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Sample records for melanoma study group

  1. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  2. Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

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    Iván Márquez-Rodas

    Full Text Available Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain.An observational study conducted by the Spanish Group of Melanoma (GEM analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments.In all, 1047 patients were analyzed, and 69 (6.6% fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma. Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%. Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups.Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

  3. A prospective phase II study of adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma-Trans Tasman Radiation Oncology Group (TROG) Study 96.06

    International Nuclear Information System (INIS)

    Burmeister, Bryan H.; Mark Smithers, B.; Burmeister, Elizabeth; Baumann, Kathryn; Davis, Sidney; Krawitz, Hedley; Johnson, Carol; Spry, Nigel

    2006-01-01

    Background: The role of adjuvant postoperative therapy after resection of localised malignant melanoma involving regional lymph nodes remains controversial. There are no randomised trials that confirm that postoperative radiation conveys a benefit in terms of regional control or survival. Methods: Two hundred and thirty-four patients with melanoma involving lymph nodes were registered on a prospective study to evaluate the effect of postoperative radiation therapy. The regimen consisted of 48 Gy in 20 fractions to the nodal basin using recommended treatment guidelines for each of the major node sites. The primary endpoints were regional in-field relapse and late toxicity. Secondary endpoints were adjacent relapse, distant relapse, overall survival, progression-free survival and time to in-field progression. Results: Adjuvant radiation therapy was well tolerated by all of the patients. As the first site of relapse, regional in-field relapses occurred in 16/234 patients (6.8%). The overall survival was 36% at 5 years. The progression-free survival and regional control rates were 27% and 91%, respectively, at 5 years. Patients with more than 2 nodes involved had a significantly worse outcome in terms of distant relapse, overall and progression-free survival. Conclusion: We believe that adjuvant radiation therapy following nodal surgery could offer a possible benefit in terms of regional control. These results require confirmation in a randomised trial

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

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

    2017-02-01

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

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

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

    2018-05-01

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

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

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

    2017-04-01

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

  7. Validity of the histopathological criteria used for diagnosing dysplastic naevi. An interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group.

    Science.gov (United States)

    de Wit, P E; van't Hof-Grootenboer, B; Ruiter, D J; Bondi, R; Bröcker, E B; Cesarini, J P; Hastrup, N; Hou-Jensen, K; MacKie, R M; Scheffer, E

    1993-01-01

    Ten (dermato)pathologists studied 50 cutaneous melanocytic lesions including common naevocellular naevi, dysplastic naevi (DN), melanomas in situ and invasive primary melanomas, with emphasis on the histological criteria of DN. Using a standardised form, 20 defined histopathological features were scored (semi)quantitatively. Concordance of diagnosis, efficacy and reproducibility of features were investigated. DN were distinguished well from the other entities (mean Po 0.87). Agreement on the degree of atypia of DN was low. The reproducibility of the scoring was best for the following features: irregular nests, lymphohistiocytic infiltrate, marked junctional proliferation and large nuclei. The overall values of these features to discriminate between DN and non-DN were better than for the other features studied. Using the presence of at least three of the four features as a condition for the diagnosis of DN, values for sensitivity, specificity and positive and negative predictive values were 0.86, 0.91, 0.96 and 0.73, respectively. On the basis of the results these features seem best suited as histological criteria for the diagnosis of DN.

  8. Melanoma

    Science.gov (United States)

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

  9. Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1.

    Science.gov (United States)

    Ge, Rui; Liu, Lin; Dai, Wei; Zhang, Weigang; Yang, Yuqi; Wang, Huina; Shi, Qiong; Guo, Sen; Yi, Xiuli; Wang, Gang; Gao, Tianwen; Luan, Qi; Li, Chunying

    2016-06-01

    Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin-induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Treatment influencing down-staging in EORTC Melanoma Group sentinel node histological protocol compared with complete step-sectioning: a national multicentre study.

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    Riber-Hansen, Rikke; Hastrup, Nina; Clemmensen, Ole; Behrendt, Nille; Klausen, Siri; Ramsing, Mette; Spaun, Eva; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

    2012-02-01

    Metastasis size in melanoma sentinel lymph nodes (SLNs) is an emerging prognostic factor. Two European melanoma treatment trials include SLN metastasis diameters as inclusion criteria. Whilst diameter estimates are sensitive to the number of sections examined, the level of this bias is largely unknown. We performed a prospective multicentre study to compare the European Organisation for Research and Treatment of Cancer (EORTC) recommended protocol with a protocol of complete step-sectioning. One hundred and thirty-three consecutive SLNs from seven SLN centres were analysed by five central sections 50μm apart (EORTC Protocol) followed by complete 250μm step-sectioning. Overall, 29 patients (21.8%) were SLN-positive. The EORTC Protocol missed eight of these metastases (28%), one metastasis measuring less than 0.1mm in diameter, seven measuring between 0.1 and 1mm. Complete step-sectioning at 250μm intervals (Extensive Protocol) missed one metastasis (3%) that measured less than 0.1mm. Thirteen treatment courses (34%) performed if inclusion was based on the Combined Protocol would not be performed if assessed by the EORTC Protocol. Thus, 10 patients would be without completion lymph node dissection (EORTC MINITUB study), whilst three patients would not be eligible for anti-CTLA4 trial (EORTC protocol 18071). The corresponding number with the Extensive Protocol would be three; one patient for the MINITUB registration study and two patients for the anti-CTLA4 study. Examining SLNs by close central sectioning alone (EORTC Protocol) misses a substantial number of metastases and underestimates the maximum metastasis diameter, leading to important changes in patient eligibility for various treatment protocols. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Study of melanoma invasion by FTIR spectroscopy

    Science.gov (United States)

    Yang, Y.; Sulé-Suso, J.; Sockalingum, G. D.

    2008-02-01

    Compared to other forms of skin cancer, a malignant melanoma has a high risk of spreading to other parts of the body. Melanoma invasion is a complex process involving changes in cell-extracellular matrix (ECM) interaction and cell-cell interactions. To fully understand the factors which control the invasion process, a human skin model system was reconstructed. HBL (a commercially available cell line) melanoma cells were seeded on a skin model with and without the presence of keratinocytes and/or fibroblasts. After 14 days culture, the skin specimens were fixed, parafin embedded and cut into 7 µm sections. The de-parafinised sections were investigated by synchrotron Fourier transformed infrared (FTIR) microspectroscopy to study skin cell invasion behaviour. The advantage of using FTIR is its ability to obtain the fingerprint information of the invading cells in terms of protein secondary structure in comparison to non-invading cells and the concentration of the enzyme (matrix-metalloproteinase) which digests protein matrix, near the invading cells. With aid of the spectral mapping images, it is possible to pinpoint the cells in non-invasion and invasion area and analyse the respective spectra. It has been observed that the protein bands in cells and matrix shifted between non-invasive and invasive cells in the reconstructed skin model. We hypothesise that by careful analysis of the FTIR data and validation by other models, FTIR studies can reveal information on which type of cells and proteins are involved in melanoma invasion. Thus, it is possible to trace the cell invasion path by mapping the spectra along the interface of cell layer and matrix body by FTIR spectroscopy.

  12. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

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    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  13. Multicenter Study of Carbon-Ion Radiation Therapy for Mucosal Melanoma of the Head and Neck: Subanalysis of the Japan Carbon-Ion Radiation Oncology Study Group (J-CROS) Study (1402 HN)

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    Koto, Masashi, E-mail: koto.masashi@qst.go.jp [Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba (Japan); Demizu, Yusuke [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno (Japan); Saitoh, Jun-ichi [Gunma University Heavy Ion Medical Center, Maebashi (Japan); Suefuji, Hiroaki [Ion Beam Therapy Center, SAGA-HIMAT Foundation, Tosu (Japan); Tsuji, Hiroshi [Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba (Japan); Okimoto, Tomoaki [Department of Radiology, Hyogo Ion Beam Medical Center, Tatsuno (Japan); Ohno, Tatsuya [Gunma University Heavy Ion Medical Center, Maebashi (Japan); Shioyama, Yoshiyuki [Ion Beam Therapy Center, SAGA-HIMAT Foundation, Tosu (Japan); Takagi, Ryo [Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba (Japan); Nemoto, Kenji [Department of Radiation Oncology, Yamagata University Faculty of Medicine, Yamagata (Japan); Nakano, Takashi [Gunma University Heavy Ion Medical Center, Maebashi (Japan); Kamada, Tadashi [Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba (Japan)

    2017-04-01

    Purpose: To evaluate the efficacy and safety of carbon-ion radiation therapy (RT) for mucosal melanoma of the head and neck (MMHN) in the Japan Carbon-Ion Radiation Oncology Study Group study. Methods and Materials: Patients with MMHN with N0-1M0 status who were treated with carbon-ion RT at 4 institutions in Japan between November 2003 and December 2014 were analyzed retrospectively. Two hundred sixty patients (male, 111; female, 149; median age, 68 years) with histologically proven MMHN were enrolled. Results: Primary sites included the nasal cavity in 178 patients, paranasal sinuses in 43, oral cavity in 27, and pharynx in 12. Eighty-six patients had T3 tumors, 147 had T4a tumors, and 27 had T4b tumors. Two hundred fifty-one patients were diagnosed with N0 disease, and 9 with N1 disease. The median total dose and number of fractions were 57.6 Gy RBE (relative biological effectiveness) and 16, respectively. Chemotherapy including dimethyl traizeno imidazole carboxamide was used concurrently in 129 patients. The median follow-up duration was 22 months (range, 1-132 months). The 2-year overall survival and local control rates were 69.4% and 83.9%, respectively. Multivariate analysis showed that gross tumor volume and concurrent chemotherapy were significant prognostic factors for overall survival. Grade 3 and grade 4 late morbidities were observed in 27 and 7 patients (5 developed ipsilateral blindness, 1 mucosal ulcer, and 1 second malignant disease in the irradiated volume), respectively. No patients developed grade 5 late morbidities. Conclusion: Carbon-ion RT is a promising treatment option for MMHN.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    1991-08-01

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

  16. Case-control study on uveal melanoma (RIFA: rational and design

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    Schmidt-Pokrzywniak Andrea

    2004-08-01

    Full Text Available Abstract Background Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. Methods/Design We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups, except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding.

  17. Comparative study of angio genesis radiopharmaceuticals for melanoma detection

    International Nuclear Information System (INIS)

    Oliveira, Erica Aparecida de

    2011-01-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99m Tc-MAG3-PEG 8 -c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99m Tc-MAG 3 -PEG 8 -c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  18. Temporal and Spatial Melanoma Trends in Austria: An Ecological Study

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    Daniela Haluza

    2014-01-01

    Full Text Available Annual solar ultraviolet radiation (UVR is mostly determined by latitude and altitude. Over the last decades, increasing UVR ground levels have been observed. Exposure to UVR is associated with a life-time risk to develop melanoma, a malign skin cancer. Thus, we hypothesized that melanoma incidence in Austria is associated with altitude of place of living and time of diagnosis. We investigated this hypothesis in an ecological study by district and year for Austrian melanoma incidence (1990–2010 and mortality (1970–2011 data. As expected, incidence rates increased with altitude (about 2% per 10 m and year (about 2%. Additionally, melanoma incidence rates were about 50% higher in urban than in rural districts. In contrast, mortality rates decreased with altitude (for males: 0.4% per 10 m, for women: 0.7% per 10 m, respectively. The observed discrepancy between incidence and mortality data could partly be explained by melanoma diagnosis at earlier tumor stage in districts with higher altitude. Possible reasons for this finding include higher awareness of patients, better diagnostic performance of medical professionals working at higher altitudes, or slower tumor growth due to protective effects of sun light-associated vitamin D synthesis.

  19. Temporal and Spatial Melanoma Trends in Austria: An Ecological Study

    Science.gov (United States)

    Haluza, Daniela; Simic, Stana; Moshammer, Hanns

    2014-01-01

    Annual solar ultraviolet radiation (UVR) is mostly determined by latitude and altitude. Over the last decades, increasing UVR ground levels have been observed. Exposure to UVR is associated with a life-time risk to develop melanoma, a malign skin cancer. Thus, we hypothesized that melanoma incidence in Austria is associated with altitude of place of living and time of diagnosis. We investigated this hypothesis in an ecological study by district and year for Austrian melanoma incidence (1990–2010) and mortality (1970–2011) data. As expected, incidence rates increased with altitude (about 2% per 10 m) and year (about 2%). Additionally, melanoma incidence rates were about 50% higher in urban than in rural districts. In contrast, mortality rates decreased with altitude (for males: 0.4% per 10 m, for women: 0.7% per 10 m, respectively). The observed discrepancy between incidence and mortality data could partly be explained by melanoma diagnosis at earlier tumor stage in districts with higher altitude. Possible reasons for this finding include higher awareness of patients, better diagnostic performance of medical professionals working at higher altitudes, or slower tumor growth due to protective effects of sun light-associated vitamin D synthesis. PMID:24398911

  20. Evaluation of the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) classification scheme for diagnosis of cutaneous melanocytic neoplasms: Results from the International Melanoma Pathology Study Group.

    Science.gov (United States)

    Lott, Jason P; Elmore, Joann G; Zhao, Ge A; Knezevich, Stevan R; Frederick, Paul D; Reisch, Lisa M; Chu, Emily Y; Cook, Martin G; Duncan, Lyn M; Elenitsas, Rosalie; Gerami, Pedram; Landman, Gilles; Lowe, Lori; Messina, Jane L; Mihm, Martin C; van den Oord, Joost J; Rabkin, Michael S; Schmidt, Birgitta; Shea, Christopher R; Yun, Sook Jung; Xu, George X; Piepkorn, Michael W; Elder, David E; Barnhill, Raymond L

    2016-08-01

    Pathologists use diverse terminology when interpreting melanocytic neoplasms, potentially compromising quality of care. We sought to evaluate the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) scheme, a 5-category classification system for melanocytic lesions. Participants (n = 16) of the 2013 International Melanoma Pathology Study Group Workshop provided independent case-level diagnoses and treatment suggestions for 48 melanocytic lesions. Individual diagnoses (including, when necessary, least and most severe diagnoses) were mapped to corresponding MPATH-Dx classes. Interrater agreement and correlation between MPATH-Dx categorization and treatment suggestions were evaluated. Most participants were board-certified dermatopathologists (n = 15), age 50 years or older (n = 12), male (n = 9), based in the United States (n = 11), and primary academic faculty (n = 14). Overall, participants generated 634 case-level diagnoses with treatment suggestions. Mean weighted kappa coefficients for diagnostic agreement after MPATH-Dx mapping (assuming least and most severe diagnoses, when necessary) were 0.70 (95% confidence interval 0.68-0.71) and 0.72 (95% confidence interval 0.71-0.73), respectively, whereas correlation between MPATH-Dx categorization and treatment suggestions was 0.91. This was a small sample size of experienced pathologists in a testing situation. Varying diagnostic nomenclature can be classified into a concise hierarchy using the MPATH-Dx scheme. Further research is needed to determine whether this classification system can facilitate diagnostic concordance in general pathology practice and improve patient care. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    1985-01-01

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

  2. Inverse association between atopy and melanoma: A case-control study

    NARCIS (Netherlands)

    Marasigan, V. (Vivien); M.-A. Morren (Marie-Anne); J. Lambert; Medaer, K. (Karen); Fieuws, S. (Steffen); T.E.C. Nijsten (Tamar); Garmyn, M. (Marjan)

    2017-01-01

    textabstractHeightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by

  3. Sentinel lymph node biopsy versus observation in thick melanoma: A multicenter propensity score matching study.

    Science.gov (United States)

    Boada, Aram; Tejera-Vaquerizo, Antonio; Ribero, Simone; Puig, Susana; Moreno-Ramírez, David; Descalzo-Gallego, Miguel A; Fierro, María T; Quaglino, Pietro; Carrera, Cristina; Malvehy, Josep; Vidal-Sicart, Sergi; Bennássar, Antoni; Rull, Ramón; Alos, Llucìa; Requena, Celia; Bolumar, Isidro; Traves, Víctor; Pla, Ángel; Fernández-Figueras, María T; Ferrándiz, Carlos; Pascual, Iciar; Manzano, José L; Sánchez-Lucas, Marina; Giménez-Xavier, Pol; Ferrandiz, Lara; Nagore, Eduardo

    2018-02-01

    The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1,211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS [adjusted hazard ratio (AHR), 0.74; 95% confidence interval (CI) 0.61-0.90); p = 0.002] and OS (AHR, 0.75; 95% CI, 0.60-0.94; p = 0.013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; p = 0.165). SLN-negative patients had better 5- and 10-year MSS compared with SLN-positive patients (65.4 vs. 51.9% and 48.3 vs. 38.8%; p = 0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. © 2017 UICC.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Comparative study of angio genesis radiopharmaceuticals for melanoma detection; Estudo comparativo de radiofarmacos para angiogenese na deteccao de melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Erica Aparecida de

    2011-07-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 {mu}L of a {mu}g/{mu}L solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for {sup 99m}Tc-MAG3-PEG{sub 8}-c(RGDyK) (7.85{+-}{+-}2.34 %ID/g) at 120 min post injection. The performance of {sup 99m}Tc-MAG{sub 3}-PEG{sub 8}-c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  6. Thick melanoma in Tuscany.

    Science.gov (United States)

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

    2017-03-14

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

  7. Study of the radiosensitivity of three melanomas grown in vitro

    International Nuclear Information System (INIS)

    Weininger, J.

    1978-05-01

    This work studies the response to gamma irradiation of three human melanoma stems. Two cellular lines come from two ganglion metastases, the third from a primitive tumor. The influence of ''out-of-cycle''(quiescent cells on the radiosenitivity of a tumoral population was investigated in parallel with ''in cycle'' cells. The materials and methods used are described, and a number of cynetic parameters of the populations are given. The results of a series of experiments carried out on the IGR 11 stem are presented; this enables the evaluation of the repair capability of potentially lethal lesions of cells remaining in the plateau phase, after irradiation, without removal of the nutritional medium. The survival curves of the 3 stems, in both the exponential growth and the ''plateau phase'', are presented. A heterotransplant model of a human melanoma to ''nude'' mice is considered. (B.G.)

  8. A phase 2 study of vatalanib in metastatic melanoma patients.

    Science.gov (United States)

    Cook, Natalie; Basu, Bristi; Biswas, Swethajit; Kareclas, Paula; Mann, Colette; Palmer, Cheryl; Thomas, Anne; Nicholson, Steve; Morgan, Bruno; Lomas, David; Sirohi, Bhawna; Mander, Adrian P; Middleton, Mark; Corrie, Pippa G

    2010-10-01

    A phase 2 study of vatalanib (PTK787/ZK222584) an oral tyrosine kinase inhibitor of VEGFR 1, 2 and 3 was undertaken in patients with metastatic melanoma. Adults with pathologically confirmed metastatic melanoma, WHO Performance status 0-2, and adequate haematological, hepatic and renal function, were treated with vatalanib until disease progression. The trial used Fleming's single stage design. Tumour control rate (CR+PR+SD) was 35% at 16 weeks, with objective response seen in only 1 patient. Median progression-free survival was 1.8 months (95% CI 1.8-3.7 months) and median overall survival was 6.5 months (95% CI 3.9-10.2 months). Vatalanib stabilised disease in a proportion of patients, although overall survival was disappointing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. miR-203 inhibits melanoma invasive and proliferative abilities by targeting the polycomb group gene BMI1

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Sun, Yong [Department of Burn and Plastic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Zhu, Wei [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhang, Haiping, E-mail: zhanghaiping_2000@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi, E-mail: lianshi_2020@163.com [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China)

    2015-01-02

    Highlights: • First reported deregulation of miR-203 and up-regulation of BMI1 in metastatic melanoma. • miR-203 decreased BMI1 expression by directly binding to 3′UTR. • Further found miR-203 overexpression suppressed cell invasion and stemness. • Re-expression of BMI1 rescued miR-203-mediated suppression. • miR-203-BMI1 axis may be potential therapeutic targets of melanoma metastasis. - Abstract: Metastasis is the major problem in malignant melanoma, posing a therapeutic challenge to clinicians. The investigation of the underlying mechanism driving this progress remains a large unmet need. In this study, we revealed a miR-203-BMI1 axis that regulated melanoma metastasis. We found significantly deregulation of miR-203 and up-regulation of BMI1 in melanoma, particularly in metastatic melanoma. An inverse correlation between the levels of miR-203 and BMI1 was further observed in melanoma tissues and cell lines. We also identified BMI1 as a downstream target gene of miR-203, which bound to the 3′UTR of BMI1. Overexpression of miR-203 was associated with decreased BMI1 expression and impaired cell invasion and tumor sphere formation activities. Re-expression of BMI1 markedly rescued miR-203-mediated suppression of these events. Taken together, our results demonstrated that miR-203 regulated melanoma invasive and proliferative abilities in part by targeting BMI1, providing new insights into potential mechanisms of melanoma metastasis.

  10. Systematic genomic and translational efficiency studies of uveal melanoma.

    Directory of Open Access Journals (Sweden)

    Chelsea Place Johnson

    Full Text Available To further our understanding of the somatic genetic basis of uveal melanoma, we sequenced the protein-coding regions of 52 primary tumors and 3 liver metastases together with paired normal DNA. Known recurrent mutations were identified in GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. The role of mutated EIF1AX was tested using loss of function approaches including viability and translational efficiency assays. Knockdown of both wild type and mutant EIF1AX was lethal to uveal melanoma cells. We probed the function of N-terminal tail EIF1AX mutations by performing RNA sequencing of polysome-associated transcripts in cells expressing endogenous wild type or mutant EIF1AX. Ribosome occupancy of the global translational apparatus was sensitive to suppression of wild type but not mutant EIF1AX. Together, these studies suggest that cells expressing mutant EIF1AX may exhibit aberrant translational regulation, which may provide clonal selective advantage in the subset of uveal melanoma that harbors this mutation.

  11. Subcellular localization and photodynamic activity of Photodithazine (glucosamine salt of chlorin e6) in murine melanoma B16-F10: an in vitro and in vivo study

    Science.gov (United States)

    Ono, Bruno Andrade; Pires, Layla; Nogueira, Marcelo Saito; Kurachi, Cristina; Pratavieira, Sebastião.

    2018-02-01

    Photodynamic therapy (PDT) is already a good option for the clinical treatment of several lesions, including mainly nonmelanoma skin cancers. However, cutaneous melanoma treatment remains a challenge when using PDT. One of the reasons for its reduced efficacy is the high pigmentation of melanoma cells. The object of our study is to evaluate the feasibility of the Photodithazine as a photosensitizer for melanoma. Photodithazine is already used in some malignant tumors with satisfactory results and has significant absorption band around 660 nm where the absorption of melanin is low. In this study, we measured the subcellular localization and photodynamic activity of Photodithazine (PDZ) in murine melanoma B16-F10 cell culture. Additionally, a PDT procedure was applied in an animal melanoma model. This first result demonstrates that Photodithazine is more localized at mitochondria in B16F10 cell culture and the cell viability is reduced to less than 90% using 1 µg/mL (PDZ) and 2 J/cm2. We also noticed a rapid PDZ (less than one hour) accumulation in a murine melanoma model. The treatment of melanoma resulted in 20 % more animal survival after one session of PDT compared with the control group. More studies are required to evaluate the cytotoxic effects of Photodithazine at human melanoma.

  12. Sinclair swine melanoma

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  13. Preliminary studies of monoclonal antibody lymphoscintigraphy in malignant melanoma

    International Nuclear Information System (INIS)

    Nelp, W.B.; Eary, J.F.; Jones, R.F.; Hellstrom, K.E.; Hellstrom, I.; Beaumier, P.L.; Krohn, K.A.

    1987-01-01

    Lymphoscintigraphy was performed at 3 and 20 hr following subcutaneous injection of 131 I anti-melanoma antibody (Fab) in 11 patients who had surgical resection of lymph nodes (neck, axilla, groin) at 24 hr for suspected metastatic melanoma. Comparable amounts of 125 I nonspecific control antibody (Fab) were co-administered. Six patients had nodal metastases and three showed positive images at both time periods. Five patients had no metastases though one was image positive. Four other nondiseased inguinal node groups were image negative. A total of 28 tumored nodes and 110 normal nodes were removed, counted and histologically examined. All metastatic tumors expressed antigen against which the specific Fab was directed. The concentrations of both specific and nonspecific Fab were similar in tumored nodes and both were significantly greater than in normal nodes showed essentially identical intranodal spatial distribution of the specific and control Fab in areas containing tumor. These preliminary results suggest the increased concentration of murine immunoglobulin (Fab) retained in diseased nodes was a nonspecific phenomenon

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

    Directory of Open Access Journals (Sweden)

    Rychetnik Lucie

    2012-12-01

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

  15. Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (>4 mm) cutaneous melanoma: an observational study.

    Science.gov (United States)

    Morera-Sendra, Natalia; Tejera-Vaquerizo, Antonio; Traves, Víctor; Requena, Celia; Bolumar, Isidro; Pla, Angel; Vázquez, Carlos; Soriano, Virtudes; Nagore, Eduardo

    2016-01-01

    The role of sentinel lymph node biopsy and the benefit of immunotherapy with interferon in thick (>4 mm) melanomas remain uncertain. Our aim was to assess the value of both sentinel lymph node (SLN) biopsy and immunotherapy in the prognosis of thick melanomas. A retrospective study based on a computerized patient database in which patients have been prospectively collected since 2005 was performed. Age, sex, location, Breslow thickness, tumor ulceration, regression, Clark level, tumor infiltrating lymphocytes, tumor mitotic rate, microscopic satellite and vascular invasion were included in the analysis. Disease-free (DFS), disease-specific (DSS) and overall (OS) survivals were evaluated by the Kaplan-Meier method and Cox regression analysis. A series of 141 patients with melanomas thicker than 4 mm were included. Multivariate regression showed a worse prognosis in SLN-positive patients with respect to SLN biopsy-negative patients (DFS, hazard ratio [HR] 2, p = 0.04; DSS, HR 2.2, p = 0.002; OS, HR 2.4, p = 0.02). The observational group was shown to have a worse prognosis than the SLN-positive group but was very similar to the clinically positive group. Immunotherapy with high-dose interferon showed a protective effect (DFS, HR 0.5, p = 0.02; DSS, HR 0.3, p = 0.001; OS, HR 0.3, p = 0.001). Our data indicate that SLN biopsy and adjuvant interferon should be considered for patients with thick melanomas.

  16. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Pastila, R.

    2006-04-15

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  17. Effect of long-wave UV radiation on mouse melanoma: An in vitro and in vivo study

    International Nuclear Information System (INIS)

    Pastila, R.

    2006-04-01

    doses of UVA irradiation. This enhancement of adhesiveness might lead to an increase in binding tumor cells to the endothelial lining of vasculature in various internal organs if occurring also in vivo. A further novel observation is that UVA induced both decline in the expression of E-cadherin adhesion molecule and increase in the expression of the N-cadherin adhesion molecule. In addition, a significant decline in homotypic melanoma-melanoma adhesion (clustering) was observed, which might result in the reduction of E-cadherin expression. It appears that UVA irradiation might reduce melanoma-melanoma interaction through decreasing the expression of E-cadherin and simultaneously enhance the adhesiveness of melanoma cells to endothelium, which in part could be mediated by N-cadherin expression. The aim of the in vivo animal study was to confirm the physiological significance of previously obtained in vitro results and to determine whether UVA radiation might increase melanoma metastasis in vivo. The use of C57BL/6 mice and syngeneic melanoma cell lines B16-F1 and B16-F10 showed that mice, which were i.v. injected with B16-F1 melanoma cells and thereafter exposed to UVA developed significantly more lung metastases when compared with the non-UVA-exposed group. To study the mechanism behind this phenomenon, the direct effect of UVA-induced lung colonization capacity was examined by the in vitro exposure of B16-F1 cells. Alternatively, the UVA-induced immunosuppression, which might be involved in increased melanoma metastasis, was measured by standard contact hypersensitivity assay (CHS). It appears that the UVA-induced increase of metastasis in vivo might be caused by a combination of UVA-induced systemic immunosuppression, and to the lesser extent, it might be caused by the increased adhesiveness of UVA irradiated melanoma cells. Finally, the UVA effect on gene expression in mouse melanoma was determined by a cDNA array, which revealed UVA-induced changes in the 9

  18. Relationships between skin cancers and blood groups--link between non-melanomas and ABO/Rh factors.

    Science.gov (United States)

    Cihan, Yasemin Benderli; Baykan, Halit; Kavuncuoglu, Erhan; Mutlu, Hasan; Kucukoglu, Mehmet Burhan; Ozyurt, Kemal; Oguz, Arzu

    2013-01-01

    This investigation focused on possible relationships between skin cancers and ABO/Rh blood groups. Between January 2005 and December 2012, medical data of 255 patients with skin cancers who were admitted to Kayseri Training and Research Hospital, Radiation Oncology and Plastic Surgery Outpatient Clinics were retrospectively analyzed. Blood groups of these patients were recorded. The control group consisted of 25701 healthy volunteers who were admitted to Kayseri Training and Research Hospital, Blood Donation Center between January 2010 and December 2011. The distribution of the blood groups of the patients with skin cancers was compared to the distribution of ABO/Rh blood groups of healthy controls. The association of the histopathological subtypes of skin cancer with the blood groups was also investigated. Of the patients, 50.2% had A type, 26.3% had O type, 16.1% had B type, and 7.5% had AB blood group with a positive Rh (+) in 77.3%. Of the controls, 44.3% had A type, 31.5% had 0 type, 16.1% had B type, and 8.1% had AB blood group with a positive Rh (+) in 87.8%. There was a statistically significant difference in the distribution of blood groups and Rh factors (A Rh (-) and 0 Rh positive) between the patients and controls. A total of 36.8% and 20.4% of the patients with basal cell carcinoma (BCC) had A Rh (+) and B Rh (+), respectively, while 39.2% and 27.6% of the controls had A Rh (+) and B Rh (+), respectively. A significant relationship was observed between the patients with BCC and controls in terms of A Rh (-) (p=0.001). Our study results demonstrated that there is a significant relationship between non-melanoma skin cancer and ABO/Rh factors.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten

    2007-01-01

    The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....

  1. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  2. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

    International Nuclear Information System (INIS)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

    2016-01-01

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

  3. Molecular Classification of Melanoma

    Science.gov (United States)

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

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

    International Nuclear Information System (INIS)

    Allen, B.J.

    1982-01-01

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

  5. Phase II study of 4'-(9-acridinylamino) methanesulfon-m- anisidide (AMSA) in metastatic melanoma.

    Science.gov (United States)

    Legha, S S; Hall, S W; Powell, K C; Burgess, M A; Benjamin, R S; Gutterman, J U; Bodey, G P

    1980-01-01

    A phase II study of AMSA in previously treated patients with metastatic malignant melanoma was conducted. The dose schedule of AMSA was 40 mg/m2/day for 3 days repeated at 3-week intervals. Among the 30 evaluable patients, one achieved a complete response, one a partial response, and four had minor responses. Side effects included mild nausea and vomiting and moderate degree of myelosuppression. AMSA has poor activity against previously treated metastatic melanoma.

  6. Primary ovarian malignant melanoma

    Directory of Open Access Journals (Sweden)

    Kostov Miloš

    2010-01-01

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

  7. A comparative study of proliferative nodules and lethal melanomas in congenital nevi from children.

    Science.gov (United States)

    Yélamos, Oriol; Arva, Nicoleta C; Obregon, Roxana; Yazdan, Pedram; Wagner, Annette; Guitart, Joan; Gerami, Pedram

    2015-03-01

    Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.

  8. Photoaging Mobile Apps in School-Based Melanoma Prevention: Pilot Study.

    Science.gov (United States)

    Brinker, Titus Josef; Brieske, Christian Martin; Schaefer, Christoph Matthias; Buslaff, Fabian; Gatzka, Martina; Petri, Maximilian Philip; Sondermann, Wiebke; Schadendorf, Dirk; Stoffels, Ingo; Klode, Joachim

    2017-09-08

    Around 90% of melanomas are caused by exposure to ultraviolet (UV) radiation and are therefore eminently preventable. Tanning behavior is mostly initiated in early adolescence, often with the belief that it increases attractiveness; the problems related to malignant melanoma and other skin cancers are too far in the future to fathom. Given the substantial amount of time children and adolescents spend in schools, as well as with their mobile phones, addressing melanoma prevention via both of these ways is crucial. However, no school-based intervention using mobile apps has been evaluated to date. We recently released a photoaging mobile app, in which a selfie is altered to predict future appearance dependent on UV protection behavior and skin type. In this pilot study, we aimed to use mobile phone technology to improve school-based melanoma prevention and measure its preliminary success in different subgroups of students with regard to their UV protection behavior, Fitzpatrick skin type and age. We implemented a free photoaging mobile phone app (Sunface) in 2 German secondary schools via a method called mirroring. We "mirrored" the students' altered 3-dimensional (3D) selfies reacting to touch on mobile phones or tablets via a projector in front of their whole grade. Using an anonymous questionnaire capturing sociodemographic data as well as risk factors for melanoma we then measured their perceptions of the intervention on a 5-point Likert scale among 205 students of both sexes aged 13-19 years (median 15 years). We measured more than 60% agreement in both items that measured motivation to reduce UV exposure and only 12.5% disagreement: 126 (63.0%) agreed or strongly agreed that their 3D selfie motivated them to avoid using a tanning bed, and 124 (61.7%) to increase use of sun protection. However, only 25 (12.5%) disagreed with both items. The perceived effect on motivation was increased in participants with Fitzpatrick skin types 1-2 in both tanning bed avoidance

  9. The Melanoma care study: protocol of a randomised controlled trial of a psycho-educational intervention for melanoma survivors at high risk of developing new primary disease.

    Science.gov (United States)

    Dieng, Mbathio; Kasparian, Nadine A; Morton, Rachael L; Mann, Graham J; Butow, Phyllis; Menzies, Scott; Costa, Daniel S J; Cust, Anne E

    2015-01-01

    Despite a good prognosis for most melanoma survivors, many experience substantial fear of new or recurrent melanoma, worry and anxiety about the future, and unmet healthcare needs. In this protocol, we outline the design and methods of the Melanoma Care Study for melanoma survivors at high risk of developing new primary disease. The objective of this study is to evaluate the efficacy and cost-effectiveness of a psycho-educational intervention for improving psychological and behavioural adjustment to melanoma risk. The study design is a two-arm randomised controlled trial comparing a psycho-educational intervention to usual care. The intervention is comprised of a newly-developed psycho-educational booklet and three telephone sessions delivered by a trained psychologist. A total of 154 melanoma survivors at high risk of developing new primary disease who are attending one of three melanoma high risk clinics in New South Wales, Australia, will be recruited. Participants will be assessed at baseline (6 weeks before their high risk clinic dermatological appointment), and then 4 weeks and 6 months after their appointment. If effectiveness of the intervention is demonstrated at 6 months, an additional assessment at 12 months is planned. The primary outcome is fear of new or recurrent melanoma, as assessed by the Fear of Cancer Recurrence Inventory (FCRI). Secondary outcomes include anxiety, depression, unmet supportive care needs, satisfaction with clinical care, knowledge, behavioural adjustment to melanoma risk, quality of life, and cost-effectiveness of the intervention from a health system perspective. Following the intention-to-treat principle, linear mixed models will be used to analyse the data to account for repeated measures. A process evaluation will also be carried out to inform and facilitate potential translation and implementation into clinical practice. This study will provide high quality evidence on the efficacy and cost-effectiveness of a psycho

  10. Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases.

    Science.gov (United States)

    Romano, Ryan C; Carter, Jodi M; Folpe, Andrew L

    2015-08-01

    Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin

  11. Xeroderma pigmentosum genes and melanoma risk.

    Science.gov (United States)

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

    2013-09-01

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

  12. Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial

    Science.gov (United States)

    Guida, Michele; Ravaioli, Alessandra; Sileni, Vanna Chiarion; Romanini, Antonella; Labianca, Roberto; Freschi, Antonio; Brugnara, Salvatore; Casamassima, Addolorata; Lorusso, Vito; Nanni, Oriana; Ridolfi, Ruggero

    2003-01-01

    Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM) in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT) vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b). Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site) were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo), all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P < .0001), lower value of total leucocytes (P=.005), CRP (P=.003), LHD (P < .0001), ESR (P < .027), fibrinogen (P < .0001), and no liver disease were strongly related to a better survival. In a multivariate analysis, using the Cox proportional hazards model, only fibrinogen (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an independent role on clinical outcome in metastatic melanoma patients. Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used. PMID:14690541

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

    Science.gov (United States)

    Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

    2012-09-19

    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. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  14. 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.

  15. The Pediatric Choroidal and Ciliary Body Melanoma Study

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18...

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

    Science.gov (United States)

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

    2008-09-01

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

  17. [Cutaneous malignant melanomas in New Caledonia. Study of the Cancer Registry (1977-1987)].

    Science.gov (United States)

    Di Schino, M; Merouze, F; Huerre, M; Grimaldi, F; Lorthioir, J M; Breda, Y; Merrien, Y

    1989-01-01

    Investigation of cancer registration files in New Caledonia over a period of 11 years (1977-1987) draws the following conclusions: --The uncorrected incidence rate of cutaneous malignant melanoma is 3.63/100,000 inhabitants/year, for all ethnic groups together. --The incidence rate in the "non-European" population is 0.6/100,000 inhabitants/year. This low incidence and the anatomo-clinical manifestations observed (lentiginous melanoma of extremities) are common in coloured people. --The incidence rate in the "European" population is 8.75/100,000 inhabitants/year is noticeably higher than the incidence in the metropolitan population. Such conclusions are in accordance with the admitted data regarding epidemiology of cutaneous melanoma in high insolation countries. Cumulated incidence rate and topography of lesions are similar in this series whatever the sex.

  18. Study of the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011.

    Science.gov (United States)

    Costa, Nilo Fernandes da; Fernandes, Nurimar Conceição; Borges, Myrlena Regina Machado Mescouto

    2015-01-01

    Cutaneous melanoma (CM) is considered serious for causing frequent metastasis, presenting high mortality, resistance to available therapies and incidences in laboring activity. To study the histopathological types of cutaneous melanoma in Palmas-TO from 2001 to 2011, according to risk factors, location of lesions, Clark levels and Breslow thickness. A descriptive, retrospective and quantitative research in reports of the Serviços de Anatomia Patológica in Palmas (SAPP) and Registro de Câncer de Base Populacional de Palmas (RCBPP). The years of highest incidences were: 2004 (8 cases/17.8%), 2008 and 2011 (7 cases each/15.6%) and 2010 (6 cases/13.3%). Among the 45 cases studied, there were predominance in patients between 41 and 60 years old, women, caucasians, farmers, located in trunk, in situ type, superficial extensive and metastatic cutaneous, Clark levels I (20%) and IV (17.7%), Breslow thickness ≤1 mm (35.5%) and 2.01 to 4 mm (24.4%). The most common histopathological types were: cutaneous melanoma in situ, superficial extensive and metastatic, followed by nodular cutaneous melanoma, and finally, by other forms. In this study, Clark levels and Breslow thickness pointed to greater importance of thin melanomas and sun exposure without appropriate protection in farmers.

  19. 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.

  20. A case-control study: occupational cooking and the risk of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Marr Anja

    2010-10-01

    Full Text Available Abstract Background A European-wide population based case-control study (European rare cancer study undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk. Methods We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Results Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis. Conclusion Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation.

  1. Analysis of trends and seasonal variation in primary cutaneous melanoma: an Irish study.

    LENUS (Irish Health Repository)

    Downes, M R

    2010-11-10

    A seasonal variation in the presentation of cutaneous melanoma has been documented in several studies. We performed a retrospective review of primary cutaneous melanomas (n = 263) from our institution to examine whether the seasonal patterns of presentation noted in the literature would be similar in Ireland, a climate with low ambient sunshine. A summer : winter ratio was determined for age, gender, subtype, location and Breslow thickness. We found an increase in total numbers of melanomas, particularly in men. The summer : winter ratio was 2.39 for all patients (95% CI 1.60-3.57, P < 0.001), with seasonal variations noted for location, thickness and subtype (excluding lentigo). Melanomas presenting over the summer tended towards a greater Breslow thickness than did those presenting in winter. This subclassification of primary cutaneous melanoma with summer : winter ratios based on patient and tumour characteristics gave remarkably similar results to previously published reports, notwithstanding the low levels of annual ambient sunshine in Ireland.

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

    Science.gov (United States)

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

    2009-11-01

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

  3. THE STUDY OF MECHANISMS OF PHOTOINDUCED APOPTOSIS IN THE SKIN MALIGNANT MELANOMA CELL MODEL

    Directory of Open Access Journals (Sweden)

    M. L. Gelfond

    2016-01-01

    Full Text Available The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2 induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

  4. Genetic testing for hereditary melanoma and pancreatic cancer: a longitudinal study of psychological outcome.

    Science.gov (United States)

    Aspinwall, Lisa G; Taber, Jennifer M; Leaf, Samantha L; Kohlmann, Wendy; Leachman, Sancy A

    2013-02-01

    CDKN2A/p16 mutations confer 76% lifetime risk of melanoma and up to 17% lifetime risk of pancreatic cancer. Our objective was to determine the short- and long-term impact of CDKN2A/p16 genetic counseling and test reporting on psychological distress, cancer worry, and perceived costs and benefits of testing. Prospective changes in anxiety, depression, and cancer worry following CDKN2A/p16 counseling and test reporting were evaluated at multiple assessments over 2 years among 60 adult members of melanoma-prone families; 37 participants completed the 2-year follow-up. Quantitative and qualitative assessments of the costs and benefits of testing were carried out. Outcomes were evaluated among unaffected noncarriers (n = 27), unaffected carriers (n = 15), and affected carriers (n = 18). Reported anxiety and depression were low. For carriers and noncarriers, anxiety decreased significantly throughout the 2-year period, whereas depression and melanoma worry showed short-term decreases. Worry about pancreatic cancer was low and decreased significantly. In all groups, test-related distress and uncertainty were low, regret was absent, and positive experiences were high. All participants (>93% at each assessment) reported at least one perceived benefit of genetic testing; only 15.9% listed any negative aspect. Carriers reported increased knowledge about melanoma risk and prevention (78.3%) and increased prevention and screening behaviors for self and family (65.2%). Noncarriers reported increased knowledge (95.2%) and emotional benefits (71.4%). Among US participants familiar with their hereditary melanoma risk through prior epidemiological research participation, CDKN2A/p16 genetic testing provides multiple perceived benefits to both carriers and noncarriers without inducing distress in general or worry about melanoma or pancreatic cancer. Copyright © 2011 John Wiley & Sons, Ltd.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  6. Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group trial

    Directory of Open Access Journals (Sweden)

    Casamassima Addolorata

    2003-12-01

    Full Text Available Abstract Purpose To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT vs bioCT. Methods A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular α-IFN-2b. Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP, lactate dehydrogenase (LDH, erytrosedimentation rate (ESR, and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2% and OS (11 Mo vs 9.5 Mo, all analyses are stratified by treatment arm. Results In univariate analysis, higher value of lymphocytes percentage (P Conclusion Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used.

  7. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-02-15

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2014-10-01

    While most cancers have shown both decreased incidence and mortality over the past several decades, the incidence of melanoma has continued to grow, and mortality has only recently stabilized in the United States and in many other countries. Certain populations, such as men >60 years of age and lower socioeconomic status groups, face a greater burden from disease. For any given stage and across all ages, men have shown worse melanoma survival than women, and low socioeconomic status groups have increased levels of mortality. Novel risk factors can help identify populations at greatest risk for melanoma and can aid in targeted early detection. Risk assessment tools have been created to identify high-risk patients based on various factors, and these tools can reduce the number of patients needed to screen for melanoma detection. Diagnostic techniques, such as dermatoscopy and total body photography, and new technologies, such as multispectral imaging, may increase the accuracy and reliability of early melanoma detection. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2018-01-24

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

  11. Molecular Prognostic Markers in Uveal Melanoma: Expression Profiling and Genomic Studies

    NARCIS (Netherlands)

    W. Gils (Walter)

    2008-01-01

    textabstractUveal Melanomas (UMs) arise from melanocytes. This cell type originates from neural crest cells and thereby uveal melanomas share their origin with pheochromocytomas, neuroblastomas, paragangliomas and cutaneous melanomas, other tumors that develop from neural crest originating cells.

  12. Ocular Melanoma

    Science.gov (United States)

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

  13. Study Groups in Denmark

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    2007-01-01

    Since 1998 European Study Groups have been held in Denmark, and Danish companies from LEGO and NOVO to very small high-tech firms have participated. I briefly describe the history, the organisation and the format of the Danish Study Groups, and highlight a few problem solutions.......Since 1998 European Study Groups have been held in Denmark, and Danish companies from LEGO and NOVO to very small high-tech firms have participated. I briefly describe the history, the organisation and the format of the Danish Study Groups, and highlight a few problem solutions....

  14. Preclinical and phase I studies of monoclonal antibodies in melanoma: Application to boron neutron capture therapy of melanoma

    International Nuclear Information System (INIS)

    Hersey, P.

    1989-01-01

    Monoclonal antibodies (MAbs) provide an attractive method of selectively localizing sufficient boron atoms around tumour cells to capture neutrons. Assuming that 10(8)-10(10) 10B atoms are needed for one capture event and that 10(3)-10(4) atoms can be coupled to each antibody molecule, then 10(5)-10(6) antibody molecules gathered on an individual cell will destroy that cell. Binding to normal tissues, on the other hand, would need to be at least 20-fold less than that to tumour tissues to avoid toxic effects of neutrons on surrounding tissues. Preclinical studies in animals show that several MAbs may bind to melanoma cells in sufficient quantities in vitro to localize the required amount of boron per cell. Whether this will occur in vivo, however, may depend not only on antigen density but a variety of other properties of the tumour cells and MAbs. These include the Ig class and affinity of the antibody and whether the antibody is internalized into the tumour cell. The ratio of uptake between tumour and normal tissue is governed by such factors as the percentage of tumour cells within a tumour expressing the antigen and whether the MAb react with normal tissues. Use of Fab or F(ab)2 preparations of the MAb may increase the uptake ratio by preventing uptake of MAb by cells with Fc receptors. In contrast to preclinical animal studies, tumour/normal tissue uptake ratios in phase I studies in humans have been disappointingly low.80 references

  15. Microculture-based chemosensitivity testing: a feasibility study comparing freshly explanted human melanoma cells with human melanoma cell lines.

    Science.gov (United States)

    Marshall, E S; Finlay, G J; Matthews, J H; Shaw, J H; Nixon, J; Baguley, B C

    1992-03-04

    The culture of cancer cells has many applications in chemosensitivity testing and new drug development. Our goal was to adapt simple semiautomated microculture methods for testing the chemosensitivity of melanoma cells freshly recovered from patients' tumors. Cells were cultured on a substrate of agarose and exposed continuously to cytotoxic drugs, the effects of which were measured by determining the uptake of [3H]thymidine 4-7 days later. Immunocytochemical staining of cells cultured with 5-bromo-2'-deoxyuridine demonstrated that tumor cells were responsible for the measured thymidine incorporation. The effects of cytotoxic drugs were calculated as logarithmic 50% inhibitory concentrations and expressed as divergences from the mean in a log-mean graph. The inhibitory effects of amsacrine, etoposide, doxorubicin, cisplatin, mitomycin C, and fluorouracil were tested. Tumors differed widely in their sensitivity to these drugs, although sensitivity to the three topoisomerase-II-directed agents was highly correlated. Cells from two non-neoplastic hematopoietic progenitor cell lines (FT and 32D) showed chemosensitivity patterns distinct from those in the melanoma cells, indicating tissue selectivity. Two established melanoma cell lines, MM-96 and FME, were tested under the same conditions and showed sensitivity typical of at least some fresh specimens. These results support the validity of melanoma cell lines as models of freshly resected melanoma cells. If successfully applied to other tumor types, such semiautomated approaches could find wide application in routine hospital laboratories for the chemosensitivity testing of patients' tumor cells.

  16. Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E1697).

    Science.gov (United States)

    Agarwala, Sanjiv S; Lee, Sandra J; Yip, Waiki; Rao, Uma N; Tarhini, Ahmad A; Cohen, Gary I; Reintgen, Douglas S; Evans, Terry L; Brell, Joanna M; Albertini, Mark R; Atkins, Michael B; Dakhil, Shaker R; Conry, Robert M; Sosman, Jeffrey A; Flaherty, Lawrence E; Sondak, Vernon K; Carson, William E; Smylie, Michael G; Pappo, Alberto S; Kefford, Richard F; Kirkwood, John M

    2017-03-10

    Purpose To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma. Patients and Methods In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m 2 /d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life. Results A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 (95% CI, 0.66 to 0.74) for OBS and 0.70, (95% CI, 0.66 to 0.74) for IFN ( P = .964). The 5-year overall survival rate was 0.83 (95% CI, 0.79 to 0.86) for OBS and 0.83 (95% CI, 0.80 to 0.86) for IFN ( P = .558). Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively ( P weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-22

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

  19. Feasibility of an online mindfulness-based program for patients with melanoma: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Russell, Lahiru; Ugalde, Anna; Milne, Donna; Krishnasamy, Meinir; O Seung Chul, Eric; Austin, David W; Chambers, Richard; Orellana, Liliana; Livingston, Patricia M

    2018-04-13

    People with a melanoma diagnosis are at risk of recurrence, developing a new primary or experiencing disease progression. Previous studies have suggested that fear of a cancer recurrence is clinically relevant in this group of patients and, if not addressed, can lead to distress. Mindfulness-based interventions have been shown to alleviate symptoms of anxiety and depression among various groups of cancer patients. Online mindfulness-based interventions have the potential to reach people unable to attend face-to-face interventions due to limitations such as cancer-related illness, transportation or time constraints. This study aims to (1) examine whether individuals with a melanoma diagnosis are willing to participate and adhere to a 6-week online mindfulness-based intervention and (2) explore potential benefits of the program on fear of cancer recurrence, worries, rumination, perceived stress and trait mindfulness to inform the design of a clinical trial. This is a single-site randomised controlled trial of a feasibility study. Seventy-five participants with stage 2c or 3 melanoma will be recruited from a melanoma outpatient clinic and randomised (2:1) either to an online mindfulness-based program (intervention) or to usual care (control). The intervention is a 6-week program specifically developed for this study. It consists of videos describing the concept of mindfulness, short daily guided meditation practices (5-10 min), automated meditation reminders and instructions for applying mindfulness in daily life to enhance wellbeing. All participants will complete questionnaires at baseline and at 6-week post-randomisation. Participants in the control group will be given access to the online program at the end of the study. Primary outcomes are overall recruitment; retention; extent of questionnaire completion; and usability and acceptability of, and adherence to, the program. The secondary outcomes are fear of cancer recurrence, worries, rumination, perceived

  20. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-01-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW’s are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  1. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    Science.gov (United States)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  2. Trends in size and treatment of recently diagnosed choroidal melanoma, 1987-1997: findings from patients examined at collaborative ocular melanoma study (COMS) centers: COMS report no. 20.

    Science.gov (United States)

    2003-08-01

    To describe time trends, from 1987 through 1997, (1) in size of choroidal melanoma among patients with recent diagnosis confirmed at a clinical center that participated in the Collaborative Ocular Melanoma Study (COMS) and (2) in choice of treatment by patients who did not enroll in one of the COMS randomized trials. Investigators at all COMS clinical centers (41 in the United States and 2 in Canada) agreed to report, in a masked fashion that did not include personal identifiers, all patients diagnosed as having choroidal melanoma during the accrual period for COMS randomized trials of radiotherapy. Information reported for patients who did not enroll in a COMS randomized trial included tumor dimensions, date of diagnosis, and initial treatment selected. Patients reported by centers that continued to report cases until 1997 and diagnosed as having choroidal melanoma no more than 1 year before evaluation at a participating COMS center contributed the data analyzed. Time trends in tumor size among patients reported and in elective treatment of patients not enrolled in COMS randomized trials. Of 8712 patients with choroidal melanoma examined, 6703 met criteria for analysis of time trend in tumor size and 4077 were analyzed for treatment trends over time. The number of cases with longest tumor basal diameter greater than 15.0 mm declined over time from 393 (30%) of 1330 cases reported in 1987 through 1989 to 345 (25%) of 1397 cases reported in 1996 or 1997. The proportion of patients eligible for COMS randomized trials who did not enroll and who elected enucleation remained stable over time for tumors of all sizes; the proportion of these patients who elected eye-conserving radiotherapy increased over time. Juxtapapillary tumors accounted for nearly half of the enucleations among ineligible patients who had tumors no larger than 15.0 mm in longest basal diameter. Among patients examined at COMS centers during 1987 through 1997, the trends observed for patients with

  3. Ethnicity and cutaneous melanoma in the city of Sao Paulo, Brazil: a case-control study.

    Directory of Open Access Journals (Sweden)

    Olinda C Luiz

    Full Text Available BACKGROUND: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogeneous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77, Italy (OR = 3.47, 95% CI: 1.41-8.57, a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93, or ≥ 2 European countries (OR = 2.82, 95% CI: 1.06-7.47; eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84 and green/blue (OR = 4.62; 95% CI 2.22-9.58; pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49; no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22; and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19. CONCLUSIONS: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.

  4. Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

    Science.gov (United States)

    Luiz, Olinda C.; Gianini, Reinaldo José; Gonçalves, Fernanda T.; Francisco, Guilherme; Festa-Neto, Cyro; Sanches, José Antonio; Gattas, Gilka J. F.; Chammas, Roger; Eluf-Neto, José

    2012-01-01

    Background Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe—Spain (OR = 3.01, 95% CI: 1.03–8.77), Italy (OR = 3.47, 95% CI: 1.41–8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05–8.93), or ≥2 European countries (OR = 2.82, 95% CI: 1.06–7.47); eye color—light brown (OR = 1.99, 95% CI: 1.14–3.84) and green/blue (OR = 4.62; 95% CI 2.22–9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21–6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03–9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03–3.19). Conclusions Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants. PMID:22558444

  5. Indoor tanning in businesses and homes and risk of melanoma and non-melanoma skin cancer in two US case-control studies

    Science.gov (United States)

    Ferrucci, Leah M.; Vogel, Rachel Isaksson; Cartmel, Brenda; Lazovich, DeAnn; Mayne, Susan T.

    2014-01-01

    Background Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based). Objective Assess where individuals tanned indoors and skin cancer risk by tanning device location. Methods Multivariate logistic regression in two US case-control studies of melanoma (1,161 cases, 1,083 controls, ages 25–59) and early-onset basal cell carcinoma (BCC) (375 cases, 382 controls, under age 40) conducted between 2004 and 2010. Results Most indoor tanners (86.4–95.1%), especially younger individuals, tanned exclusively in businesses. Persons who used indoor tanning exclusively in businesses were at increased risk of melanoma (OR=1.82, 95% CI=1.47–2.26) and BCC (OR=1.69, 95% CI=1.15–2.48) compared to non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (OR=4.14, 95% CI=1.75–9.78); 67.6% used sun lamps. Limitations Self-reported tanning, potential recall bias. Conclusion Business only tanning, despite claims of “safe" tanning, was positively associated with a significant risk of melanoma and BCC. Home tanning was uncommon and mostly from sun lamps which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer. PMID:25062934

  6. Color transparency study group

    International Nuclear Information System (INIS)

    Appel, J.A.; Pordes, S.; Botts, J.; Bunce, G.; Farrar, G.

    1990-01-01

    The group studied the relatively new notion of color transparency, discussed present experimental evidence for the effect, and explored several ideas for future experiments. This write-up summarizes these discussions. 11 refs., 1 fig

  7. Barriers and Facilitators to Melanoma Prevention and Control Behaviors Among At-Risk Children.

    Science.gov (United States)

    Wu, Yelena P; Parsons, Bridget G; Mooney, Ryan; Aspinwall, Lisa G; Cloyes, Kristin; Hay, Jennifer L; Kohlmann, Wendy; Grossman, Douglas; Leachman, Sancy A

    2018-04-06

    Melanoma prevention is essential for children who are at elevated risk for the disease due to family history. However, children who carry a familial risk for the disease do not optimally adhere to recommended melanoma preventive behaviors. The current study sought to identify perceived barriers to and facilitators of children's engagement in melanoma preventive behaviors among children at elevated risk for melanoma due to family history of the disease (i.e., having a parent with a history of melanoma) from both parents' and childrens' perspectives. Qualitative methods were employed and consisted of separate focus group discussions with children (ages 8-17 years, n = 37) and their parents (n = 39). Focus group transcripts were coded using content analysis. Parents and children reported a number of barriers and facilitators, including on the individual (e.g., knowledge and awareness, preferences), social (e.g., peer influences, family modeling and communication), and contextual (e.g., healthcare provider communication) levels. The identified categories of barriers and facilitators both confirm and extend the literature documenting the reasons children who are at elevated risk for melanoma do not engage in melanoma prevention and control behaviors. Programs aiming to decrease melanoma risk among children of melanoma survivors could help families address their barriers to preventive behavior implementation and build on facilitators. Melanoma survivors and their children could benefit from support on their interactions with healthcare providers, schools, peers, and other caregivers about melanoma prevention.

  8. HTB140 melanoma cells under proton irradiation and/or alkylating agents

    Science.gov (United States)

    Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

    2007-09-01

    Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

  9. Melanoma genetics

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The incidence of melanoma in Denmark has immensely increased over the last 10 years making Denmark a high risk country for melanoma. In the last two decades multiple public campaigns have sought to increase the awareness of melanoma. Family history of melanoma is a known major risk factor...... but previous studies have shown that self-reported family history of melanoma is highly inaccurate. These studies are 15 years old and we wanted to examine if a higher awareness of melanoma has increased the accuracy of self-reported family history of melanoma. We examined the family history of 181 melanoma...

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

    LENUS (Irish Health Repository)

    de Blacam, C

    2012-02-01

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using chi(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

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

    LENUS (Irish Health Repository)

    de Blacam, C

    2011-04-17

    BACKGROUND: A predominance of melanomas on the left side of the body has recently been described. No associations between tumour laterality and gender, age or anatomical site have been identified. AIM: The aim of this study was to investigate the prevalence of left-sided melanomas in an Irish population and to examine potential associations with various patient and tumour characteristics. METHODS: A retrospective chart review of patients with cutaneous melanoma who were treated over a 10-year period was carried out. Lateral distribution of melanoma on either side of the body was compared using χ(2) analysis and evaluated by gender, age group, anatomic location, histologic subtype and Breslow depth. RESULTS: More melanomas occurred on the left side (57%, P = 0.015), and this finding was particularly significant in females. For both genders combined, there were no statistically significant differences in laterality by age group, anatomic location, type of melanoma and Breslow depth. There were significantly more superficial spreading melanomas on the left side in both men and women. CONCLUSIONS: This study demonstrates a predominance of left-sided melanomas in Irish patients. While a number of demographic and molecular associations have been proposed, further research is required to fully explain this phenomenon.

  13. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

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

  14. Expression of the chondroitin sulphate proteoglycan molecular complex in six human melanoma xenograft lines studied by flow cytometry and immunohistochemistry.

    Science.gov (United States)

    Nagelhus, T A; Rofstad, E K

    1993-06-01

    The expression of the chondroitin sulphate proteoglycan (CSP) molecular complex in six human melanoma xenograft lines (BEX-t, COX-t, HUX-t, ROX-t, SAX-t, WIX-t) was studied by flow cytometry and immunohistochemistry using the monoclonal antibodies 9.2.27, ME31.3, G7A5, and NKI.M6. The two methods and the four antibodies gave consistent results. The six melanoma lines could be divided into three distinct groups of two lines each; expression was high in the HUX-t and ROX-t lines and intermediate in the BEX-t and SAX-t lines, whereas the COX-t and WIX-t lines were negative. The mean number of epitopes per cell for 9.2.27 was approximately twice as high as for ME31.3, G7A5, and NKI.M6 and was estimated to range from 0.8 +/- 0.1 x 10(5) to 1.9 +/- 0.2 x 10(5) in the positive xenograft lines. The expression of the CSP complex was heterogeneous. The immunofluorescence histograms measured by flow cytometry were therefore broad for all tumour lines. A significant fraction of the HUX-t cells was negative or weakly stained. These cells appeared as clear negative patches in the immunohistochemical preparations. Moreover, most morphologically intact tumour cells adjacent to necrotic areas did not show significant expression of the CSP complex, irrespective of tumour line. These cells were probably hypoxic and thus resistant to radiation therapy. The expression of the CSP complex in the xenograft lines was similar to that reported for melanoma in man.

  15. Weekly 24-hour continuous infusion interleukin-2 for metastatic melanoma and renal cell carcinoma: a phase I study.

    Science.gov (United States)

    Perez, E A; Scudder, S A; Meyers, F A; Tanaka, M S; Paradise, C; Gandara, D R

    1991-02-01

    Twenty-nine patients with biopsy-confirmed metastatic melanoma (17) or metastatic renal cell carcinoma (12) were treated with escalating doses or recombinant human interleukin-2 (IL-2) administered as weekly 24-h intravenous infusions. Patients received from 3 to 12 x 10(6) C.U./m2 (18-72 x 10(6) I.U./m2) weekly over a treatment period of 1 to 16 weeks, with a median of eight weekly cycles administered. Patients in all treatment groups experienced non-life-threatening systemic side effects consisting of fever, nausea, vomiting, fluid retention, and diarrhea. Grade III hypotension was seen in four of six patients (67%) at 12 x 10(6) C.U./m2, and represented the dose-limiting toxicity. Grade IV hypotension occurred in 1 of 14 patients at 6 x 10(6) C.U./m2; no other grade IV toxicities were observed. Grade III fever occurred in 3 of 11 patients (27%) treated at 3 x 10(6) C.U./m2, 3 of 14 patients (21%) at 6 x 10(6) C.U./m2, and 3 of 6 patients (50%) at 9 x 10(6) C.U./m2. An objective response was observed in 3 of 28 evaluable patients (10%): 1 complete response and 1 partial response in renal cell cancer, and 1 partial response in a melanoma patient. We conclude that for future studies, the recommended dose of IL-2 given as a weekly 24-h infusion is 9 x 10(6) C.U./m2 and that a low rate of objective tumor response can be obtained in patients with melanoma and renal cell carcinoma using this regimen.

  16. Validation of anti-FXR1 antibodies in the canine species and application to an immunohistochemical study of canine oral melanomas

    Directory of Open Access Journals (Sweden)

    Laura Nordio

    2017-05-01

    Full Text Available FXR1 (Fragile X mental retardation-related protein 1 is a cytoplasmic RNA binding protein, which genetic expression has been related to metastatic potential in human melanoma. The aims of the present study were: the validation of two commercially available clones of polyclonal anti-human FXR1 antibody in dogs; their application to investigate FXR1 expression in a group of canine oral melanomas. Anti-FXR1 antibody was not previously validated in the canine species. Two different commercially available polyclonal anti-FXR1 antibodies (respectively made in goat and in rabbit were used. FXR1 protein in canine serum was identified by western blot after SDS-PAGE, using human serum as control. FXR1 immunohistochemical expression was tested in a series of normal tissues, that are expected to express FXR1, and in 31 cases of oral melanomas. The final immunohistochemical protocol used heat-induced unmasking and overnight incubation. FXR1 protein bands in canine serum were detected by tested antibodies, in a more specific way by the rabbit antibody. FXR1 immunohistochemical staining was positive in all tested organs, with different levels of expression. FXR1 was also expressed in 31/31 tested melanomas, with variable intensity and percentage of positive cells (Figure 1. Equal results were achieved with the two antibodies in 8 cases of melanoma, whereas there were variable differences in 22, and one case stained only with goat antibody. The rabbit antibody gave less background staining. This study validated anti-FXR1 antibodies for use in the canine species. This protein was expressed in various normal tissues, as well as in the tested neoplasms. Significance of different level of expression is undergoing evaluation with further studies.

  17. Studies on the uptake of para-boronophenylalanine in melanoma cells

    International Nuclear Information System (INIS)

    Papageorges, M.; Elstad, C.A.; Meadows, G.G.; Gavin, P.R.; Sande, R.D.; Bauer, W.F.

    1992-01-01

    Cell-associated boron levels adequate for neutron capture therapy (NCT) have been demonstrated in-vitro using cultured melanoma cells and in-vivo using xenografts in mice. Preliminary in-vivo studies performed by researchers at the College of Veterinary Medicine, Washington State University (WSU), using a spontaneous canine melanoma model, showed subtherapeutic tumor concentrations of para-boronophenylananine (p-BPA) in a large proportion of dogs. Possible explanations include poor solubility of p-BPA at physiological pH, physiological differences between transplanted and spontaneous tumors, and lack of metabolic incorporation at the cellular level. Reports of in-vitro p-BPA uptake studies are few and contradictory, and the kinetics of boron uptake at the average p-BOA blood concentration achieved in dogs (100 mg/L) is unknown. In-vitro and in-vivo experiments were designed to study boron loading in melanoma cells and to test the hypothesis that short-term tyrosine and phenylalanine deprivation can increase the uptake of p-BPA

  18. Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients

    Directory of Open Access Journals (Sweden)

    Alejandro Martin-Gorgojo

    2018-03-01

    Full Text Available The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

  19. Cutaneous melanoma in situ: translational evidence from a large population-based study.

    Science.gov (United States)

    Mocellin, Simone; Nitti, Donato

    2011-01-01

    Cutaneous melanoma in situ (CMIS) is a nosologic entity surrounded by health concerns and unsolved debates. We aimed to shed some light on CMIS by means of a large population-based study. Patients with histologic diagnosis of CMIS were identified from the Surveillance Epidemiology End Results (SEER) database. The records of 93,863 cases of CMIS were available for analysis. CMIS incidence has been steadily increasing over the past 3 decades at a rate higher than any other in situ or invasive tumor, including invasive skin melanoma (annual percentage change [APC]: 9.5% versus 3.6%, respectively). Despite its noninvasive nature, CMIS is treated with excision margins wider than 1 cm in more than one third of cases. CMIS is associated with an increased risk of invasive melanoma (standardized incidence ratio [SIR]: 8.08; 95% confidence interval [CI]: 7.66-8.57), with an estimated 3:5 invasive/in situ ratio; surprisingly, it is also associated with a reduced risk of gastrointestinal (SIR: 0.78, CI: 0.72-0.84) and lung (SIR: 0.65, CI: 0.59-0.71) cancers. Relative survival analysis shows that persons with CMIS have a life expectancy equal to that of the general population. CMIS is increasingly diagnosed and is often overtreated, although it does not affect the life expectancy of its carriers. Patients with CMIS have an increased risk of developing invasive melanoma (which warrants their enrollment in screening programs) but also a reduced risk of some epithelial cancers, which raises the intriguing hypothesis that genetic/environmental risk factors for some tumors may oppose the pathogenesis of others.

  20. Palladium-103 plaque radiotherapy for choroidal melanoma: an 11-year study

    International Nuclear Information System (INIS)

    Finger, Paul T.; Berson, Anthony; Ng, Tracy; Szechter, Andrzej

    2002-01-01

    Purpose: To describe 11 years of experience with 103 Pd ophthalmic plaque brachytherapy for intraocular melanoma. Methods and Materials: Since 1990, 152 patients have been diagnosed with uveal melanoma, found to be negative for metastatic disease, and treated with 103 Pd radioactive plaque radiotherapy. This study presents the first 100 patients treated with 103 Pd and followed for ≥2 years. Plaques were sewn to the episclera to cover the base of the intraocular tumor. Treatment involved delivery of a mean apical radiation dose of 80.5 Gy during 5-7 days' continuous treatment. Patients were evaluated for local tumor control, visual acuity, radiation damage (retinopathy, optic neuropathy, cataract), and metastatic disease. Results: Patients in this series were followed for a mean of 4.6 years (55.4 months). 103 Pd seeds were found to be equivalent to 125 I with respect to plaque manufacture and ease of dosimetric calculations. We noted a local control rate of 96% and six secondary enucleations. Including the enucleated patients, the visual acuity evaluations revealed that 35% lost six or more lines of vision and 73% had vision of 20/200 or better. Conclusion: Long-term results now exist describing the use of 103 Pd plaque radiotherapy for uveal (iris, ciliary body, and choroidal) melanoma. Compared with the results from centers using 125 I, patients in this series experienced equivalent local control rates and better visual function

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

    Directory of Open Access Journals (Sweden)

    Philipp Tschandl

    2017-08-01

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

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

    Science.gov (United States)

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

    2011-11-01

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

  3. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies

    International Nuclear Information System (INIS)

    Pozzi, Oscar R.; Edreira, Martin M.; Castiglia, Silvia G.; Soroa, Victoria E.

    1999-01-01

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[ 131 I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

  4. Dabrafenib for Treating Unresectable, Advanced or Metastatic BRAF V600 Mutation-Positive Melanoma: An Evidence Review Group Perspective.

    Science.gov (United States)

    Fleeman, Nigel; Bagust, Adrian; Beale, Sophie; Boland, Angela; Dickson, Rumona; Dwan, Kerry; Richardson, Marty; Dundar, Yenal; Davis, Helen; Banks, Lindsay

    2015-09-01

    The National Institute for Health and Care Excellence (NICE) invited GlaxoSmithKline, the manufacturer of dabrafenib, to submit evidence for the clinical and cost effectiveness of dabrafenib for the treatment of unresectable, advanced or metastatic BRAF V600 mutation-positive melanoma in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the company and provides a summary of the Appraisal Committee's (AC) final decision in October 2014. The clinical evidence for dabrafenib was derived from an ongoing phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BREAK-3) involving 230 patients randomized 2:1 to receive either dabrafenib or dacarbazine. A significant improvement in median progression-free survival (PFS) but not overall survival (OS) was reported in the dabrafenib arm compared with dacarbazine. Vemurafenib is considered a more appropriate comparator than is dacarbazine. The clinical evidence for vemurafenib was derived from a completed phase III, randomized, double-blind, placebo-controlled, international, multicentre clinical trial (BRIM-3) involving 675 patients randomized 1:1 to receive either vemurafenib or dacarbazine. A significant improvement in median PFS and OS was reported in the vemurafenib arm compared with dacarbazine. As there is no direct evidence comparing dabrafenib versus vemurafenib, the company presented an indirect treatment comparison (ITC) that demonstrated no statistical differences between dabrafenib and vemurafenib for PFS or OS. The ERG expressed concerns with the ITC, mainly in relation to the validity of the assumptions underpinning the methodology; the ERG concluded this resulted in findings that are unlikely to be robust or reliable. Dabrafenib and

  5. European multicenter study on melanoma immunoscintigraphy by means of 99mTc-labelled monoclonal antibody fragments

    International Nuclear Information System (INIS)

    Siccardi, A.G.; Viale, G.; Natali, P.G.; Scassellati, G.A.; Ferrone, S.

    1990-01-01

    A total of 493 melanoma patients were investigated by 20 European nuclear medicine departments by means of the same 99m Tc-labelled immunoradiopharmaceutical and the same immunoscintigraphy (ISG) protocol. (i) No chemical or clinical toxicity was detected during or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): In 231 (80%) of them, 402/402 lesions were imaged; in the remaining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already documented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: About 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicenter Study which had previously been carried out with 258 melanoma patients. (orig.)

  6. RARE METASTASES OF MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Marija Trenkić-Božinović

    2014-09-01

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

  7. 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.

  8. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

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

  9. [Study of migration and distribution of bone marrow cells transplanted animals with B16 melanoma ].

    Science.gov (United States)

    Poveshchenko, A F; Solovieva, A O; Zubareva, K E; Strunkin, D N; Gricyk, O B; Poveshchenko, O V; Shurlygina, A V; Konenkov, V I

    2017-01-01

    Purpose. Reveal features migration and distribution of syngeneic bone marrow cells (BMC) and subpopulations (MSC) after transplantation into the recipient carrier B16 melanoma bodies. Methods. We used mouse male and female C57BL/6 mice. Induction of Tumor Growth: B16 melanoma cells implanted subcutaneously into right hind paw of female C57BL/6 mice at a dose of 2.5 x 105 cells / mouse. migration study in vivo distribution and BMC and MSC was performed using genetic markers - Y-chromosome specific sequence line male C57Bl/6 syngeneic intravenous transplantation in females using the polymerase chain reaction (PCR) in real time on Authorized Termal Cycler - Light Cycler 480 II / 96 (Roche). Introduction suspension of unseparated bone marrow cells, mesenchymal stem cells from donor to recipient male mice (syngeneic recipient female C57BL/6), followed by isolation of recipients of organs was performed at regular intervals, then of organ recipients isolated DNA. Results. It was shown that bone marrow cells positive for Y-chromosome in migrate lymphoid (lymph nodes, spleen, bone marrow) or in non-lymphoid organs (liver, heart, brain, skin) syngeneic recipients. In addition to the migration of cells from the bone marrow to other organs, there is a way back migration of cells from the circulation to the bone marrow. B16 melanoma stimulates the migration of transplanted MSCs and BMC in bone marrow. It is found that tumor growth enhanced migration of transplanted bone marrow cells, including populations of MSCs in the bone marrow. In the early stages of tumor formation MSC migration activity higher than the BMC. In the later stages of tumor formation undivided population of bone marrow cells migrate to the intense swelling compared with a population of MSCs. Conclusion. The possibility of using bone marrow MSCs for targeted therapy of tumor diseases, because migration of MSCs in tumor tissue can be used to effectively deliver anticancer drugs.

  10. The clinical impact of PET scanning in patients with melanoma: A prospective study

    International Nuclear Information System (INIS)

    Kalff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A.

    1998-01-01

    Full text: Small series have shown that PET scanning using F-18 fluorodeoxyglucose (FDG), can quite accurately stage patients melanoma. At this Institute these patients are only sent for PET imaging if they have high risk melanomas ( >3 Clarke's grade primaries) or there remains any significant doubt as to their clinical staging or management after the completion of conventional screening. This prospective study examines how PET scan findings influenced the clinical management decisions in 53 patients (29 males, mean age 54±13 yrs: range 31-81 yrs) Referring doctors were asked to indicate reason for the PET scan, stage their patients on the basis of all their current investigations, and to indicate their management plans prior to PET scanning. Follow-up of subsequent patient management at 2-4 weeks post PET scan was then obtained and compared to pre PET plans. PET was used to stage 26 patients, restage 17, follow-up 5, assess recurrence in 3, and other in 2 patients. To date follow-up has shown that in 32/49 (65%) patients PET was used to triage patients to locoregional surgery (10 patients), radical radiotherapy (5 patients), or to continuing follow-up only (17 patients). Three further high risk patients with negative PET scans had sentinel mode biopsy. In only 13 patients was management already determined, with planned treatment being changed in 6. Four patients have not had their post PET scan review yet. To date proven false negative PET scans have occurred in 3 cases, 2 sentinel node biopsies showed microscopic disease, and one scan incorrectly labelled gall-bladder melanoma as hydro-nephrotic kidney. Interestingly in 3 cases, PET discovered other unsuspected tumours (rectum x 2, plasmacytoma). PET scanning has been incorporated into routine management to triage most high risk patients, but it still alters interventions in half of those patients where management has already been planned. PET clearly misses small volume disease, the importance of which is

  11. The Danish Melanoma Database

    DEFF Research Database (Denmark)

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

    2016-01-01

    melanoma and 780 with in situ tumors were registered. The coverage is currently 93% compared with the Danish Pathology Register. MAIN VARIABLES: The main variables include demographic, clinical, and pathological characteristics, including Breslow's tumor thickness, ± ulceration, mitoses, and tumor...... studies are based on DMD data. CONCLUSION: DMD holds unique detailed information about tumor characteristics, the surgical treatment, and follow-up of Danish melanoma patients. Registration and monitoring is currently expanding to encompass even more clinical parameters to benefit both patient treatment...

  12. Pathway-based analysis of a melanoma genome-wide association study: analysis of genes related to tumour-immunosuppression.

    Directory of Open Access Journals (Sweden)

    Nils Schoof

    Full Text Available Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs in 43 genes (39 genomic regions related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp=0.002, as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp=0.006 and secretion of suppressive factors (p(emp=0.0004, thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.

  13. Melanoma survivorship: research opportunities.

    Science.gov (United States)

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

    2007-03-01

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

  14. Online, game-based education for melanoma recognition: A pilot study.

    Science.gov (United States)

    Maganty, Nishita; Ilyas, Muneeb; Zhang, Nan; Sharma, Amit

    2018-04-01

    To evaluate the effectiveness of a game-based learning (GBL) intervention, Tapamole, in improving recognition of the features of melanoma (MM) compared to a written education intervention. Tapamole, an online education intervention, was developed using GBL. Participants were voluntarily recruited from the Dermatology waiting room and randomized to three groups: game, pamphlet, and no intervention. Participants completed a pre-intervention survey, post-intervention survey, and test on MM recognition. Clustered binary data equations were used to calculate sensitivity, specificity, and accuracy for each group and GEE model with log link was used to compare measures between groups. Sixty participants were recruited. The sensitivity for MM recognition in the game group was 100% compared to 95% for the pamphlet group. The specificity (40.8% vs 53.3%) and accuracy (60.6% vs 67.2%) of the game and pamphlet groups were similar. Participants in the game group reported higher enjoyment than those in the pamphlet group. GBL was as effective as the written intervention in identifying features of MM. With increasing use of the Internet for health information, it is critical to have effective online education interventions. GBL education tools are effective, enjoyable, and should be used to improve MM patient education. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Familial melanoma associated with dominant ultraviolet radiation sensitivity

    International Nuclear Information System (INIS)

    Ramsay, R.G.; Chen, P.; Imray, F.P.; Kidson, C.; Lavin, M.F.; Hockey, A.

    1982-01-01

    Sensitivity to ultraviolet radiation was studied in lymphoblastoid cell lines derived from 32 members of two families with histories of multiple primary melanomas in several generations. As assayed by colony formation in agar or by trypan blue exclusion following irradiation, cellular sensitivity showed a bimodal distribution. All persons with melanoma or multiple moles were in the sensitive group, while some family members exhibited responses similar to those of controls. Cells from four cases of sporadic melanoma showed normal levels of sensitivity. The data are consistent with a dominantly inherited ultraviolet light sensitivity associated with these examples of familial melanoma. Spontaneous and ultraviolet light-induced sister chromatid exchange frequencies were similar to those in control cell lines. No defect in excision repair was detected in any of the above cell lines, but the sensitive group showed postirradiation inhibition of DNA replication intermediate between controls and an excision-deficient xeroderma pigmentosum cell line

  16. Temozolomide and interferon-alpha in metastatic melanoma: a phase II study of the Italian Melanoma Intergroup.

    Science.gov (United States)

    Ridolfi, Ruggero; Romanini, Antonella; Sileni, Vanna Chiarion; Michiara, Maria; Guida, Michele; Biasco, Guido; Poletti, Paola; Amaducci, Laura; Leoni, Maurizio; Ravaioli, Alessandra

    2004-08-01

    Temozolomide (TMZ) is a new oral alkylating agent which has proven to be as active as dacarbazine (DTIC) in the treatment of melanoma, but with a lower toxicity. A multicentric phase II trial was conducted in an out-patient setting to determine the therapeutic activity and safety of TMZ in combination with interferon-alpha (IFN-alpha). From June 2000 to July 2001, 41 patients were recruited to receive TMZ 200 mg/m orally on days 1-5 every 28 days and with 5 MU IFN-alpha subcutaneously three times a week, continuously for eight cycles or until disease progression occurred. Of the 40 treated patients, two complete responses (5%) and three partial responses (7.5%) were observed, with a median duration of 4 months (range, 1.5-13.5 months). Thirteen patients (32.5%) had stable disease for a median of 2.5 months. Time to progression was 2.6 months and the median overall survival was 11.8 months. Nine patients (22.5%) developed brain metastases. The grade 4 toxicity observed in seven patients was of a transient haematological nature. This combination therapy is well tolerated but does not appear to increase the response rate or overall survival with respect to TMZ alone or to chemotherapeutic regimens. Further and more complex associations of these two drugs could be investigated in specific subsets of patients, in particular to evaluate its real efficacy in preventing brain metastases. Copyright 2004 Lippincott Williams & Wilkins

  17. Multimodal microscopy of immune cells and melanoma for longitudinal studies

    Science.gov (United States)

    Entenberg, David; Aranda, Iana; Li, Yongbiao; Toledo-Crow, Ricardo; Schaer, David; Li, Yanyun

    2006-02-01

    Intravital microscopy of cancer is a well established tool that provides direct visualization of the tumor cycle. It traditionally involves one of several strategies: invasive subcutaneous (SC) implantation of tumors followed by surgical opening of skin flaps for imaging, techniques utilizing skin fold chambers and implanted optical windows or intradermal injections under 200μm from the skin surface. All of these techniques allow the use of fluorescent proteins as markers for biologically significant constituents. However, observation methods utilizing skin-flaps, skin-fold chambers and optical windows are invasive and tend to alter the immune environment of the tissue and/or limit the duration of studies that can be performed. If implanted correctly, intradermally injected tumors can be minimally invasive, will not require biopsies or surgical intervention to observe and are accessible for direct transdermal imaging with a number of in vivo modalities. We present our work in the development of a small animal intravital microscopy workstation that allows the acquisition of different contrast imaging modalities: reflectance confocal, wide field epifluorescence, multiphoton and second harmonic generation (SHG). The images are acquired pair-wise simultaneously and sequentially in time. The aim of our instrumentation is to gather all information generated by the single probing beam via the reflected or back-scattered signal, SHG signal and various fluorescence signals. Additionally, we also present our development of a microscopic tissue navigation technique to mark, label and track sites of interest. This technique enables us to revisit sites periodically and record, with different imaging contrasts, their biological changes over time.

  18. [Melanoma in organ transplant patients].

    Science.gov (United States)

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

    2000-02-01

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

  19. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A. [ISRCTN75125874

    Directory of Open Access Journals (Sweden)

    Ridolfi Ruggero

    2006-02-01

    Full Text Available Abstract Background High-dose interferon alfa-2b (IFNalfa-2b, according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. Methods Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm, or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC three times per week × 48 weeks (High Dose Interferon, HDI, arm. Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. Results The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9% (p = 0.0074, yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week (p = 0.003. Conclusion Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.

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

    Science.gov (United States)

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

    2015-12-01

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

  1. Pediatric Melanoma and Drug Development

    Directory of Open Access Journals (Sweden)

    Klaus Rose

    2018-03-01

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

  2. Management of advanced melanoma

    International Nuclear Information System (INIS)

    Nathanson, L.

    1986-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  4. Comparison of parameters affecting GNP-loaded choroidal melanoma dosimetry; Monte Carlo study

    Science.gov (United States)

    Sharabiani, Marjan; Asadi, Somayeh; Barghi, Amir Rahnamai; Vaezzadeh, Mehdi

    2018-04-01

    The current study reports the results of tumor dosimetry in the presence of gold nanoparticles (GNPs) with different sizes and concentrations. Due to limited number of works carried out on the brachytherapy of choroidal melanoma in combination with GNPs, this study was performed to determine the optimum size and concentration for GNPs which contributes the highest dose deposition in tumor region, using two phantom test cases namely water phantom and a full Monte Carlo model of human eye. Both water and human eye phantoms were simulated with MCNP5 code. Tumor dosimetry was performed for a typical point photon source with an energy of 0.38 MeV as a high energy source and 103Pd brachytherapy source with an average energy of 0.021 MeV as a low energy source in water phantom and eye phantom respectively. Such a dosimetry was done for different sizes and concentrations of GNPs. For all of the diameters, increase in concentration of GNPs resulted in an increase in dose deposited in the region of interest. In a certain concentration, GNPs with larger diameters contributed more dose to the tumor region, which was more pronounced using eye phantom. 100 nm was reported as the optimum size in order to achieve the highest energy deposition within the target. This work investigated the optimum parameters affecting macroscopic dose enhancement in GNP-aided brachytherapy of choroidal melanoma. The current work also had implications on using low energy photon sources in the presence of GNPs to acquire the highest dose enhancement. This study is conducted through four different sizes and concentrations of GNPs. Considering the sensitivity of human eye tissue, in order to report the precise optimum parameters affecting radiosensitivity, a comprehensive study on a wide range of sizes and concentrations are required.

  5. Malignant melanoma of the skin among workers in a telecommunications industry: mortality study 1976-83.

    Science.gov (United States)

    DeGuire, L; Cyr, D; Thériault, G; Provencher, S; Iturra, H; Case, B W

    1992-10-01

    An incidence study of malignant melanoma of the skin (MMS), conducted previously among the workers of four plants of a large telecommunications industry located in Montreal, Canada, showed a standardised incidence ratio of 2.7 (95% confidence interval (95% CI) 1.3-5.02) for the years 1976 to 1983. To describe more precisely the magnitude of the problem a mortality study was started among the same population (n = 9590) for the same period (1976-83). At the end of 1983, 9180 workers were alive, 261 were dead, and 149 (1.5%) were not traced. Standardised mortality ratios (SMRs) for all causes of death were surprisingly low for men (SMR = 0.57; 95% CI 0.50-0.64) and women (SMR = 0.56; 95% CI 0.37-0.82). The SMRs for major causes of death were also less than expected. These results may be explained by a pronounced selection bias (healthy worker effect) and by the short duration of follow up (eight years). For MMS, two deaths occurred among men (SMR = 2.00; 95% CI 0.24-7.22) and one among women (SMR = 4.81; 95% CI 0.12-26.78). A third man who died of MMS was miscoded as having a primary pulmonary melanoma. Including this case increased the SMR for MMS to 3.00 (95% CI 0.62-8.77; p = 0.08). Polyvinyl chloride and polychlorinated biphenyls were used in the plants and some of the workers did soldering. A planned case-control study will investigate other possible exposures at work.

  6. The nature and structure of psychological distress in people at high risk for melanoma: a factor analytic study.

    Science.gov (United States)

    Kasparian, Nadine A; Sansom-Daly, Ursula; McDonald, Roderick P; Meiser, Bettina; Butow, Phyllis N; Mann, Graham J

    2012-08-01

    This study examined the psychometric properties of two commonly used measures of psychological distress, the Hospital Anxiety and Depression Scale (HADS) and the Impact of Events Scale (IES) in a sample of individuals at high risk of developing melanoma due to strong family history. One hundred thirty-two individuals with a known family-specific CDKN2A mutation (74% response rate) completed a mailed, self-administered questionnaire including the HADS and the IES. Initial correlational analyses were followed by both exploratory and confirmatory factor analyses, according to a predetermined procedure for order of analyses. Exploratory factor analyses found that neither a two-, three- or four-factor solution satisfactorily accounted for all IES items in the present sample. By contrast, a unidimensional account of the data emerged to best account for all IES items, leaving no items unaccounted for. In contrast, the traditional two-factor (anxiety and depression) structure of the HADS appeared to fit the data well. The traditional, two-factor (intrusion and avoidance) structure of the IES was not borne out within this familial melanoma cohort. Assessment of a single dimension of emotional distress in response to melanoma risk may facilitate more meaningful explorations of psychological adjustment in this context. These findings also raise questions about whether a post-traumatic stress framework is indeed the most appropriate framework to capture the unique nature of melanoma- or cancer-related distress. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Pigmentary traits, family history of melanoma and the risk of endometriosis: a cohort study of US women.

    Science.gov (United States)

    Kvaskoff, Marina; Han, Jiali; Qureshi, Abrar A; Missmer, Stacey A

    2014-02-01

    Endometriosis has been associated with a higher risk of cutaneous melanoma, but the mechanisms underlying this association are unknown.Some constitutional factors known to influence melanoma risk have been associated with endometriosis in some retrospective studies. However, prospective data are scarce, and more research is needed to confirm this potentially novel endometriosis risk profile. To investigate the relationships between pigmentary traits, family history of melanoma and endometriosis risk, we analysed data from the Nurses’ Health Study II, a cohort of 116 430 female US nurses aged 25–42 years at inclusion in 1989. Data were collected every 2 years with 20 years of follow-up for these analyses. We used Cox proportional hazards regression models to compute relative risks(RRs) and 95% confidence intervals (CIs). During 1 212 499 woman-years of follow-up, 4763 cases of laparoscopically-confirmed endometriosis were reported among premenopausal Caucasian women. Endometriosis risk was increased with presence of naevi on the lower legs (RR=1.08, 95% CI=1.021.14) and higher level of skin’s burning reaction to sun exposure in childhood/adolescence (‘burn with blisters’: RR=1.20,95% CI=1.061.36) compared with ‘practically none’;P(trend)=0.0006) and family history of melanoma (RR=1.13, 95%CI=1.011.26). This assessment reports modest associations between several pigmentary traits, family history of melanoma and endometriosis risk,corroborating the results from previous retrospective studies. Our findings call for further research to better understand the mechanisms under lying these associations.

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

    Science.gov (United States)

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

    2017-02-01

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

  9. Improvement of the quality of BRAF testing in melanomas with nationwide external quality assessment, for the BRAF EQA group

    International Nuclear Information System (INIS)

    Emile, Jean-François; Hofman, Paul; Sabourin, Jean-Christophe; Laurent-Puig, Pierre; Tisserand, Julie; Bergougnoux, Loic; Nowak, Frédérique; Faucher, Gladwys; Surel, Sylvie; Lamy, Aude; Lecorre, Delphine; Helias-Rodzewicz, Zofia

    2013-01-01

    Knowledge about tumour gene mutation status is essential for the treatment of increasing numbers of cancer patients, and testing quality has a major impact on treatment response and cost. In 2012, 4,629 tests for BRAF p.V600 were performed in France, in patients with melanomas. Two batches of unstained melanoma sections were sent, in May and November 2012, to the 46 laboratories supported by the French National Institute of Cancer (INCa). An external quality assessment (EQA) evaluated mutation status, response times and compliance with INCa recommendations. All the French laboratories involved in testing participated in the EQA. Fourteen different methods were used to detect BRAF mutations, most consisting of combinations of in-house techniques. False responses were noted in 25/520 cases (4.8%), 11 of which concerned confusion between p.V600E and p.V600K. Thus, 2.7% of responses would have led to inappropriate treatment. Within six months, mean response times decreased from 22 to 12 days (P<0.001), and the percentage of samples evaluated by a pathologist for tumour cell content increased, from 75.2% to 96.9% (P<0.001). Despite the use of non-certified methods, the false response rate was low. Nationwide EQA can improve the quality of molecular pathology tests on tumours

  10. Ability Grouping in Social Studies.

    Science.gov (United States)

    Social Education, 1992

    1992-01-01

    Presents a position statement of the National Council for the Social Studies (NCSS). Reports that the NCSS objects to ability grouping in social studies. Argues that ability grouping disadvantages minority, handicapped, and low ability students. Suggests that ability grouping undermines the democratic ideals that should be the basis of the social…

  11. Immunohistochemical detection of XIAP in melanoma.

    Science.gov (United States)

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

    2008-03-01

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

  12. Study to determine whether intraoperative frozen section biopsy improves surgical treatment of non-melanoma skin cancer.

    Science.gov (United States)

    Nicoletti, Giovanni; Brenta, Federica; Malovini, Alberto; Musumarra, Gaetano; Scevola, Silvia; Faga, Angela

    2013-03-01

    Skin cancers are the most common types of cancer and their incidence has shown an increase of ∼4 to 8% per year over the last 40 years. The majority of skin cancers (∼97%) are non-melanoma skin cancers, mainly represented by basal cell (80%) and squamous cell carcinomas (20%). The use of intra-operative frozen section remains controversial in the surgical treatment of non-melanoma skin cancer, being commonly considered an optional tool, the reliability and effectiveness of which remain questionable. A large retrospective study was conducted to examine 670 surgical excisions of non-melanoma skin cancers of the head and neck in 481 patients over a period of nine years, between May, 2002 and December, 2011, at the Plastic and Reconstructive Surgery Unit of the University of Pavia, Salvatore Maugeri Research and Care Institute, Pavia, Italy. Results demonstrated the paradoxical ineffectiveness of an intra-operative frozen section biopsy in pursuing higher rates of radical excision in non-melanoma skin cancers. Nevertheless, a more detailed analysis on the use of frozen sections focusing on the various anatomical sites of the body demonstrated a reverse trend in the eyelids and canthi, where a higher success rate (87.50 vs. 69.77%) in the surgical treatment of non-melanoma skin cancers was obtained with the use of an intra-operative frozen section biopsy. Results of the present study suggested that intra-operative frozen section biopsy be routinely used in the surgical treatment of nonmelanoma skin tumors involving the eyelids and canthi.

  13. Primary mediastinal melanoma presenting as superior vena cava syndrome: A case study

    Directory of Open Access Journals (Sweden)

    Ann C Gaffey

    2016-03-01

    Full Text Available The rates of melanoma have increased over the past 30 years. Malignant melanoma most commonly occurs in the skin with secondary involvement of other organs. Here, we present an extremely rare case of malignant melanoma of the mediastinum with presentation of superior vena cava syndrome without clinical evidence of extrathoracic disease. The incidence of this clinical presentation is uncommon, resulting in only a handful of case reports in the literature. [Arch Clin Exp Surg 2016; 5(1.000: 56-58

  14. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

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

  15. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-05

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

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

    Science.gov (United States)

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

    2018-02-01

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

  17. 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.

  18. 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

  19. 131/123 iodine labeled benzamides for the detection of melanomas and metastases. Synthesis, labeling, animal experiences and preliminary clinical studies; Benzamidas marcadas con 131/123 iodo para deteccion de melanomas y metastasis. Sintesis, marcacion, estudio en animales y primeros estudios clinicos

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi, Oscar R; Edreira, Martin M; Castiglia, Silvia G [Comision Nacional de Energia Atomica, Ezeiza (Argentina). Dept. de Radioquimica; Zarlenga, Ana C; Arashiro, Jorge G; Parma, P [Instituto de Oncologia Angel H. Roffo, Buenos Aires (Argentina); Soroa, Victoria E [Hospital Clinicas Jose de San Martin, Buenos Aires (Argentina)

    1999-07-01

    Radioiodine labeled benzamides are being studied as radiopharmaceuticals for the detection of melanomas and metastases. With this purpose the synthesis and labeling of N-(2-diethylaminoethyl)-3-[{sup 131}I]-4-methoxybenzamide (IMBA) has been carried out. Tissue distribution of the labeled compound has been studied in C 57 mice, showing a fast renal excretion. The labeled benzamide was also injected in mice with previously induced subcutaneous melanomas and lung metastases using B 16-F0 murine melanoma cells. The tumors show a good uptake of the labeled benzamide. The melanoma/other tissues uptake ratio is suitable for scintigraphic detection. Clinical studies in patients are under way. (author)

  20. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Nausicaa Clemente

    2018-01-01

    Full Text Available Aim: To develop an innovative delivery system for temozolomide (TMZ in solid lipid nanoparticles (SLN, which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies.

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

    Science.gov (United States)

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

  2. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Science.gov (United States)

    Ferrara, Benedetta; Biasibetti, Elena; Schiffer, Davide; Mellai, Marta; Annovazzi, Laura; Cangemi, Luigi; Muntoni, Elisabetta; Dianzani, Umberto

    2018-01-01

    Aim: To develop an innovative delivery system for temozolomide (TMZ) in solid lipid nanoparticles (SLN), which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies. PMID:29364157

  3. Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

    2003-07-01

    Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Reduced frequency of non-melanoma skin cancer in 72,739 patients with psoriasis: a retrospective study.

    Science.gov (United States)

    Paradisi, Andrea; Didona, Biagio; Tabolli, Stefano; Ricci, Francesco; Sobrino, Luciano; Panebianco, Annarita; Abeni, Damiano

    2017-08-01

    Chronic inflammatory conditions, such as psoriasis, may pose an increased risk of cancer due to impaired immunosurveillance resulting from chronic inflammation and immunosuppressive medications. To compare the risk of non-melanoma skin cancer (NMSC) in a retrospective cohort of 72,739 psoriasis patients and 25,956 non-dermatological patients. A record linkage was performed for data on hospitalizations, and the occurrence of NMSC was compared by computing the relative risk (RR) and modelled using multiple logistic regression. Overall, the occurrence of NMSC was 9.6‰ (95% CI: 8.9-10.3‰) in psoriasis patients and 19.6‰ (95% CI: 18.0-21.4‰) in non-dermatological patients (RR = 0.49; 95% CI: 0.44-0.55). The simultaneous adjustment for gender, age, and phototherapy yielded a RR of 0.84 (95% CI: 0.75-0.95). With regards to phototherapy, the occurrence of NMSC was significantly higher among psoriasis patients who underwent phototherapy relative to those who did not (27.0‰ vs. 9.3‰). In this large retrospective study, we found that patients with psoriasis had a 16% lower probability of having NMSC when compared to a group of non-dermatological patients. Further studies, preferably with a prospective longitudinal design to collect more precise data, are needed to corroborate our findings.

  6. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naïve patients with metastatic uveal melanoma.

    Directory of Open Access Journals (Sweden)

    Lisa Zimmer

    Full Text Available Up to 50% of patients with uveal melanoma (UM develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM.We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs, including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC v.4.0. Primary endpoint was the OS rate at 12 months.Forty five pretreated (85% and eight treatment-naïve (15% patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7-8.1, median progression-free survival 2.8 months (95% CI 2.5-2.9. The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%, none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%, including 19 grade 3-4 events (36%. One drug-related death due to pancytopenia was observed.Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines.ClinicalTrials.gov NCT01355120.

  7. Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

    Science.gov (United States)

    Zimmer, Lisa; Vaubel, Julia; Mohr, Peter; Hauschild, Axel; Utikal, Jochen; Simon, Jan; Garbe, Claus; Herbst, Rudolf; Enk, Alexander; Kämpgen, Eckhart; Livingstone, Elisabeth; Bluhm, Leonie; Rompel, Rainer; Griewank, Klaus G.; Fluck, Michael; Schilling, Bastian; Schadendorf, Dirk

    2015-01-01

    Purpose Up to 50% of patients with uveal melanoma (UM) develop metastatic disease with limited treatment options. The immunomodulating agent ipilimumab has shown an overall survival (OS) benefit in patients with cutaneous metastatic melanoma in two phase III trials. As patients with UM were excluded in these studies, the Dermatologic Cooperative Oncology Group (DeCOG) conducted a phase II to assess the efficacy and safety of ipilimumab in patients with metastatic UM. Patients and Methods We undertook a multicenter phase II study in patients with different subtypes of metastatic melanoma. Here we present data on patients with metastatic UM (pretreated and treatment-naïve) who received up to four cycles of ipilimumab administered at a dose of 3 mg/kg in 3 week intervals. Tumor assessments were conducted at baseline, weeks 12, 24, 36 and 48 according to RECIST 1.1 criteria. Adverse events (AEs), including immune-related AEs were graded according to National Cancer Institute Common Toxicity Criteria (CTC) v.4.0. Primary endpoint was the OS rate at 12 months. Results Forty five pretreated (85%) and eight treatment-naïve (15%) patients received at least one dose of ipilimumab. 1-year and 2-year OS rates were 22% and 7%, respectively. Median OS was 6.8 months (95% CI 3.7–8.1), median progression-free survival 2.8 months (95% CI 2.5–2.9). The disease control rate at weeks 12 and 24 was 47% and 21%, respectively. Sixteen patients had stable disease (47%), none experienced partial or complete response. Treatment-related AEs were observed in 35 patients (66%), including 19 grade 3–4 events (36%). One drug-related death due to pancytopenia was observed. Conclusions Ipilimumab has very limited clinical activity in patients with metastatic UM. Toxicity was manageable when treated as per protocol-specific guidelines. Trial Registration ClinicalTrials.gov NCT01355120 PMID:25761109

  8. Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study.

    Science.gov (United States)

    El Sayed, Salah Mohamed; Mohamed, Walaa Gamal; Seddik, Minnat-Allah Hassan; Ahmed, Al-Shimaa Ahmed; Mahmoud, Asmaa Gamal; Amer, Wael Hassan; Helmy Nabo, Manal Mohamed; Hamed, Ahmed Roshdi; Ahmed, Nagwa Sayed; Abd-Allah, Ali Abdel-Rahman

    2014-07-01

    3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP

  9. RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers

    Directory of Open Access Journals (Sweden)

    Van L.T. Hoang

    2017-08-01

    Full Text Available Identification of appropriate reference genes (RGs is critical to accurate data interpretation in quantitative real-time PCR (qPCR experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.

  10. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    Science.gov (United States)

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

  11. An optimization study for radioiodination of a new synthesized benzamide derivative as an analogue tracer for malignant melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban A.; Aglan, Hany; Seddik, Usama [Atomic Energy Authority, Cairo (Egypt). Nuclear Research Center; EL-Kafrawy, Ahmed F. [Ain Shams Univ., Cairo (Egypt). Faculty of Science

    2017-03-01

    Iodobenzamides are reported to possess some affinity for melanoma. This study describes the synthesis of a new benzamide analogue, N-(2-diethylamino-ethyl)-4-(4-chloro-nicotinamido)-5-[{sup 125}I]iodo-2 -methoxybenz amide ([{sup 125}I]H4) designed to target melanoma. The synthesis was simply achieved in four steps. There were two PyCIU/DIPEA amide condensations and a transfer hydrogenation using an ammonium formate hydrogen donor. The radioiodination step was carried out with {sup 125}I via an electrophilic substitution reaction. The reaction conditions were optimized. The labeled compound was purified by HPLC. The maximum radiochemical yield was found to be 78% at a radiochemical purity of 98%. All compounds were characterized by MS and NMR techniques. The log P value for [{sup 125}I]H4 was found as 3.96±0.5.

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

    Science.gov (United States)

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

    2016-05-01

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

  13. Spice Blocks Melanoma Growth

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

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

  14. Predictive value of early {sup 18}F-FDG PET/CT studies for treatment response evaluation to ipilimumab in metastatic melanoma: preliminary results of an ongoing study

    Energy Technology Data Exchange (ETDEWEB)

    Sachpekidis, Christos; Pan, Leyun; Dimitrakopoulou-Strauss, Antonia [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Larribere, Lionel [German Cancer Research Center, Clinical Cooperation Unit Dermato-Oncology, Heidelberg (Germany); Haberkorn, Uwe [German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany); Hassel, Jessica C. [University Hospital Heidelberg, Skin Cancer Center, Department of Dermatology, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany)

    2014-10-31

    Ipilimumab is a newly approved immunotherapeutic agent that has been shown to provide a survival benefit in patients with metastatic melanoma. {sup 18}F-FDG PET/CT has demonstrated very satisfying results in detecting melanoma metastases in general. Using {sup 18}F-FDG PET/CT we monitored patients with metastatic melanoma undergoing ipilimumab therapy during the course of treatment. The aim of our study was to evaluate the role of {sup 18}F-FDG PET/CT performed after two cycles of ipilimumab in predicting the final response to therapy. In 22 patients suffering from unresectable metastatic melanoma, scheduled for ipilimumab treatment PET/CT scanning was performed before the start of treatment (baseline scan), after two cycles of treatment (early response) and at the end of treatment after four cycles (late response). Evaluation of the patient response to treatment on PET was based on the European Organization for Research and Treatment of Cancer 1999 criteria. Progression-free survival (PFS) and overall survival (OS) data are presented. After the end of treatment, 15 patients were characterized as having progressive metabolic disease (PMD) and five as having stable metabolic disease (SMD), and two patients showed a partial metabolic response (PMR). Early PET/CT performed after two ipilimumab cycles predicted treatment response in 13 of the 15 PMD patients, in five of the five SMD patients and in neither of the two PMR patients. Both patients with PMR showed pseudoprogression after the second cycle and were therefore wrongly classified. According to the patients' clinical outcome, patients with late PMD had a median PFS of 3.6 months (mean 5.6 months), while patients with late SMD had a median PFS of 9.8 months (mean 9.0 months). In comparison, patients with early PMD had a median PFS of 2.7 months (mean 5.5 months) and patients with early SMD had a median PFS of 6.3 months (mean 7.5 months). The difference in PFS between the two groups was statistically

  15. 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...

  16. Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases.

    Science.gov (United States)

    Ramos-Vara, J A; Beissenherz, M E; Miller, M A; Johnson, G C; Pace, L W; Fard, A; Kottler, S J

    2000-11-01

    Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.

  17. Contribution of whole body F-18-FDG-PET and lymphoscintigraphy to the assessment of regional and distant metastases in cutaneous malignant melanoma. A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Klein, M.; Freedman, N.; Marciano, R.; Moshe, S.; Chisin, R. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Medical Biophysics and Nuclear Medicine; Lotem, M. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Oncology; Gimon, Z. [Hadassah Univ. Hospital, Jerusalem (Israel). Dept. of Surgery

    2000-05-01

    Aim: This pilot study describes use of whole body PET (WB PET) for staging of melanoma. WB PET in conjunction with lymphoscintigraphy (LS) for evaluating status of the sentinel lymph node (SLN) in primary melanoma was investigated with comparison to histopathological results. WB PET was also used both for primary and metastatic melanoma for screening for distant metastases, restaging and follow-up. Methods: Group I: 17 patients with primary cutaneous melanoma underwent LS, WB PET and SLN dissection. WB PET findings were compared with biopsy results at the SLN site and were used for screening for distant metastases. Group II: 17 patients with a history of melanoma underwent WB PET for follow-up and/or restaging. Results were confirmed or refuted by other radiological modalities or by biopsy of clinical follow-up. Results: Group I: Out of 20 SLNs identified by LS in the 17 patients, 18 were negative on WB PET and 2 were positive. 19/20 WB PET findings were confirmed either by histopathology or by clinical follow-up (20 mo). Accuracy was 94% for the assessment of the status of the SLN. Group II: WB PET findings altered staging and treatment in 12/17 patients and confirmed the validity of treatment in 3/17 patients. Overall, in 15/17 patients (88%), WB PET had an impact on treatment strategy. (orig.) [German] Ziel: Diese Pilot-Studie beschreibt die Anwendung der Ganzkoerper-PET (WB PET) zum Staging beim Melanom. Bei primaerem Melanom wurde WB PET in Verbindung mit der Lymphszintigraphie (LS) angewandt und mit der Histopathologie verglichen, um den Status des Sentinel Lymph Node (SLN) zu untersuchen. Zusaetzlich wurde WB PET fuer primaere und metastatische Melanome zum Screening auf Fernmetastasen, zum Restaging und zum Follow-up benutzt. Methoden: Gruppe I: 17 Patienten mit primaerem kutanem Melanom erhielten LS, WB PET und eine operative SLN-Entfernung. Die WB PET-Ergebnisse wurden mit den SLN-Biopsien verglichen und zum Screening fuer Fernmetastasen benutzt. Gruppe

  18. The diagnostic value and histologic correlate of distinct patterns of shiny white streaks for the diagnosis of melanoma: A retrospective, case-control study.

    Science.gov (United States)

    Verzi, Anna Eliza; Quan, Victor L; Walton, Kara E; Martini, Mary C; Marghoob, Ashfaq A; Garfield, Erin M; Kong, Betty Y; Isales, Maria Cristina; VandenBoom, Timothy; Zhang, Bin; West, Dennis P; Gerami, Pedram

    2018-05-01

    Shiny white streaks (SWSs) are best visualized with polarized dermoscopy and correlate with dermal fibroplasia histopathologically. SWSs have been described at higher frequencies in melanomas than in benign nevi. We assessed the diagnostic value of different patterns of SWSs and their histologic correlate in melanocytic lesions. Polarized dermoscopic images of 1507 histopathologically diagnosed melanocytic neoplasms were analyzed for presence and pattern of SWSs. Histology was also reviewed for correlation. Among 1507 melanocytic neoplasms, SWSs were observed in 31 of 144 melanomas (22%) and 22 of 1363 benign neoplasms (1.6%) (P < .001). The sensitivity and specificity of SWSs for melanoma were 22% and 98%, respectively. Diffuse SWSs exhibited the greatest diagnostic value for melanoma, with sensitivity of 11.8% and specificity of 99.5%. Focal central and peripheral SWSs were comparable in diagnostic significance. The presence of SWSs was highly uncommon in dysplastic nevi, whereas in certain benign subgroups of nevi such as Spitz nevi and atypical genital special site nevi, SWSs were not uncommon. Diffuse SWSs correlated with greater breadth of deep fibroplasia than focal SWSs (P = .009), and SWSs correlated with greater Breslow depth among melanomas (P = .007). This study was retrospective. Polarized dermoscopy is a valuable diagnostic tool in the identification of SWSs, a feature that is highly specific for melanoma. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  19. 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.

  20. Clear Cell Sarcoma (Malignant Melanoma of Soft Parts: A Clinicopathologic Study of 52 Cases

    Directory of Open Access Journals (Sweden)

    O. Hocar

    2012-01-01

    Full Text Available Clear cell sarcomas are aggressive, rare soft tissue tumors and their classification among melanoma or sarcoma is still undetermined due to their clinical, pathologic, and molecular properties found in both types of tumors. This is a retrospective study of 52 patients with CCS seen between April 1979 and April 2005 in two institutions. The EWS-ATF-1 fusion transcript was studied in 31 patients and an activating mutation of the BRAF or NRAS gene was researched in 22 patients. 30 men and 22 women, with a mean age of 33 were studied. Forty-three tumors (82.69% were located in the extremities, specially the foot (19 tumors. Median initial tumor size was 4.8 cm (1 to 15 cm. Necrosis involving more than 50% of the tumor cells was found in 14 cases (26.92%. High mitotic rate (>10 was found in 25 cases (48.07%. The EWS/ATF-1 translocation was found in 28 (53.84% of 31 patients studied, and mutation of BRAF or NRAS was found in only 2 of 22 patients analyzed cases (3.84%. Among the tumor-associated parameters, only tumor size (>4 cm emerged as a significant prognostic factor. Forty-nine patients had a localized disease at diagnosis (94.23% and underwent surgical resection immediately (90% or after neoadjuvant chemotherapy (CT (10%. Various CT regimens were used in 37 patients (71.15% with no significant efficacy. The 5- and 10-year OS rates were 59% and 41%, respectively. Tumor size was the only emerging prognosis factor in our series. Complete surgical resection remains the optimal treatment for this aggressive chemoresistant tumor.

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

    DEFF Research Database (Denmark)

    Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

    2017-01-01

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

  2. Genetic analysis of the vitamin D receptor gene in two epithelial cancers: melanoma and breast cancer case-control studies

    International Nuclear Information System (INIS)

    Barroso, Eva; Arias, Jose I; Zamora, Pilar; Blanco, Monserrat; Lazaro, Pablo; Benitez, Javier; Ribas, Gloria; Fernandez, Lara P; Milne, Roger L; Pita, Guillermo; Sendagorta, Elena; Floristan, Uxua; Feito, Marta; Aviles, Jose A; Martin-Gonzalez, Manuel

    2008-01-01

    Vitamin D serum levels have been found to be related to sun exposure and diet, together with cell differentiation, growth control and consequently, cancer risk. Vitamin D receptor (VDR) genotypes may influence cancer risk; however, no epidemiological studies in sporadic breast cancer (BC) or malignant melanoma (MM) have been performed in a southern European population. In this study, the VDR gene has been evaluated in two epithelial cancers BC and MM. We have conducted an analysis in 549 consecutive and non-related sporadic BC cases and 556 controls, all from the Spanish population, and 283 MM cases and 245 controls. Genotyping analyses were carried out on four putatively functional SNPs within the VDR gene. An association with the minor allele A of the non-synonymous SNP rs2228570 (rs10735810, FokI, Met1Thr) was observed for BC, with an estimated odds ratio (OR) of 1.26 (95% CI = 1.02–1.57; p = 0.036). The synonymous variant rs731236 (TaqI) appeared to be associated with protection from BC (OR = 0.80, 95%CI = 0.64–0.99; p = 0.047). No statistically significant associations with MM were observed for any SNP. Nevertheless, sub-group analyses revealed an association between rs2228570 (FokI) and absence of childhood sunburns (OR = 0.65, p = 0.003), between the 3'utr SNP rs739837 (BglI) and fair skin (OR = 1.31, p = 0.048), and between the promoter SNP rs4516035 and the more aggressive tumour location in head-neck and trunk (OR = 1.54, p = 0.020). In summary, we observed associations between SNPs in the VDR gene and BC risk, and a comprehensive analysis using clinical and tumour characteristics as outcome variables has revealed potential associations with MM. These associations required confirmation in independent studies

  3. Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study.

    Science.gov (United States)

    Espinosa, Enrique; Soriano, Virtudes; Malvehy, Josep; Berrocal, Alfonso; Martínez de Prado, Purificación; Quindós, María; Soria, Ainara; Márquez-Rodas, Iván; Palacio, Isabel; Cerezuela, Pablo; López-Vivanco, Guillermo; Alonso, Lorenzo; Samaniego, Elia; Ballesteros, Ana; Puértolas, Teresa; Díaz-Beveridge, Rodrigo; de la Cruz-Merino, Luis; López Castro, Rafael; López López, Rafael; Stevinson, Kendall; Del Barrio, Patricia; Tornamira, Maria V; Guillém, Vicente; Martín-Algarra, Salvador

    2016-06-01

    Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.

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

    International Nuclear Information System (INIS)

    Robsahm, Trude E; Karagas, Margaret R; Rees, Judy R; Syse, Astri

    2014-01-01

    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

  5. A retrospective study comparing the accuracy of prehistology diagnosis and surgical excision of malignant melanomas by general practitioners and hospital specialists.

    Science.gov (United States)

    Bakhai, M; Hopster, D; Wakeel, R

    2010-01-01

    A retrospective study was carried out to compare the overall standard of surgical excision of malignant melanomas (MMs) between general practitioners (GPs) and hospital specialists before and after the introduction of the UK melanoma guidelines between 1989 and 2006. In total, 213 melanoma excision reports were examined and surgical excision margins recorded. The results showed a significant difference in the rate of adequate surgical excision margins (at all levels of Breslow thickness) between GPs and hospital specialists, with hospital specialists excising melanomas with safe surgical excision margins at a significantly higher rate compared with GPs. Since the introduction of the guidelines in 2002, GPs showed a significant improvement in the completeness of melanoma excision but remained poor at prehistology diagnosis and in particular at taking adequate excision margins. Implementation of the guidelines has not produced significant improvements in adequacy of excision margins in both primary and secondary care. The results show that hospital specialists maintained a high standard of prehistological diagnosis and completeness of excision throughout the time of the study, performing at a significantly higher standard compared with GPs. Our conclusions concur with the UK melanoma guidelines and the National Institute for Health and Clinical Excellence guidelines, which suggest that lesions suspicious for melanoma should be urgently referred to a dermatologist or plastic surgeon for surgical excision and should not be surgically excised in primary care, particularly if lesions have a Breslow thickness > 2 mm. We suggest that the new guidelines need to be more aggressively implemented in primary care and guidance introduced to improve the accuracy of diagnosis, with better training provided for GPs.

  6. Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.

    Science.gov (United States)

    Viray, Hollis; Bradley, William R; Schalper, Kurt A; Rimm, David L; Gould Rothberg, Bonnie E

    2013-08-01

    The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

  7. Preclinical study of selective thermal neutron capture treatment of pigs having spontaneous melanoma using melanin productive activity

    International Nuclear Information System (INIS)

    Miyashita, Ichiro; Sawaya, Hiroshi; Nomura, Toyoichiro

    1980-01-01

    Four pigs having spontaneous melanoma were irradiated with 0.5 - 2 x 10 13 n/cm 2 of thermal neutron under remote anesthesia. Compounds of 10 B used in this experiment were 10 B 12 -chlorpromazine ( 10 B 12 -CPZ), 10 B-dopa, and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA), and they were injected into melanoma or regions around melanoma. After irradiation of thermal neutron, melanoma tended to reduce in four pigs, and melanoma cells in white fur and hair bulb disappeared in 3 of 4 pigs. Hematological examinations and blood chemistry tests did not show any changes in blood findings both before and after the irradiation, and white blood cell counts were within a normal range. Dermatitis following the irradiation disappeared one week later. Histological changes one month after the irradiation indicated that many melanophages feeding melanosome replaced melanoma cells, which suggested disintegration of melanoma cells. Marked effectiveness of this treatment was recognized in each pig. 10 B-BPA.HCI was injected into one pig twice, and its accumulation in melanoma and normal regions around melanoma was expressed as boron concentrations. As a result, the accumulation in melanoma (6.6 μg/g wet tissue) was 3.1 times as much as that in normal regions around melanoma (2.1 μg/g wet tissue). (Tsunoda, M.)

  8. Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies [Corrigendum

    Directory of Open Access Journals (Sweden)

    Legut M

    2015-09-01

    Full Text Available Anacardic acid enhances the anticancer activity of liposomal mitoxantrone towards melanoma cell lines – in vitro studies [Corrigendum]Legut M, Lipka D, Filipczak N, et al. Int J Nanomedicine. 2014;9:653–668.The authors advise the Acknowledgment on page 666 is missing the final sentence:This study was supported by: the Wrocław Research Centre EIT+ under the Biotechnologies and Advanced Medical Technologies project; BioMed (POIG.01.01.02-02-003/08, financed by the European Regional Development Fund (Operational Programme Innovative Economy, 1.1.2 #8221.Read the original article

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

    Science.gov (United States)

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

    2017-11-01

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

  10. Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

    Science.gov (United States)

    Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

    2018-01-01

    Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

  11. Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

    International Nuclear Information System (INIS)

    Zenda, Sadamoto; Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi

    2011-01-01

    Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

  12. Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Zenda, Sadamoto [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan)

    2011-09-01

    Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

  13. Approach to Malign Melanoma in Anorectal Area

    Directory of Open Access Journals (Sweden)

    Huseyin Pulat

    2014-12-01

    Full Text Available Aim: Anorectal malign melanoma comprise 0.2-1 % of all malign melanoma. They are extremely aggressive. Most patients are lost beacuse of incurable systemic illness. In our study, we aim to evaluate the results of surgical and oncological follow-up of our patients that we operated because of anorectal malign melanoma. Material and Method: Our 4 patients operated because of anorectal malign melanoma between October 2008 and April 2013 were analysed. The patients were analysed in terms of demographic datas, complaint and its time, physical examination and imaging findings, treatment procedure, local recurrence or presence of metastasis and follow-up results.Results: Our study group comprised 4 people (2 men and 2 women with the mean age of 64,2 years. The main complaint was rectal bleeding. The avarage complaint duration was 7.5 months. In all patients, anorectal mass was detected after physical examination and imaging studies. Biopsies of the mass were reported to be consistent with malign melanoma. With the further studies, one patient was detected to have metastasis in liver. Abdominoperineal resection was applied to one patient after wide local excision and to three patients during the first aplication. The avarage follow-up time was 19,25 months. The avarage diameter of tumor was 3,9 cm. One patient was applied lymph node dissection because of recurrence in iliac region. The avarage stay time at hospital of the patients who had no postoperative problems was 9,7 days. During follow-up time, three of the patients died because of common metastasis. A patient followed regularly is still continuing his life without illness in his postoperative 22nd month. Discussion: Anorectal malign melanoma is a rare, with a bad prognosis and a late diagnosed entity as it has a similarity with benign illnesses which are mostly seen in anorectal area in terms of clinical symptoma. To correct the prognosis of the illness, the suitable surgery and adjuvant treatment

  14. Malignant melanoma and radiotherapy: past myths, excellent local control in 146 studied lesions at Georgetown University, and improving future management

    International Nuclear Information System (INIS)

    Jahanshahi, Pooya; Nasr, Nadim; Unger, Keith; Batouli, Ali; Gagnon, Gregory J.

    2012-01-01

    Introduction: Once thought to be radioresistant, emerging cellular and clinical evidence now suggests melanoma can respond to large radiation doses per fraction. Materials and Methods: We conducted a retrospective study of all patients treated with stereotactic radiosurgery and stereotactic body radiotherapy at Georgetown University Hospital from May 2002 through November 2008 and studied the classic extrapolated total dose corrected for volume (ETD vol ) model for predicting melanoma tumor response. Region-specific tumor outcomes were categorized by RECIST criteria and local control curves were estimated and analyzed when stratified by ETD vol thresholds by use of the Kaplan–Meier method. Results: Follow-up information was available for 78 lesions (49 intracranial, 8 spinal, and 21 body) with mean follow-up period of 9.2 (range, 2–36) months. 1-year local control rates for intracranial, spinal, and body tumors were 84, 100, and 72%, respectively. Treatments in general were well-tolerated. Increased ETD vol (p < 0.001) among intracranial sites resulted from larger (p < 0.001) doses per fraction combined with smaller (p < 0.001) tumor diameters. Intracranial 6-, 12-, and 24-month local control rates when treated above ETD vol threshold of 230 Gy were all 90 vs. 89, 80, and 53% below this threshold. Body 6- and 12-month local control rates when treated above ETD vol threshold of 100 Gy were 100 and 80% vs. 74 and 59% below this threshold. Discussion: By tailoring to melanoma’s unique radiobiology with large radiation doses per fraction, favorable local control was safely achieved. The ETD vol model combines the important factor of dose per fraction in melanoma treatment with a volume correction factor to predict tumor response. Although limited sample size may have prevented reaching statistical significance for local control improvements using ETD vol thresholds, optimal thresholds may exist to improve future tumor responses and further research is required.

  15. Depression, anxiety and quality of life in long-term survivors of malignant melanoma: a register-based cohort study.

    Directory of Open Access Journals (Sweden)

    Manfred E Beutel

    Full Text Available The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma.In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2% completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7 and depression (PHQ-9 and the EORTC Quality of Life Questionnaire (EORTC QLQ 30. Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population.An average of 8.4 (5.7 to 12.2 years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients. Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women, but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases.Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

  16. Alternative Dose for Choroidal Melanoma Treated With an Iodine-125 Radioactive Plaque: A Single-Institution Retrospective Study

    International Nuclear Information System (INIS)

    Saconn, Paul A.; Gee, Christopher J.; Greven, Craig M.; McCoy, Thomas P.; Ekstrand, Kenneth E.; Greven, Kathryn M.

    2010-01-01

    Purpose: The Collaborative Ocular Melanoma Study (COMS) established iodine-125 plaque brachytherapy as an accepted standard treatment for medium-size choroidal melanoma. In the COMS, the prescription dose was 85 Gy. This is a retrospective review of our outcomes in patients treated with lower doses than those used in the COMS. Methods and Materials: From 1990 to 2004, 62 patients were treated with iodine-125 plaque brachytherapy for choroidal melanoma. COMS eye plaques were used with dose prescribed to the apex of the tumor. The median and average dose rates at the tumor apex were 63.5 cGy/h and 62.7 cGy/h, respectively. The median and average total doses were 63.0 Gy and 62.5 Gy (range, 56-69 Gy), respectively. The median and mean durations of implant were 100.0 hours and 101.1 hours (range, 71-165 hours). Results: Median follow-up time was 58.2 months. The 5-year outcomes including overall survival, disease-free survival, cause-specific survival, local failure, secondary enucleation rate, and visual acuity (VA) <20/200 were estimated using the Kaplan-Meier method. Overall, there were 7 local failures, 4 distant failures, and 10 secondary enucleations (6 due to local failure and 4 due to treatment complications). Univariate analysis was performed to identify significant prognostic factors associated with disease-free survival (baseline VA in tumor eye, tumor shape), cause-specific survival (diabetic retinopathy), local failure (none found), secondary enucleation rate (diabetic retinopathy, basal tumor dimension) and VA <20/200 (diabetic retinopathy, tumor shape, age, retinal detachment, treatment depth, and history of vision-limiting condition). Conclusions: Our survival and local control outcomes are comparable to those of the COMS. However, VA at 5 years seems to be better. Lower doses of radiation could potentially lead to better visual outcomes.

  17. Apoptosis, energy metabolism, and fraction of radiobiologically hypoxic cells: a study of human melanoma multicellular spheroids.

    Science.gov (United States)

    Rofstad, E K; Eide, K; Skøyum, R; Hystad, M E; Lyng, H

    1996-09-01

    The magnitude of the fraction of radiobiologically hypoxic cells in tumours is generally believed to reflect the efficiency of the vascular network. Theoretical studies have suggested that the hypoxic fraction might also be influenced by biological properties of the tumour cells. Quantitative experimental results of cell energy metabolism, hypoxia- induced apoptosis, and radiobiological hypoxia are reported here. Human melanoma multicellular spheroids (BEX-c and WIX-c) were used as tumour models to avoid confounding effects of the vascular network. Radiobiological studies showed that the fractions of hypoxic cells in 1000-microM spheroids were 32 +/- 12% (BEX-c) and 2.5 +/- 1.1% (WIX-c). The spheroid hypoxic volume fractions (28 +/- 6% (BEX-c) and 1.4 +/- 7% (WIX-c)), calculated from the rate of oxygen consumption per cell, the cell packing density, and the thickness of the viable rim, were similar to the fractions of radiobiologically hypoxic cells. Large differences between tumours in fraction of hypoxic cells are therefore not necessarily a result of differences in the efficiency of the vascular network. Studies of monolayer cell cultures, performed to identify the biological properties of the BEX-c and WIX-c cells leading to this large difference in fraction of hypoxic cells, gave the following results: (1) WIX-c showed lower cell surviving fractions after exposure to hypoxia than BEX-c, (2) WIX-c showed higher glucose uptake and lactate release rates than BEX-c both under aerobic and hypoxic conditions, and (3) hypoxia induced apoptosis in WIX-c but not in BEX-c. These observations suggested that the difference between BEX-c and WIX-c spheroids in fraction of hypoxic cells resulted partly from differences in cell energy metabolism and partly from a difference in capacity to retain viability under hypoxic stress. The induction of apoptosis by hypoxia was identified as a phenomenon which has an important influence on the magnitude of the fraction of

  18. Indoor tanning in businesses and homes and risk of melanoma and nonmelanoma skin cancer in 2 US case-control studies.

    Science.gov (United States)

    Ferrucci, Leah M; Vogel, Rachel Isaksson; Cartmel, Brenda; Lazovich, DeAnn; Mayne, Susan T

    2014-11-01

    Indoor tanning increases skin cancer risk. Beyond early research describing melanoma and sun lamps, few recent reports describe where individuals indoor tan and whether skin cancer risk varies by location (business, home-based). We sought to assess where individuals tanned indoors and skin cancer risk by tanning device location. Multivariate logistic regression was conducted in 2 US case-control studies of melanoma (1161 cases, 1083 controls, ages 25-59 years) and early-onset basal cell carcinoma (375 cases, 382 controls, agetanned exclusively in businesses. Persons who used indoor tanning exclusively in businesses were at increased risk of melanoma (odds ratio 1.82, 95% confidence interval 1.47-2.26) and basal cell carcinoma (odds ratio 1.69, 95% confidence interval 1.15-2.48) compared with non-users. Melanoma risk was also increased in the small number who reported tanning indoors only at home relative to non-users (odds ratio 4.14, 95% confidence interval 1.75-9.78); 67.6% used sun lamps. Self-reported tanning and potential recall bias are limitations. Business-only tanning, despite claims of "safe" tanning, was positively associated with a significant risk of melanoma and basal cell carcinoma. Home tanning was uncommon and mostly from sun lamps, which were rarely used by younger participants. Regardless of location, indoor tanning was associated with increased risk of skin cancer. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-12-01

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

  20. Effect of DETOX as an adjuvant for melanoma vaccine.

    Science.gov (United States)

    Schultz, N; Oratz, R; Chen, D; Zeleniuch-Jacquotte, A; Abeles, G; Bystryn, J C

    1995-04-01

    The identification of effective adjuvants is critical for tumor vaccine development. Towards this end, we examined whether the immunogenicity of a melanoma vaccine could be potentiated by DETOX, an adjuvant consisting of monophosphoryl lipid A (MPL) and purified mycobacterial cell-wall skeleton (CWS). Nineteen patients with resected stage III melanoma were immunized with a polyvalent melanoma antigen vaccine (40 micrograms) admixed with DETOX, q3 wks x 4. Seven patients received vaccine + low-dose DETOX (10 micrograms MPL + 100 micrograms CWS) and 12 received vaccine + high-dose DETOX (20 micrograms MPL + 200 micrograms CWS). A non-randomized control group of 35 patients was treated similarly with 40 micrograms vaccine + alum. One week after the fourth vaccine immunization, melanoma antibodies were increased over baseline in 7/7 (100%) patients treated with vaccine + low-dose DETOX, 8/12 (67%) patients treated with vaccine + high-dose DETOX, and in 4/19 (21%) of vaccine + alum patients. For the entire DETOX group, the antibody response rate was 15/19 (79%) compared 4/19 (21%) in the alum group (p or = 15 mm increase in DTH response over baseline) was induced in 50% of the entire DETOX group versus in 47% of the alum group. Median disease-free (DF) survival for the entire DETOX group was 17.8 months compared with 32.1 months in the alum group (p DETOX markedly potentiated antibody but had little effect on DTH responses to melanoma vaccine immunization. It did not appear to improve disease-free survival in comparison to alum in this non-randomized study.

  1. The Ignition Physics Study Group

    International Nuclear Information System (INIS)

    Sheffield, J.

    1987-01-01

    In the US magnetic fusion program there have been relatively few standing committees of experts, with the mandate to review a particular sub-area on a continuing basis. Generally, ad hoc committees of experts have been assembled to advise on a particular issue. There has been a lack of broad, systematic and continuing review and analysis, combining the wisdom of experts in the field, in support of decision making. The Ignition Physics Study Group (IPSG) provides one forum for the systematic discussion of fusion science, complementing the other exchanges of information, and providing a most important continuity in this critical area. In a similar manner to the European program, this continuity of discussion and the focus provided by a national effort, Compact Ignition Tokamak (CIT), and international effort, Engineering Test Reactor (ETR), are helping to lower those barriers which previously were an impediment to rational debate

  2. Pregnancy and melanoma.

    Science.gov (United States)

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

    2016-10-01

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

  3. The biochemical characterization, stabilization studies and the antiproliferative effect of bromelain against B16F10 murine melanoma cells.

    Science.gov (United States)

    São Paulo Barretto Miranda, Íngara Keisle; Fontes Suzart Miranda, Anderson; Souza, Fernanda Vidigal Duarte; Vannier-Santos, Marcos André; Pirovani, Carlos Priminho; Pepe, Iuri Muniz; Rodowanski, Ivanoé João; Ferreira, Katiúcia Tícila de Souza Eduvirgens; Mendes Souza Vaz, Luciano; de Assis, Sandra Aparecida

    2017-06-01

    The current study aims to extract bromelain from different parts (stem, crown, peels, pulp and leaves) of Ananas comosus var. comosus AGB 772; to determine of optimum pH and temperature; to test bromelain stability in disodium EDTA and sodium benzoate, and to investigate its pharmacological activity on B16F10 murine melanoma cells in vitro. The highest enzymatic activity was found in bromelain extracted from the pulp and peel. The optimum bromelain pH among all studied pineapple parts was 6.0. The optimum temperature was above 50 °C in all bromelain extracts. The fluorescence analysis confirmed the stability of bromelain in the presence of EDTA and sodium benzoate. Bromelain was pharmacologically active against B16F10 melanoma cells and it was possible verifying approximately 100% inhibition of tumor cell proliferation in vitro. Since bromelain activity was found in different parts of pineapple plants, pineapple residues from the food industry may be used for bromelain extraction.

  4. Ultrasonic characterisation of malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    John Sheila

    1998-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-11-01

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

  7. Lymphatic mapping and sentinel node biopsy in early stage melanoma: study of the first 100 cases in Institut Gustave Roussy

    International Nuclear Information System (INIS)

    Buffard, V.; Duvillard, P.; Mamelle, G.; Lumbroso, J.; Ricard, M.; Kolb, F.; Sleilati, F.; Spatz, A.

    2005-01-01

    Introduction: We report the data of the first 100 patients who underwent sentinel lymph node biopsy (SLND) in our institution using lymphoscintigraphy only. Patients and methods: From 1998 to 2000, 100 consecutive patients (53 men and 47 women) with stage I or II melanoma (mean Breslow: 3.11 mm) underwent a SLND. Localisation of the sentinel node was performed by preoperative lymphoscintigraphy and hand held gamma probe detection. The sentinel node was examined by routine histology and immunohistochemistry for PS100 and HMB-45. If the sentinel node contained tumor cells, a complete lymphadenectomy was performed. Results: Lymphoscintigraphy was performed for 97 patients. The SLN was identified in 97% of cases (94/97) and excised in 95% of cases (92/97). The rate of SLN metastasis was 19/92 patients (21%), correlated with Breslow index ( 4 mm: 46%). A mean number of 1.81 lymph node per patient was analysed. The mean follow-up was 26 months with a relapse in 14 patients, 5 of them having a metastatic sentinel node. Three patients had a recurrence at the site of the SLND although they had initially a negative sentinel node. Conclusion: The identification and metastatic rates of sentinel nodes are similar to those of the literature. More studies are needed to determine whether lymphoscintigraphy alone is efficient for successful SLND in melanoma. (author)

  8. The positioning of palliative care in acute care: A multiperspective qualitative study in the context of metastatic melanoma.

    Science.gov (United States)

    Fox, Jennifer; Windsor, Carol; Connell, Shirley; Yates, Patsy

    2016-06-01

    The positioning and meaning of palliative care within the healthcare system lacks clarity which adds a level of complexity to the process of transition to palliative care. This study explores the transition to the palliative care process in the acute care context of metastatic melanoma. A theoretical framework drawing on interpretive and critical traditions informs this research. The pragmatism of symbolic interactionism and the critical theory of Habermas brought a broad orientation to the research. Integration of the theoretical framework and grounded-theory methods facilitated data generation and analysis of 29 interviews with patients, family carers, and healthcare professionals. The key analytical findings depict a scope of palliative care that was uncertain for users of the system and for those working within the system. Becoming "palliative" is not a defined event; nor is there unanimity around referral to a palliative care service. As such, ambiguity and tension contribute to the difficulties involved in negotiating the transition to palliative care. Our findings point to uncertainty around the scopes of practice in the transition to palliative care. The challenge in the transition process lies in achieving greater coherency of care within an increasingly specialized healthcare system. The findings may not only inform those within a metastatic melanoma context but may contribute more broadly to palliative practices within the acute care setting.

  9. The Queensland study of Melanoma: Environmental and Genetic Associations (Q-MEGA). Study design, baseline characteristics, and repeatability of phenotype and sun exposure measures

    Science.gov (United States)

    Baxter, Amanda J.; Hughes, Maria Celia; Kvaskoff, Marina; Siskind, Victor; Shekar, Sri; Aitken, Joanne F.; Green, Adele C.; Duffy, David L.; Hayward, Nicholas K.; Martin, Nicholas G.; Whiteman, David C.

    2013-01-01

    Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia which has the world’s highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland study of Melanoma: Environmental and Genetic Associations, which followed-up four population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. 3,471 participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002–2005. Updated data on environmental and phenotypic risk factors, and 2,777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from six to 17 years later, are also described. PMID:18361720

  10. Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

    Science.gov (United States)

    Weber, Damien C; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escudé, Lluis; Caro, Monica; Pötter, Richard; Goitein, Gudrun; Lomax, Antony J; Miralbell, Raymond

    2005-10-01

    A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. Target coverage of all simulated uveal melanomas was equally conformal with the

  11. Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study

    International Nuclear Information System (INIS)

    Weber, Damien C.; Bogner, Joachim; Verwey, Jorn; Georg, Dietmar; Dieckmann, Karin; Escude, Lluis; Caro, Monica; Poetter, Richard; Goitein, Gudrun; Lomax, Antony J.; Miralbell, Raymond

    2005-01-01

    Purpose: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). Method and Materials: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 deg right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the 'goal' for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI 95% ), and inhomogeneity coefficient. Results: Target coverage of all simulated uveal

  12. 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...

  13. Mucosal melanoma of the head and neck: a population-based study from Slovenia, 1985-2013.

    Science.gov (United States)

    Plavc, Gaber; But-Hadžić, Jasna; Aničin, Aleksandar; Lanišnik, Boštjan; Didanović, Vojislav; Strojan, Primož

    2016-10-14

    To assess the incidence and to review experience with the treatment of mucosal melanoma of the head and neck (MMHN) in Slovenia between 1985 and 2013. The National Cancer Registry database and clinical records with outcome data of identified patients treated during the period 1985-2013 in Slovenia were reviewed. In a 29-year period, 61 patients with MMHN were identified, representing 0.5 % of all head and neck malignant tumors and 42 % of all mucosal melanomas in Slovenia. 72 % originated in the sinonasal tract and were predominantly (78 %) diagnosed as a local disease. Regional metastases at diagnosis were more frequent in patients with oral/oropharyngeal primary (44 %; sinonasal MMHN 11 %, p = 0.006). Curative intent treatment was given to 48 (79 %) patients. The overall survival (OS) rates at 2 and 5 years for the whole cohort were 43 % and 18 %, respectively, and for the curative intent group 53 % and 24 %, respectively. In the latter group, multivariate analyses showed postoperative radiotherapy (PORT) to be predictive for locoregional control (LRC) (hazard ratios [HR] for surgery with PORT vs. surgery alone: 1.0 vs. 3.9, p = 0.037), whereas only the World Health Organization performance status (HR for grade 0 vs. grade 1 vs. grade >1: 1.0 (p = 0.022) vs. 1.2 (p = 0.640) vs. 7.7 (p = 0.008)) significantly influenced OS. MMHN is a rare tumor with a poor prognosis. Combination of surgery and PORT offers the best prospects for LRC but without improvement of OS. Due to potential toxicity of high-dose RT such treatment is indicated in patients in whom LRC outweighs the risks of serious adverse effects.

  14. Cutaneous melanoma in women

    Directory of Open Access Journals (Sweden)

    Mi Ryung Roh, MD

    2015-02-01

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

  15. Genetics of familial melanoma

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  16. 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.

  17. Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics.

    Science.gov (United States)

    Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew

    2018-01-01

    Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

  18. The synthetic parasite-derived peptide GK1 increases survival in a preclinical mouse melanoma model.

    Science.gov (United States)

    Pérez-Torres, Armando; Vera-Aguilera, Jesús; Hernaiz-Leonardo, Juan Carlos; Moreno-Aguilera, Eduardo; Monteverde-Suarez, Diego; Vera-Aguilera, Carlos; Estrada-Bárcenas, Daniel

    2013-11-01

    The therapeutic efficacy of a synthetic parasite-derived peptide GK1, an immune response booster, was evaluated in a mouse melanoma model. This melanoma model correlates with human stage IIb melanoma, which is treated with wide surgical excision; a parallel study employing a surgical treatment was carried out as an instructive goal. C57BL/6 mice were injected subcutaneously in the flank with 2×10(5) B16-F10 murine melanoma cells. When the tumors reached 20 mm3, mice were separated into two different groups; the GK1 group, treated weekly with peritumoral injections of GK1 (10 μg/100 μL of sterile saline solution) and the control group, treated weekly with an antiseptic peritumoral injection of 100 μL of sterile saline solution without further intervention. All mice were monitored daily for clinical appearance, tumor size, and survival. Surgical treatment was performed in parallel when the tumor size was 20 mm3 (group A), 500 mm3 (group B), and >500 mm3 (group C). The GK1 peptide effectively increased the mean survival time by 9.05 days, corresponding to an increase of 42.58%, and significantly delayed tumor growth from day 3 to 12 of treatment. In addition, tumor necrosis was significantly increased (pcancers remains to be determined, and surgical removal remains a challenge for any new experimental treatment of melanoma in mouse models.

  19. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  20. [Telomerase activity in uveal melanomas].

    Science.gov (United States)

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

    2000-05-01

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

  1. On the interplay of telomeres, nevi and the risk of melanoma.

    Directory of Open Access Journals (Sweden)

    Clara Bodelon

    Full Text Available The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk. We performed a systematic analysis of telomere-related genes and tagSNPs within these genes, in relation to the risk of melanoma, dysplastic nevi, and nevus count combining data from four studies conducted in Italy. In addition, we examined whether telomere length measured in peripheral blood leukocytes is related to the risk of melanoma, dysplastic nevi, number of nevi, or telomere-related SNPs. A total of 796 cases and 770 controls were genotyped for 517 SNPs in 39 telomere-related genes genotyped with a custom-made array. Replication of the top SNPs was conducted in two American populations consisting of 488 subjects from 53 melanoma-prone families and 1,086 cases and 1,024 controls from a case-control study. We estimated odds ratios for associations with SNPs and combined SNP P-values to compute gene region-specific, functional group-specific, and overall P-value using an adaptive rank-truncated product algorithm. In the Mediterranean population, we found suggestive evidence that RECQL4, a gene involved in genome stability, RTEL1, a gene regulating telomere elongation, and TERF2, a gene implicated in the protection of telomeres, were associated with melanoma, the presence of dysplastic nevi and number of nevi, respectively. However, these associations were not found in the American samples, suggesting variable melanoma susceptibility for these genes across populations or chance findings in our discovery sample. Larger studies across different populations are necessary to clarify these associations.

  2. Proteomic analyses for profiling regulated proteins/enzymes by Fucus vesiculosus fucoidan in B16 melanoma cells: A combination of enzyme kinetics functional study.

    Science.gov (United States)

    Wang, Zhi-Jiang; Zheng, Li; Yang, Jun-Mo; Kang, Yani; Park, Yong-Doo

    2018-06-01

    Fucoidans are complex sulfated polysaccharides that have a wide range of biological activities. Previously, we reported the various effects of Fucus vesiculosus fucoidan on tyrosinase and B16 melanoma cells. In this study, to identify fucoidan-targeted proteins in B16 melanoma cells, we performed a proteomics study and integrated enzyme kinetics. We detected 19 candidate proteins dysregulated by fucoidan treatment. Among the probed proteins, the enzyme kinetics of two candidate enzymes, namely lactate dehydrogenase (LDH) as an upregulated protein and superoxide dismutase (SOD) as a downregulated enzyme, were determined. The enzyme kinetics results showed that Fucus vesiculosus fucoidan significantly inhibited LDH catalytic function while it did not affect SOD activity even at a high dose, while only slightly decreased activity (up to 10%) at a low dose. Based on our previous and present observations, fucoidan could inhibit B16 melanoma cells growth via regulating proteins/enzymes expression levels such as LDH and SOD known as cell survival biomarkers. Interestingly, both expression level and enzyme catalytic activity of LDH were regulated by fucoidan, which could directly induce the apoptotic effect on B16 melanoma cells along with SOD downregulation. This study highlights how combining proteomics with enzyme kinetics can yield valuable insights into fucoidan targets. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-15

    Sarcoidosis is a systemic inflammatory disease characterized by the development of noncaseating granulomas in multiple organ systems. Many hematologic malignancies and solid tumors, including melanoma, have been associated with sarcoidosis. We describe the clinical and pathologic findings of a 54-year-old man with melanoma-associated sarcoidosis. In addition, we not only review the literature describing characteristics of other melanoma patients with sarcoidosis, but also the features of melanoma patients with antineoplastic therapy-associated sarcoidosis. Sarcoidosis has been described in 80 melanoma patients; sufficient information for analysis was provided in 39 of these individuals. In 43.6% of individuals (17 out of 39), sarcoidosis was directly associated with melanoma; in 56.4% of oncologic patients (22 out of 39), sarcoidosis was induced by antineoplastic therapy that had been administered for the treatment of their metastatic melanoma. The discovery of melanoma preceded the development of sarcoidosis in 12 of the 17 (70.5%) individuals who did not receive systemic treatment. Pulmonary and/or cutaneous manifestations of sarcoidosis were common among both groups of patients. Most patients did not require treatment for sarcoidosis. Melanoma patients—either following antineoplastic therapy or without systemic treatment—may be at an increased risk to develop sarcoidosis. In antineoplastic therapy naive melanoma patients, a common etiologic factor—such as exposure to ultraviolet light—may play a role in their developing melanoma and sarcoidosis.

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

    Science.gov (United States)

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

    2010-06-01

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

  5. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  6. Chronic diseases requiring hospitalization and risk of non-melanoma skin cancers-A population based study from Denmark

    DEFF Research Database (Denmark)

    Jensen, Annette Ø; Olesen, Anne B; Dethlefsen, Claus

    2008-01-01

    We examined the associations between chronic diseases requiring hospitalization and the risk of non-melanoma skin cancers (NMSCs) in a population-based case-control study of 4,187 patients diagnosed with a first primary NMSC in 1995 in Denmark. From the National Patient Registry covering all Danish.......99-15)), and skin diseases (IRR 5.28 (95% CI: 1.95-14)). Our study supports the presence of an association between certain chronic diseases and NMSC, and further suggests that these results unlikely are due to bias.Journal of Investigative Dermatology advance online publication, 4 October 2007; doi:10.1038/sj...... hospitals, we obtained data on hospitalizations with chronic diseases, recorded before the date of NMSC diagnosis. Using incidence density sampling, we selected 10 age-, gender-, and residence-matched controls from the Danish Civil Registration System. We used conditional logistic regression to compute...

  7. A Fast-Track Referral System for Skin Lesions Suspicious of Melanoma: Population-Based Cross-Sectional Study from a Plastic Surgery Center

    Directory of Open Access Journals (Sweden)

    Reem Dina Jarjis

    2016-01-01

    Full Text Available Introduction. To minimize delay between presentation, diagnosis, and treatment of cutaneous melanoma (CM, a national fast-track referral system (FTRS was implemented in Denmark. The aim of this study was to analyze the referral patterns to our department of skin lesions suspicious of melanoma in the FTRS. Methods. Patients referred to the Department of Plastic Surgery and Breast Surgery in Zealand University Hospital were registered prospectively over a 1-year period in 2014. A cross-sectional study was performed analyzing referral patterns, including patient and tumor characteristics. Results. A total of 556 patients were registered as referred to the center in the FTRS for skin lesions suspicious of melanoma. Among these, a total of 312 patients (56.1% were diagnosed with CM. Additionally, 41 (7.4% of the referred patients were diagnosed with in situ melanoma. Conclusion. In total, 353 (63.5% patients had a malignant or premalignant melanocytic skin lesion. When only considering patients who where referred without a biopsy, the diagnostic accuracy for GPs and dermatologists was 29% and 45%, respectively. We suggest that efforts of adequate training for the referring physicians in diagnosing melanocytic skin lesions will increase diagnostic accuracy, leading to larger capacity in secondary care for the required treatment of malignant skin lesions.

  8. Risk of melanoma in people with HIV/AIDS in the pre- and post-HAART eras: a systematic review and meta-analysis of cohort studies.

    Science.gov (United States)

    Olsen, Catherine M; Knight, Lani L; Green, Adèle C

    2014-01-01

    Following the introduction of highly active antiretroviral therapy (HAART) the risk of AIDS-defining cancers decreased but incidence of many non-AIDS-defining cancers has reportedly increased in those with HIV/AIDS. Whether melanoma risk has also changed in HIV/AIDS patients post-HAART is unknown and therefore we evaluated this in comparison with the risk before HAART. Systematic review and meta-analysis. We searched Medline, Embase and ISI science citation index databases to April 2013. All cohort studies of patients diagnosed with HIV/AIDS that permitted quantitative assessment of the association with melanoma were eligible. Detailed quality assessment of eligible studies was conducted, focussing particularly on adjustment for ethnicity, a priori considered essential for an unbiased assessment of melanoma risk. Data were pooled using a random effects model. From 288 articles, we identified 21 that met the inclusion criteria, 13 presenting data for the post-HAART era and 8 for the pre-HAART era. Post-HAART the pooled relative risk (pRR) for the association between HIV/AIDS and melanoma was 1.26 (95% CI, 0.97-1.64) and 1.50 (95% CI 1.12-2.01) among studies that accounted for ethnicity, with evidence of significant heterogeneity (P = 0.004, I2 = 55.5). Pre-HAART pRRs were 1.26 (95% CI 1.11-1.43; P het = 0.82) and 1.28 (95% CI 1.10-1.49) among studies adjusted for ethnicity. People with HIV/AIDS remain at a significantly increased risk of developing melanoma in the post-HAART era. White skinned people with HIV/AIDS should be screened regularly and counselled against excessive sun exposure.

  9. Communication Among Melanoma Family Members

    Science.gov (United States)

    Bowen, Deborah J; Albrecht, Terrance; Hay, Jennifer; Eggly, Susan; Harris-Wei, Julie; Meischke, Hendrika; Burke, Wylie

    2017-01-01

    Interventions to improve communication among family members may facilitate information flow about familial risk and preventive health behaviors. This is a secondary analysis of the effects of an interactive website intervention aimed at increasing communication frequency and agreement about health risk among melanoma families. Participants were family units, consisting of one family member with melanoma identified from a previous research study (the case) and an additional first degree relative and a parent of a child 0–17. Family triads were randomized to receive access to the website intervention or to serve as control families. Family communication frequency and agreement about melanoma prevention behaviors and beliefs were measured at baseline and again at one year post randomization. Intervention participants of all three types significantly increased the frequency of communication to their first degree relatives (Parents, siblings, children; range =14–18 percentage points; all pcommunication about cancer risk. PMID:28248624

  10. Early phase II study on BNCT in metastatic malignant melanoma using the boron carrier BPA (EORTC protocol 11011)

    International Nuclear Information System (INIS)

    Wittig, Andrea; Sauerwein, Wolfgang; Moss, Raymond

    2006-01-01

    The aim of the trial is to examine the clinical response of metastatic melanoma following BNCT with BPA. The trial contains an optional biodistribution sub-study, which is done if operable metastases are removed prior BNCT. BNCT is applied in 2 fractions at the HFR in Petten. In cases of diffuse brain metastases the whole brain is irradiated homogeneously using 5 irradiation beams from different directions. Up to now 4 patients suffering from multiple brain metastases (more than 20) have been included. In all cases we observed a partial response or no change in the irradiated volume. However, none of the patients survived more than 3 months. The pharmacokinetic of the BPA can be predicted very precisely using a two-compartment model. The treatment can be performed safety. (author)

  11. Enhanced expression of melanoma progression markers in mouse model of sleep apnea

    Directory of Open Access Journals (Sweden)

    S. Perini

    2016-07-01

    Full Text Available Introduction: Obstructive sleep apnea has been associated with higher cancer incidence and mortality. Increased melanoma aggressivity was reported in obstructive sleep apnea patients. Mice exposed to intermittent hypoxia (IH mimicking sleep apnea show enhanced melanoma growth. Markers of melanoma progression have not been investigated in this model. Objective: The present study examined whether IH affects markers of melanoma tumor progression. Methods: Mice were exposed to isocapnic IH to a nadir of 8% oxygen fraction for 14 days. One million B16F10 melanoma cells were injected subcutaneously. Immunohistochemistry staining for Ki-67, PCNA, S100-beta, HMB-45, Melan-A, TGF-beta, Caspase-1, and HIF-1alpha were quantified using Photoshop. Results: Percentage of positive area stained was higher in IH than sham IH group for Caspase-1, Ki-67, PCNA, and Melan-A. The greater expression of several markers of tumor aggressiveness, including markers of ribosomal RNA transcription (Ki-67 and of DNA synthesis (PCNA, in mice exposed to isocapnic IH than in controls provide molecular evidence for a apnea–cancer relationship. Conclusions: These findings have potential repercussions in the understanding of differences in clinical course of tumors in obstructive sleep apnea patients. Further investigation is necessary to confirm mechanisms of these descriptive results. Keywords: Apnea, Melanoma, Biological markers

  12. The benefit of a sentinel lymph node biopsy and adjuvant therapy in thick (>4 mm) melanoma: multicenter, retrospective study of 291 Japanese patients.

    Science.gov (United States)

    Fujisawa, Yasuhiro; Otsuka, Fujio

    2012-10-01

    The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

  13. A simpler method of preprocessing MALDI-TOF MS data for differential biomarker analysis: stem cell and melanoma cancer studies

    Directory of Open Access Journals (Sweden)

    Tong Dong L

    2011-09-01

    Full Text Available Abstract Introduction Raw spectral data from matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF with MS profiling techniques usually contains complex information not readily providing biological insight into disease. The association of identified features within raw data to a known peptide is extremely difficult. Data preprocessing to remove uncertainty characteristics in the data is normally required before performing any further analysis. This study proposes an alternative yet simple solution to preprocess raw MALDI-TOF-MS data for identification of candidate marker ions. Two in-house MALDI-TOF-MS data sets from two different sample sources (melanoma serum and cord blood plasma are used in our study. Method Raw MS spectral profiles were preprocessed using the proposed approach to identify peak regions in the spectra. The preprocessed data was then analysed using bespoke machine learning algorithms for data reduction and ion selection. Using the selected ions, an ANN-based predictive model was constructed to examine the predictive power of these ions for classification. Results Our model identified 10 candidate marker ions for both data sets. These ion panels achieved over 90% classification accuracy on blind validation data. Receiver operating characteristics analysis was performed and the area under the curve for melanoma and cord blood classifiers was 0.991 and 0.986, respectively. Conclusion The results suggest that our data preprocessing technique removes unwanted characteristics of the raw data, while preserving the predictive components of the data. Ion identification analysis can be carried out using MALDI-TOF-MS data with the proposed data preprocessing technique coupled with bespoke algorithms for data reduction and ion selection.

  14. Phenotypic and functional characteristics of blood natural killer cells from melanoma patients at different clinical stages.

    Directory of Open Access Journals (Sweden)

    Giulia Fregni

    Full Text Available Melanomas are aggressive skin tumors characterized by high metastatic potential. Immunotherapy is a valuable alternative for metastatic melanoma patients resistant to chemotherapy. Natural Killer (NK cells are efficient anti-tumor cytotoxic effectors. We previously showed that blood NK cells from stage IV metastatic melanoma patients display decreased NK receptors and that chemotherapy modifies the functional status of blood NK cells. To investigate the role of NK cells along melanoma progression, we have here studied NK cells from patients at different stages of the disease. First, we showed that ex vivo NK cells from certain stage III-IV patients displayed low degranulation potential. Using a dynamic label-free assay, we found that immunoselected IL-2 activated blood NK cells from patients efficiently lysed melanoma cells through NKp46 and NKG2D receptors, independently to the clinical stage. Moreover, the ex vivo phenotype of circulating NK cells from 33 patients (stage I to IV was extensively analyzed. NK cells from patients displayed higher variability in the percentages of Natural Cytotoxicity Receptors (NCR and Natural Killer Group 2D (NKG2D receptor expression compared to donor NK cells. The main defect was the decreased expression of NCR1 (NKp46 by NK cells from metastatic patients. Interestingly, we found a positive correlation between the NK cell percentages of NKp46 and the duration of stage IV in melanoma patients. Finally, we showed that NK cells infiltrated primary melanomas and displayed a predominant peritumoral distribution. These results are new arguments for the development of NK-based therapies in melanoma patients.

  15. Treatment patterns and outcomes of Stage IIIB/IIIC melanoma in France, Germany and the UK: A retrospective and prospective observational study (MELABIS).

    Science.gov (United States)

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

    2017-05-01

    Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011. Data were obtained from patients' medical records and a patient survey. Forty-nine centres provided data on 558 patients: 53.6% had Stage IIIB disease; 58.2% were of working age (<65 years), 22.5% reported a change in employment status due to melanoma, 8% were on long-term sick leave; and 35.1% were deceased over the study period. Overall median distant metastases-free survival was 23.4 months and median disease-free survival was 13.3 months. Hospitalisation frequency increased during distant metastatic/terminal disease phases. Adjuvant therapy was received by 7.0% (14/199) of patients in France, 2.6% (5/195) in the UK, and 33.5% (55/164) in Germany. Low-dose interferon was used more frequently than other regimens. High-dose interferon was associated with discontinuation in 28.6% and dose delay/reduction in 33.3% of patients. Rapid disease progression combined with increased use of healthcare resources in later phases of disease result in a high burden-of-illness for patients and healthcare providers. The use of adjuvant interferon therapy varies considerably in this population in the countries studied, highlighting the need for improved treatments for melanoma. © 2017 John Wiley & Sons Ltd.

  16. Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab.

    Science.gov (United States)

    Weber, Jeffrey; Gibney, Geoffrey; Kudchadkar, Ragini; Yu, Bin; Cheng, Pingyan; Martinez, Alberto J; Kroeger, Jodie; Richards, Allison; McCormick, Lori; Moberg, Valerie; Cronin, Heather; Zhao, Xiuhua; Schell, Michael; Chen, Yian Ann

    2016-04-01

    The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naïve and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3-4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune-related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. ©2016 American Association for Cancer Research.

  17. Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

    Science.gov (United States)

    Brockley, L K; Cooper, M A; Bennett, P F

    2013-01-01

    The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

  18. New Safety Margins for Melanoma Surgery: Nice Possibility for Drinking of "Just That Cup of Coffee"?

    Science.gov (United States)

    Tchernev, Georgi; Chokoeva, Anastasiya Atanasova

    2017-06-15

    The American Joint Committee on Cancer (AJCC's) skin melanoma surgical treatment recommendations from 2011 are characterised by a prima facie "freedom of choice" regarding how extensive should be the excisions for melanomas with tumour thickness up to 2 mm and melanoma in situ. It is unclear why the recommended surgical security margins vary between 0.5 and 1 cm for melanoma in situ, whereas for melanomas with a tumour thickness of up to 1.99 mm, the range of variation is also between 1 and 2 cm, without specifying when the surgical field should be broader and, narrower, accordingly. This "uncertainty or lack of intent" of the guilders often leads to the same surgical approach to melanomas at different stages, or to a different approach in cases of melanomas at the same stage, in contrast. Therefore, this should be defined as wrong, logically. We present 3 patients with cutaneous melanomas, treated with similar fields of surgical security. Current issues, generated within the framework of melanoma's surgery guided by the recommendations of the AJCC are also discussed. A new surgical approach in patients with melanoma is recommended, discussed for the first time in world literature. We hypothesize that the introduction of a certain recommendations for a 2 cm surgical field in all directions during the initial excision, combined with the parallel performance of a sentinel lymph node biopsy, will lead in fact to several important advantages: 1) avoiding of the secondary excision in at least 70% - 90% of the patients (depending on the tumor thickness), 2) minimizing the risk of lymphatic effusion change and misinterpretation of the sentinel lymph node biopsy's results in patients with secondary excision; 3) optimization of the surgical team's work; 4) minimizing the possibility of unprepared/uninformed personnel to take part in decisions for treating a specific disease such as skin melanoma, 4) facilitating the appropriate patients' group selection at the appropriate

  19. Assessment of the influence of one's education on early diagnosis of multiple primary cancer in patients with uveal melanoma.

    Science.gov (United States)

    Mierzwa-Dobranowska, Marzena; Romanowska-Dixon, Bozena

    2012-01-01

    This study will show a comparison of two groups of patients with uveal melanoma; one group with multiple primary cancer, and a second group with no identifiable second cancer, in terms of education and occupation. Study concerns 240 patients, who were isolated from patients being treated with uveal melanoma at the Department of Ophthalmology and Ocular Oncology Jagiellonian University Medical College in the period from 1998 to 2007. On the basis of medical history and medical records 97 patients were diagnosed with the one or more independent primary cancers. These patients were subjected to comparative analysis with a group of 143 patients with uveal melanoma as a control group. Analyzing the impact of education on the recognition of multiple primary cancer, there were significantly more frequent diagnoses of second primary cancers among patients with secondary and higher education than among those who had primary and vocational education. Among the obtained data on patients in the study group, the largest occupational group (according to the ISCO-88 (COM)) constituted "professionals". In the control group prevailed "craft and related trades workers". The results suggest the great importance of knowledge about risk factors for the development of cancer among patients with uveal melanoma and the ensuing more scrupulous search for succesive primary neoplasm and indicate the neccesity of organizing broad prophylactic actions. uveal melanoma, multiple primary cancer.

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

    Science.gov (United States)

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

    2017-11-01

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

  1. Simulants of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Gérald E. Piérard

    2015-08-01

    Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

  2. Southeastern Cancer Study Group: breast cancer studies

    International Nuclear Information System (INIS)

    Smalley, R.V.; Bartolucci, A.A.; Moore, M.

    1983-01-01

    During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) of CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome

  3. BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

    Science.gov (United States)

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

    2014-01-01

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

  4. International Study Group Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Raubenheimer, Tor O

    2000-07-18

    The focus of the ISG work was on advancing the accelerator design and supporting technologies. This is a complex process which involves a close interaction between theoretical analysis of the collider design and R and D progress on hardware components. The sequence of efforts took place roughly in the following order: (1) Optimization of the collider parameters and definition of system and subsystem requirements, (2) Identification of design strategies and options, and (3) Development of specific technologies to achieve these requirements. Development and testing of the required components, and R and D on manufacturing techniques have been important activities of the ISG. Experiments at the major test facilities such as the ATF at KEK and ASSET at SLAC have also played a significant role in the ISG studies.

  5. Targeting Glutamatergic Signaling and the PI3 Kinase Pathway to Halt Melanoma Progression

    Directory of Open Access Journals (Sweden)

    Stephen A. Rosenberg

    2015-02-01

    Full Text Available Our group has previously reported that the majority of human melanomas (>60% express the metabotropic glutamate receptor 1 (GRM1 and that the glutamate release inhibitor riluzole, a drug currently used to treat amyotrophic lateral sclerosis, can induce apoptosis in GRM1-expressing melanoma cells. Our group previously reported that in vitro riluzole treatment reduces cell growth in three-dimensional (3D soft agar colony assays by 80% in cells with wildtype phosphoinositide 3-kinase (PI3K pathway activation. However, melanoma cell lines harboring constitutive activating mutations of the PI3K pathway (PTEN and NRAS mutations showed only a 35% to 40% decrease in colony formation in soft agar in the presence of riluzole. In this study, we have continued our preclinical studies of riluzole and its effect on melanoma cells alone and in combination with inhibitors of the PI3 kinase pathway: the AKT inhibitor, API-2, and the mammalian target of rapamycin (mTOR inhibitor, rapamycin. We modeled these combinatorial therapies on various melanoma cell lines in 3D and 2D systems and in vivo. Riluzole combined with mTOR inhibition is more effective at halting melanoma anchorage-independent growth and xenograft tumor progression than either agent alone. PI3K signaling changes associated with this combinatorial treatment shows that 3D (nanoculture modeling of cell signaling more closely resembles in vivo signaling than monolayer models. Riluzole combined with mTOR inhibition is effective at halting tumor cell progression independent of BRAF mutational status. This makes this combinatorial therapy a potentially viable alternative for metastatic melanoma patients who are BRAF WT and are therefore ineligible for vemurafenib therapy.

  6. Malignant melanoma - a warning

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  7. Primary malignant melanoma

    Directory of Open Access Journals (Sweden)

    A. Ferhat Mısır

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Martyna Śniegocka

    2018-04-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  10. Radioiodinated methylene blue for melanoma targeting: Chemical characterisation and tumour selectivity of labelled components

    International Nuclear Information System (INIS)

    Blower, Philip J.; Clark, Katherine; Link, Eva M.

    1997-01-01

    Radioiodinated methylene blue contains a mixture of components showing selective uptake in human pigmented melanoma, and it has potential for imaging and therapy. Nuclear magnetic resonance and mass spectroscopic studies show that the majority of the radioactivity (85%) is in the form of monoiodinated methylene blue, 4-iodo-3-methylamino-7-dimethylaminophenaza thionium chloride. The amino group ortho-to iodine has become demethylated to a mono-methylamino group. The remainder (15%) of the mixture is the doubly labelled 4,5-diiodo-3,7-bis(methylamino) phenazathionium chloride. The separated components show similar tumour selectivity in athymic mice bearing human pigmented melanomas

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

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    . Chemotherapeutic agents including interferons, cytokines, biological agents and radiation therapy for brain metastases have been reported as adjuvant and palliative options while considering malignant melanomas in general. The average recurrence-free interval was 2.59 years. Nine of the 12 reports documented follow-up in their patients. Two of these 9 (22.2% patients died. Conclusions Primary melanoma of the colon is a rare clinical entity. Whenever a seemingly primary melanoma is detected in an atypical location such as the colon, it is prudent to conduct a thorough clinical investigation to consider the possibility of metastatic disease. Further studies are needed to document the long term follow-up, survival advantage and safety of the management approaches employed in patients with primary colonic melanoma. Based on current data, surgical resection appears to be appropriate management for primary colonic melanomas; unless the disease has metastasized to distant sites where surgery may have a limited palliative role.

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

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

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

  13. Sun protection and skin self-examination in melanoma survivors.

    Science.gov (United States)

    Mujumdar, Urvi J; Hay, Jennifer L; Monroe-Hinds, Yvette C; Hummer, Amanda J; Begg, Colin B; Wilcox, Homer B; Oliveria, Susan A; Berwick, Marianne

    2009-10-01

    Patients diagnosed with melanoma are at risk for developing recurrent and second primary disease. Skin self-examination (SSE) and sun protection are standard clinical recommendations to minimize risk. In this study we examined performance of these behaviors in individuals with melanoma drawn from the general population. Potential participants (N=148) with a first primary melanoma diagnosed in 2000 were identified through a population-based cancer registry in New Jersey, USA. One hundred and fifteen individuals participated in a 30 min telephone interview concerning behavioral adherence with SSE and sun protection, self-efficacy for performing these behaviors, and perceived risk of developing another skin cancer. We utilized logistic regression to estimate potential associations of demographic, medical, and psychosocial factors with SSE and sun protection, respectively. Seventeen percent of subjects reported performing comprehensive SSE at least once every two months and 23% engaged in regular sun protection. Utilization of SSE was related to the presence of moles (OR=4.2, 95% CI: 1.1-15) and higher SSE self-efficacy (OR=14.4, 95% CI: 1.9-112). Regular sun protection was related to older age (>60 years; OR=3.3, 95% CI: 1.3-8.7), being female (OR=2.8, 95% CI: 1.1-7.3), and higher sun protection self-efficacy (OR=5.0, 95% CI: 1.4-18). These factors remained significant in multivariate models. In this group of primary melanoma survivors, the rates of SSE and sun protection are comparable to, but do not exceed, general population estimates. This study provides justification for further research to address barriers to prevention and control behaviors in melanoma survivors.

  14. Gingival osteogenic melanoma in two dogs.

    Science.gov (United States)

    Ellis, Angela E; Harmon, Barry G; Miller, Debra L; Northrup, Nicole C; Latimer, Kenneth S; Uhl, Elizabeth W

    2010-01-01

    Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

  15. Common Group Problems: A Field Study.

    Science.gov (United States)

    Weinberg, Sanford B.; And Others

    1981-01-01

    A field study of a naturally functioning group (N=125) was conducted to identify common group problems. Trained observers attended group meetings and described the problems encountered. Difficulties of cohesion, leadership, sub-group formation, and personality conflict were identified. (RC)

  16. Association between month of birth and melanoma risk: fact or fiction?

    Science.gov (United States)

    Fiessler, Cornelia; Pfahlberg, Annette B; Keller, Andrea K; Radespiel-Tröger, Martin; Uter, Wolfgang; Gefeller, Olaf

    2017-04-01

    Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  17. Radiation sensitivity of B-16 melanoma

    International Nuclear Information System (INIS)

    Griem, M.L.; Malkinson, F.D.; Kalis, J.B.; Shefner, A.

    1984-01-01

    A model has been developed for radiation studies of melanoma. Β-16 melanoma (NCI), carried by subcutaneous implant in C57BL/6NCr mice was implanted instramuscularly into the right rear leg of female B6C3F1 mice. Test mice were inoculated with 1 x 10/sup 5/, 5 x 10/sup 5/, and 1 x 10/sup 6/ tumor cells to determine an appropriate tumor challenge for a reproducible and suitable median survival time. A challenge inoculum of 5 x 10/sup 5/ tumor cells was subsequently chosen as the standard tumor dose for test animals used in subsequent radiation dose response studies. Tumor-bearing test animals were treated with 500, 1000, 1500, or 2000 rads of 250 kV x-rays either 4 days or 14 days after tumor implantation. Only the tumorbearing leg of the test mouse was exposed during irradiation; the animal was otherwise protected by lead shielding. The median survival time of tumorbearing unirradiated mice was 24.4 days. Radiation on day 4 postinoculation was more effective than radiation administered on day 14. Median survival time for the 4 radiation dose groups given x-rays on day 4 were 31.0, 38.2, 59.0, and 60.0 days with progressive increases in radiation dose. Median survival times for mice irradiated on day 14 were 26.8, 31.8, 34.8, and 49.2 days as the radiation doses increased. This mouse melanoma model can be used in combined modality studies

  18. 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...

  19. [Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

    Science.gov (United States)

    Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

    Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

  20. [Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

    Science.gov (United States)

    Omlor, G; Dill-Müller, D; Gross, G; Kautz, G; Schüder, G; Zaun, H; Feifel, G

    1996-01-01

    Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

  1. 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.

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

    Science.gov (United States)

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

    2018-02-01

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

  3. BAP1 has a survival role in cutaneous melanoma.

    Science.gov (United States)

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

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Goldenberg A

    2015-08-01

    Full Text Available Alina Goldenberg,1 Igor Vujic,2,3 Martina Sanlorenzo,2,4 Susana Ortiz-Urda2 1Department of Internal Medicine/Dermatology, University of California, San Diego, 2Mt Zion Cancer Research Center, University of California San Francisco, San Francisco, CA, USA; 3Department of Dermatology, The Rudolfstiftung Hospital, Academic Teaching Hospital, Medical University Vienna, Vienna, Austria; 4Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy Introduction: Melanoma is the most deadly type of skin cancer with 75% of all skin cancer deaths within the US attributed to it. Risk factors for melanoma include ultraviolet exposure, genetic predisposition, and phenotypic characteristics (eg, fair skin and blond hair. Whites have a 27-fold higher incidence of melanoma than African-Americans (AA, but the 5-year survival is 17.8% lower for AA than Whites. It is reported continuously that AA have more advanced melanomas at diagnosis, and overall lower survival rates. This minority melanoma paradox is not well understood or studied. Objective: To explore further, the possible explanations for the difference in melanoma severity and survival in AA within the US. Methods: Qualitative review of the literature. Results: Lack of minority-targeted public education campaigns, low self-risk perception, low self-skin examinations, intrinsic virulence, vitamin D differences, and physician mistrust may play a role in the melanoma survival disparity among AA. Conclusion: Increases in public awareness of melanoma risk among AA through physician and media-guided education, higher index of suspicion among individuals and physicians, and policy changes can help to improve early detection and close the melanoma disparity gap in the future. Keywords: acral, advanced, African-American, disparity, melanoma, survival

  5. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

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

  6. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

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

  7. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  8. MiR-221 and -222-based therapeutic approach in melanoma and GIST (Gastrointestinal Stromal Tumor): in vitro and in vivo preclinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Care, A; Bonci, D [Department of Haematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome (Italy); Peschle, C [IRCCS MultiMedica, Milan (Italy)

    2009-07-01

    Micro RNAs (miRs) are small ({approx}22 nucleotides) non coding RNAs involved in gene expression, as negative regulators of specific mRNA targets. Growing evidences indicated miR functional roles in all the main biological processes, including cancer where they can act as oncogenes as well as tumor suppressor genes. Several studies reported the involvement of miR- 221 and -222 in the induction and/or progression of different neoplasias. We have analyzed miR-221/-222 functional role in a panel of differently staged melanoma cell lines and primary bioptic samples, showing their capabilities to regulate two distinct, but functionally convergent pathways of melanocyte transformation through the cell cycle inhibitor p27Kip and c-kit receptor. We also demonstrated the lack of the tumor suppressor gene PLZF as a direct cause of miR-221/-222 up regulation in melanoma cells. In vitro and, more important, in vivo studies confirmed that suppression of miR-221/-222 strongly reduced melanoma growth and dissemination.

  9. MiR-221 and -222-based therapeutic approach in melanoma and GIST (Gastrointestinal Stromal Tumor): in vitro and in vivo preclinical studies

    International Nuclear Information System (INIS)

    Care, A.; Bonci, D.; Peschle, C.

    2009-01-01

    Micro RNAs (miRs) are small (∼22 nucleotides) non coding RNAs involved in gene expression, as negative regulators of specific mRNA targets. Growing evidences indicated miR functional roles in all the main biological processes, including cancer where they can act as oncogenes as well as tumor suppressor genes. Several studies reported the involvement of miR- 221 and -222 in the induction and/or progression of different neoplasias. We have analyzed miR-221/-222 functional role in a panel of differently staged melanoma cell lines and primary bioptic samples, showing their capabilities to regulate two distinct, but functionally convergent pathways of melanocyte transformation through the cell cycle inhibitor p27Kip and c-kit receptor. We also demonstrated the lack of the tumor suppressor gene PLZF as a direct cause of miR-221/-222 up regulation in melanoma cells. In vitro and, more important, in vivo studies confirmed that suppression of miR-221/-222 strongly reduced melanoma growth and dissemination

  10. Literature Study Groups: Literacy Learning "with Legs"

    Science.gov (United States)

    Parsons, Sue Christian; Mokhtari, Kouider; Yellin, David; Orwig, Ryan

    2011-01-01

    Literature study groups help promote critical thinking and improve reading skills. These groups, in general, are characterized by: (1) a flexible grouping--usually determined by a reader's choice of a given book at a given time; (2) participant-centered dialogue, where the teacher takes on the role of facilitator and expert participant rather than…

  11. Melanoma during pregnancy

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-04-20

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

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

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali

    2012-01-01

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

  15. In vitro and in vivo studies on the cytotoxicity of irradiated silk fibroin against mouse melanoma tumor cell

    International Nuclear Information System (INIS)

    Byun, Eui-Baek; Sung, Nak-Yun; Kwon, Sun-Kyu; Song, Beom-Seok; Kim, Jae-Hun; Choi, Jong-il; Hwang, Han-Joon; Byun, Myung-Woo; Lee, Ju-Woon

    2009-01-01

    The physicochemical properties of proteins can be altered by irradiation. But, it is rarely that the researches on the functional properties of irradiated proteins have been reported. Fibroin is a fibrous protein derived from silkworm Bombyx mori and has been suggested as a biomaterial for biomedical application. Therefore, fibroin was selected as a model protein and was examined with the irradiation effects on the cytotoxicity of fibroin on tumor cell. The cytotoxicity of fibroin against mouse melanoma cell (B16BL6) showed a significant increase dependent upon the increase of irradiation dose. And also, the splenocyte proliferation activities of fibroin were increased by gamma irradiation. In addition, the oral administration of irradiated fibroin significantly increased the inhibition rate of tumor growth in tumor-bearing mouse model. The reason might be due to the change of protein structure by gamma irradiation and is being studied. From these result, it could be concluded that the irradiated fibroin might be a potential candidate as a valuable product in food and medical industry.

  16. In vitro and in vivo studies on the cytotoxicity of irradiated silk fibroin against mouse melanoma tumor cell

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Eui-Baek [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Division of Bioresources and Biosciences, Faculty of Agriculture, Graduate school of Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581 (Japan); Sung, Nak-Yun [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kwon, Sun-Kyu [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Graduate school of Food and Biotechnology, Korea University, Jochiwon 339-800 (Korea, Republic of); Song, Beom-Seok; Kim, Jae-Hun; Choi, Jong-il [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Hwang, Han-Joon [Graduate school of Food and Biotechnology, Korea University, Jochiwon 339-800 (Korea, Republic of); Byun, Myung-Woo [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Ju-Woon [Team for Radiation Food Science and Biotechnology, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: sjwlee@kaeri.re.kr

    2009-07-15

    The physicochemical properties of proteins can be altered by irradiation. But, it is rarely that the researches on the functional properties of irradiated proteins have been reported. Fibroin is a fibrous protein derived from silkworm Bombyx mori and has been suggested as a biomaterial for biomedical application. Therefore, fibroin was selected as a model protein and was examined with the irradiation effects on the cytotoxicity of fibroin on tumor cell. The cytotoxicity of fibroin against mouse melanoma cell (B16BL6) showed a significant increase dependent upon the increase of irradiation dose. And also, the splenocyte proliferation activities of fibroin were increased by gamma irradiation. In addition, the oral administration of irradiated fibroin significantly increased the inhibition rate of tumor growth in tumor-bearing mouse model. The reason might be due to the change of protein structure by gamma irradiation and is being studied. From these result, it could be concluded that the irradiated fibroin might be a potential candidate as a valuable product in food and medical industry.

  17. Appearance of choroidal melanoma on high resolution MRI using 1.5 T and a dedicated surface coil in 200 consecutive patients

    International Nuclear Information System (INIS)

    Lemke, A.J.; Hosten, N.; Frenzel, D.; Richter, M.; Felix, R.; Bornfeld, N.; Bechrakis, N.E.

    1998-01-01

    Purpose: Choroidal melanomas usually present a characteristic appearance in MRI. Differing characteristics can cause problems in differential diagnosis between melanomas and other masses in the globe. The purpose of this study was to evaluate the appearance of choroidal melanomas with MRI in a large consecutive patient group. Methods: In a prospective study, 200 patients with choroidal melanomas were investigated with MRI using a 1.5 T scanner and a 5 cm surface coil. Both quantitative and qualitative evaluation of the resulting images was performed. Results: 78.5% of the melanomas presented with homogeneous signal intensities within the tumor due to a homogeneous pigmentation whereas 21.5% of the melanomas demonstrated a mixed pigmentation. Signal intensities of the homogeneous melanomas in the plain T 1 -WI were moderately or markedly hyperintense compared to the vitreous in 29.3% and moderately or markedly hypointense in the T 2 -WI in 37.1%. An accompanying retinal detachment was found in 65.5% and an extraocular growth in 7.0%. Conclusions: In 10% to 37% we observed the typical well known MR appearance, including homogenous high signal in the T 1 -WI and low signals in the T 2 -WI. For further differentiation, morphological criteria (e.g. shape, size, and position) were used, which are also discussed. (orig.) [de

  18. In vivo UVA irradiation of mouse is more efficient in promoting pulmonary melanoma metastasis than in vitro

    Science.gov (United States)

    2011-01-01

    Background We have previously shown in vitro that UVA increases the adhesiveness of mouse B16-F1 melanoma cells to endothelium. We have also shown in vivo that UVA exposure of C57BL/6 mice, i.v. injected with B16-F1 cells, increases formation of pulmonary colonies of melanoma. The aim of the present animal study was to confirm the previously observed in vivo UVA effect and to determine whether in vitro UVA-exposure of melanoma cells, prior the i.v. injection, will have an enhancing effect on the pulmonary colonization capacity of melanoma cells. As a second aim, UVA-derived immunosuppression was determined. Methods Mice were i.v. injected with B16-F1 cells into the tail vein and then immediately exposed to UVA. Alternatively, to study the effect of UVA-induced adhesiveness on the colonization capacity of B16-F1 melanoma, cells were in vitro exposed prior to i.v. injection. Fourteen days after injection, lungs were collected and the number of pulmonary nodules was determined under dissecting microscope. The UVA-derived immunosuppression was measured by standard contact hypersensitivity assay. Results and Discussion Obtained results have confirmed that mice, i.v. injected with B16-F1 cells and thereafter exposed to UVA, developed 4-times more of melanoma colonies in lungs as compared with the UVA non-exposed group (p UVA-induced changes in the adhesive properties of melanoma cells do not alone account for the 4-fold increase in the pulmonary tumor formation. Instead, it suggests that some systemic effect in a mouse might be responsible for the increased metastasis formation. Indeed, UVA was found to induce moderate systemic immunosuppression, which effect might contribute to the UVA-induced melanoma metastasis in mice lungs. PMID:21645404

  19. Study to determine whether intraoperative frozen section biopsy improves surgical treatment of non-melanoma skin cancer

    OpenAIRE

    NICOLETTI, GIOVANNI; BRENTA, FEDERICA; MALOVINI, ALBERTO; MUSUMARRA, GAETANO; SCEVOLA, SILVIA; FAGA, ANGELA

    2012-01-01

    Skin cancers are the most common types of cancer and their incidence has shown an increase of ∼4 to 8% per year over the last 40 years. The majority of skin cancers (∼97%) are non-melanoma skin cancers, mainly represented by basal cell (80%) and squamous cell carcinomas (20%). The use of intra-operative frozen section remains controversial in the surgical treatment of non-melanoma skin cancer, being commonly considered an optional tool, the reliability and effectiveness of which remain questi...

  20. 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.

  1. WWC Study Review Guide: Group Design Studies

    Science.gov (United States)

    What Works Clearinghouse, 2018

    2018-01-01

    Underlying all What Works Clearinghouse (WWC) products are WWC Study Review Guides, which are intended for use by WWC certified reviewers to assess studies against the WWC evidence standards. As part of an ongoing effort to increase transparency, promote collaboration, and encourage widespread use of the WWC standards, the Institute of Education…

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

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

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

  3. Recurrence and survival after neck dissections in cutaneous head and neck melanoma

    DEFF Research Database (Denmark)

    Andersen, Peter Stemann; Chakera, Annette Hougaard; Thamsborg, Andreas Key Milan

    2014-01-01

    INTRODUCTION: An important prognostic factor in head and neck melanoma is the status of the regional lymph nodes since the presence of metastatic disease in the nodes greatly aggravates the prognosis. There is no consensus on the surgical treatment algorithm for this group. Our aim was to study i...

  4. Ultraviolet Radiation Exposure and the Incidence of Oral, Pharyngeal and Cervical Cancer and Melanoma: An Analysis of the SEER Data.

    Science.gov (United States)

    Adams, Spencer; Lin, Jie; Brown, Derek; Shriver, Craig D; Zhu, Kangmin

    2016-01-01

    Based on the hypothesis that ultraviolet radiation (UVR) exposure can cause DNA damage that may activate dormant viruses such as human papilloma virus, a recent ecological study, which estimated state-level UVR exposure, reported positive correlations between annual UVR exposure and the incidence of oral, pharyngeal, and cervical cancer in 16 U.S. states using the International Agency for Research on Cancer (IARC) data. The purpose of the current study was to further investigate whether the annual UVR level, estimated on a county level, is associated with incidence rates of such cancers using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 data. If UVR exposure is associated with incidence of these cancer types, we would expect to see a similar or stronger association with melanoma because UVR exposure is a well-demonstrated risk factor for this disease. Thus, we also included melanoma in the study. The study subjects were White and Black individuals with oral, pharyngeal, cervical cancer or melanoma diagnosed between 1973 and 2011 from the SEER 18 data. UVR was estimated at the county level and grouped into high-, medium- and low-exposure levels. Age-adjusted incidence rates of cancer were calculated and compared among the UVR exposure groups. The comparisons were also stratified by sex and race. There was an inverse association between UVR exposure and incidence of oral, pharyngeal, and cervical cancer. The inverse association was also observed for melanoma. When stratified by race and sex, the inverse associations remained except for melanoma among Blacks. In contrast to a previous study, our study found that there were inverse associations between UVR exposure and the incidence of oral, pharyngeal, and cervical cancer, as well as of melanoma. Our findings are in agreement with several other published studies reporting no positive correlation between UVR exposure and the incidence rates of oral, pharyngeal, and cervical

  5. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna

    2012-02-01

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

  6. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  7. Immunoscintigraphy of malignant melanomas

    International Nuclear Information System (INIS)

    Nicol, L.; Sandron, A.; Herry, J.Y.; Chevrant-Breton, J.

    1990-01-01

    This work is part of a multicentric European evaluation of the monoclonal antibody 225.28s targeted against malignant melanoma and its metastases. Twenty-eight patients (12 males, 16 females, mean age: 53 yrs), who had initially been treated by resection of the primary tumour, were included in the study. Twenty-three of the 26 metastases more than 1 cm in diameter were visualized by immunoscintigraphy. The sensitivity of the procedure (88%) is limited however by the small size of the lesions and their depth, as well as by background noise caused by circulating antibodies. Immunoscintigraphy enables non-invasive investigation of the whole body and can detect lesions that other conventional complementary explorations fail to identify [fr

  8. Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

    Science.gov (United States)

    White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

    2014-05-01

    The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Socioeconomic status and non-melanoma skin cancer: a nationwide cohort study of incidence and survival in Denmark

    DEFF Research Database (Denmark)

    Steding-Jessen, M; Birch-Johansen, F; Jensen, A

    2010-01-01

    The two main types of non-melanoma skin cancer differ with the pattern of exposure to ultraviolet radiation (UVR): basal cell carcinoma (BCC) appears to be more closely related to intermittent solar exposure and sunburn, while the risk for squamous cell carcinoma (SCC) is a result of lifetime...

  10. Persistent postoperative pain and sensory changes following lymph node excision in melanoma patients

    DEFF Research Database (Denmark)

    Slagelse, Charlotte; Petersen, Karin L; Dahl, Jørgen B

    2014-01-01

    Studies on complications related to chronic nerve injury following sentinel lymph node biopsy (SLNB) and complete lymph node dissection (CLND) for melanoma are sparse. This review summarizes the existing literature on pain and neuropathic complications in melanoma patients undergoing SLNB...

  11. Peptides in melanoma therapy.

    Science.gov (United States)

    Mocellin, Simone

    2012-01-01

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

  12. GdNCT of spontaneous canine melanoma

    International Nuclear Information System (INIS)

    Mitin, V.N.; Kulakov, V.N.; Khokhlov, V.F.

    2006-01-01

    The effectiveness of GdNCT has been studied in dogs with spontaneous melanoma of the mucousmembrane of the oral cavity patients on the NCT base at the IRT MEPhI reactor. The control group with melanomas was treated with neutrons. Fourteen canine patients were selected in the Clinic of Experimental Therapy affiliated with the RCRC RAMS. The calculation of doses has shown that the total dose of energy release depending on Gd concentration in the target can be several times higher than the dose produced by the reactor neutron beam. The calculations were carried out using the diffusion pharmacokinetic model. The gadolinium drug dipentast was administered intratumorally immediately prior to irradiation. The tumor size was estimated by measuring it in three projections. The tumor was irradiated for 60-90 minutes with a thermal neutron flux of 0.7x10 9 n/cm 2 s. The dose on tumor was 80-120 Gy, on surrounding tissues - 12-15 Gy. The treatment plan included immunotherapy with Roncoleikin in a dose of (15-10)x10 3 IE/kg. The results of GdNCT are still under observation. The results conform to those obtained by us earlier in cell cultures and inoculated experimental tumors. GdNCT is also effective in combination with immunotherapy. (author)

  13. 31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

    Science.gov (United States)

    Lyng, H; Olsen, D R; Petersen, S B; Rofstad, E K

    1995-04-01

    The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Occupational exposure to ultraviolet radiation and risk of non-melanoma skin cancer in a multinational European study.

    Directory of Open Access Journals (Sweden)

    Simona Surdu

    Full Text Available BACKGROUND: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC. However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV radiation. OBJECTIVES: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. METHODS: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC. Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. RESULTS: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR 0.47, 95% confidence interval (CI 0.27-0.80; similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure. CONCLUSIONS: The protective effect of occupational exposure to natural UV radiation was unexpected, but limited to light-skinned people, suggesting adequate sun-protection behaviors. Further investigations focusing on variations in the individual genetic susceptibility and potential interactions with environmental and other relevant factors are planned.

  15. WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

    Science.gov (United States)

    Sasse, Andre D; Sasse, Emma C; Clark, Luciana Go; Clark, Otavio Augusto Camara

    2018-02-06

    Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. Eighteen studies met our criteria and were included in the meta

  16. Integrative Genome Comparison of Primary and Metastatic Melanomas

    Science.gov (United States)

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

    2010-01-01

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

  17. Iodine-125 radiation of posterior uveal melanoma

    International Nuclear Information System (INIS)

    Packer, S.

    1987-01-01

    Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula

  18. Iodine-125 radiation of posterior uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S.

    1987-12-01

    Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula.

  19. The combined use of surgical debulking and diode laser photocoagulation for limbal melanoma treatment: a retrospective study of 21 dogs.

    Science.gov (United States)

    Andreani, Valentina; Guandalini, Adolfo; D'Anna, Nunzio; Giudice, Chiara; Corvi, Roberta; Di Girolamo, Nicola; Sapienza, John S

    2017-03-01

    To evaluate effectiveness and safety of debulking and diode laser photocoagulation (DPC) for the treatment of limbal melanoma (LM). Retrospective multi-institutional case series. Medical records of animals diagnosed with LM at the Centro Veterinario Specialistico (CVS) and at the Long Island Veterinary Specialists from 1994 to 2014 were retrieved. Signalment, location, extent of tumors, recurrence rate, and early and late complications were reported. Patient follow-up information was obtained from veterinary ophthalmologists, primary care veterinarians, and where appropriate, owners. Twenty-one eyes of 21 dogs (13 females and 8 males) were included in this study. The dogs' average age was 6 years (range: 7 months-11 years). The follow-up period ranged from 1-108 months (median 48 months) after the last DPC procedure. Long-term follow-up was obtained by telephone interviews in 6 of 20 cases and by clinical re-evaluations in 14 of 20 cases. The most common early complications were a moderate anterior uveitis and peripheral corneal edema (21/21 eyes). Late complications included corneal fibrosis and/or pigmentation (20/21). In one case, a severe bullous keratopathy associated with extensive corneal fibrosis was observed (1/21). One case was blind due to concurrent Sudden Acquired Retinal Degeneration (SARD). However, after surgery 2 of 20 eyes lost vision and one of these was enucleated. Debulking, in addition to diode laser photocoagulation, was technically straightforward to perform, minimally invasive, well tolerated, and highly successful in this case series. © 2016 American College of Veterinary Ophthalmologists.

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

    Science.gov (United States)

    2017-06-05

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

  1. Primary Anorectal Melanoma: An Update

    Directory of Open Access Journals (Sweden)

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

    2012-01-01

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

  2. Spontaneous Splenic Rupture in Melanoma

    Directory of Open Access Journals (Sweden)

    Hadi Mirfazaelian

    2014-01-01

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

  3. Melanoma survival is superior in females across all tumour stages but is influenced by age.

    Science.gov (United States)

    Khosrotehrani, Kiarash; Dasgupta, Paramita; Byrom, Lisa; Youlden, Danny R; Baade, Peter D; Green, Adele C

    2015-10-01

    Among patients with invasive melanoma, females are known to have higher survival than males globally. However, this survival advantage has not been explored in thin melanomas, the most common form of the disease. In addition, it is unclear if this advantage is true across all age groups. We aimed to compare melanoma survival between males and females by clinical stage and within age groups. Melanomas from 1995 to 2008 were extracted from the Queensland Cancer Registry and the Surveillance, Epidemiology, and End Results (SEER) Program, and melanoma-specific deaths were ascertained up to 2011. Flexible parametric survival models compared survival between groups. The Queensland cohort of 28,979 patients experienced 1712 melanoma deaths and the SEER cohort of 57,402 patients included 6929 melanoma deaths. Survival rates were in favour of females across nearly all tumour stages, including thin invasive tumours in both cohorts after adjusting for demographic and clinical factors [odds ratio (OR) death female:male for stage I melanoma = 0.64 in Queensland; and OR = 0.79 in the US, both P age categories. In particular, the survival advantage was inconsistent in females with stage I melanoma aged under 60. Females with melanoma have a survival advantage over males including in stage I melanomas. However, this advantage is dependent on age at diagnosis, suggesting an underlying biological mechanism influenced by age that exists from the very early stages of the disease.

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

    Science.gov (United States)

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

    2016-05-24

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

  5. Prevalence of variations in melanoma susceptibility genes among Slovenian melanoma families

    Directory of Open Access Journals (Sweden)

    Besic Nikola

    2008-09-01

    Full Text Available Abstract Background Two high-risk genes have been implicated in the development of CM (cutaneous melanoma. Germline mutations of the CDKN2A gene are found in CDK4 gene reported to date. Beside those high penetrance genes, certain allelic variants of the MC1R gene modify the risk of developing the disease. The aims of our study were: to determine the prevalence of germline CDKN2A mutations and variants in members of families with familial CM and in patients with multiple primary CM; to search for possible CDK4 mutations, and to determine the frequency of variations in the MC1R gene. Methods From January 2001 until January 2007, 64 individuals were included in the study. The group included 28 patients and 7 healthy relatives belonging to 25 families, 26 patients with multiple primary tumors and 3 children with CM. Additionally 54 healthy individuals were included as a control group. Mutations and variants of the melanoma susceptibility genes were identified by direct sequencing. Results Seven families with CDKN2A mutations were discovered (7/25 or 28.0%. The L94Q mutation found in one family had not been previously reported in other populations. The D84N variant, with possible biological impact, was discovered in the case of patient without family history but with multiple primary CM. Only one mutation carrier was found in the control group. Further analysis revealed that c.540C>T heterozygous carriers were more common in the group of CM patients and their healthy relatives (11/64 vs. 2/54. One p14ARF variant was discovered in the control group and no mutations of the CDK4 gene were found. Most frequently found variants of the MC1R gene were T314T, V60L, V92M, R151C, R160W and R163Q with frequencies slightly higher in the group of patients and their relatives than in the group of controls, but the difference was statistically insignificant. Conclusion The present study has shown high prevalence of p16INK4A mutations in Slovenian population of

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

    Science.gov (United States)

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

    2017-10-16

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

  7. Potential Role of Meiosis Proteins in Melanoma Chromosomal Instability

    International Nuclear Information System (INIS)

    Lindsey, S. F.; Byrnes, D. M.; Eller, M. S.; Rosa, A. M.; Dabas, N.; Escandon, J.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.; Grichnik, J. M.

    2013-01-01

    Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis"could impact chromosomal instability in melanoma and other cancers.

  8. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma.

    Science.gov (United States)

    Byrum, Stephanie D; Larson, Signe K; Avaritt, Nathan L; Moreland, Linley E; Mackintosh, Samuel G; Cheung, Wang L; Tackett, Alan J

    2013-03-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression.

  9. Xenogeneic murine tyrosinase DNA vaccine for malignant melanoma of the digit of dogs.

    Science.gov (United States)

    Manley, C A; Leibman, N F; Wolchok, J D; Rivière, I C; Bartido, S; Craft, D M; Bergman, P J

    2011-01-01

    Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving >952, >1,093, 321, and 76 days, respectively. The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  10. 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

  11. Psychosocial Care Needs of Melanoma Survivors: Are They Being Met?

    Directory of Open Access Journals (Sweden)

    Sabine Fischbeck

    Full Text Available Patients who have survived malignant melanoma for more than five years may lack the opportunity to talk about their burden. As a consequence their psychosocial care needs remain undetected and available supportive interventions may not be utilised. Therefore, the psychosocial burden of this patient group needs to be assessed using specific screening instruments. The aim of this study was to investigate the psychosocial burden of long-term melanoma survivors, their psychosocial care needs and the determinants of these needs. We wanted to find out if the use of professional support corresponds to the care needs defined by experts. Using the cancer registry of Rhineland-Palatinate, melanoma patients diagnosed at least 5 years before the survey were contacted by physicians. N = 689 former patients completed the Hornheide Questionnaire (short form HQ-S to identify psychosocial support need (scale cut off ≥ 16 or item-based cut-off score and the potential psychosocial determinants of these needs. Additionally, they were asked about their utilisation of the professional support system. More than one third (36% of them was in need for professional psychosocial support. The highest burden scores concerned worry about tumour progression. Younger age (< 50, higher general fatigue, higher symptom burden, lower general health, negative social interactions and unfulfilled information needs were significant predictors of the need for psychosocial intervention. Related to the percentage of survivors identified as 'in need', the professional support system was underused. Further studies should investigate whether using the HQ-S to routinely identify burdened melanoma patients could lead to better fulfilment of their intervention needs, ultimately enhancing health-related quality of life.

  12. Three Conceptual Replication Studies in Group Theory

    Science.gov (United States)

    Melhuish, Kathleen

    2018-01-01

    Many studies in mathematics education research occur with a nonrepresentative sample and are never replicated. To challenge this paradigm, I designed a large-scale study evaluating student conceptions in group theory that surveyed a national, representative sample of students. By replicating questions previously used to build theory around student…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-07-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    Science.gov (United States)

    Bonmarin, Mathias; Le Gal, Frédérique-Anne

    2014-04-01

    This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

    Science.gov (United States)

    Vaseghi, Golnaz; Taki, Mohamad Javad; Javanmard, Shaghayegh Haghjooy

    2017-10-01

    Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis. Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls. C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

  18. Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line

    Directory of Open Access Journals (Sweden)

    Golnaz Vaseghi

    2017-10-01

    Full Text Available Objective(s: Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. Materials and Methods: In the treatment group, melanoma (B1617 was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis. Results: Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls.  Conclusion: C. sativa decreased tau and stathmin gene expression and cancer metastasis.  The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

  19. Biodistribution dosimetric study of radiopharmaceutical 99mTc Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings

    International Nuclear Information System (INIS)

    Soriano, Sarah Canuto Silva

    2015-01-01

    The labeling of Ixolaris with 99m Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer 99m Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The 99m Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with 99m Tc, a range of effective

  20. Advanced Melanoma Facebook Live Event

    Science.gov (United States)

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

  1. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

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

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

  2. ACSNI study group on human factors

    International Nuclear Information System (INIS)

    1993-01-01

    Organisational failures are now recognised as being as important as mechanical failures or individual human errors in causing major accidents such as the capsize of the Herald of Free Enterprise or the Pipa Alpha disaster. The Human Factors Study Group of the Advisory Committee on the Safety of Nuclear Installations was set up to look at the part played by human factors in nuclear risk and its reduction. The third report of the Study Group considers the role played by organisational factors and management in promoting nuclear safety. Actions to review and promote a safety culture are suggested. Three main conclusions are drawn and several recommendations made. (UK)

  3. A questionnaire to measure melanoma risk, knowledge and protective behaviour: assessing content validity in a convenience sample of Scots and Australians.

    Science.gov (United States)

    Gillespie, Helen S; Watson, Tony; Emery, Jon D; Lee, Amanda J; Murchie, Peter

    2011-08-25

    The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice. A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia). In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores. 540 people completed the questionnaire, 273 Scots (50.6%). 133 (24.6%) Scots and 83 (15.4%) Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2%) Scots and 190 (35.2%) Australians personally knew someone with melanoma. Australians had higher knowledge (p behaviour (p behaviours in Australians than in Scottish people. This was expected and supports the content validity of the questionnaire and its value as a future research tool in the Scottish population.

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

    Science.gov (United States)

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

    2010-06-01

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

  5. A pilot study of SPECT/CT-based mixed-reality navigation towards the sentinel node in patients with melanoma or Merkel cell carcinoma of a lower extremity.

    Science.gov (United States)

    van den Berg, Nynke S; Engelen, Thijs; Brouwer, Oscar R; Mathéron, Hanna M; Valdés-Olmos, Renato A; Nieweg, Omgo E; van Leeuwen, Fijs W B

    2016-08-01

    To explore the feasibility of an intraoperative navigation technology based on preoperatively acquired single photon emission computed tomography combined with computed tomography (SPECT/CT) images during sentinel node (SN) biopsy in patients with melanoma or Merkel cell carcinoma. Patients with a melanoma (n=4) or Merkel cell carcinoma (n=1) of a lower extremity scheduled for wide re-excision of the primary lesion site and SN biopsy were studied. Following a Tc-nanocolloid injection and lymphoscintigraphy, SPECT/CT images were acquired with a reference target (ReTp) fixed on the leg or the iliac spine. Intraoperatively, a sterile ReTp was placed at the same site to enable SPECT/CT-based mixed-reality navigation of a gamma ray detection probe also containing a reference target (ReTgp).The accuracy of the navigation procedure was determined in the coronal plane (x, y-axis) by measuring the discrepancy between standard gamma probe-based SN localization and mixed-reality-based navigation to the SN. To determine the depth accuracy (z-axis), the depth estimation provided by the navigation system was compared to the skin surface-to-node distance measured in the computed tomography component of the SPECT/CT images. In four of five patients, it was possible to navigate towards the preoperatively defined SN. The average navigational error was 8.0 mm in the sagittal direction and 8.5 mm in the coronal direction. Intraoperative sterile ReTp positioning and tissue movement during surgery exerted a distinct influence on the accuracy of navigation. Intraoperative navigation during melanoma or Merkel cell carcinoma surgery is feasible and can provide the surgeon with an interactive 3D roadmap towards the SN or SNs in the groin. However, further technical optimization of the modality is required before this technology can become routine practice.

  6. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de; Koch, Silvia A., E-mail: silvia.koch@web.de [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Lotz, Gösta, E-mail: goesta.lotz@kgu.de [University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany); Willinek, Winfried, E-mail: w.willinek@bk-trier.de [Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany); Engelke, Christoph, E-mail: engelke@ekweende.de [Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany); Brüning, Roland, E-mail: r.bruening@asklepios.com; Zeile, Martin, E-mail: m.zeile@asklepios.com [Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany); Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de [Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany); Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de [Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  7. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    International Nuclear Information System (INIS)

    Vogl, Thomas J.; Koch, Silvia A.; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-01-01

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  8. Longitudinal studies of the 18F-FDG kinetics after ipilimumab treatment in metastatic melanoma patients based on dynamic FDG PET/CT.

    Science.gov (United States)

    Sachpekidis, Christos; Anwar, Hoda; Winkler, Julia K; Kopp-Schneider, Annette; Larribere, Lionel; Haberkorn, Uwe; Hassel, Jessica C; Dimitrakopoulou-Strauss, Antonia

    2018-06-05

    Immunotherapy has raised the issue of appropriate treatment response evaluation, due to the unique mechanism of action of the immunotherapeutic agents. Aim of this analysis is to evaluate the potential role of quantitative analysis of 2-deoxy-2-( 18 F)fluoro-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) data in monitoring of patients with metastatic melanoma undergoing ipilimumab therapy. 25 patients with unresectable metastatic melanoma underwent dynamic PET/CT (dPET/CT) of the thorax and upper abdomen as well as static, whole body PET/CT with 18 F-FDG before the start of ipilimumab treatment (baseline PET/CT), after two cycles of treatment (interim PET/CT) and at the end of treatment after four cycles (late PET/CT). The evaluation of dPET/CT studies was based on semi-quantitative (standardized uptake value, SUV) calculation as well as quantitative analysis, based on two-tissue compartment modeling and a fractal approach. Patients' best clinical response, assessed at a mean of 59 weeks, was used as reference. According to their best clinical response, patients were dichotomized in those demonstrating clinical benefit (CB, n = 16 patients) and those demonstrating no clinical benefit (no-CB, n = 9 patients). No statistically significant differences were observed between CB and no-CB regarding either semi-quantitative or quantitative parameters in all scans. On contrary, the application of the recently introduced PET response evaluation criteria for immunotherapy (PERCIMT) led to a correct classification rate of 84% (21/25 patients). Quantitative analysis of 18 F-FDG PET data does not provide additional information in treatment response evaluation of metastatic melanoma patients receiving ipilimumab. PERCIMT criteria correlated better with clinical response.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  10. Facilitating peer learning in study groups

    DEFF Research Database (Denmark)

    Adriansen, Hanne Kirstine; Madsen, Lene Møller

    2009-01-01

    In 2008 University of Aarhus, Denmark, issued a report concerning student experience with the study environment. Among the university's eight faculties, the Danish School of Education (DPU) held the sad record of having the lowest student well-being. This led to an action research project...... 'Facilitating study environment' at one of DPU's educations in spring 2009. The pilot project consisted of three elements: Facilitated study groups, a student bar with facilitated activities, and academic identity events. Subsequently, we have studied students' experiences with the project. This paper outlines...... the preliminary results from the facilitated study groups. After one term (February-May), student satisfaction with both the social and the disciplinary environment had increased. The project shows how academic and social integration can be achieved with minimum faculty member involvement. This is done by relying...

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

    Science.gov (United States)

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

    1998-03-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  13. Effect of Genistein on vasculogenic mimicry formation by human uveal melanoma cells

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    Gu Haijuan

    2009-09-01

    Full Text Available Abstract Background Vasculogenic mimicry (VM was increasingly recognized as a form of aggressive melanoma acquiring blood supply. Genistein had attracted much attention as a potential anticancer agent. Therefore, we examined the effect of Genistein on VM in human uveal melanoma cells. Methods VM structure was detected by periodic acid-Schiff (PAS staining for uveal melanoma C918 cells cultured on the three-dimensional type I collagen gels after exposed to Genistein. We used reverse transcription polymerase chain reaction (RT-PCR and Western Blot analysis to examine the effect of Genistein on vascular endothelial cadherin (VE-cadherin mRNA and protein expression. The nude mice models of human uveal melanoma C918 cells were established to assess the number of VM using immunohistochemical and PAS double-staining. Results Genistein inhibited the survival of C918 cells in vitro. The ectopic model study showed that VM in tumor tissue sections were significantly reduced by Genistein in vivo. In vitro, the VM structure was found in control, 25 and 50 μM Genistein-treatment groups but not in 100 and 200 μM. RT-PCR and Western Blot showed that 100 and 200 μM concentration of Genistein could significantly decrease VE-cadherin mRNA and protein expression of C918 cells compared with control (P 0.05. Conclusion Genistein inhibits VM formation of uveal melanoma cells in vivo and in vitro. One possible underlying molecular mechanism by which Genistein could inhibit VM formation of uveal melanoma is related to down-regulation of VE-cadherin.

  14. Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

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    Daryoush Shahbazi-Gahrouei

    2006-11-01

    Full Text Available BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI contrast agents, Gd-hematoporphyrin (Gd-H and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP were synthesized and tested in nude mice with human melanoma (MM-138 xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138 were studied in 30 (five groups of six nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA on proton relaxation times was measured in tumors and other organs. T1 values, signal enhancement and the Gd concentration for different contrast agent solutions were also investigated. RESULTS: The porphyrin agents showed higher relaxivity compared to the clincal agent, Gd-DTPA. A significant 16% and 21% modification in T1 relaxation time of the water in human melanoma tumors grafted in the nude mice was revealed 24 hours after injection of Gd-TCP and Gd-H, respectively. The percentage of injected Gd localized to the tumor measured by inductively coupled plasma atomic emission spectrometry (ICP-AES was approximately 21% for Gd-TCP and 28% for Gd-H which were higher than that of Gd-DTPA (10%. CONCLUSIONS: The high concentration of Gd in the tumor is indicative of a selective retention of the compounds and indicates that Gd-TCP and Gd-H are promising MR imaging contrast agents for melanoma detection. Gd-porphyrins have considerable promise for further diagnostic applications in magnetic resonance imaging. KEY WORDS: MRI, porphyrin-based contrast agent, hematoporphyrin, melanoma.

  15. Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients

    Directory of Open Access Journals (Sweden)

    Buckley Michael T

    2008-11-01

    Full Text Available Abstract Background Different Insulin-like Growth Factor Binding Proteins (IGFBPs have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression. Methods The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56 prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients. Results Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01 A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 μg/ml vs. 3.4 μg/ml, respectively, p = 0.09. However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients. Conclusion Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.

  16. Selenium for the Prevention of Cutaneous Melanoma

    Directory of Open Access Journals (Sweden)

    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  17. Selenium for the Prevention of Cutaneous Melanoma

    Science.gov (United States)

    Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

    2013-01-01

    The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

  18. Metacognition and Group Differences: A Comparative Study

    Science.gov (United States)

    Al-Hilawani, Yasser A.

    2014-01-01

    In this study, metacognition refers to performing visual analysis and discrimination of real life events and situations in naïve psychology, naïve physics, and naïve biology domains. It is used, along with measuring reaction time, to examine differences in the ability of four groups of students to select appropriate pictures that correspond with…

  19. Report of the Public Cryptography Study Group.

    Science.gov (United States)

    American Council on Education, Washington, DC.

    Concerns of the National Security Agency (NSA) that information contained in some articles about cryptography in learned and professional journals and in monographs might be inimical to the national security are addressed. The Public Cryptography Study Group, with one dissenting opinion, recommends that a voluntary system of prior review of…

  20. Snowmass Fusion Summer Study Group workshop

    International Nuclear Information System (INIS)

    Clement, S.

    1999-01-01

    The Snowmass Fusion Summer Study Group workshop, has taken place at Snowmass, Colorado, 11-23 July 1999. Its purpose was to discuss opportunities and directions in fusion energy science for the next decade. About 300 experts from all fields in the magnetic and inertial fusion communities attended, coming mostly from the US, but with some foreign participation

  1. Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in scotland.

    Science.gov (United States)

    MacKie, R. M.; Aitchison, T.

    1982-01-01

    A case-control study of occupational and recreational sun exposure, Mediterranean and other sun-exposed holidays, tanning history and history of isolated episodes of severe sunburn has been carried out on 113 patients with cutaneous malignant melanoma and 113 age- and sex-matched controls. Social class and skin type were also considered in the analysis of the data which involved the use of conditional multiple logistic regression. A highly significant increase in the history of severe sunburn was recorded in melanoma patients of both sexes in the 5-year period preceding presentation with their tumour. Higher social class and negative history of recreational sun exposure were also significantly increased in patients by comparison with controls. In the male group severe sunburn, lack of occupational sun exposure and higher social class were significant factors while in the female group only severe sunburn was significantly increased in the melanoma patients. This study thus provides evidence to suggest that short intense episodes of UV exposure resulting in burning may be one of the aetiological factors involved in subsequent development of melanoma. PMID:7150488

  2. Ambulatory Melanoma Care Patterns in the United States

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  4. Analysis of the B-RAFV600E mutation in cutaneous melanoma patients with occupational sun exposure

    Science.gov (United States)

    CANDIDO, SAVERIO; RAPISARDA, VENERANDO; MARCONI, ANDREA; MALAPONTE, GRAZIA; BEVELACQUA, VALENTINA; GANGEMI, PIETRO; SCALISI, AURORA; McCUBREY, JAMES A.; MAESTRO, ROBERTA; SPANDIDOS, DEMETRIOS A.; FENGA, CONCETTINA; LIBRA, MASSIMO

    2014-01-01

    Sun-exposure is one of the risk factors associated with the development of a cutaneous neoplasm. In melanoma, the Ras-Raf-MEK-ERK (MAPK) signaling pathway is constitutively activated through multiple mechanisms, including B-RAF mutation. It has been hypothesized that B-RAF mutations in melanocytic lesions arise from DNA damage induced by ultraviolet (UV) radiation. However, it is still discussed if B-RAF mutations are associated with melanoma patients exposed to the sun. Therefore, in the present study, the known B-RAFV600E mutation was analysed in melanoma samples from 30 indoor and 38 outdoor workers. B-RAFV600E mutation was detected in 52 and 73% of outdoor workers and indoor workers, respectively. Of note, this mutation was identified in 12 of 14 (85%) melanoma of the trunk diagnosed in indoor workers and in 9 of 19 (47%) samples from outdoor workers (p=0.03). By analyzing melanomas of other body sites, no statistical difference in the frequency of B-RAFV600E mutation was identified between the groups of workers. It appears that the mutation detected among indoor workers may be associated with a recreational or intermittent exposure to the sun, as usually the trunk is a sun-protected body site. Overall, these data indicate that the B-RAFV600E mutation detected in melanoma is not associated with a chronic exposure to the sun. Mutations detected in other genes may also contribute to melanoma development in the subset of patients exposed to UV radiation. PMID:24424406

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

    Science.gov (United States)

    Abou Asa, S

    2017-07-01

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

  6. Malignant melanoma in children: imaging spectrum

    International Nuclear Information System (INIS)

    Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

    1996-01-01

    Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

  7. Characterization of long noncoding RNA and messenger RNA signatures in melanoma tumorigenesis and metastasis.

    Directory of Open Access Journals (Sweden)

    Siqi Wang

    Full Text Available The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear. In this study, we investigated lncRNA and messenger RNA (mRNA expression profiles in primary melanomas, metastatic melanomas and normal skin samples from the Gene Expression Omnibus database. We used GSE15605 as the training set (n = 74 and GSE7553 as the validation set (n = 58. In three comparisons (primary melanoma versus normal skin, metastatic melanoma versus normal skin, and metastatic melanoma versus primary melanoma, 178, 295 and 48 lncRNAs and 847, 1758, and 295 mRNAs were aberrantly expressed, respectively. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses to examine the differentially expressed mRNAs, and potential core lncRNAs were predicted by lncRNA-mRNA co-expression networks. Based on our results, 15 lncRNAs and 144 mRNAs were significantly associated with melanoma tumorigenesis and metastasis. A subsequent analysis suggested a critical role for a five-lncRNA signature during melanoma tumorigenesis and metastasis. Low expression of U47924.27 was significantly associated with decreased survival of patients with melanoma. To the best of our knowledge, this study is the first to explore the expression patterns of lncRNAs and mRNAs during melanoma tumorigenesis and metastasis by re-annotating microarray data from the Gene Expression Omnibus (GEO microarray dataset. These findings reveal potential roles for lncRNAs during melanoma tumorigenesis and metastasis and provide a rich candidate

  8. The enigmatic role of nucleophosmin in malignant melanoma: Does it have an effect?

    Directory of Open Access Journals (Sweden)

    Aylin Orgen Calli

    2011-01-01

    Full Text Available Background: Melanoma is quite a heterogeneous group of diseases of the skin. Prognostic markers of tumor behavior are important to precisely assign individual patients for appropriate treatment protocols. Aim: The aim of our first study was to investigate nucleophosmin expression in melanoma patients and to determine its relationship with the tumor characterictics and patient prognosis. Materials and Methods: We analyzed the immunohistochemical expression of nucleophosmin in 55 melanoma patients. The immunostaining pattern was classified into two groups: Diffuse nuclear and nucleolar relocalization. We also investigated the relationship between the expression of nucleophosmin and the clinicopathological parameters sucssh as Clark level, tumor thickness, stage, histological type, location, and survey. Results: In all cases the neoplastic cells were strongly positive for nucleophosmin (14 cases diffuse nuclear, 41 cases nucleolar relocalization. No correlation was demonstrated between the expression pattern of nucleophosmin and the clinicopathological parameters and survey. Conclusions: The implications of our results, nevertheless, are that the immunohistochemical detection of nucleophosmin is not a valuable tool for predicting the outcome of patients with melanoma or identifying subgroups of patients who may be at a higher risk.

  9. Ascertaining serum levels of trace elements in melanoma patients using PIXE and HR-ICPMS

    Science.gov (United States)

    Bernardes, S.; Tabacniks, M. H.; Santos, I. D. A. O.; Oliveira, A. F.; Shie, J. N.; Sarkis, J. E. S.; Oliveira, T.

    2014-01-01

    Melanoma is a serious and deadly form of skin cancer. However, patients' chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at São Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.

  10. Ascertaining serum levels of trace elements in melanoma patients using PIXE and HR-ICPMS

    Energy Technology Data Exchange (ETDEWEB)

    Bernardes, S., E-mail: suene@if.usp.br [Physics Institute, University of São Paulo (Brazil); Tabacniks, M.H. [Physics Institute, University of São Paulo (Brazil); Santos, I.D.A.O.; Oliveira, A.F.; Shie, J.N. [São Paulo Federal University (UNIFESP), São Paulo (Brazil); Sarkis, J.E.S.; Oliveira, T. [Institute of Energy and Nuclear Research (IPEN), Laboratory of Chemical Characterization (LCQ), Center for Chemistry and the Environment - CQMA, Sao Paulo (Brazil)

    2014-01-01

    Melanoma is a serious and deadly form of skin cancer. However, patients’ chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at São Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.

  11. An Endogenous Electron Spin Resonance (ESR signal discriminates nevi from melanomas in human specimens: a step forward in its diagnostic application.

    Directory of Open Access Journals (Sweden)

    Eleonora Cesareo

    Full Text Available Given the specific melanin-associated paramagnetic features, the Electron Spin Resonance (ESR, called also Electron Paramagnetic Resonance, EPR analysis has been proposed as a potential tool for non-invasive melanoma diagnosis. However, studies comparing human melanoma tissues to the most appropriate physiological counterpart (nevi have not been performed, and ESR direct correlation with melanoma clinical features has never been investigated. ESR spectrum was obtained from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non-melanoma tissues and an endogenous ESR signal (g = 2.005 was found in human melanoma cells and in primary melanoma tissues explanted from mice, while it was always absent in non-melanoma samples. These characteristics of the measured ESR signal strongly suggested its connection with melanin. Quantitative analyses were then performed on paraffin-embedded human melanoma and nevus sections, and validated on an independent larger validation set, for a total of 112 sections (52 melanomas, 60 nevi. The ESR signal was significantly higher in melanomas (p = 0.0002 and was significantly different between "Low Breslow's and "High Breslow's" depth melanomas (p<0.0001. A direct correlation between ESR signal and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001. The eu/pheomelanin ratio was found to be significantly different in melanomas "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas "High Breslow's depth". Finally, ROC analysis using ESR data discriminated melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In the present study we report for the first time that ESR signal in human paraffin-embedded nevi is significantly lower than signal in human melanomas suggesting that spectrum variations may be related to qualitative melanin differences specifically occurring in melanoma cells. We therefore conclude that this ESR signal

  12. Case-control study of smoking and non-melanoma skin cancer.

    Science.gov (United States)

    Rollison, Dana E; Iannacone, Michelle R; Messina, Jane L; Glass, L Frank; Giuliano, Anna R; Roetzheim, Richard G; Cherpelis, Basil S; Fenske, Neil A; Jonathan, Kristen A; Sondak, Vernon K

    2012-02-01

    To investigate the association between cigarette smoking and basal and squamous cell carcinomas (BCC and SCC) of the skin, a clinic-based case-control study was conducted in Tampa, FL. Patients with histologically confirmed BCC/SCC were recruited from a university dermatology clinic (n = 215 BCC, 165 SCC). Controls were comprised of individuals with no history of skin cancer who screened negative for skin cancer upon physical examination at the affiliated cancer screening or primary care clinics (n = 315). Information on smoking and other risk factors was obtained from self-administered questionnaires. After adjustment for age, sex, and other skin cancer-risk factors, ever smoking was not associated with BCC (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 0.83-1.92), but was statistically significantly associated with SCC (OR = 1.97, 95% CI = 1.19-3.26), with significant trends observed for SCC associated with increasing cigarettes per day (p = 0.01) and pack-years smoked (p = 0.01). Among men, smoking ≥20 pack-years was associated with non-significant increased risks of BCC (OR = 1.90, 95% CI = 0.88-4.12) and SCC (OR = 1.97, 95% CI = 0.84-4.66), whereas among women, no association was observed with BCC (OR = 0.98, 95% CI = 0.39-2.46) while a statistically significant three-fold risk was observed with SCC (OR = 3.00, 95% CI = 1.02-8.80). Cigarette smoking is more strongly associated with SCC than BCC, particularly among women.

  13. The effect of low-level laser irradiation (In-Ga-Al-AsP - 660 nm) on melanoma in vitro and in vivo

    International Nuclear Information System (INIS)

    Frigo, Lúcio; Luppi, Juliana SS; Favero, Giovani M; Maria, Durnavei A; Penna, Sócrates C; Bjordal, Jan M; Bensadoun, Rene J; Lopes-Martins, Rodrigo AB

    2009-01-01

    It has been speculated that the biostimulatory effect of Low Level Laser Therapy could cause undesirable enhancement of tumor growth in neoplastic diseases. The aim of the present study is to analyze the behavior of melanoma cells (B16F10) in vitro and the in vivo development of melanoma in mice after laser irradiation. We performed a controlled in vitro study on B16F10 melanoma cells to investigate cell viability and cell cycle changes by the Tripan Blue, MTT and cell quest histogram tests at 24, 48 and 72 h post irradiation. The in vivo mouse model (male Balb C, n = 21) of melanoma was used to analyze tumor volume and histological characteristics. Laser irradiation was performed three times (once a day for three consecutive days) with a 660 nm 50 mW CW laser, beam spot size 2 mm 2 , irradiance 2.5 W/cm 2 and irradiation times of 60s (dose 150 J/cm 2 ) and 420s (dose 1050 J/cm 2 ) respectively. There were no statistically significant differences between the in vitro groups, except for an increase in the hypodiploid melanoma cells (8.48 ± 1.40% and 4.26 ± 0.60%) at 72 h post-irradiation. This cancer-protective effect was not reproduced in the in vivo experiment where outcome measures for the 150 J/cm 2 dose group were not significantly different from controls. For the 1050 J/cm 2 dose group, there were significant increases in tumor volume, blood vessels and cell abnormalities compared to the other groups. LLLT Irradiation should be avoided over melanomas as the combination of high irradiance (2.5 W/cm 2 ) and high dose (1050 J/cm 2 ) significantly increases melanoma tumor growth in vivo

  14. Eye imaging with a 3.0-T MRI using a surface coil - a study on volunteers and initial patients with uveal melanoma

    International Nuclear Information System (INIS)

    Lemke, Arne-Joern; Hengst, Susanne Anja; Kazi, Iris; Felix, Roland; Alai-Omid, Minouche

    2006-01-01

    MRI of uveal melanoma using 1.5-T technology and surface coils has developed into a standard procedure. The purpose of the study was to evaluate the feasibility of 3.0-T technology in eye imaging. To optimize the MRI sequences for clinical eye imaging with 3.0-T, six healthy volunteers were conducted using a 4.0-cm surface coil. Evaluation criteria were the signal-to-noise-ratio (SNR), contrast-to-noise-ratio (CNR) and image quality. A further six patients with uveal melanoma were examined with 1.5- and 3.0-T under retrobulbar anesthesia. During 3.0-T examinations of volunteers, eye movements caused significant artifacts. On the contrary, excellent imaging quality was reached in examinations of patients under retrobulbar anesthesia at 3.0 T. Subjective assessment showed no significant difference between 1.5 and 3.0 T in patients. Due to the increased SNR, the 3.0-T technique has the potential to improve eye imaging, but the higher susceptibility to motion artifacts limits the clinical use of this technique to patients receiving retrobulbar anesthesia. (orig.)

  15. Immunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

    1990-01-01

    Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

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

    Science.gov (United States)

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

    2001-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Elton Rexhepaj

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

  18. Quantification of microRNA-21 and microRNA-125b in melanoma tissue

    DEFF Research Database (Denmark)

    Wandler, Anne; Riber-Hansen, Rikke; Hager, Henrik

    2017-01-01

    Although microRNAs (miRNAs) have emerged as potent mediators of melanoma development and progression, a precise understanding of their oncogenic role remains unclear. In this study, we analysed formalin-fixed and paraffin-embedded tissues from two separate melanoma cohorts and from a series...... the important involvement of different miRNAs in melanoma biology and may serve as solid basics for further miRNA investigations in melanoma formalin-fixed and paraffin-embedded tissue. In particular, there is increased expression of miR-21 in melanomas compared with benign nevi....

  19. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 10 12 , γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10 B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

  20. The effects of a cyclooxygenase-2 (COX-2 expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production

    Directory of Open Access Journals (Sweden)

    Marshall Jean-Claude

    2007-01-01

    Full Text Available Abstract Background Cyclooxygenase-2 (COX-2 expression has previously been identified in uveal melanoma although the biological role of COX-2 in this intraocular malignancy has not been elucidated. This study aimed to investigate the effect of a COX-2 inhibitor on the proliferation rate of human uveal melanoma cells, as well as its effect on the cytotoxic response of macrophages. Methods Human uveal melanoma cell lines were transfected to constitutively express COX-2 and the proliferative rate of these cells using two different methods, with and without the addition of Amfenac, was measured. Nitric oxide production by macrophages was measured after exposure to melanoma-conditioned medium from both groups of cells as well as with and without Amfenac, the active metabolite of Nepafenac. Results Cells transfected to express COX-2 had a higher proliferation rate than those that did not. The addition of Amfenac significantly decreased the proliferation rate of all cell lines. Nitric oxide production by macrophages was inhibited by the addition of melanoma conditioned medium, the addition of Amfenac partially overcame this inhibition. Conclusion Amfenac affected both COX-2 transfected and non-transfected uveal melanoma cells in terms of their proliferation rates as well as their suppressive effects on macrophage cytotoxic activity.

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

    Directory of Open Access Journals (Sweden)

    Jason Ezra Hawkes

    2013-06-01

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

  2. WITHDRAWN: Systemic treatments for metastatic cutaneous melanoma.

    Science.gov (United States)

    Crosby, Tom; Fish, Reg; Coles, Bernadette; Mason, Malcolm

    2018-02-07

    Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo. To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments. Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted. Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care. Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently. No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma. There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.

  3. Increased UV-induced sister-chromatid exchange in cultured fibroblasts of first-degree relatives of melanoma patients

    International Nuclear Information System (INIS)

    Knees-Matzen, S.; Roser, M.; Reimers, U.; Ehlert, U.; Weichenthal, M.; Breitbart, E.W.; Ruediger, H.W.

    1991-01-01

    Cultured fibroblasts of 17 first-degree relatives of familial melanoma patients and six first-degree relatives of cutaneous melanoma (CMM) patients with multiple CMM primaries were tested for in vitro sensitivity to UV light. Fibroblasts of nine familial CMM patients with a known UV-sensitivity and 19 healthy probands served as a control. Sister chromatid exchange (SCE) was used as a parameter to detect UV-induced genotoxic damage. The authors found significantly (p less than 0.001) increased UV-induced SCE levels in familial melanoma patients, as well as in first-degree relatives of familial melanoma patients (p less than 0.001) after UV-A,B irradiation (375 J/m2), compared to the healthy probands without a family history of CMM. A significant (p less than 0.001) increase of UV-induced SCE was also observed in the relatives of CMM patients with multiple CMM primaries. In addition, the spontaneous SCE were significantly increased (p less than 0.05) in familial CMM patients. This study shows that increased UV sensitivity is a familial phenomenon. It is consistent with the concept of a genetic predisposition to CMM, which is based on increased UV sensitivity and may help to define groups with an elevated risk of developing cutaneous malignant melanoma

  4. GAB2 amplifications refine molecular classification of melanoma.

    Science.gov (United States)

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

    2009-07-01

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

  5. The risk of melanoma associated with ambient summer ultraviolet radiation.

    Science.gov (United States)

    Pinault, Lauren; Bushnik, Tracey; Fioletov, Vitali; Peters, Cheryl E; King, Will D; Tjepkema, Michael

    2017-05-17

    Depletion of the ozone layer has meant that ambient ultraviolet radiation (UVR) has increased in recent decades. At the same time, the incidence of skin cancers, including melanoma, has risen. The relatively few large-scale studies that linked ambient UVR to melanoma found a trend toward rising incidence closer to the equator, where UVR estimates are highest. Similar research has not been conducted in Canada, where ambient UVR is generally lower than in countries further south. Modelled UVR data for the months of June through August during the 1980-to-1990 period were spatially linked in Geographic Information Systems to 2.4 million white members of the 1991 Canadian Census Health and Environment Cohort and tracked for melanoma diagnosis over an 18-year period (1992 to 2009). Standard Cox proportional hazards models were used to estimate melanoma risk associated with increases of ambient summer UVR, assigned by residence at baseline. Models were adjusted for age, sex and socioeconomic (SES) characteristics. Separate analyses by body site of melanoma were conducted. Effect modification of the association between ambient UVR and melanoma by sex, age, outdoor occupation and selected SES characteristics was evaluated. Differences of one standard deviation (446 J/m², or 7% of the mean) in average ambient summer UVR were associated with an increased hazard ratio (HR) for melanoma of 1.22 (95% CI: 1.19 to 1.25) when adjusting for sex, age and SES characteristics. The HR for melanoma in relative UVR (per 1 standard deviation) was larger for men (HR = 1.26; 95% CI: 1.21 to 1.30) than for women (HR = 1.17; 95% CI: 1.13 to 1.22). Ambient summer UVR is associated with a greater risk of melanoma among the white population, even in a country where most people live within a narrow latitudinal belt. A stronger association between melanoma and ambient UVR was evident among men and among people of lower SES.

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Lymphoscintigraphy in melanoma patients using Tc-99m dextran

    International Nuclear Information System (INIS)

    Marciano, D.; Padgett, H.; Henze, E.; Carlson, C.; Bennett, L.R.

    1984-01-01

    Surgical removal of regional lymph nodes draining the site of a melanoma is a generally practiced procedure. It is often difficult in many cases of truncal melanomas near the midline or near the waistline to determine which group or groups of nodes to remove. Colloidal Au-198, Tc-99m sulfur colloid, and Tc-99m antimony sulfur colloid have all been used and have given useful clinical information. Objections, however, have been raised to the local radiation dose with these compounds. To reduce this problem while obtaining greater information on lymph flow, the authors have studied dextran, a macromolecule commonly used as plasma substitute. Dextran (average mol. wt. 72,000) labeled with Tc-99m has been used to study lymph drainage from the site of truncal melanoma in 29 patients. Serial images in the first hour following intradermal injection clearly demonstrate tracer in efferent lymphatics within 5 to 10 minutes, and brief pooling in the regional lymph nodes between 20 and 60 minutes. When compared with particulate tracers such as micro Tc-99m sulfur colloid, the Tc-99m dextran appears to move much faster through the lymphatics. Overall distribution of the Tc-99m dextran to lymph nodes is very similar to previous findings with micro Tc-99m sulfur colloid. Dextran drainage to more than one group of regional nodes was seen in 12/29 patients as compared with 17/50 patients using micro Tc-99m sulfur colloid. The superior images with Tc-99m dextran appear to make it the agent of choice

  8. Melanoma Risk Prediction Models

    Science.gov (United States)

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

  9. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the June 2015 CDC Vital Signs report. Skin cancer is the most common form of cancer in the U.S. In 2011, there were more than 65,000 cases of melanoma, the most deadly form of skin cancer. Learn how everyone can help prevent skin cancer.

  10. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

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

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

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

  12. Cell proliferation and expression of connexins differ in melanotic and amelanotic canine oral melanomas.

    Science.gov (United States)

    Teixeira, Tarso Felipe; Gentile, Luciana Boffoni; da Silva, Tereza Cristina; Mennecier, Gregory; Chaible, Lucas Martins; Cogliati, Bruno; Roman, Marco Antonio Leon; Gioso, Marco Antonio; Dagli, Maria Lucia Zaidan

    2014-03-01

    Melanoma is a malignant neoplasm occurring in several animal species, and is the most frequently found tumor in the oral cavity in dogs. Melanomas are classified into two types: melanotic and amelanotic. Prior research suggests that human amelanotic melanomas are more aggressive than their melanotic counterparts. This study evaluates the behavior of canine melanotic and amelanotic oral cavity melanomas and quantifies cell proliferation and the expression of connexins. Twenty-five melanomas (16 melanotic and 9 amelanotic) were collected from dogs during clinical procedures at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo, Brazil. After diagnosis, dogs were followed until death or euthanasia. Histopathology confirmed the gross melanotic or amelanotic characteristics and tumors were classified according to the WHO. HMB45 or Melan A immunostainings were performed to confirm the diagnosis of amelanotic melanomas. Cell proliferation was quantified both by counting mitotic figures and PCNA positive nuclei. Expressions of connexins 26 and 43 were evaluated by immunohistochemistry, qRT-PCR and Western blot. Dogs bearing amelanotic melanomas presented a shorter lifespan in comparison to those with melanotic melanomas. Cell proliferation was significantly higher in amelanotic melanomas. Expressions of Connexins 26 and 43 were significantly reduced in amelanotic melanomas. The results presented here suggest that oral cavity melanotic and amelanotic melanomas differ regarding their behavior, cell proliferation and connexin expression in dogs, indicating a higher aggressiveness of amelanotic variants.

  13. Environmental studies group. Annual report for 1978

    International Nuclear Information System (INIS)

    Hunt, D.C.; Hurley, J.D.

    1980-01-01

    Group projects included radioecological studies of aquatic and terrestrial systems, land management activities, foodstuff monitoring, dust transport studies including fugitive dust measurements and modeling, and several support programs involving evaluation of the plant's ambient air samplers and airborne tritium monitoring techniques. Some salient results from the several project reports include determination of an appropriate model for mechanically generated fugitive dust dispersion, a radionuclide inventory of Smart Ditch Pond (Pond D-1), a coefficient of community determination for two terrestrial sample plots on the plant site buffer zone, a natality and mortality rate determination for fawns in the plant deer herd (including one positive coyote-kill determination), inlet loss and filter paper collection efficiencies for the plant ambient air samplers, and differential tritium sampling measurements of the vapor in Building 771 stack effluent

  14. Environmental studies group. Annual report for 1978

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, D. C.; Hurley, J. D. [eds.

    1980-08-21

    Group projects included radioecological studies of aquatic and terrestrial systems, land management activities, foodstuff monitoring, dust transport studies including fugitive dust measurements and modeling, and several support programs involving evaluation of the plant's ambient air samplers and airborne tritium monitoring techniques. Some salient results from the several project reports include determination of an appropriate model for mechanically generated fugitive dust dispersion, a radionuclide inventory of Smart Ditch Pond (Pond D-1), a coefficient of community determination for two terrestrial sample plots on the plant site buffer zone, a natality and mortality rate determination for fawns in the plant deer herd (including one positive coyote-kill determination), inlet loss and filter paper collection efficiencies for the plant ambient air samplers, and differential tritium sampling measurements of the vapor in Building 771 stack effluent.

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

    Science.gov (United States)

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

    2010-12-01

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

  16. Oncogenesis of melanoma B16 cell clones mutagenized by space environment

    International Nuclear Information System (INIS)

    Guo Yupeng; Yang Hongsheng; Tang Jingtian; Xu Mei; Geng Chuanying; Fang Qing; Xu Bo; Li Hongyan; Xiang Xing; Pan Lin

    2005-01-01

    Objective: To explore the oncogenesis of the melanoma B16 cell clones mutagenized by space environment, and find the B16 cell clones with remarkably mutated immunogenicity. Methods: B16 cells were carried by the Chinese 20th recoverable satellite to the outer space, and were harvested after 18 days' spaceflight and then monocloned. Four cell clones, which were randomly selected from the total 110 clones obtained , and the control clone were routinely cultured. The cultured cells were injected to 10 groups of C57BL/6J mice, 82.1 mice in each group. Five groups of mice received hypodermic injection and another 5 groups of mice received abdominal injection. The survival time was observed in abdominal injection groups. The mice in hypodermic injection groups were sacrificed after 14 days, the tumor, spleen and thymus were weighted, and the serum IL-2 concentration was determined. Moreover, the melanoma tumor tissues were examined histopathologically. Results: An experiment program suitable to screening space mutagenesis of B16 tumor cell clones in vivo and the observation indices were basically established. One clone was found out which was remarkably different from the control clone in latent period of tumor formation, tumor weight, survival time of the tumor-bearing mice and the expression of IL-2. Conclusions: Cultured melanoma B16 cells could be mutated by outer space environment. The further study will be focused on the influence of space environment on immunogenicity of mutagenized B16 cells. (authors)

  17. Is it sufficient to repeat LINEAR accelerator stereotactic radiosurgery in choroidal melanoma?

    Science.gov (United States)

    Furdova, A; Horkovicova, K; Justusova, P; Sramka, M

    One day session LINAC based stereotactic radiosurgery (SRS) at LINAC accelerator is a method of "conservative" attitude to treat the intraocular malignant uveal melanoma. We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm). The first plan was compared and the best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram). In our clinical study in the group of 125 patients with posterior uveal melanoma treated with SRS, in 2 patients (1.6 %) was repeated SRS indicated. Patient age of the whole group ranged from 25 to 81 years with a median of 54 TD was 35.0 Gy. In 2 patients after 5 year interval after stereotactic radiosurgery for uveal melanoma stage T1, the tumor volume increased to 50 % of the primary tumor volume and repeated SRS was necessary. To find out the changes in melanoma characteristics after SRS in long term interval after irradiation is necessary to follow up the patient by an ophthalmologist regularly. One step LINAC based stereotactic radiosurgery with a single dose 35.0 Gy is one of treatment options to treat T1 to T3 stage posterior uveal melanoma and to preserve the eye globe. In some cases it is possible to repeat the SRS after more than 5 year interval (Fig. 8, Ref. 23).

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2016-02-01

    primary melanoma manifests additional high-risk features. Additional studies are underway in order to further elucidate the mechanism of these metastases. Copyright © 2016. Published by Elsevier B.V.

  20. Promoting early detection of melanoma during the mammography experience

    Directory of Open Access Journals (Sweden)

    A.K. Rzepecki, BS

    2017-12-01

    Full Text Available Background: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman’s risk of developing a melanoma. Objective: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE to a population of women who are already invested in preventive health. Methods: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women’s Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. Results: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560. Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. Conclusion: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women. Keywords: melanoma, skin self-examination, skin cancer screening

  1. Report of JLC site study group

    CERN Document Server

    Hasegawa, T; Yamashita, S

    2003-01-01

    This study group selected some good sites for construction of JLC (Electron-Positron Linear Collider) on the basis of investigation of data and field survey. The aims, activity, use of underground of private land, conditions of site, selection of site at present and future, summary and proposal are reported. 9 sites (Hidaka, Kitakami, Murayama, Abukuma, Kitaibaraki, Aichi and Gifu, Takamatsu, Hiroshima and Seburi range) are selected for the construction on the basis of firm ground and 4 sites (Okinawa, Harima, Tsukuba and Mutsuogawara) for development and researches. 9 sites area consists of plutonic rock or old strata of Paleozoic era. Many problems in each site are reported. There are three following proposals; 1) the self-governing communities of the sites have to understand JLC and start to construct it by information, 2) a site evaluation committee consists of specialist of civil engineering, building, social and natural environment and disaster prevention and 3) the vibration test should be carried out ...

  2. Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival

    Directory of Open Access Journals (Sweden)

    Sercan Göde

    2017-06-01

    Full Text Available Background: Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. Aims: To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Study Design: Retrospective cross-sectional study. Methods: Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86 years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Results: Median tumour size was 20 mm (interquartile range=27.5 mm. Pigmentation was present in 7 (41.2% cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13. Melan A was positive in 7 (41.2% patients, ulceration was present in 6 cases (35.3%, and necrosis was present in (47.1% 8 cases. Six patients (35.3% were positive for S100, 14 (82.4% specimens stained positive for HMB-45 and C-KIT (CD117 was positive in 9 cases (52.9%. Three patients (16.7% developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Conclusion: Although C-KIT positive sinonasal malignant melanoma patients (52.9% can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma

  3. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    International Nuclear Information System (INIS)

    Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2013-01-01

    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 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. These findings suggest that LAT1 could be a new therapeutic target for MM

  4. Kinase fusions are frequent in Spitz tumors and spitzoid melanomas

    Science.gov (United States)

    Esteve-Puig, Rosaura; Botton, Thomas; Yeh, Iwei; Lipson, Doron; Otto, Geoff; Brennan, Kristina; Murali, Rajmohan; Garrido, Maria; Miller, Vincent A.; Ross, Jeffrey S; Berger, Michael F.; Sparatta, Alyssa; Palmedo, Gabriele; Cerroni, Lorenzo; Busam, Klaus J.; Kutzner, Heinz; Cronin, Maureen T; Stephens, Philip J; Bastian, Boris C.

    2014-01-01

    Spitzoid neoplasms are a group of melanocytic tumors with distinctive histopathologic features. They include benign tumors (Spitz nevi), malignant tumors (spitzoid melanomas), and tumors with borderline histopathologic features and uncertain clinical outcome (atypical Spitz tumors). Their genetic underpinnings are poorly understood, and alterations in common melanoma-associated oncogenes are typically absent. Here we show that spitzoid neoplasms harbor kinase fusions of ROS1 (17%), NTRK1 (16%), ALK (10%), BRAF (5%), and RET (3%) in a mutually exclusive pattern. The chimeric proteins are constitutively active, stimulate oncogenic signaling pathways, are tumorigenic, and are found in the entire biologic spectrum of spitzoid neoplasms, including 55% of Spitz nevi, 56% of atypical Spitz tumors, and 39% of spitzoid melanomas. Kinase inhibitors suppress the oncogenic signaling of the fusion proteins in vitro. In summary, kinase fusions account for the majority of oncogenic aberrations in spitzoid neoplasms, and may serve as therapeutic targets for metastatic spitzoid melanomas. PMID:24445538

  5. Synthesis and biodistribution study of 3-iodo-4-hydroxyphenyl-cysteamine for detection of malignant melanoma based on specific enzyme of melanin formation

    International Nuclear Information System (INIS)

    Nishii, R.; Nagamachi, S.; Tamura, S.; Kawai, K.; Nishimura, K.; Kinuya, S.; Uehara, T.; Tonami, N.; Arano, Y.

    2002-01-01

    Purpose: The aim of our study is to develop a new radiopharmaceutical labeled with radioiodine for detection and therapy of tumors, which have affinity to a characteristic metabolism in tumor. 3-Iodo-4-hydroxyphenyl-L-cysteine (I- L-PC), which we have reported previously, was found to have an interaction for tyrosinase, an essential and rate-limiting enzyme to melanin biosynthesis. In this study, considering higher affinity for tyrosinase, we synthesized 3-iodo-4-hydroxyphenylcysteamine (I-PCA) that was an amine derivative of I-L-PC and examined biodistribution study in melanoma-bearing mice. Method/Materials: 4-Hydroxyphenylcysteamine (4-PCA) was synthesized and radioiodinated in our laboratory. Synthesis of 4-PCA was confirmed by 1 H-NMR, mass spectrometry and elemental analysis. 125 I-PCA was prepared by conventional chloramine-T method under a no-carrier added condition. 125 I-PCA was purified by Sep-Pak-C-18 cartridge and the labeling efficiency and radiochemical purity were examined by TLC analysis. Biodistribution study of I-PCA was performed using B16 melanoma-bearing C57BL6 mice. The radioactivities of each organ were measured and % injected dose / g wet tissue was determined. Moreover, the tumor-to-blood ratio (T/B ratio) and tumor-to-muscle ratios (T/M ratio) of 125 I-PCA were also evaluated and were compared with 125 I-L-PC, 67 Ga-citrate, 125 I-L-AMT and 123 I-MIBG. Results: Radiosynthesis of 125 I-PCA was carried out conveniently and efficiently within only 15 min. A labeling efficiency of more than 73 % resulted in the labeling of 4-PCA to 125 I-PCA. After the simple Sep-Pak purification, no-carrier added 125 I-PCA with radiochemical purity greater than 90 % was obtained. The biodistribution of 125 I-PCA showed rapid blood clearance, renal excretion and low accumulation in normal tissue, while increase of accumulation in the tumor for 30 min. As a consequence, T/B ratio reached approximately 1.6 ± 0.3 and T/M ratio increased up to 8.7 ± 3.2 at 60

  6. Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

    International Nuclear Information System (INIS)

    Wadabayashi, Nobutoshi; Ichihashi, Masamitsu; Honda, Chihiro; Mishima, Yutaka.

    1994-01-01

    Malignant melanoma occurs not only in the skin but also in ocular tissues. Ocular melanoma located superficially as in conjunctiva can be treated successfully by BNCT. In the present study, we investigated 10 B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10 B concentration in melanoma after administration of 10 B-BPA by oral or drip infusion ranged from 10.4 to 21.5 ppm. The boron concentrations in lens and vitreous body were lower than blood level, whereas higher than blood in sclera and palpebral skin. These results suggest that we can treat such a superficial melanoma lesions as conjunctival melanoma by BNCT using 10 B 1 -BPA. (author)

  7. Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

    Science.gov (United States)

    van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

    2018-01-19

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi. Multicenter, retrospective case series. Patients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment. Next-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples. Mutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis. In 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi. Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of

  8. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P.; Cheng, Elaine; Davis, Matthew J.; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C.; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M.; Brash, Douglas E.; Stern, David F.; Materin, Miguel A.; Lo, Roger S.; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K.; Hayward, Nicholas K.; Lifton, Richard P.; Schlessinger, Joseph; Boggon, Titus J.; Halaban, Ruth (Yale-MED); (UCLA); (Queens)

    2012-10-11

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  9. LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

    Science.gov (United States)

    Lian, Christine Guo; Xu, Yufei; Ceol, Craig; Wu, Feizhen; Larson, Allison; Dresser, Karen; Xu, Wenji; Tan, Li; Hu, Yeguang; Zhan, Qian; Lee, Chung-wei; Hu, Di; Lian, Bill Q.; Kleffel, Sonja; Yang, Yijun; Neiswender, James; Khorasani, Abraham J.; Fang, Rui; Lezcano, Cecilia; Duncan, Lyn M.; Scolyer, Richard A.; Thompson, John F.; Kakavand, Hojabr; Houvras, Yariv; Zon, Leonard; Mihm, Martin C.; Kaiser, Ursula B.; Schatton, Tobias; Woda, Bruce A.; Murphy, George F.; Shi, Yujiang G.

    2013-01-01

    SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that “loss of 5-hmC” is an epigenetic hallmark of melanoma with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of 5-hmC landscape in the melanoma epigenome. We show that down-regulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy. PMID:22980977

  10. Group heterogeneity increases the risks of large group size: a longitudinal study of productivity in research groups.

    Science.gov (United States)

    Cummings, Jonathon N; Kiesler, Sara; Bosagh Zadeh, Reza; Balakrishnan, Aruna D

    2013-06-01

    Heterogeneous groups are valuable, but differences among members can weaken group identification. Weak group identification may be especially problematic in larger groups, which, in contrast with smaller groups, require more attention to motivating members and coordinating their tasks. We hypothesized that as groups increase in size, productivity would decrease with greater heterogeneity. We studied the longitudinal productivity of 549 research groups varying in disciplinary heterogeneity, institutional heterogeneity, and size. We examined their publication and citation productivity before their projects started and 5 to 9 years later. Larger groups were more productive than smaller groups, but their marginal productivity declined as their heterogeneity increased, either because their members belonged to more disciplines or to more institutions. These results provide evidence that group heterogeneity moderates the effects of group size, and they suggest that desirable diversity in groups may be better leveraged in smaller, more cohesive units.

  11. A questionnaire to measure melanoma risk, knowledge and protective behaviour: Assessing content validity in a convenience sample of Scots and Australians

    Directory of Open Access Journals (Sweden)

    Lee Amanda J

    2011-08-01

    Full Text Available Abstract Background The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice. Method A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia. In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores. Results 540 people completed the questionnaire, 273 Scots (50.6%. 133 (24.6% Scots and 83 (15.4% Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2% Scots and 190 (35.2% Australians personally knew someone with melanoma. Australians had higher knowledge (p , level of concern (p and protective behaviour (p scores than the Scottish. Australian nationality was the strongest independent predictor of a higher knowledge score (p , followed by a previous skin cancer diagnosis (p = 0.003, personal knowledge of someone with melanoma (p = 0.011, female gender (p = 0.005 and higher education status (p (R2 = 0.163. Conclusion The questionnaire detected higher levels of knowledge and skin cancer protective behaviours in Australians than in Scottish people. This was expected and supports the content

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

    Science.gov (United States)

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

    2017-02-01

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

  13. Surgery of Primary Melanomas

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2010-05-01

    Full Text Available 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.

  14. Surgery of Primary Melanomas

    Energy Technology Data Exchange (ETDEWEB)

    Rutkowski, Piotr, E-mail: rutkowskip@coi.waw.pl; Zdzienicki, Marcin; Nowecki, Zbigniew I. [Soft Tissue/Bone Sarcoma and Melanoma Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland); Akkooi, Alexander C. J. van [Erasmus University Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

    2010-05-11

    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.

  15. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Rutkowski, Piotr; Zdzienicki, Marcin; Nowecki, Zbigniew I.; Akkooi, Alexander C. J. van

    2010-01-01

    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. Human malignant melanomas in nude mice

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Directory of Open Access Journals (Sweden)

    John C Morris

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

  18. Melanoma awareness and prevalence of dermoscopic examination among internet users: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Grazyna Kaminska-Winciorek

    2016-12-01

    Full Text Available Introduction : Melanoma presents the greater threat to health the later the disease is detected and treated, although treatment results can be improved by the widespread use of dermoscopy. However, scarce data are available concerning the awareness of dermoscopy and the frequency of its performance in the non-patient population. Aim: To assess the awareness of melanoma detection by dermoscopic examination among the audience of a scientific website. Material and methods : Respondents were invited to participate in an online cross-sectional survey. They were asked to complete an online questionnaire designed by the authors. The preliminary analysis of 5,154 collected forms and the exclusion of incomplete forms yielded 4,919 fully completed questionnaires; the resulting database was analyzed statistically using logistic regression with the R software program (95% CI. Results: Less than two-fifths (39.2% of respondents reported ever having sought the advice of a medical professional (dermatologist or other specialist, and 25.4% of the respondents had undergone dermoscopy at least once in their life. Furthermore, approximately one-tenth of respondents (10.7% were not aware of this detection tool. The study respondents gained knowledge about dermoscopic examination from television and magazines. The performance of dermoscopy was more increasingly associated with inhabitants of larger locales, the use of higher-SPF sunscreens, and greater awareness of the relationship between the risk of melanoma and sunburn. Conclusions : Awareness of melanoma and sun care varied within the analyzed population. A subset of individuals at high risk of melanoma was identified. This group included those who engaged in risky sun exposure behaviors and who had never been examined by dermoscopy.

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Centers for Disease Control (CDC) Podcasts

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

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

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

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

  2. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  3. Changes in visual acuity in patients with malignant melanoma of the uvea treated with stereotactic radiosurgery (presentation)

    International Nuclear Information System (INIS)

    Mackova, K.; Waczultkova, I.; Furdova, Ad.; Furdova, Al.

    2013-01-01

    The goal was to assess the changes in visual acuity before and after 6 months of treatment, depending on the dose in risk structures (lens, optic nerve). This is a retrospective study of 19 patients group treated in 2011. The average age of the group was (57.3 ± 12.4) years (31-73 years). The analysis of the studied group did not demonstrate dependence of the tumour presence on gender. Higher prevalence of tumours was observed in the elderly population. Considered relationship of worse diagnosis with higher age (r = 0.39; p = 0.13) we could not prove to be significant due to the small group of patients. The median of melanoma volume was 0.77 cm 3 (0.11 to 1.76 cubic centimetres). The mean dose applied to melanoma was 37.34 Gy (Gy 36.74 to 44.65).

  4. 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....

  5. CCR 20th Anniversary Commentary: MAPK/ERK Pathway Inhibition in Melanoma-Kinase Inhibition Redux.

    Science.gov (United States)

    Davar, Diwakar; Kirkwood, John M

    2015-12-15

    In the January 15, 2012, issue of Clinical Cancer Research, Kirkwood and colleagues published a study comparing the MEK inhibitor selumetinib with temozolomide in unselected metastatic melanoma. Although selumetinib did not improve survival or response, most responders had BRAF-activating mutations, and selumetinib has since demonstrated efficacy in BRAF-mutant melanoma. This study laid the groundwork for the evaluation of BRAF/MEK inhibitors in BRAF-mutant melanoma. ©2015 American Association for Cancer Research.

  6. Radiation biology of malignant melanoma

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  7. The Women in the Army Study Group

    Science.gov (United States)

    1976-12-01

    learned faster and did a much better job of it. We were s3mpl1"’Vperimenting from a training standpoint to see what the possibilitie, were. Whether or not...Director and conducted by members of the WAC. Some officers (few) have attended officers’ courses with male personnel. Recruits receive theory and...becomes clear. Israel, regardless of perception, conscripts and utilizes women to offset manpower shortages. Feminist groups have little impact in israel

  8. Understanding weight stigmatization: a focus group study.

    Science.gov (United States)

    Cossrow, N H; Jeffery, R W; McGuire, M T

    2001-01-01

    The purpose of this research was to investigate, in a nonclinical sample of adults, thoughts on and experiences with weight stigmatization. Focus groups were used to collect information. Participants were recruited through a newspaper advertisement and flyers posted in public places in Minneapolis and St. Paul. During the focus groups, participants were led in a discussion about their thoughts on weight stigmatization and personal experiences of being treated differently or poorly because of their weight. Six gender-specific focus groups consisted of 31 adult volunteers (17 women and 14 men). Perceptions of weight-based stereotypes and weight stigmatization and personal reports of having been treated differently or poorly owing to weight were measured. Participants reported a variety of experiences of being treated differently or poorly because of their weight. These included teasing, harassment, slurs and insults, negative judgments and assumptions, and perceived discrimination. Participants reported that such experiences occurred at home, among friends and strangers, at work, and in health care settings. Women reported a greater number and a greater variety of negative experiences than men. The results indicated that participants experienced weight-based stigmatization in many aspects of their lives. Awareness of these experiences may assist in the development of treatments for overweight individuals.

  9. A case study in finite groups

    International Nuclear Information System (INIS)

    Bauer, M.; Itzykson, C.

    1990-01-01

    Recent investigations on the classification of rational conformal theories have suggested relations with finite groups. It is not known at present if this is more than a happy coincidence in simple cases or possibly some more profound link exploiting the analogy between fusion rules and decompositions of tensor products of group representations or even in a more abstract context q-deformations of Lie algebras for roots of unity. Although finite group theory is a very elaborate subject the authors review on a slightly non-trivial example some of its numerous aspects, in particular those related to rings of invariants. The hope was to grasp, if possible, some properties which stand a chance of being related to conformal theories. Subgroups of SU(2) were found to be related to the A-D-E classification of Wess-Zumino-Witten models based on the corresponding affine Lie algebra. Extending the investigations to SU(3) the authors have picked one of its classical subgroups as a candidate of interest

  10. Lymphoscintigraphic Identification of Sentinel Nodes in Malignant Melanoma

    International Nuclear Information System (INIS)

    Andries, G.; Dindelegan, G.; Ciule, Larisa; Cosgarea, Rodica; Cobzac, Gh.

    2006-01-01

    Full text: The most important prognostic factor in malignant melanoma is the presence or absence of metastasis in lymph nodes. It has been demonstrated the orderly progression of different types of tumours. Sentinel lymph node identification is done lymphoscintigraphically, followed by surgical excision and morpho pathological exam. Material and methods: We studied 33 patients with malignant melanoma (age 26-84 years) divided in 2 subgroups: group A without gamma probe (18 patients) and group B with gamma probe (15 patients). The lymphoscintigraphy (LS) was performed with a totally dose of 20-30 MBq of 99mTc-nanocoloid (Amersham) injected peritumoral or pericicatriceal in 4-6 points in volume of 0,1-0,2 ml per point. Acquisition was performed dynamic for 10-15 min and static at 30-60 min p.i. on perpendicular projections. Patent blue dye was injected prior surgery. In group A has performed sentinel node excision (13 patients) or ELND (4), one patient has died before surgery. In group B sentinel nodes were surgically excised with gamma probe and ELND was performed in patients with positive lymph nodes. Histopathologically, sentinel nodes were stained with HE and in 6 cases with HMB45. Results: In group A we identified the sentinel nodes scintigraphically in all patients (median 1,83±-1,50 nodes, range 1-7). Surgically with PBD were identified 1,69±1,18 sentinel nodes, in 2 patients the SN lymphadenectomy was negative. All nodes excised were histopathologically negative, but in 4 patients loco-regional recurrence or distant metastasis developed. In group B we identified scintigraphically 33 SNs (median 2,20±1,37 nodes, range 1-5) and 4 in transit nodes in 14 patients, 24 of them being blue dye positive (80%), in 1 patient LS was negative. With gamma probe surgeon excised 39 radioactive nodes and 1 SN blue dye positive only, 10 of them being histopathologically positive (25% node metastasis). No metastasis were identified after ELND in patients with positive SNs

  11. Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in melanoma-bearing animals

    International Nuclear Information System (INIS)

    Chen, F.D.; Hsieh, B.T.; Wang, H.E.; Ou, Y.H.; Yang, W.K.; Whang-Peng, J.; Liu, R.S.; Knapp, F.F.; Ting, G.; Yen, S.H.

    2001-01-01

    In this study, the effectiveness of a 188 Re labeled sulfur colloid with two particle size ranges was used to evaluate the effectiveness of this agent on melanoma tumors in mice in terms of animal lifespan. Methods: Two separate group of animals were used for investigating biodistribution and survival time. A total of 188 B16F10-melanoma-bearing BDF 1 mice were injected intraperitoneally with 3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after intraperitoneal inoculation of 5x10 5 B16F10 melanoma cells/2ml. For group 1, 30 mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In group 2, 158 mice were divided into 9 groups (n=16∼18/groups)each receiving respectively tumor alone, tumor with normal saline, cold colloid or hot colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid groups was further divided into two groups, one receiving smaller particle sizes ( 188 Re-sulfur colloid is an effective agent in controlling tumor cells in the abdominal cavity in animals

  12. Preventing Melanoma PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2015-06-02

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

  13. Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

    Science.gov (United States)

    2017-11-15

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

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

    OpenAIRE

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

    2018-01-01

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

  15. Melanoma NOS1 expression promotes dysfunctional IFN signaling.

    Science.gov (United States)

    Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria Libera; De Giorgi, Valeria; Bedognetti, Davide; Dai, Cuilian; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Zhang, Qianbing; Chouchane, Lotfi; Weiss, Geoffrey R; Slingluff, Craig L; Lee, Peter P; Rosenberg, Steven A; Alter, Harvey; Yao, Kaitai; Wang, Ena; Marincola, Francesco M

    2014-05-01

    In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

  16. Structure-activity relationship of prenyl-substituted polyphenols from Artocarpus heterophyllus as inhibitors of melanin biosynthesis in cultured melanoma cells.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2007-09-01

    A series of prenylated, flavone-based polyphenols, compounds 1-8, were isolated from the wood of Artocarpus heterophyllus. These compounds, which have previously been shown not to inhibit tyrosinase activity, were found to be active inhibitors of the in vivo melanin biosynthesis in B16 melanoma cells, with little or no cytotoxicity. To clarify the structural requirement for inhibition, some structure-activity relationships were studied, in comparison with related compounds lacking prenyl side chains. Our experiments indicate that both prenyl and OH groups, as well as the type of substitution pattern, are crucial for the inhibition of melanin production in B16 melanoma cells.

  17. Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to-Mesenchymal Transition

    OpenAIRE

    Kushiro, Kyoko; Chu, Randy A.; Verma, Akanksha; Núñez, Nomelí P.

    2011-01-01

    Metastatic melanoma is one of the most deadly and evasive types of cancer. On average, cancer patients with metastatic melanoma survive only 6–9 months after diagnosis. Epidemiological and animal studies suggest that obesity increases the metastatic ability of malignant melanoma, though the mechanism is not known. In the present studies, we assessed the ability of 3T3L1 adipocytes to modulate B16BL6 melanoma cell invasion and the Epithelial-to-Mesenchymal Transition (EMT). For this purpose, w...

  18. Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

    Science.gov (United States)

    Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

    2015-01-01

    The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

  19. Profile of ipilimumab and its role in the treatment of metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Patel SP

    2011-12-01

    Full Text Available Sapna P Patel, Scott E WoodmanMelanoma Medical Oncology Department, University of Texas, MD Anderson Cancer Center, Houston, TX, USAAbstract: Melanoma is an immunogenic cancer. However, the ability of the immune system to eradicate melanoma tumors is affected by intrinsic negative regulatory mechanisms. Multiple immune-modulatory therapies are currently being developed to optimize the immune response to melanoma tumors. Two recent Phase III studies using the monoclonal antibody ipilimumab, which targets the cytotoxic T-lymphocyte antigen (CTLA-4, a negative regulator of T-cell activation, have demonstrated improvement in overall survival of metastatic melanoma patients. This review highlights the clinical trial data that supports the efficacy of ipilimumab, the immune-related response criteria used to evaluate clinical response, and side-effect profile associated with ipilimumab treatment.Keywords: ipilimumab, melanoma, T-cells, CTLA-4

  20. Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

    Science.gov (United States)

    Kamyab, Kambiz; Kazemi, Sheyda; Azimi, Pourya; Azizpour, Arghavan; Ghandi, Narges; Pirooz, Elham; Noormohammadpour, Pedram; Mirshams-Shahshahani, Mostafa; Daneshpazhooh, Maryam

    2017-11-01

    The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations. © 2017 The Australasian College of Dermatologists.

  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. Systemic treatments for metastatic cutaneous melanoma.

    Science.gov (United States)

    Pasquali, Sandro; Hadjinicolaou, Andreas V; Chiarion Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

    2018-02-06

    The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000. To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma. We searched the following databases up to October 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers and the ASCO database in February 2017, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We considered RCTs of systemic therapies for people with unresectable lymph node metastasis and distant metastatic cutaneous melanoma compared to any other treatment. We checked the reference lists of selected articles to identify further references to relevant trials. Two review authors extracted data, and a third review author independently verified extracted data. We implemented a network meta-analysis approach to make indirect comparisons and rank treatments according to their effectiveness (as measured by the impact on survival) and harm (as measured by occurrence of high-grade toxicity). The same two review authors independently assessed the risk of bias of eligible studies according to Cochrane standards and assessed evidence quality based on the GRADE criteria. We included 122 RCTs (28,561 participants). Of these, 83 RCTs, encompassing 21 different comparisons, were included in meta-analyses. Included participants were men and women with a mean age of 57.5 years who were recruited from hospital settings. Twenty-nine studies included people whose cancer had spread to their brains. Interventions were categorised into five groups: conventional

  3. Cognitive distance, absorptive capacity and group rationality: a simulation study.

    Directory of Open Access Journals (Sweden)

    Petru Lucian Curşeu

    Full Text Available We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members and cognitive distance (as the distance between the most rational group member and the rest of the group on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality. Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

  4. Cognitive distance, absorptive capacity and group rationality: a simulation study.

    Science.gov (United States)

    Curşeu, Petru Lucian; Krehel, Oleh; Evers, Joep H M; Muntean, Adrian

    2014-01-01

    We report the results of a simulation study in which we explore the joint effect of group absorptive capacity (as the average individual rationality of the group members) and cognitive distance (as the distance between the most rational group member and the rest of the group) on the emergence of collective rationality in groups. We start from empirical results reported in the literature on group rationality as collective group level competence and use data on real-life groups of four and five to validate a mathematical model. We then use this mathematical model to predict group level scores from a variety of possible group configurations (varying both in cognitive distance and average individual rationality). Our results show that both group competence and cognitive distance are necessary conditions for emergent group rationality. Group configurations, in which the groups become more rational than the most rational group member, are groups scoring low on cognitive distance and scoring high on absorptive capacity.

  5. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis......, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. Objectives  In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun...... months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. Results  The UVR dose of recently diagnosed...

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

    International Nuclear Information System (INIS)

    Algazi, Alain P; Soon, Christopher W; Daud, Adil I

    2010-01-01

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

  7. Photodynamic therapy for melanoma: efficacy and immunologic effects

    Science.gov (United States)

    Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

    2014-02-01

    Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

  8. Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

    Science.gov (United States)

    Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

    2017-01-01

    At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

  9. Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort.

    Science.gov (United States)

    Cho, Hyunje G; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Assimes, Themistocles; Han, Jiali; Stefanick, Marcia; Tang, Jean Y; Sarin, Kavita Y

    2018-07-01

    Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk. We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women. Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset. Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma. Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort. Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  11. Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.

    Science.gov (United States)

    Yu, Huan; Ma, Meng; Yan, Junya; Xu, Longwen; Yu, Jiayi; Dai, Jie; Xu, Tianxiao; Tang, Huan; Wu, Xiaowen; Li, Siming; Lian, Bin; Mao, Lili; Chi, Zhihong; Cui, Chuanliang; Guo, Jun; Kong, Yan

    2017-12-04

    Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target. A total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated. In our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain. Coexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain.

  12. Melanoma detection using a mobile phone app

    Science.gov (United States)

    Diniz, Luciano E.; Ennser, K.

    2016-03-01

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

  13. Vaccines against advanced melanoma.

    Science.gov (United States)

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

    2013-01-01

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

  14. Melanoma Lentiginoso Acral

    Directory of Open Access Journals (Sweden)

    Gloria Andrea Vargas Suaza

    2008-12-01

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

  15. Biodistribution dosimetric study of radiopharmaceutical {sup 99mT}c Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings; Estudo dosimetrico da biodistribuicao do radiofarmaco Ixolaris-{sup 99m}Tc em camundongos para diagnostico de melanoma atraves de imagem molecular e modelo translacional para humanos

    Energy Technology Data Exchange (ETDEWEB)

    Soriano, Sarah Canuto Silva

    2015-07-01

    The labeling of Ixolaris with {sup 99m}Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer {sup 99m}Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The {sup 99m}Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with {sup 99m

  16. Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV-A feasibility study

    International Nuclear Information System (INIS)

    Fabel, M.; Tengg-Kobligk, H. von; Giesel, F.L.; Delorme, S.; Kauczor, H.-U.; Bornemann, L.; Dicken, V.; Kopp-Schneider, A.; Moser, C.

    2008-01-01

    Therapy monitoring in oncological patient care requires accurate and reliable imaging and post-processing methods. RECIST criteria are the current standard, with inherent disadvantages. The aim of this study was to investigate the feasibility of semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma compared to manual volumetric analysis and RECIST. Multislice CT was performed in 47 patients, covering the chest, abdomen and pelvis. In total, 227 suspicious, enlarged lymph nodes were evaluated retrospectively by two radiologists regarding diameters (RECIST), manually measured volume by placement of ROIs and semi-automated volumetric analysis. Volume (ml), quality of segmentation (++/-) and time effort (s) were evaluated in the study. The semi-automated volumetric analysis software tool was rated acceptable to excellent in 81% of all cases (reader 1) and 79% (reader 2). Median time for the entire segmentation process and necessary corrections was shorter with the semi-automated software than by manual segmentation. Bland-Altman plots showed a significantly lower interobserver variability for semi-automated volumetric than for RECIST measurements. The study demonstrated feasibility of volumetric analysis of lymph node metastases. The software allows a fast and robust segmentation in up to 80% of all cases. Ease of use and time needed are acceptable for application in the clinical routine. Variability and interuser bias were reduced to about one third of the values found for RECIST measurements. (orig.)

  17. Renormalization group study of scalar field theories

    International Nuclear Information System (INIS)

    Hasenfratz, A.; Hasenfratz, P.

    1986-01-01

    An approximate RG equation is derived and studied in scalar quantum field theories in d dimensions. The approximation allows for an infinite number of different couplings in the potential, but excludes interactions containing derivatives. The resulting non-linear partial differential equation can be studied by simple means. Both the gaussian and the non-gaussian fixed points are described qualitatively correctly by the equation. The RG flows in d=4 and the problem of defining an ''effective'' field theory are discussed in detail. (orig.)

  18. Group-analytic training groups for psychology students: A qualitative study

    DEFF Research Database (Denmark)

    Nathan, Vibeke Torpe; Poulsen, Stig

    2004-01-01

    This article presents results from an interview study of psychology students' experiences from group-analytic groups conducted at the University of Copenhagen. The primary foci are the significance of differences in themotivation participants'  personal aims of individual participantsfor particip......This article presents results from an interview study of psychology students' experiences from group-analytic groups conducted at the University of Copenhagen. The primary foci are the significance of differences in themotivation participants'  personal aims of individual participantsfor...... participation in the group, the impact of the composition of participants on the group process, and the professional learning through the group experience. In general the interviews show a marked satisfaction with the group participation. In particular, learning about the importance of group boundaries...

  19. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    International Nuclear Information System (INIS)

    Takabe, Piia; Bart, Geneviève; Ropponen, Antti; Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna

    2015-01-01

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma

  20. Italian Euromelanoma Day Screening Campaign (2005-2007) and the planning of melanoma screening strategies.

    Science.gov (United States)

    Seidenari, Stefania; Benati, Elisa; Ponti, Giovanni; Borsari, Stefania; Ferrari, Chiara; Albertini, Giuseppe; Altomare, Gianfranco; Arcangeli, Fabio; Aste, Nicola; Bernengo, Maria Grazia; Bongiorno, Maria Rita; Borroni, Giovanni; Calvieri, Stefano; Chimenti, Sergio; Cusano, Francesco; Fracchiolla, Claudio; Gaddoni, Giuseppe; Girolomoni, Giampiero; Guarneri, Biagio; Lanzoni, Anna; Lombardi, Mara; Lotti, Torello; Mariotti, Antonio; Marsili, Franco; Micali, Giuseppe; Parodi, Aurora; Peris, Ketty; Peserico, Andrea; Quaglino, Pietro; Santini, Marcello; Schiavon, Sergio; Tonino, Camillo; Trevisan, Giusto; Tribuzi, Paola; Valentini, Paolo; Vena, Gino A; Virgili, Annarosa

    2012-01-01

    Although no study has definitively shown that unfocused screening of skin cancer is effective, many campaigns have been organized with the aim of increasing awareness on melanoma risk factors. The objective of this study was to analyse the results of the Skin Cancer Screening Day in Italy during the period 2005-2007, to determine the priorities for melanoma control plans in a Mediterranean country. A total of 5002 patients were screened by dermatologists in 31 cities. Individuals who considered themselves to have many naevi and those with a family history of melanoma showed a higher number of common and atypical naevi. Ten melanomas, 20 basal cell carcinomas and two squamous cell carcinomas were histopathologically confirmed. Our observations provide the following suggestions for melanoma prevention strategies: (a) an unfocused campaign is suitable to inform the public about the importance of self-examination of the skin, but is not useful to identify a larger number of melanomas; and (b) melanoma screening campaigns should focus on a selected population, which meets rigorous risk criteria to maintain higher cost-effectiveness. The financial support to effective melanoma screening programmes could be increased, especially in southern populations where lower levels of self-surveillance and socioeconomic conditions represent risk factors for late identification of melanoma.

  1. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    Energy Technology Data Exchange (ETDEWEB)

    Takabe, Piia, E-mail: piia.takabe@uef.fi [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Bart, Geneviève [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland); Ropponen, Antti [University of Eastern Finland, Institute of Clinical Medicine, 70211 Kuopio (Finland); Rilla, Kirsi; Tammi, Markku; Tammi, Raija; Pasonen-Seppänen, Sanna [University of Eastern Finland, Institute of Biomedicine, 70211 Kuopio (Finland)

    2015-09-10

    Malignant skin melanoma is one of the most deadly human cancers. Extracellular matrix (ECM) influences the growth of malignant tumors by modulating tumor cells adhesion and migration. Hyaluronan is an essential component of the ECM, and its amount is altered in many tumors, suggesting an important role for hyaluronan in tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this study we produced a MV3 melanoma cell line with inducible expression of the hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and decreased melanoma cell adhesion, migration and proliferation by cell cycle arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan oligosaccharides, while the effect on cell proliferation was receptor independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting that inhibition of MAP-kinase signaling was responsible for these suppressive effects on the malignant phenotype of MV3 melanoma cells. - Highlights: • Inducible HAS3-MV3 melanoma cell line was generated using Lentiviral transduction. • HAS3 overexpression inhibits MV3 cell migration via hyaluronan–receptor interaction. • HAS3 overexpression decreases MV3 melanoma cell proliferation and adhesion. • ERK1/2 phosphorylation is downregulated by 50% in HAS3 overexpressing cells. • The results suggest that hyaluronan has anti-cancer like effects in melanoma.

  2. Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis

    DEFF Research Database (Denmark)

    D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A

    2017-01-01

    Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported...... in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined...... with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response...

  3. Study on school lunch of four groups

    OpenAIRE

    大迫, 康子; 小住, フミ子; Yasuko, OSAKO; Fumiko, OZUMI

    1984-01-01

    There are many small islands, villages and fishing ports in Kagoshima. This study was designed to investigate whether a local color in school lnuch exist or not. It was found that the school lunch served in small island had the best nutritional quantity and quality and menu contents. Contradictionus results, vitamin deficiency in village and protein deficiency in fishing ports, were also obtained. There is a correlation between lunch cost and menu contents. The shotage of potatos and beans ob...

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

    Centers for Disease Control (CDC) Podcasts

    2011-10-19

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

  5. Growth inhibitory activity of Ankaferd hemostat on primary melanoma cells and cell lines

    Directory of Open Access Journals (Sweden)

    Seyhan Turk

    2017-02-01

    Full Text Available Objective: Ankaferd hemostat is the first topical hemostatic agent about the red blood cell–fibrinogen relations tested in the clinical trials. Ankaferd hemostat consists of standardized plant extracts including Alpinia officinarum, Glycyrrhiza glabra, Thymus vulgaris, Urtica dioica, and Vitis vinifera. The aim of this study was to determine the effect of Ankaferd hemostat on viability of melanoma cell lines. Methods: Dissimilar melanoma cell lines and primary cells were used in this study. These cells were treated with different concentrations of Ankaferd hemostat to assess the impact of different dosages of the drug. All cells treated with different concentrations were incubated for different time intervals. After the data had been obtained, one-tailed T-test was used to determine whether the Ankaferd hemostat would have any significant inhibitory impact on cell growth. Results: We demonstrated in this study that cells treated with Ankaferd hemostat showed a significant decrease in cell viability compared to control groups. The cells showed different resistances against Ankaferd hemostat which depended on the dosage applied and the time treated cells had been incubated. We also demonstrated an inverse relationship between the concentration of the drug and the incubation time on one hand and the viability of the cells on the other hand, that is, increasing the concentration of the drug and the incubation time had a negative impact on cell viability. Conclusion: The findings in our study contribute to our knowledge about the anticancer impact of Ankaferd hemostat on different melanoma cells.

  6. The fibrinolytic system facilitates tumor cell migration across the blood-brain barrier in experimental melanoma brain metastasis

    International Nuclear Information System (INIS)

    Perides, George; Zhuge, Yuzheng; Lin, Tina; Stins, Monique F; Bronson, Roderick T; Wu, Julian K

    2006-01-01

    Patients with metastatic tumors to the brain have a very poor prognosis. Increased metastatic potential has been associated with the fibrinolytic system. We investigated the role of the fibrinolytic enzyme plasmin in tumor cell migration across brain endothelial cells and growth of brain metastases in an experimental metastatic melanoma model. Metastatic tumors to the brain were established by direct injection into the striatum or by intracarotid injection of B16F10 mouse melanoma cells in C57Bl mice. The role of plasminogen in the ability of human melanoma cells to cross a human blood-brain barrier model was studied on a transwell system. Wild type mice treated with the plasmin inhibitor epsilon-aminocaproic acid (EACA) and plg -/- mice developed smaller tumors and survived longer than untreated wild type mice. Tumors metastasized to the brain of wild type mice treated with EACA and plg -/- less efficiently than in untreated wild type mice. No difference was observed in the tumor growth in any of the three groups of mice. Human melanoma cells were able to cross the human blood-brain barrier model in a plasmin dependent manner. Plasmin facilitates the development of tumor metastasis to the brain. Inhibition of the fibrinolytic system could be considered as means to prevent tumor metastasis to the brain

  7. Environmental Studies Group progress report for 1979

    International Nuclear Information System (INIS)

    Hunt, D.C.; Hurley, J.D.

    1981-01-01

    The 1979 progress report gives descriptions, results, and/or status on programs involving (1) physical transport of radionuclides in blowing dust, (2) radionuclide distributions in the sediment of area water bodies, (3) management of open space lands (including a remote sensing program) at Rocky Flats, (4) the ecology and radioecology of terrestrial open space areas in Plant site lands, (5) biological pathways for radionuclide transport, (6) evaluations of environmental monitoring data on radionuclides in air and water, (7) results of a special soil sampling program on lands adjacent to the Plant site, and (8) two special programs - one concerning evaluations of epidemiological studies of health effects purported to be related to the Plant, and a second that specifies information on accumulations of material in process building filter plenums required for evaluation of potential accidents

  8. Lymph-scintigraphic identification of sentinel lymph nodes in breast carcinoma and malignant melanoma patients

    International Nuclear Information System (INIS)

    Sergieva, S; Bajchev, G.; Aleksandrova, E.

    1999-01-01

    It is the purpose of the study to assay the possibilities of lymphoscintigraphy (LS) in evaluating local lymphatic drainage and sentinel lymph nodes (SLNs) location in patients presenting breast carcinoma and malignant melanoma. Twenty-nine women with breast carcinoma (TI-IIa clinical stage, age range 31 to 74 y) and 7 patients with malignant melanoma (Clark III-V) are scanned in the period 1997 through 1998. 99m Tc-sulphur colloid (Solco Lymphoscint, SORIN) with mean size of particles 50 nm is used. Planar images are obtained at 20 and 120-180 min after sc injection in the region of primary tumor, at mean radioactivity 20 MBq per injection site in a volume 0.2-0.3 ml. In the breast cancer patients Patent Blue V or Mitoxantrone is injected around the tumor twice - 20 and 3 to 1/2 hours prior to surgery. In malignant melanoma patients immunoscintigraphy using 740 MBq 99m Tc-anti-melanoma monoclonal antibodies (Technemab-K-1) is carried out before lymph node dissection. SLNs are visualized in 25 patients (86.2%) with breast cancer. In 21 (72%) patients to 4 SLNs are scanned in level I of the local axillary region, in 4 cases (14%) - in the region of axillary level II, in one female patient (3%) - at axillary level III, and in 3 patients (10%) i psilateral internal mammary lymph nodes are scanned. Two patients are suspected for the so-called s kip t ype of tumor lymphatic dissemination. In 4 patients no SLN images are visible. In breast carcinoma patients SLN are additionally stained blue and following intraoperative revision, evidence of metastatic involvement is established in 12 instances (41.3%). In 3 patients with melanoma in the abdomen and back SLNs are located in the region of inguinal and axillary lymph node groups, while in 3 patients presenting lesions to the surface of extremities only local lymph nodes draining the melanoma are visualized. Immunoscintigraphy shows enhanced uptake in the region of SLNs in 3 cases with the metastatic changes in them

  9. Vitamin D and melanoma: state of the art and possible therapeutic uses.

    Science.gov (United States)

    Paolino, Giovanni; Moliterni, Elisa; Corsetti, Paola; Didona, Dario; Bottoni, Ugo; Calvieri, Stefano; Mattozzi, Carlo

    2017-12-15

    Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun- exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

  10. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    International Nuclear Information System (INIS)

    Misu, Masayasu; Ouji, Yukiteru; Kawai, Norikazu; Nishimura, Fumihiko; Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2015-01-01

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage

  11. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Misu, Masayasu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Ouji, Yukiteru, E-mail: oujix@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Kawai, Norikazu [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nishimura, Fumihiko [Department of Neurosurgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Nakamura-Uchiyama, Fukumi [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Yoshikawa, Masahide, E-mail: myoshika@naramed-u.ac.jp [Department of Pathogen, Infection and Immunity, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan)

    2015-08-07

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage.

  12. Oncogenic mutations in melanomas and benign melanocytic nevi of the female genital tract.

    Science.gov (United States)

    Tseng, Diane; Kim, Julie; Warrick, Andrea; Nelson, Dylan; Pukay, Marina; Beadling, Carol; Heinrich, Michael; Selim, Maria Angelica; Corless, Christopher L; Nelson, Kelly

    2014-08-01

    The genetic heterogeneity of melanomas and melanocytic nevi of the female genital tract is poorly understood. We aim to characterize the frequency of mutations of the following genes: BRAF, NRAS, KIT, GNA11, and GNAQ in female genital tract melanomas. We also characterize the frequency of BRAF mutations in female genital tract melanomas compared with melanocytic nevi. Mutational screening was performed on the following female genital tract melanocytic neoplasms: 25 melanomas, 7 benign melanocytic nevi, and 4 atypical melanocytic nevi. Of the 25 female genital tract melanoma specimens queried, KIT mutations were detected in 4 (16.0%), NRAS mutations in 4 (16.0%), and BRAF mutations in 2 (8.0%) samples. Two of the tumors with KIT mutations harbored double mutations in the same exon. No GNAQ or GNA11 mutations were identified among 11 melanomas screened. BRAF V600E mutations were detected in 7 of 7 benign melanocytic genital nevi (100%) and 3 of 4 atypical genital nevi (75%). Our study is limited by the small sample size of this rare subset of melanomas. KIT, NRAS, and BRAF mutations are found in a subset of female genital tract melanomas. Screening for oncogenic mutations is important for developing and applying clinical therapies for melanomas of the female genital tract. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Patrick A. Ott

    2013-10-01

    Full Text Available Constitutive upregulation of the MAPK pathway by a BRAFV600 mutation occurs in about half of melanomas. This leads to increased oncogenic properties such as tumor cell invasion, metastatic potential, and resistance to apoptosis. Blockade of the MAPK pathway with highly specific kinase inhibitors induces unprecedented tumor response rates in patients with advanced BRAFV600 mutant melanoma. Immune checkpoint blockade with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 and programed death-1/PD-L1 has also demonstrated striking anti-tumor activity in patients with advanced melanoma. Tumor responses are likely limited by multiple additional layers of immune suppression in the tumor microenvironment. There is emerging preclinical and clinical evidence suggesting that MAPK inhibition has a beneficial effect on the immunosuppressive tumor microenvironment, providing a strong rationale for combined immunotherapy and MAPK pathway inhibition in melanoma. The T cell response has been the main focus in the studies reported to date. Since dendritic cells (DCs are important in the induction of tumor-specific T cell responses, the impact of MAPK pathway activation in melanoma on DC function is critical for the melanoma directed immune response. BRAFV600E melanoma cells modulate DCs through the MAPK pathway because its blockade in melanoma cells can reverse suppression of DC function. As both MEK/BRAF inhibition and immune checkpoint blockade have recently taken center stage in the treatment of melanoma, a deeper understanding of how MAPK pathway inhibition affects the tumor immune response is needed.

  14. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  15. Preoperative nuclear scans in patients with melanoma

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  16. Podoplanin Expression in Canine Melanoma.

    Science.gov (United States)

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

    2016-12-01

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

  17. What Does Melanoma Look Like?

    Science.gov (United States)

    ... begins in melanocytes ( cells that make the pigment melanin ). Below are photos of melanoma that formed on ... Services Website Linking U.S. Department of Health and Human Services National Institutes of Health National Cancer Institute ...

  18. Podoplanin Expression in Canine Melanoma

    OpenAIRE

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

    2016-01-01

    A type I transmembrane protein, podoplanin (PDPN), is expressed in several normal cells such as lymphatic endothelial cells or pulmonary type I alveolar cells. We recently demonstrated that anticanine PDPN monoclonal antibody (mAb), PMab-38, recognizes canine PDPN of squamous cell carcinomas, but does not react with lymphatic endothelial cells. Herein, we investigated whether PMab-38 reacts with canine melanoma. PMab-38 reacted with 90% of melanoma cells (9/10 cases) using immunohistochemistr...

  19. Primary Anorectal Melanoma

    Directory of Open Access Journals (Sweden)

    Maliha Khan

    2014-03-01

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

  20. Occupational exposure to electromagnetic fields and sex-differential risk of uveal melanoma

    DEFF Research Database (Denmark)

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

    2010-01-01

    The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries.......The association between occupational exposure to electromagnetic fields (EMF) and the risk of uveal melanoma was investigated in a case-control study in nine European countries....

  1. Regional control of melanoma neck node metastasis after selective neck dissection with or without adjuvant radiotherapy

    NARCIS (Netherlands)

    Hamming-Vrieze, Olga; Balm, Alfons J. M.; Heemsbergen, Wilma D.; Hooft van Huysduynen, Thijs; Rasch, Coen R. N.

    2009-01-01

    OBJECTIVE: To examine the effect of adjuvant radiotherapy on regional control of melanoma neck node metastasis. DESIGN: A single-institution retrospective study. SETTING: Tertiary care cancer center. PATIENTS: The study included 64 patients with melanoma neck node metastasis who were treated with

  2. Targeted alpha therapy for melanoma : from bench to bedside

    International Nuclear Information System (INIS)

    Allen, B.J.; Rizvi, S.M.A.; Li, Y.; Tsui, W.; Douglas, S.; Raja, C.; Graham, P.; Smart, R.; Butler, P.; Kearsley, J.; Thompson, J.

    2001-01-01

    Full text: The control of metastatic melanoma remains an elusive objective. Targeted alpha therapy (TAT) offers a new approach to the control of micrometastases and regression of tumours. The alpha emitting immunoconjugate (AIC) against malignant melanoma has been prepared by chelating Bi-213 to the anti-melanoma antibody 9.2.27, and injected locally at 2 d post-inoculation of 1.5 million melanoma cells, or intralesionally into skin tumours. Human subjects receive 50μCi intralesional dose, escalating to 1 mCi. The clearances from the tumour, kidneys and bladder are monitored by a NaI detector that detects the 440 keV gamma ray. Blood samples and tumour photographs are taken at O. 2 and 4 weeks; tumours are excised at 4 weeks. Isolated cancer cells and preangiogenic cell clusters in mice can be eliminated with 25 μCi local AIC injection, and intra-lesional injections of 100 μCi are sufficient to completely regress melanomas with volumes up to 300 mm 3 without side-effects. Systemic TAT with a single administration is less effective with 100% growth delay of tumours observed, and ∼20% complete inhibition. The clinical TAT trial for recurrent subcutaneous melanoma has been approved by the NSW Radiation Advisory Committee and the SES Human Ethics Committee. In a world first phase 1 study, the first 5 subjects have been treated by intralesional injection, 3 at 50 μCi, and 2 at 150 μCi. All subjects having unchanged blood profiles at 2 and 4 weeks post-therapy. Tumour volumes appear little changed. However, histology of a 3 cm melanoma shows that almost complete cell kill occurred at 150 μCi, with only a few small cell clusters surviving. Local TAT inhibits tumourogenesis and intralesional TAT completely regresses melanoma in mice. Intralesional TAT for melanoma in human subjects is non-toxic so far and appears to be a promising modality. The ultimate objective is to apply systemic TAT for the control of melanoma micrometastases. Copyright (2001) Australasian

  3. miR-193b Regulates Mcl-1 in Melanoma.

    Science.gov (United States)

    Chen, Jiamin; Zhang, Xiao; Lentz, Cindy; Abi-Daoud, Marie; Paré, Geneviève C; Yang, Xiaolong; Feilotter, Harriet E; Tron, Victor A

    2011-11-01

    MicroRNAs play important roles in gene regulation, and their expression is frequently dysregulated in cancer cells. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells, suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed at a significantly lower level in malignant melanoma than in benign nevi. Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is inversely correlated with the level of miR-193b. Overexpression of miR-193b in melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1 knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737 sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on the expression of Mcl-1 seems to be mediated by direct interaction between miR-193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl-1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1 and that down-regulation of miR-193b in vivo could be an early event in melanoma progression. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Prognostic Factors and Decision Tree for Long-term Survival in Metastatic Uveal Melanoma.

    Science.gov (United States)

    Lorenzo, Daniel; Ochoa, María; Piulats, Josep Maria; Gutiérrez, Cristina; Arias, Luis; Català, Jaum; Grau, María; Peñafiel, Judith; Cobos, Estefanía; Garcia-Bru, Pere; Rubio, Marcos Javier; Padrón-Pérez, Noel; Dias, Bruno; Pera, Joan; Caminal, Josep Maria

    2017-12-04

    The purpose of this study was to demonstrate the existence of a bimodal survival pattern in metastatic uveal melanoma. Secondary aims were to identify the characteristics and prognostic factors associated with long-term survival and to develop a clinical decision tree. The medical records of 99 metastatic uveal melanoma patients were retrospectively reviewed. Patients were classified as either short (≤ 12 months) or long-term survivors (> 12 months) based on a graphical interpretation of the survival curve after diagnosis of the first metastatic lesion. Ophthalmic and oncological characteristics were assessed in both groups. Of the 99 patients, 62 (62.6%) were classified as short-term survivors, and 37 (37.4%) as long-term survivors. The multivariate analysis identified the following predictors of long-term survival: age ≤ 65 years (p=0.012) and unaltered serum lactate dehydrogenase levels (p=0.018); additionally, the size (smaller vs. larger) of the largest liver metastasis showed a trend towards significance (p=0.063). Based on the variables significantly associated with long-term survival, we developed a decision tree to facilitate clinical decision-making. The findings of this study demonstrate the existence of a bimodal survival pattern in patients with metastatic uveal melanoma. The presence of certain clinical characteristics at diagnosis of distant disease is associated with long-term survival. A decision tree was developed to facilitate clinical decision-making and to counsel patients about the expected course of disease.

  5. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma

    Science.gov (United States)

    Ilieva, Kristina M.; Correa, Isabel; Josephs, Debra H.; Karagiannis, Panagiotis; Egbuniwe, Isioma U.; Cafferkey, Michiala J.; Spicer, James F.; Harries, Mark; Nestle, Frank O.; Lacy, Katie E.; Karagiannis, Sophia N.

    2014-01-01

    Malignant melanoma is associated with poor clinical prognosis; however, novel molecular and immune therapies are now improving patient outcomes. Almost 50% of melanomas harbor targetable activating mutations of BRAF which promote RAS-RAF-MEK-ERK pathway activation and melanoma proliferation. Recent evidence also indicates that melanomas bearing mutant BRAF may also have altered immune responses, suggesting additional avenues for treatment of this patient group. The small molecule inhibitors selective for mutant BRAF induce significant but short-lived clinical responses in a proportion of patients, but also lead to immune stimulatory bystander events, which then subside with the emergence of resistance to inhibition. Simultaneous BRAF and MEK inhibition, and especially combination of BRAF inhibitors with new immunotherapies such as checkpoint blockade antibodies, may further enhance immune activation, or counteract immunosuppressive signals. Pre-clinical evaluation and ongoing clinical trials should provide novel insights into the role of immunity in the therapy of BRAF-mutant melanoma. PMID:25385327

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

    Directory of Open Access Journals (Sweden)

    Martin Udart

    2001-01-01

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

  7. Cutaneous melanoma – guidelines for diagnostics and therapy in 2016

    Directory of Open Access Journals (Sweden)

    Piotr Rutkowski

    2016-02-01

    Full Text Available Dermoscopy is currently the standard method for clinical differential diagnosis of cutaneous melanoma and for qualifying a lesion for excisional biopsy. Full thickness excisional biopsy of suspicious melanomatous skin lesions likely to be diagnosed as early melanomas is crucial in establishing the diagnosis and defining prognostic factors. Early diagnosis and surgical removal of cutaneous melanoma not only improves patients’ prognosis but is also associated with approximately 90% likelihood of cure. The next steps in the therapeutic management of cutaneous melanoma following excisional biopsy are radical scar excision with adequate margins and sentinel lymph node biopsy. Radical lymph node dissection is recommended in the case of regional lymph node metastases. High-risk patients (lymph node involvement and/or ulcerated primary lesion should be advised to participate in prospective clinical trials on adjuvant therapy. Melanoma patients with distant metastases are still characterized by poor outcomes. In patients with metastatic disease testing for the presence of BRAF gene mutation is mandatory. Patients with metastatic disease should be considered for participation in clinical trials. Long-term survival is confined to a selected group of patients undergoing resection of isolated metastatic lesions. In systemic – mainly first-line – therapy of patients with BRAF V600 mutation the BRAF inhibitor vemurafenib or dabrafenib (preferentially in combination with a MEK inhibitor may be employed and independently of mutational status immunotherapy with anti-PD-1 antibodies (nivolumab or pembrolizumab and eventually ipilimumab (anti-CTLA4 antibody may be used.

  8. Cost-effectiveness analysis in melanoma detection: A transition model applied to dermoscopy.

    Science.gov (United States)

    Tromme, Isabelle; Legrand, Catherine; Devleesschauwer, Brecht; Leiter, Ulrike; Suciu, Stefan; Eggermont, Alexander; Sacré, Laurine; Baurain, Jean-François; Thomas, Luc; Beutels, Philippe; Speybroeck, Niko

    2016-11-01

    The main aim of this study is to demonstrate how our melanoma disease model (MDM) can be used for cost-effectiveness analyses (CEAs) in the melanoma detection field. In particular, we used the data of two cohorts of Belgian melanoma patients to investigate the cost-effectiveness of dermoscopy. A MDM, previously constructed to calculate the melanoma burden, was slightly modified to be suitable for CEAs. Two cohorts of patients entered into the model to calculate morbidity, mortality and costs. These cohorts were constituted by melanoma patients diagnosed by dermatologists adequately, or not adequately, trained in dermoscopy. Effectiveness and costs were calculated for each cohort and compared. Effectiveness was expressed in quality-adjusted life years (QALYs), a composite measure depending on melanoma-related morbidity and mortality. Costs included costs of treatment and follow-up as well as costs of detection in non-melanoma patients and costs of excision and pathology of benign lesions excised to rule out melanoma. The result of our analysis concluded that melanoma diagnosis by dermatologists adequately trained in dermoscopy resulted in both a gain of QALYs (less morbidity and/or mortality) and a reduction in costs. This study demonstrates how our MDM can be used in CEAs in the melanoma detection field. The model and the methodology suggested in this paper were applied to two cohorts of Belgian melanoma patients. Their analysis concluded that adequate dermoscopy training is cost-effective. The results should be confirmed by a large-scale randomised study. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study