.00%,手术方式以外阴广泛切除术和局部扩大切除术为主,8例患者应用了辅助治疗方法(免疫治疗、放疗、化疗)。随访时间1~98个月,失访2例,随访率87.50%,随访期内因复发或转移死亡9例,死亡率56.70%。外阴恶黑患者平均生存期37.10个月,3年生存率(除外失访和生存不足3年患者)为55.50%,仅3例患者现无瘤生存;阴道恶黑患者中1例生存期为17个月,2例现带瘤平均生存34.00个月,1例失访。结论原发性外阴阴道恶黑恶性程度高,治疗应以手术为主,辅以免疫、放化疗,早期诊断、合理分期、早期治疗、定期随诊是改善预后的关键因素。%Objective To investigate the clinical characteristics, treatment and the prognostic factors in patients with the primary malignant melanoma of vulva and vagina.MethodsThe clinical data of 16 patients with primary malignant melanoma of vulva and vagina, admitted to the first affiliated hospital of Dalian Medical University from 1995.6 to 2010.2 were analyzed retrospectively.Results Of the 16 cases, there were 12 cases of primary malignant melanoma of vulva(75%), 4 cases of primary malignant melanoma of vagina(25%).The rate of surgery was 81%, radical vulvectomy and extended resection were the main forms of the operations, and 8 cases was received the secondary treatment methods (immunotherapy, radiotherapy, chemotherapy). The flow-up time was from 1 to 98 months, 2 cases were out of flow-up, and the flow-up rate was 87.5%.During the flow-up time, 9 patients died of recrudescence or metastasis, and the death rate was 56.7%.The mean survival

  1. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    Institute of Scientific and Technical Information of China (English)

    Michael; J; Ricci; Jeffrey; A; Medin; Ronan; S; Foley

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.

  2. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    Science.gov (United States)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  3. PELVIC ACTINOMYCOSIS MIMICKING A LOCALLY ADVANCED PELVIC MALIGNANCY--CASE REPORT.

    Science.gov (United States)

    Velenciuc, Natalia; Velenciuc, I; Makkai Popa, S; Roată, C; Ferariu, D; Luncă, S

    2016-01-01

    We present the case of a former user of an intrauterine contraceptive device (IUD) for 10 years, diagnosed with a bulky, fixed pelvic tumor involving the internal genital organs and the recto sigmoid, causing luminal narrowing of the rectum, interpreted as locally advanced pelvic malignancy, probably of genital origin. Intraoperatively, a high index of suspicion made us collect a sample from the fibrous wall of the tumor mass, large Actinomyces colonies were thus identified. Surgery consisted in debridement, removal of a small amount of pus and appendectomy, thus avoiding a mutilating and useless surgery. Specific antibiotic therapy was administered for 3 months, with favorable postoperative and long-term outcomes. Pelvic actinomycosis should always be considered in the differential diagnosis of pelvic tumors in women using an IUD. The association of long-term antibiotic treatment is essential to eradicate the infection and prevent relapses. PMID:27483724

  4. [Choroidal melanoma - evolution and prognosis].

    Science.gov (United States)

    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.

  5. Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution

    Directory of Open Access Journals (Sweden)

    Tuca A

    2012-06-01

    Full Text Available Albert Tuca1, Ernest Guell2, Emilio Martinez-Losada3, Nuria Codorniu41Cancer and Hematological Diseases Institute, Hospital Clínic de Barcelona, Barcelona, Spain; 2Palliative Care Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 3Palliative Care Unit, Institut Català Oncologia Badalona, Barcelona, Spain; 4Medical Oncology Department, Institut Català Oncologia L'Hospitalet, Barcelona, SpainAbstract: Malignant bowel obstruction (MBO is a frequent complication in advanced cancer patients, especially in those with abdominal tumors. Clinical management of MBO requires a specific and individualized approach that is based on disease prognosis and the objectives of care. The global prevalence of MBO is estimated to be 3% to 15% of cancer patients. Surgery should always be considered for patients in the initial stages of the disease with a preserved general status and a single level of occlusion. Less invasive approaches such as duodenal or colonic stenting should be considered when surgery is contraindicated in obstructions at the single level. The priority of care for inoperable and consolidated MBO is to control symptoms and promote the maximum level of comfort possible. The spontaneous resolution of an inoperable obstructive process is observed in more than one third of patients. The mean survival is of no longer than 4–5 weeks in patients with consolidated MBO. Polymodal medical treatment based on a combination of glucocorticoids, strong opioids, antiemetics, and antisecretory drugs achieves very high symptomatic control. This review focuses on the epidemiological aspects, diagnosis, surgical criteria, medical management, and factors influencing the spontaneous resolution of MBO in advanced cancer patients.Keywords: malignant bowel obstruction, cancer, intestinal obstruction, bowel occlusion

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

    Directory of Open Access Journals (Sweden)

    Z. J. Casariego

    2004-12-01

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

  7. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H;

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was prospecti......In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was...

  8. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H;

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was prospecti......In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was...

  9. 宫颈原发性恶性黑色素瘤6例临床病理分析%Primary malignant melanoma of uterine cervix:a clinicopathological analysis of six cases

    Institute of Scientific and Technical Information of China (English)

    方三高; 石群立; 肖华亮; 肖蔚; 马强; 周晓军

    2012-01-01

    目的:探讨宫颈原发性恶性黑色素瘤(primary malignant melanoma of the u-terine cervix)的临床病理学特征、诊断及鉴别诊断.方法:检测6例原发性宫颈恶性黑色素瘤的组织病理学和免疫组化结果并复习文献.结果:患者28岁~ 83岁,平均53岁.主要临床表现为阴道不规则流血、阴道分泌物增多及发现宫颈肿物.肿瘤大体检查呈息肉样、溃疡状或平坦形.镜下肿瘤组织结构复杂、细胞形态多样,主要由胞质透亮的上皮样细胞和梭形细胞组成,核呈多形性,嗜酸性核仁显著,黑色素颗粒或有或无.免疫组化显示HMB-45和Melan-A或S-100表达呈阳性.结论:宫颈原发性恶性黑色素瘤罕见,借助于临床病理特点及免疫组化检查可与其它类似病变鉴别.%Objective; To study the clinical and pathologic features,diagnosis and differential diagnosis of primary melanoma of the uterine cervix. Methods; Six cases of primary malignant melanoma in the cervix were analysed by morphologic and immunohistochemical techniques with review of the related literatures. Results;The patients were between 26 and 83 years of age (average 53 years) at diagnosis who presented with symptoms of abnormal viginal bleedings or apocenosis with cervical masses. Grossly,the cervical neoplasms were appeared as polypoid , ulcerated or flat in shape. Histologically, the tumors were composed of variety of tissue patterns and cell types but mainly assumed as epithelial-like cells with pleomorphic nuclei and prominent eosinophilic nucleolae or spindle cells with/without melanin granule, which exhibited positive immunostaining for HMB-45 and Melan-A or S-100 protein. Conclusions;Primary ma-, lignant melanoma of the uterine cervix is extremely rare. It can be differentiated from other tumor-mimicking lesions based on the clinicopathologic features and immunohistochemical findings.

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

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

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

  11. Melanoma biomarkers: Vox clamantis in deserto (Review)

    OpenAIRE

    AL-SHAER, MAYS; GOLLAPUDI, DIVYA; PAPAGEORGIO, CHRIS

    2010-01-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecu...

  12. Development of primary malignant melanoma during treatment with a TNF-α antagonist for severe Crohn’s disease: a case report and review of the hypothetical association between TNF-α blockers and cancer

    Directory of Open Access Journals (Sweden)

    Kouklakis G

    2013-03-01

    Full Text Available George Kouklakis,1 Eleni I Efremidou,2 Michael Pitiakoudis,3 Nikolaos Liratzopoulos,2 Alexandros Ch Polychronidis2 1Endoscopy Unit, 2First Surgical Department, 3Second Surgical Department, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece Abstract: It is recognized that immunosuppression may lead to reduced immune surveillance and tumor formation. Because of the immunosuppressive properties of tumor necrosis factor (TNF-alpha (TNF-α antagonists, it is plausible that these biologics may increase the risk of the occurrence of malignancies or the reactivation of latent malignancies. TNF-α antagonists have gained momentum in the field of dermatology for treating rheumatoid arthritis and psoriasis, and they have revolutionized the treatment of other inflammatory autoimmune diseases such as refractory Crohn's disease. However, there is accumulating evidence that TNF-α inhibitors slightly increase the risk of cancer, including malignant melanoma (MM. The authors herein report the case of a 54-year-old female patient who developed a primary MM during treatment with adalimumab for severe Crohn’s disease resistant to successive medical therapies. The patient had been receiving this TNF-α blocker therapy for 3 years before the occurrence of MM. After wide surgical excision of the lesion and staging (based on Breslow thickness and Clark level, evaluation with a whole-body computed tomography scan was negative for metastatic disease. The long duration of the adalimumab therapy and the patient's lack of a predisposition to skin cancer suggest an association between anti-TNF-α drugs and melanocytic proliferation. The authors also review the literature on the potential association between anti-TNF regimens and the occurrence of malignancies such as melanocytic proliferations. There is a substantial hypothetical link between anti-TNF-α regimens such as adalimumab and the potential for cancers

  13. Exploiting in situ antigen generation and immune modulation to enhance chemotherapy response in advanced melanoma: A combination nanomedicine approach.

    Science.gov (United States)

    Lu, Yao; Wang, Yuhua; Miao, Lei; Haynes, Matthew; Xiang, Guangya; Huang, Leaf

    2016-08-28

    Therapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment in order to facilitate and enhance CTL activity, and induction of memory T-cells to prolong tumor rejection. While traditional as well as modern vaccines rely upon delivery of both antigen and adjuvant, a variety of clinically relevant cancers lack ideal immunogenic antigens. Building upon recent efforts, we instead chose to exploit chemotherapy-induced apoptosis to allow for in situ antigen generation in a combination, nanomedicine-based approach. Specifically, lipid-coated cisplatin nanoparticles (LPC) and CpG-encapsulated liposomes (CpG-Lipo) were prepared for the temporally-controlled and multifaceted treatment of an advanced in vivo model of melanoma. Such combination therapy established strong synergistic effects, both in apoptotic extent and subsequent abrogation of tumor growth, which were due largely to both an enhanced cytotoxic T-cell recruitment and a reduction of immune-suppressive mediators in the microenvironments of both spleens and tumor. These results underlie a prolonged host lifespan in the combination approach (45 days) as compared with control (25 days, p < 0.02), providing promise toward a personalized approach to nanomedicine by establishing effect synergy in host-specific immunotherapy following chemotherapy. PMID:27235608

  14. A cancer vaccine induces expansion of NY-ESO-1-specific regulatory T cells in patients with advanced melanoma.

    Science.gov (United States)

    Ebert, Lisa M; MacRaild, Sarah E; Zanker, Damien; Davis, Ian D; Cebon, Jonathan; Chen, Weisan

    2012-01-01

    Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.

  15. The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-α-induced apoptosis

    International Nuclear Information System (INIS)

    Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-α in combination with IFN-γ in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-α-resistant B16/F10.9 melanoma cells. A low dose of TNF-α 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-α-resistant F10.9 melanoma cells to TNF-α-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-α 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-α 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-α-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-α-resistant melanoma cells to TNF-α-induced apoptosis, may provide a new target for immunotherapy

  16. Oral Xeloda plus bi-platinu two-way combined chemotherapy in treatment of advanced gastrointestinal malignancies

    OpenAIRE

    Fan, Li; LIU, WEN-CHAO; ZHANG, YAN-JUN; Ren, Jun; Pan, Bo-Rong; Liu, Du-Hu; Chen, Yan; Yu, Zhao-Cai

    2005-01-01

    AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy.

  17. Factors associated with the designation of a health care proxy and writing advance directives for patients suffering from haematological malignancies

    OpenAIRE

    Trarieux-Signol, Sophie; Moreau, Stéphane; Gourin, Marie-Pierre; Penot, Amélie; Edoux de Lafont, Geoffroy; Preux, Pierre-Marie; Bordessoule, Dominique

    2014-01-01

    Background During the last few decades, patients’ rights have been reinforced in many countries by acts of law. Measures now include health care proxies to uphold the doctor-patient relationship and advance directives for end-of-life patients. These could be relevant tools as early as the initial diagnosis of haematological malignancies because of the uncertain disease course. The aim of this research was to assess the factors associated with the designation of a proxy and writing advance dir...

  18. 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

    Directory of Open Access Journals (Sweden)

    Mohandas eC

    2016-04-01

    Full Text Available 3,5-dihydroxy-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 towards 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 towards 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 DETS-induced cytotoxicity in melanoma cells was confirmed by comparing the cytotoxicity

  19. Current Research and Development of Chemotherapeutic Agents for Melanoma

    Directory of Open Access Journals (Sweden)

    Kyaw Minn Hsan

    2010-04-01

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

  20. Drivers of melanoma susceptibility

    OpenAIRE

    Robles Espinoza, Carla Daniela

    2015-01-01

    Cutaneous melanoma is a cancer of melanocytes, the pigment-producing cells in our skin. It is one of the most aggressive human malignancies, constituting only about 2% of all dermatological cancers but being responsible for over 75% of all deaths from skin cancer. It has recently become a major public health problem, as it is now the fifth most common cancer in the United Kingdom after its incidence more than quadrupled in the last three decades. For these reasons, understanding the biologica...

  1. Biliary stenting in advanced malignancy: an analysis of predictive factors for survival

    Directory of Open Access Journals (Sweden)

    Afshar M

    2014-12-01

    Full Text Available Mehran Afshar,1 Koudeza Khanom,2 Yuk Ting Ma,1,3 Pankaj Punia1 1Cancer Centre, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Trust, Birmingham, UK; 2St James Institute of Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, UK; 3School of Cancer Sciences, University of Birmingham, Birmingham, UK Purpose: Stenting of the biliary tree is a common palliative procedure to relieve obstructive jaundice in advanced malignancy. Although effective in relief of biliary obstruction and palliation of symptoms, little information is available on predictive factors for survival post-procedure. This retrospective study sought to assess factors influencing post-procedure survival in cancer patients after biliary stenting. Methods: Case notes of all patients from a regional academic cancer center, who underwent biliary stenting for obstructive jaundice related to malignancy during 2008 and 2009 were reviewed. We collected epidemiological, biochemical, treatment and survival data on all patients. We used Kaplan–Meyer analysis to assess survival from day of first biliary stenting (adjusted for cancer types, and the Cox proportional hazards model for univariate and multivariate analysis. Results: One hundred and ninety-four patients were included in the final analysis. Most cases were related to pancreatic cancer or cholangiocarcinoma (89 and 46 cases respectively. Median survival for all patients was 143 days. In multivariate analysis serum albumin ≥34 g/L at the time of procedure (hazard ratio 0.573; 95% confidence interval 0.424–0.773, P<0.001 and chemotherapy post-stent (hazard ratio 0.636; 95% confidence interval 0.455–0.889, P=0.008 were two independent prognostic factors predicting a better survival post-stenting. The 30 day mortality post-procedure in the 194 patients was 12%. Conclusion: This study suggests that stenting of the biliary tree in cases of malignant obstruction allows durable palliation of symptoms even in

  2. Preparing clinical-grade myeloid dendritic cells by electroporation-mediated transfection of in vitro amplified tumor-derived mRNA and safety testing in stage IV malignant melanoma

    Directory of Open Access Journals (Sweden)

    Allred Jacob B

    2006-08-01

    Full Text Available Abstract Background Dendritic cells (DCs have been used as vaccines in clinical trials of immunotherapy of cancer and other diseases. Nonetheless, progress towards the use of DCs in the clinic has been slow due in part to the absence of standard methods for DC preparation and exposure to disease-associated antigens. Because different ex vivo exposure methods can affect DC phenotype and function differently, we studied whether electroporation-mediated transfection (electrotransfection of myeloid DCs with in vitro expanded RNA isolated from tumor tissue might be feasible as a standard physical method in the preparation of clinical-grade DC vaccines. Methods We prepared immature DCs (IDCs from CD14+ cells isolated from leukapheresis products and extracted total RNA from freshly resected melanoma tissue. We reversely transcribed the RNA while attaching a T7 promoter to the products that we subsequently amplified by PCR. We transcribed the amplified cDNA in vitro and introduced the expanded RNA into IDCs by electroporation followed by DC maturation and cryopreservation. Isolated and expanded mRNA was analyzed for the presence of melanoma-associated tumor antigens gp100, tyrosinase or MART1. To test product safety, we injected five million DCs subcutaneously at three-week intervals for up to four injections into six patients suffering from stage IV malignant melanoma. Results Three preparations contained all three transcripts, one isolate contained tyrosinase and gp100 and one contained none. Electrotransfection of DCs did not affect viability and phenotype of fresh mature DCs. However, post-thaw viability was lower (69 ± 12 percent in comparison to non-electroporated cells (82 ± 12 percent; p = 0.001. No patient exhibited grade 3 or 4 toxicity upon DC injections. Conclusion Standardized preparation of viable clinical-grade DCs transfected with tumor-derived and in vitro amplified mRNA is feasible and their administration is safe.

  3. Identification of donor melanoma in a renal transplant recipient.

    Science.gov (United States)

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

    1992-12-01

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

  4. Segmental neurofibromatosis and malignancy.

    Science.gov (United States)

    Dang, Julie D; Cohen, Philip R

    2010-01-01

    Segmental neurofibromatosis is an uncommon variant of neurofibromatosis type I characterized by neurofibromas and/or café-au-lait macules localized to one sector of the body. Although patients with neurofibromatosis type I have an associated increased risk of certain malignancies, malignancy has only occasionally been reported in patients with segmental neurofibromatosis. The published reports of patients with segmental neurofibromatosis who developed malignancy were reviewed and the characteristics of these patients and their cancers were summarized. Ten individuals (6 women and 4 men) with segmental neurofibromatosis and malignancy have been reported. The malignancies include malignant peripheral nerve sheath tumor (3), malignant melanoma (2), breast cancer (1), colon cancer (1), gastric cancer (1), lung cancer (1), and Hodgkin lymphoma (1). The most common malignancies in patients with segmental neurofibromatosis are derived from neural crest cells: malignant peripheral nerve sheath tumor and malignant melanoma. The incidence of malignancy in patients with segmental neurofibromatosis may approach that of patients with neurofibromatosis type I. PMID:21137621

  5. Establishment of lung metastasis model of human primary malignant melanoma in the small intestine in nude mice%人原发性小肠恶性黑色素瘤裸鼠肺转移模型的建立

    Institute of Scientific and Technical Information of China (English)

    张宁; 脱帅; 杨波; 刘秋珍

    2009-01-01

    目的 建立原发性小肠恶性黑色素瘤肺转移动物模型.方法 采用人原发性小肠恶性黑色素瘤肺转移瘤的新鲜瘤组织块植入裸鼠小肠黏膜层内,当裸鼠体内形成肺转移瘤后重复筛选4次,再将肺转移瘤植入另一只裸鼠小肠黏膜行鼠问连续传代.观察原位移植成瘤率和转移率,进行形态学、染色体核型和流式细胞仪分析.结果 建成的人原发性小肠恶性黑色素瘤裸鼠肺转移模型命名为HSIM-0601,瘤细胞胞质内可见大量黑色素颗粒及黑色素复合体,S-100、HMB-45呈阳性表达.染色体数57~59条;流式细胞DNA指数值1.49,均为异倍体.HSIM-0601已传至26代,共移植裸鼠173只,成瘤率和液氮冻存复苏成活率均为100%.肺转移率为100%(173/173),淋巴结转移率为61.3%(106/173).结论 首次成功地建立了人原发性小肠恶性黑色素瘤裸鼠原位移植肺转移模型HSIM-0601.完整地模拟了人小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤肺转移机制和抗转移治疗提供了理想的动物模型.%Objective To provide an ideal animal model for exploring the pathogenesis and experimental treatment of malignant melanoma in the small intestine.Methods Fresh tissue of lung metastatic lesions from patients with malignant melanoma of the smallintestine were transplanted into mucosa of the small intestine in nude mice.After 4 times of screening.the tissue of the lung metastatic lesions from the nude mice were transplanted into the small intestine of additionat nude mice.Tumorgenecity and metastasis of transplanted tumors were observed,and were analyzed by morphology,karyotype and flow cytometry.Results A lung metastatic model of human primary malignant melanoma of the small intestine in nude mice was successfully constructed and named HSIM-0601.Massive melanin granules and melanin complex were seen in cytoplasm of tumor cells.Immunohistochemical straining of S-100 and

  6. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

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

  7. Retrospective analysis of role of interstitial brachytherapy using template (MUPIT in locally advanced gynecological malignancies

    Directory of Open Access Journals (Sweden)

    Nandwani Pooja

    2007-01-01

    Full Text Available Aim : The aim of this retrospective study was to assess treatment outcomes for patients with locally advanced gynecological malignancies being treated with interstitial brachytherapy using Martinez universal perineal interstitial template (MUPIT and to study the acute and late sequelae and survival after treatment by this technique. Materials and Methods : Ninety seven patients untreated with histopathological confirmation of carcinoma of cervix (37 vault (40 and vagina (20 were treated by combination of external beam RT (EBRT using megavoltage irradiation to pelvis to dose of 4000-5000 cGy followed by interstitial brachytherapy using MUPIT between September 2001 to March 2005. Median age was 46 years. Only those patients who were found unsuitable for conventional brachytherapy or in whom intracavitatory radiotherapy was found to be unlikely to encompass a proper dose distribution were treated by interstitial template brachytherapy using MUPIT application and were enrolled in this study. The dose of MUPIT was 1600-2400 cGy in 4-6# with 400 cGy /# and two fractions a day with minimum gap of six hours in between two fractions on micro-HDR. Criteria for inclusion of patients were as follows: Hb minimum 10 gm/dl, performance status - 70% or more (Karnofsy scale, histopathological confirmation FIGO stage IIB-IIIB (excluding frozen pelvis. Results : Among the 97 patients studied, 12 patients lost to follow-up and hence they were excluded from the study. Follow-up of rest of the patients was then done up to September 2006. The duration of follow-up was in the range of 20-60 months. Parameters studied were local control rate, complication rate, mortality rate and number of patients developing systemic metastasis. Local control was achieved in 56/85 (64.7% and complication rate was 15/85 (17.6%. Local control was better for nonbulky tumors compared bulky tumors irrespective of stage of disease. Local control was better in patients with good regression of

  8. DOES URINARY DIVERSION IMPROVE THE QUALITY OF LIFE IN OBSTRUCTIVE UROPATHY SECONDARY TO ADVANCED PELVIC MALIGNANCY?

    Directory of Open Access Journals (Sweden)

    Shivashankarappa

    2016-02-01

    Full Text Available INTRODUCTION The incidence of patients presenting with advanced pelvic malignancy with obstructive uropathy is high in our country. Relentless progress of the malignancy will cause deterioration of renal function, aggravation of pain, infection, deterioration of Quality of Life (QOL, uremia and death. Decreased renal function is considered as a contraindication for palliative chemo and radiotherapy. However urinary diversion in these patients will lead to improvement in renal function and may help in administration of palliative therapy and thus, improve the quality of life of these patients. MATERIALS AND METHODS The present study includes the obstructive uropathy patients secondary to pelvic malignancy referred to our institution for urinary diversion between Jan 2010 to Dec 2014. Total 40 patients were included, of which, 25 patients underwent PCN, 9 patients retrograde DJ stenting, 4 patients refused the treatment, 2 patients were not fit for any intervention due to coagulopathy & comorbid conditions. Of 34 treated patients, 30 were female patients and 4 were male patients. All the patients were explained about the procedure and proper consent taken. Laboratory investigations like CBC, coagulation profile, LFT, routine urine analysis, urine C&S and serum electrolytes were carried out. Haemodialysis was done for 10 patients whose serum creatinine was >6mg% & potassium >6meq. USG guided PCN insertion was done in 8 patients, and in those who failed in this procedure, fluoroscopic C-ARM guided PCN insertion done in 17 patients. Post operatively RFT and serum electrolytes were assessed on 3, 7, 15, & 30th day. PCN catheter was changed once in 3 months. RESULTS 8 patients succeeded in USG guided PCN insertion and 17 patients who failed USG PCN insertion, was done under C–Arm guidance. 3 patients received blood transfusion. No deaths were seen during or post procedure in the hospital. Renal functions improved and normalised in most of the

  9. Autophagy- An emerging target for melanoma therapy [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Abibatou Ndoye

    2016-07-01

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

  10. Genetics of Melanoma

    Directory of Open Access Journals (Sweden)

    Janet eWangari-Talbot

    2013-01-01

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

  11. Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    Michiya Kobayashi; Junichi Sakamoto; Tsutomu Namikawa; Ken Okamoto; Takehiro Okabayashi; Kengo Ichikawa; Keijiro Araki

    2006-01-01

    AIM: To examine the paclitaxel concentrations in plasma and ascites after its intravenous administration in patients with ascites due to peritonitis carcinomatosa resulting from advanced gastric cancer.METHODS: Two patients with ascites due to peritonitis carcinomatosa resulting from gastric cancer were included in this study. The paclitaxel concentrations in plasma and ascites were investigated for 72 h in case 1 and 168 h in case 2 after intravenous administration.RESULTS: The paclitaxel concentration in plasma peaked immediately after administration, followed by rapid decrease below the threshold value of 0.1 μmol (85 ng/mL) within 24 h. In contrast, the paclitaxel concentration in ascites increased gradually for 24 h after administration to a level consistent with the level found in plasma. After 24 h the level of paclitaxel in ascites and plasma became similar, with the optimal level being maintained up to 72 h following administration.CONCLUSION: The concentration of paclitaxel in ascites is maintained within the optimal level for the treatment of cancer cells for up to 72 h after intravenous administration. Paclitaxel is a promising drug for the treatment of malignant ascites of gastric cancer.

  12. Results of chest wall resection for recurrent or locally advanced breast malignancies.

    Science.gov (United States)

    Veronesi, Giulia; Scanagatta, Paolo; Goldhirsch, Aron; Rietjens, Mario; Colleoni, Marco; Pelosi, Giuseppe; Spaggiari, Lorenzo

    2007-06-01

    Between 1998 and 2003 we observed 15 women who underwent full thickness chest wall resection (FTCWR) followed by plastic reconstruction for locally recurrent or primary breast cancer. Preoperative symptoms were: pain (5 patients), malodorous ulceration (3 patients), presence of tumour mass (4 patients) and thoracic deformity (2 patients). One patient was asymptomatic. Surgery was partial sternectomy with rib resection in 9 patients, rib resection alone in 5, and total sternectomy in one. No perioperative mortality or major morbidity occurred; minor complications occurred in 3 patients (20%). Five of the six surviving patients reported a positive overall outcome in a telephonic interview. Median overall and disease-free survival were 23.4 and 17.5 months, respectively. In conclusion, FTCWR is a safe procedure with low morbidity and mortality that can provide good symptoms palliation in patients with locally advanced breast malignancies, so it should be considered more often by interdisciplinary care providers in those patients who fail to respond to classic multimodality treatment.

  13. Perineural extension of facial melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kalina, Peter [Mayo Clinic, Department of Radiology, Rochester, Minnesota (United States); Bevilacqua, Paula

    2005-05-01

    A 64-year-old man presented with a pigmented cutaneous lesion on the right side of his face along with right facial numbness. Histological examination revealed malignant melanoma. Magnetic resonance imaging (MRI) revealed perineural extension along the entire course of the maxillary division of the right trigeminal nerve. This is a rare but important manifestation of the spread of head and neck malignancy. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Cindy L. Lamerson

    2012-01-01

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

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

    Science.gov (United States)

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

    2010-07-01

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

  16. Tumor Heterogeneity in Uveal Melanomas

    NARCIS (Netherlands)

    H.W. Mensink (Hanneke)

    2010-01-01

    textabstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults with an incidence of 7-10/ million and has a predilection for hematogenous dissemination to the liver. Despite improvements in diagnosis and treatment of this intraocular tumor, there has not been a change in

  17. Chemotherapy for Melanoma.

    Science.gov (United States)

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

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

  18. Engineering nanomedicines for improved melanoma therapy: progress and promises.

    Science.gov (United States)

    Bei, Di; Meng, Jianing; Youan, Bi-Botti C

    2010-11-01

    Once metastatic, melanoma remains one of the most aggressive and morbid malignancies. Moreover, in past decades, the overall survival for advanced unresectable melanoma exhibited a constancy of poor prognosis. Low response rates and serious adverse effects have been characteristic of standard therapy based on a combination of chemotherapeutic agents or immunotherapy with IL-2. For example, the chemotherapy including dacarbazine, carmustin, cisplatin and tamoxifen is known as 'Dartmouth regimen' while the CVD regimen comprises carmustine, vinblastine and dacarbazine. Thus, there is an urgent and critical need to reformulate these bioactive agents using nanoscience and nanotechnology as alternative strategies. This article overviews current design and evaluation of nanomedicine undertaken to address this unmet medical need. The nanomedicines studied include polymeric nanoparticles, liposomes, polymersomes, dendrimers, cubosomes, niosomes and nanodiamonds. In this preclinical article, nanotechnology provides hope for effective treatment of this aggressive and largely treatment-resistant disease. PMID:21128721

  19. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Carpano, Marina; Perona, Marina; Rodriguez, Carla [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A. [Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín (Argentina); Brandizzi, Daniel; Cabrini, Romulo [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); School of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Pisarev, Mario [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires (Argentina); Juvenal, Guillermo Juan [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina)

    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. Experimental Studies of Boronophenylalanine (10BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    International Nuclear Information System (INIS)

    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 (10BPA) 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 4 106 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 10B 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 (R2 = 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 (R2 = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual

  1. Melanoma biomarkers: Vox clamantis in deserto (Review).

    Science.gov (United States)

    Al-Shaer, Mays; Gollapudi, Divya; Papageorgio, Chris

    2010-05-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically. PMID:22966315

  2. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037)

    DEFF Research Database (Denmark)

    Weber, Jeffrey S; D'Angelo, Sandra P; Minor, David;

    2015-01-01

    BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemothe......BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice...

  3. Cutaneous melanoma in solid organ transplant patients.

    Science.gov (United States)

    Russo, I; Piaserico, S; Belloni-Fortina, A; Alaibac, M

    2014-08-01

    Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma. PMID:25068225

  4. Short-term clinical outcome of carbon ion radiotherapy for cutaneous malignant melanoma%碳离子束治疗皮肤恶性黑色素瘤的近期疗效

    Institute of Scientific and Technical Information of China (English)

    蔡宏懿; 肖国青; 张晓文; 王小虎; 高力英; 张红; 冉俊涛; 张秋宁; 李强; 刘志强; 赵林

    2010-01-01

    Objective To evaluate the toxicity and efficacy of carbon ion radiotherapy for cutaneous malignant melanoma. Methods Form December 2006 to May 2009, 13 patients with superficial malignant melanoma were treated with carbon ion radiotherapy in the Institute of Modern Physics, Chinese Academy of Sciences. The total dose was 60 -66 GyE in 6 -12 fractions within 6 -12 days. The disease was Stage Ⅱ_a in 2, Ⅱ_b in 3, Ⅱ_c in 5, and Ⅲ_c in 3 patients. The toxicities were assessed according to the Radiation Therapy Oncology Group (RTOG) criteria, and the efficacy was evaluated with WHO criteria. Results The median follow-up time was 13.5 months (range, 1 -25 months) and the follow-up rate was 100%. Of the 13 patients, 10(77%) achieved complete remission (CR), and 3(23%) partial remission (PR). The overall response rate (RR) was 100%, and the median survival time was 21.3 months (95% CI, 18. 1 -24.5 months). The grade 0, 1,2 and 3 skin reaction occurred in 3, 6, 2 and 2 patients, respectively. The hematologic toxicities were mild. Conclusions Carbon ion radiotherapy is a safe and effective treatment for cutaneous malignant melanoma.%目的 评价碳离子(~(12)C~(6+))束对皮肤恶性黑色素瘤放射治疗的近期疗效和副反应.方法 13例皮肤恶性黑色素瘤患者分6批接受~(12)C~(6+)束放射治疗,其中Ⅱ_a期2例,Ⅱ_b期3例,Ⅱ_c期5例,Ⅲ_c期3例.照射总剂量60~66 GyE分6~12 d,单次剂量2.2~4.4 GyE,1次/d,连续治疗.采用RTOG标准和WHO近期疗效标准分别评价副反应和近期疗效.结果 中位随访时间为13.5个月(1~25个月),随访率为100%.13例患者中完全缓解10例,部分缓解3例,有效率为100%,中位生存时间为21.3个月(95%可信区间为18.1~24.5个月).皮肤反应0级3例,1级6例,2级2例,3级2例.血液系统副反应治疗前后无明显改变.结论 ~(12)C~(6+)束治疗皮肤恶性黑色素瘤近期疗效好,且并发症轻.

  5. A Phase II Study of Fotemustine Plus Dacarbazine with Dendritic Cell Vaccines as First-Line Therapy for Chinese Patients with Advanced Acral Lentiginous Melanoma

    Institute of Scientific and Technical Information of China (English)

    Lu Si; Zhi-hong Chi; Xiang-qing Yuan; Chuan-liang Cui; Xi-nan Sheng; Jun Guo

    2009-01-01

    Objective: To investigate fotemustine plus dacarbazine (DTIC) with dendritic cell (DC) vaccines on patients with advanced acral lentiginous melanoma (ALM). Fotemustine is a cytotoxic alkylating agent with a remarkable antitumor activity as single agent but also in association with (DTIC). DC is the strongest antigen presenting cell which could induce durable clinical responses. Methods: This was a single-center study. Between July 2003 and June 2006, twenty-eight chemotherapy-naive patients of advanced ALM received fotemustine 100 mg/m2, d1, 12, DTIC 400 mg/d d2(6, DC vaccines subcutaneously d7, 9, 13 repeated every 28 days. Ten HLA-A02+24+ patients received vaccines pulsed with melanoma antigen derived peptides, melanoma antigen recognized by T-cells 1 (Mart-1) and S-100. Eighteen patients received DC loaded with allogeneic melanoma lysate. The primary end-point was progression free survival (PFS). Secondary end-points were overall survival (OS), overall response rate (ORR) and toxicity. Tumor assessment was performed every 8 weeks and evaluated according to response evaluation criteria in solid tumors (RECIST). Results: The 15 men and 13 women had a median age of 51 years. 16 patients had stage M1c disease and 11/16 had liver metastasis. Patients received an average of 3.82(1.25 cycles. Follow-up for the 18 surviving patients ranged from 7(41 months with a median of 12 months. Median PFS was 8.5 months (95% CI: 7.86(15.21) with 12 patients remaining progression free. Only 10 patients died. Median OS was 12 months (95% CI: 10.33(18.24). ORR (CR+PR) was 35.7% including 3 complete response (CR) and 7 partial response (PR). Six patients had disease stable. A total of 19 Grade III/IV toxicities were observed including thrombocytopenia (n=8), neutropenia (n=5), fatigue (n=6) and hypersensitivity reaction (n=1). One patient died of Grade IV thrombocytopenia. Conclusion: Fotemustine and dacarbazine plus DC vaccines are safe and tolerable to Chinese ALM patients. The

  6. Present status and recent advances in living donor liver transplantation for malignant hepatic tumors

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Qin; Yasutsugu Takada; Shinji Uemoto; Koichi Tanaka

    2008-01-01

    BACKGROUND:Living donor liver transplantation (LDLT) has been increasingly used to treat hepatic tumors worldwide in recent years, and is currently the most effective alternative to deceased donor liver transplantation to overcome the problem of organ shortage. LDLT has played an enormous role in treating early malignant hepatic tumors. But the indication of LDLT for malignant hepatic tumors is based on indeifnite criteria. This review summarizes the recent studies in LDLT for treating malignant hepatic tumors. DATA SOURCES:A literature research of the PubMed database was conducted and research articles were reviewed. RESULTS:The current data on LDLT for malignant hepatic tumors, combined with our hospital experience, indicated that if a patient with hepatocellular carcinoma (HCC) who meets with the conventional Milan criteria cannot undergo tumor resection because of poorly preserved liver function, and a cadaveric graft is dififcult to obtain within six months, LDLT may be selected. In a patient with recurrence of HCC after conventional therapies, feasibility, optimal timing, and efifcacy of LDLT as a second-line treatment should be determined. CONCLUSIONS:Tumor recurrence is related to the biological behavior and staging of the tumor. New immunosuppressors which have anti-tumor effects and inhibit the immune system need to be developed. The indications of LDLT for hepatic malignant tumors should be selected meticulously.

  7. Stereotactic Ablative Radiosurgery for Locally-Advanced or Recurrent Skull Base Malignancies with Prior External Beam Radiation Therapy

    Directory of Open Access Journals (Sweden)

    Karen Mann Xu

    2015-03-01

    Full Text Available Purpose: Stereotactic ablative radiotherapy (SABR is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival and toxicities in SABR for the treatment of malignant skull base tumors. Methods and Materials: A total of 31 patients and 40 locally-advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013 were retrospectively reviewed. The local control rate (LC, progression-free survival rate (PFS, overall survival rate (OS and toxicities were reported.Results: The median follow-up time of all patients was 11.4 months (range: 0.6-67.2 months. The median tumor volume was 27 cm3 (range: 2.4-205 cm3. All patients received prior EBRT with a median radiation dose of 64 Gy (range: 24-75.6 Gy delivered in 12 to 42 fractions. 20 patients had surgeries prior to SABR. 19 patients received chemotherapy. Specifically, 8 patients received concurrent cetuximab (ErbituxTM with SABR. The median time-to-progression (TTP was 3.3 months (range: 0-16.9 months. For the 29 patients (93.5% who died, the median time from the end of first SABR to death was 10.3 months (range: 0.5-41.4 months. The estimated 1-year overall survival (OS rate was 35%. The estimated 2-year OS rate was 12%. Treatment was well-tolerated without grade 4 or 5 treatment-related toxicities.Conclusions: SABR has been shown to achieve low toxicities in locally-advanced or recurrent, previously irradiated head and neck malignancies invading the skull base.

  8. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab.

    Science.gov (United States)

    Yuan, Jianda; Adamow, Matthew; Ginsberg, Brian A; Rasalan, Teresa S; Ritter, Erika; Gallardo, Humilidad F; Xu, Yinyan; Pogoriler, Evelina; Terzulli, Stephanie L; Kuk, Deborah; Panageas, Katherine S; Ritter, Gerd; Sznol, Mario; Halaban, Ruth; Jungbluth, Achim A; Allison, James P; Old, Lloyd J; Wolchok, Jedd D; Gnjatic, Sacha

    2011-10-01

    Ipilimumab, a monoclonal antibody against cytotoxic T lymphocyte antigen 4 (CTLA-4), has been shown to improve survival in patients with advanced metastatic melanoma. It also enhances immunity to NY-ESO-1, a cancer/testis antigen expressed in a subset of patients with melanoma. To characterize the association between immune response and clinical outcome, we first analyzed NY-ESO-1 serum antibody by ELISA in 144 ipilimumab-treated patients with melanoma and found 22 of 140 (16%) seropositive at baseline and 31 of 144 (22%) seropositive following treatment. These NY-ESO-1-seropositive patients had a greater likelihood of experiencing clinical benefit 24 wk after ipilimumab treatment than NY-ESO-1-seronegative patients (P = 0.02, relative risk = 1.8, two-tailed Fisher test). To understand why some patients with NY-ESO-1 antibody failed to experience clinical benefit, we analyzed NY-ESO-1-specific CD4(+) and CD8(+) T-cell responses by intracellular multicytokine staining in 20 NY-ESO-1-seropositive patients and found a surprising dissociation between NY-ESO-1 antibody and CD8 responses in some patients. NY-ESO-1-seropositive patients with associated CD8(+) T cells experienced more frequent clinical benefit (10 of 13; 77%) than those with undetectable CD8(+) T-cell response (one of seven; 14%; P = 0.02; relative risk = 5.4, two-tailed Fisher test), as well as a significant survival advantage (P = 0.01; hazard ratio = 0.2, time-dependent Cox model). Together, our data suggest that integrated NY-ESO-1 immune responses may have predictive value for ipilimumab treatment and argue for prospective studies in patients with established NY-ESO-1 immunity. The current findings provide a strong rationale for the clinical use of modulators of immunosuppression with concurrent approaches to favor tumor antigen-specific immune responses, such as vaccines or adoptive transfer, in patients with cancer.

  9. Molecular Targeted Approaches for Advanced BRAF V600, N-RAS, c-KIT, and GNAQ Melanomas

    Directory of Open Access Journals (Sweden)

    Ponti Giovanni

    2014-01-01

    Full Text Available The introduction of a newly developed target therapy for metastatic melanomas poses the challenge to have a good molecular stratification of those patients who may benefit from this therapeutic option. Practically, BRAF mutation status (V600E is commonly screened although other non-V600E mutations (i.e., K-R-M-D could be found in some patients who respond to therapy equally to the patients harboring V600E mutations. Furthermore, other mutations, namely, N-RAS, KIT, and GNAQ, should be sequenced according to distinct melanoma specific subtypes and clinical aspects. In our report, a practical flow chart is described along with our experience in this field.

  10. A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

    Science.gov (United States)

    2016-09-19

    Advanced Solid Tumors With Alterations of FGFR1, 2 and/or 3;; Squamous Lung Cancer With FGFR1 Amplification;; Bladder Cancer With FGFR3 Mutation or Fusion; Advanced Solid Tumors With FGFR1 Amplication,; Advanced Solid Tumors With FGFR2 Amplication,; Advanced Solid Tumors With FGFR3 Mutation

  11. Comparison of testing methods for the detection of BRAF V600E mutations in malignant melanoma: pre-approval validation study of the companion diagnostic test for vemurafenib.

    Directory of Open Access Journals (Sweden)

    Fernando Lopez-Rios

    Full Text Available BACKGROUND: The cobas 4800 BRAF V600 Mutation Test is a CE-marked and FDA-approved in vitro diagnostic assay used to select patients with metastatic melanoma for treatment with the selective BRAF inhibitor vemurafenib. We describe the pre-approval validation of this test in two external laboratories. METHODS: Melanoma specimens were tested for BRAF V600 mutations at two laboratories with the: cobas BRAF Mutation Test; ABI BRAF test; and bidirectional direct sequencing. Positive (PPA and negative (NPA percent agreements were determined between the cobas test and the other assays. Specimens with discordant results were tested with massively parallel pyrosequencing (454. DNA blends with 5% mutant alleles were tested to assess detection rates. RESULTS: Invalid results were observed in 8/116 specimens (6·9% with Sanger, 10/116 (8·6% with ABI BRAF, and 0/232 (0% with the cobas BRAF test. PPA was 97·7% for V600E mutation for the cobas BRAF test and Sanger, and NPA was 95·3%. For the cobas BRAF test and ABI BRAF, PPA was 71·9% and NPA 83·7%. For 16 cobas BRAF test-negative/ABI BRAF-positive specimens, 454 sequencing detected no codon 600 mutations in 12 and variant codon 600 mutations in four. For eight cobas BRAF test-positive/ABI BRAF-negative specimens, four were V600E and four V600K by 454 sequencing. Detection rates for 5% mutation blends were 100% for the cobas BRAF test, 33% for Sanger, and 21% for the ABI BRAF. Reproducibility of the cobas BRAF test was 111/116 (96% between the two sites. CONCLUSIONS: It is feasible to evaluate potential companion diagnostic tests in external laboratories simultaneously to the pivotal clinical trial validation. The health authority approved assay had substantially better performance characteristics than the two other methods. The overall success of the cobas BRAF test is a proof of concept for future biomarker development.

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

    Science.gov (United States)

    2016-05-05

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

  13. Primary Malignant Amelanotic Melanoma in the Female Genital Tract:A Report of Six Cases and a Review of the Literature

    Institute of Scientific and Technical Information of China (English)

    Jusheng An; Lingying Wu; Bin Li; Haizhen Lu; Ning Li; Shaokang Ma

    2008-01-01

    OBJECTIVE To analyze the clinical characteristics,pathologic diagnosis,treatment and prognosis of amelanotic melanoma in the female genital tract (AMFGT).METHODS The medical records of 6 patients with AMFGT between 1991 and 2006 in our hospital were reviewed.RESULTS Of these cases,4 were preliminarily misdiagnosed as chorioepithelioma,sarcoma,adenocarcinoma or lymphoma.Two patients were determined to have AMFGT preoperatively after positive immunohistochemical staining for both S-100 protein and HMB-45.Specimens removed from all 6 cases were tested for immunohistochemical staining,as well as H & E histochemical stains.S-100 and vimentin were both positive in all patients,and HMB-45 was positive in 3 out of 5 patients.Four patients recurred (at 6,6,12 and 19 months) after primary treatments.Three patients died (at 13,18 and 19 months) after the initial diagnosis.CONCLUSION Because of an absence of pigmentation AMFGT is extremely difficult to diagnose.Combined immunohistochemical staining,such as the S-100 protein,HMB-45 and vimentin etc,is important in the evaluation of AMFGT.Correct diagnosis plays a crucial role in the treatment of this disease.

  14. A Case of Melanoma Associated Leukoderma

    Directory of Open Access Journals (Sweden)

    Özer Arıcan

    2010-06-01

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

  15. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  16. Novel anti-melanoma treatment:focus on immunotherapy

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  17. Addition of an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy improves survival in advanced malignancies.

    Science.gov (United States)

    Lasalvia-Prisco, Eduardo; Goldschmidt, Pablo; Galmarini, Felipe; Cucchi, Silvia; Vázquez, Jesús; Aghazarian, Martha; Lasalvia-Galante, Eduardo; Golomar, Wilson; Gordon, William

    2012-12-01

    Studies have shown that cancer requires two conditions for tumor progression: cancer cell proliferation and an environment permissive to and conditioned by malignancy. Chemotherapy aims to control the number and proliferation of cancer cells, but it does not effectively control the two best-known conditions of the tumor-permissive environment: neoangiogenesis and tolerogenic immunity. Many malignant diseases exhibit poor outcomes after treatment with chemotherapy. Therefore, we investigated the potential benefits of adding an induction regimen of antiangiogenesis and antitumor immunity to chemotherapy in poor outcome disease. In a prospective, randomized trial, we included patients with advanced, unresectable pancreatic adenocarcinomas, non-small cell lung cancer, or prostate cancer. Two groups of each primary condition were compared: group 1 (G1), n = 30, was treated with the standard chemotherapy and used as a control, and group 2 (G2), n = 30, was treated with chemotherapy plus an induction regimen of antiangiogenesis and antitumor immunity. This induction regimen included a low dose of metronomic cyclophosphamide, a high dose of Cox-2 inhibitor, granulocyte colony-stimulating factor, a sulfhydryl (SH) donor, and a hemoderivative that contained autologous tumor antigens released from patient tumors into the blood. After treatment, the G2 group demonstrated significantly longer survival, lower blood level of neoangiogenesis and immune-tolerance mediators, and higher blood levels of antiangiogenesis and antitumor immunity mediators compared with the G1 group. Toxicity and quality of life were not significantly different between the groups. In conclusion, in several advanced malignancies of different primary localizations, an increase in survival was observed by adding an induction regimen of antiangiogenesis and antitumor immunity to standard chemotherapy.

  18. Feasibility of combined operation and perioperative intensity-modulated brachytherapy of advanced/recurrent malignancies involving the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Strege, R.J.; Eichmann, T.; Mehdorn, H.M. [University Hospital Schleswig-Holstein, Kiel (Germany). Dept. of Neurosurgery; Kovacs, G.; Niehoff, P. [University Hospital Schleswig-Holstein, Kiel (Germany). Interdisciplinary Brachytherapy Center; Maune, S. [University Hospital Schleswig-Holstein, Kiel (Germany). Dept. of Otolaryngology; Holland, D. [University Hospital Schleswig-Holstein, Kiel (Germany). Dept. of Ophthalmology

    2005-02-01

    Purpose: To assess the technical feasibility and toxicity of combined operation and perioperative intensity-modulated fractionated interstitial brachytherapy (IMBT) in advanced-stage malignancies involving the skull base with the goal of preserving the patients' senses of sight. Patients and Methods: This series consisted of 18 consecutive cases: ten patients with paranasal sinus carcinomas, five with sarcomas, two with primitive neuroectodermal tumors (PNETs), and one with parotid gland carcinoma. After, in most cases, subtotal surgical resection (R1-R2: carried out so that the patients' senses of sight were preserved), two to twelve (mean five) afterloading plastic tubes were placed into the tumor bed. IMBT was performed with an iridium-192 stepping source in pulsed-dose-rate/high-dose-rate (PDR/HDR) afterloading technique. The total IMBT dose, ranging from 10 to 30 Gy, was administered in a fractionated manner (3-5 Gy/day, 5 days/week). Results: Perioperative fractionated IMBT was performed in 15 out of 18 patients and was well tolerated. Complications that partially prevented or delayed IMBT in some cases included cerebrospinal fluid leakage (twice), meningitis (twice), frontal brain syndrome (twice), afterloading tube displacement (twice), seizure (once), and general morbidity (once). No surgery- or radiation-induced injuries to the cranial nerves or eyes occurred. Median survival times were 33 months after diagnosis and 16 months after combined operation and IMBT. Conclusion: Perioperative fractionated IMBT after extensive but vision-preserving tumor resection seems to be a safe and well-tolerated treatment of advanced/recurrent malignancies involving the skull base. These preliminary state suggest that combined operation and perioperative fractionated IMBT is a palliative therapeutic option in the management of fatal malignancies involving the base of the skull, a strategy which leaves the patients' visual acuity intact. (orig.)

  19. Orbital amelanotic melanoma in xeroderma pigmentosum: A rare association

    OpenAIRE

    Rizvi Syed; Amitava Abadan; Mehdi Ghazala; Sharma Rajeev; Alam Mohammad

    2008-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder of DNA repair in which the body′s normal ability to repair damage caused by ultraviolet light is deficient. This leads to a 1000-fold increased risk of cutaneous and ocular neoplasms. Ocular neoplasms occurring in XP in order of frequency are squamous cell carcinoma, basal cell carcinoma and melanoma. Malignant melanomas occur at an early age in patients with XP. We report a case of XP with massive orbital melanoma i...

  20. Germline CDKN2A/ARF alterations in human melanoma

    OpenAIRE

    Hashemi, Jamileh

    2002-01-01

    Approximately 10% of cases of human cutaneous malignant melanoma (CMM) have been estimated to occur in individuals with a familial predisposition, frequently in association with dysplastic nevus syndrome (DNS). The genetics of familial melanoma is complex and heterogeneous. To date only two melanoma predisposing genes have been identified. The CDKN2A/ARF locus on human chromosome 9p21 encodes two distinct cell cycle regulatory proteins, p16 and p14ARF. Germline alterations i...