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Sample records for advanced melanoma results

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

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

    2016-07-01

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

  2. Nivolumab-Based Treatments for Advanced Melanoma

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

  3. Treating advanced melanoma: current insights and opportunities

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    Tronnier M

    2014-09-01

    Full Text Available Michael Tronnier, Christina Mitteldorf Department of Dermatology, Klinikum Hildesheim GmbH, Hildesheim, Germany Abstract: Whereas thin melanomas have an excellent prognosis after sufficient surgical treatment, melanoma disease in advanced stages is still a therapeutic challenge. After decades of frustrating studies, new therapeutic strategies have come up in the past few years. On the one hand, increasing insights into the molecular aberrations in melanoma have led to specific "targeted" therapies to affect only the mutated tumor cells, as in many other types of cancers. Today there are few "targeted" substances which are already approved and successfully used for single or combination therapy, but many others are under development. While on the other hand, nonpersonalized strategy substances have been developed successfully inducing an immunologic tumor response. Both kinds of therapy have been found to result in an improvement not only of the response rate, but also of the overall survival in metastatic disease, which represents a milestone in melanoma therapy. However, using these therapies there is still much to learn regarding the effects, the side effects, and the limitations of these promising substances. Keywords: melanoma, treatment, targeted therapy, immunotherapy, BRAF, CTLA-4

  4. 20-year long-term results of the use of external beam radiotherapy for primary advanced, recurrent and metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Purpose: The use of external beam radiotherapy (RT) is regarded only as 'last resort' approach in the multidisciplinary management of malignant melanoma (MM). We have analyzed the initial tumor response and the long-term local control, survival rate and relevant prognostic factors in patients with locally advanced, recurrent and metastatic MM who have been treated at our institution over the past 20 years. Methods: Between 1977 - 1995, a total of 2917 consecutive patients have been entered in the malignant melanoma registry of our university hospital. Just 121 (4%) out of these 2917 (4%) consecutive patients, i.e. 56 females and 65 males with histologically proven and clinically staged malignant melanoma (MM), have been selected during their disease process to receive external beam RT due to their advanced stage of the disease. The primary histology was nodular melanoma (NM) in 51 (47%) pts., superficial spreading melanoma (SSM) in 35 (32%) pts.; acral-lentiginous melanoma (ALM) in 8 (7%) pts. and lentigo maligna melanoma (LMM) in 4 (5%) pts.. The specific clinical indication for the application of RT was primarily for palliative reasons in the advanced clinical UICC stages II and IV: (a) 11 (9%) pts had residual disease (R1-2) after resection of a primary or recurrent MM (UICC II); (b) 57 (47%) pts suffered from regional lymph node metastases (33 pts.) or in-transit metastases (24 pts.) (UICC III); and (c) 53 (44%) pts had distant metastases at various body sites (7 pts. with M1a; 46 pts. with M1b) (UICC IV). The mean interval between the first diagnosis and actual application of the external beam radiotherapy (RT) was 19 months (range: 3 - 186 months). In most cases conventional RT and only in a few cases hypofractionated RT was applied with 2 - 6 Gy single dose fractions up to a median total RT dose of 48 Gy (range: 20 - 60 Gy). Results: The median follow-up of the patients (FU) was 9 years (range: 0.3 - 15.5 yrs.). With regard to UICC stages, an initial

  5. Updates in Therapy for Advanced Melanoma

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    Bhavana P. Singh

    2016-01-01

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

  6. Dabrafenib Plus Trametinib for Advanced Melanoma

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

  7. In situ photoimmunotherapy for melanoma: preliminary clinical results

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

    2006-02-01

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

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

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    Bhattacharya Chitralekha

    2012-11-01

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

  9. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

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    Ho Jonhan

    2012-10-01

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

  10. Melanoma

    Science.gov (United States)

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

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

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    Asmar R

    2016-02-01

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

  12. Testing Adjuvant Ipilimumab in Advanced Melanoma

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

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

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

    2015-03-01

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

  14. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

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    Toyama, Shingo [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Tokumaru, Sunao [Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga (Japan); Mizota, Atsushi [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Ohnishi, Yoshitaka [Department of Ophthalmology, Wakayama Medical University, Wakayama (Japan); Tsujii, Hirohiko [Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-06-01

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.

  15. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

    International Nuclear Information System (INIS)

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose of C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG

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

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    Coventry BJ

    2015-04-01

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

  17. Melanoma

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

  18. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    International Nuclear Information System (INIS)

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1–250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5–371.5 CMCs ml−1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma. (paper)

  19. Spotlight on pembrolizumab in the treatment of advanced melanoma

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    Rajakulendran T

    2015-06-01

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

  20. Sorafenib in advanced melanoma: a critical role for pharmacokinetics?

    OpenAIRE

    Pécuchet, N; Lebbe, C; Mir, O; Billemont, B; Blanchet, B; Franck, N; Viguier, M; Coriat, R.; Tod, M; Avril, M-F; Goldwasser, F

    2012-01-01

    Background: Inter-patient pharmacokinetic variability can lead to suboptimal drug exposure, and therefore might impact the efficacy of sorafenib. This study reports long-term pharmacokinetic monitoring of patients treated with sorafenib and a retrospective pharmacodynamic/pharmacokinetic analysis in melanoma patients. Patients and methods: Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid). In the absence of limiting toxicity, dose escalation...

  1. A Case of Pediatric Melanoma: Treatment Considerations in Advanced Disease

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    Albino, Frank P; Wood, Benjamin C.; Oh, Albert; Rogers, Gary F.; Sauerhammer, Tina

    2015-01-01

    Summary: We document a 3-year-old healthy African American girl who developed malignant melanoma on her lower extremity. The clinical appearance offered little indication of the lesion’s severity (T4), and only the history of de novo presentation and disproportionate growth raised clinical suspicion. This case report highlights the subtle clinical findings of this condition and presents controversies related to surgical management of pediatric melanoma.

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

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

    2012-01-01

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

  3. Advances in personalized targeted treatment of metastatic melanoma and non-invasive tumor monitoring

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    MelZiman

    2013-03-01

    Full Text Available Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management.

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

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    Wen-Jen Hwu

    2011-12-01

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

  5. [Melanoma research in Hungary: promising results in a previously orphan tumor].

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    Balázs, Margit; Vízkeleti, Laura; Ecsedi, Szilvia; Ádány, Róza; Rásó, Erzsébet; Hegedûs, Balázs; Ladányi, Andrea; Tóvári, József; Tímár, József

    2015-12-01

    Melanoma research has a two decade history in Hungary and is based on three groups located at the National Institute of Oncology (NIO), the University of Debrecen (DU) and Semmelweis University (SU). Previously we have summarized the achievements of the NIO group in this Journal, now this paper summarizes the recent results of their collaborations. The research group of DU revealed several novel genetic alterations in the melanoma genome which might have clinical relevance as prognosticators or predictors in light of the novel target therapies. Data indicating unique, perhaps melanoma-specific epigenetic changes during progression might be even more important, identifying novel genes otherwise not detected as genetically altered ones. The research group in Budapest extensively used experimental human melanoma models and demonstrated the host sex as a key factor in progression due to the specific function of NK cells. Identification of functional glucocorticoid receptor in human melanoma might lead to therapeutic exploitation similar to certain leukemias. Studies on extracellular matrix revealed collagen XVII and CD44 splice variants as progression associated factors of melanoma. Since the double wild type genotype of melanoma is lacking effective therapy, data on the use of FGFR2, c-met or cannabinoid receptor as target can be important. On the other hand, experimental data on the antitumoral effects of heparin derivatives or bisphosphonate in melanoma models can also be encouraging. PMID:26665186

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

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-01

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

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. BNCT for skin melanoma in extremities: Updated Argentine clinical results

    International Nuclear Information System (INIS)

    As part of phase I/II melanoma BNCT clinical trial conducted in Argentina in a cooperative effort of the Argentine Atomic Energy Commission (CNEA) and the Oncology Institute Angel H. Roffo (IOAHR), 7 patients (6 female-1 male) received eight treatment sessions covering ten anatomical areas located in extremities. Mean age of the patients was 64 years (51-74). The treatments were performed between October 2003 and June 2007. All patients presented multiple subcutaneous skin metastases of melanoma and received an infusion containing ∼14 gr/m2 of 10borophenyl-alanine (BPA) followed by the exposition of the area to a mixed thermal-epithermal neutron beam at the RA-6 reactor. The maximum prescribed dose to normal skin ranged from 16.5 to 24 Gy-Eq and normal tissue administered dose varied from 15.8 to 27.5 Gy-Eq. Considering evaluable nodules, 69.3% of overall response and 30.7% of no changes were seen. The toxicity was acceptable, with 3 out of 10 evaluable areas showing ulceration (30% toxicity grade 3).

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

    Directory of Open Access Journals (Sweden)

    Improta G

    2015-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. 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; Kirkin, A F; Dzhandzhugazyan, K N; Rosenberg, J

    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...... 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...

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

    International Nuclear Information System (INIS)

    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

  16. Immunotherapy of metastatic melanoma by reversal of immune suppression

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-01-01

    Beginning with the observation that the human enteorvirus, Poliovirus Sabin 1, will lyse human melanoma cells in culture, clinical trials involving two patients with advance melanoma were performed. Parenteral injection of the viable Poliovirus into cutaneous melanoma metastases followed in 24 hours by oral administration of cyclophosphamide. The results of these two trials are described.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-15

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

  18. BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma: a potential neoadjuvant strategy.

    Science.gov (United States)

    Sloot, Sarah; Zager, Jonathan S; Kudchadkar, Ragini R; Messina, Jane L; Benedict, Jacob J; Gonzalez, Ricardo J; DeConti, Ronald; Turner, Leslie M; McCardle, Timothy; Smalley, Keiran S M; Weber, Jeffrey S; Sondak, Vernon K; Gibney, Geoffrey T

    2016-02-01

    Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months (range 1.2-29.4 months). Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival. PMID:26731560

  19. Oral Melanoma

    Directory of Open Access Journals (Sweden)

    A Forouzandeh

    2002-02-01

    Full Text Available Melanoma is a malignant tumor that originates from melanocyte cells. Its oral type is rare. The goal of this investigation was to determine the prevalence of oral malignant melanoma in Iran, as determined by age, sex and location. This research reviewed 623 cases of oral and non-oral malignant melanoma in Immam-Khomeini hospital, Mearaj cancer institute and department of oral pathology of dental faculty, Tehran University of Medical Sciences in a period of 19 years from 1981-1999. The results showed that 54 cases of biopsy lesions were melanoma of oral cavity that included 7.8% of these lesions. The mean age incidence of oral melanoma was 55.5(between 26-86 years. The most prevalent sites were palate (37.1% and alveolar mucosa (20.4% and less common sites included floor of mouth. buccal mucosa and tongue.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    International Nuclear Information System (INIS)

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

  2. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascular glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site

  3. Ruthenium-106 brachytherapy for uveal melanomas. Preliminary results: a single institutional experience; Braquiterapia com rutenio-106 em melanomas uveais. Resultados preliminares: experiencia uni-instuticional

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Rodrigo Souza; Giordani, Adelmo Jose; Segreto, Helena Regina Comodo; Segreto, Roberto Araujo [Universidade Federal de Sao Paulo/Escola Paulista de Medicina (Unifesp/EPM), Sao Paulo, SP (Brazil). Departamento de Medicina. Setor de Radioterapia ; Erwenne, Clelia Maria; Teixeira, Luiz Fernando [Universidade Federal de Sao Paulo/Escola Paulista de Medicina (UNIFESP/EPM), Sao Paulo, SP (Brazil). Dept. de Oftalmologia]. E-mail: segreto. dmed@epm.br

    2007-03-15

    Objective: To analyze the early response of uveal melanomas in patients treated with ruthenium-106 brachytherapy. Materials And Methods: In the period between April 2002 and July 2003, 20 patients diagnosed with uveal melanoma were submitted to ruthenium-106 brachytherapy. The calculated dose delivered at the apex of the tumor ranged between 55 Gy and 100 Gy. Patients with lesions greater than 5 mm were submitted to transpupillary thermotherapy concomitantly with ophthalmic plaque insertion. Results: As regards the lesions site, 75% of the lesions were located in the choroid, 15% in the iris, and the remainder 10% in the ciliary body. In a median 19-month-follow-up, the progression-free survival for brachytherapy was 69%, and 87% for associated brachytherapy and transpupillary thermotherapy. A significant tumor height reduction was observed after treatment. No patient was submitted to enucleation. Conclusion: Our preliminary results show that ruthenium-106 brachytherapy is an appropriate method for conservative treatment of patients with uveal melanomas in terms of local management, ocular and visual acuity preservation with an acceptable complications incidence rate. (author)

  4. A review of advanced genetic testing for clinical prognostication in uveal melanoma.

    Science.gov (United States)

    Werdich, Xiang Q; Jakobiec, Frederick A; Singh, Arun D; Kim, Ivana K

    2013-01-01

    Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools. PMID:24010756

  5. A Possible Association between Melanoma and Prostate Cancer. Results from a Case-Control-Study

    Directory of Open Access Journals (Sweden)

    Alina Goldenberg

    2015-04-01

    Full Text Available Melanoma and prostate cancer are the fifth and first most common cancers in men within the United States, respectively. The association between the two cancers lies in the mutual androgen-dependence. However, the relationship between prostate cancer history and melanoma development remains to be further elucidated. We aim to determine the odds of history of prostate cancer among men with melanoma as compared to time-frame, clinic, and provider-matched controls without melanoma within a single academic surgical center. We present a case-control study comparing men treated for melanoma and non-melanoma cancer by a single provider between 2010 and 2014 within an academic dermatologic surgical center. Overall, there were nine cases of prostate cancer among the melanoma group and two cases amongst the controls—a statistically significant difference in both uni- and multivariable analyses (p = 0.057 [95% CI 1, 23.5], p = 0.042 [95% CI 1.1, 129], respectively. Body mass index, alcohol use, and skin type II were significant risk factors for melanoma (p = 0.011 [95% CI 1, 1.3], 0.005 [95% CI 1.4, 7], 0.025 [95% CI 1.1, 3.3], respectively. There were more immunosuppressed controls (p = 0.002; however, the melanoma patients had a significantly longer duration of immunosuppression (11.6 vs. 1.9 years, p < 0.001 [95% CI 0.03, 0.5]. Melanoma screenings for men should include questions on prostate cancer history. Prostate cancer patients may benefit from more frequent and comprehensive melanoma screening.

  6. Cutaneous melanoma

    International Nuclear Information System (INIS)

    The study of boron neutron capture therapy (BNCT) for malignant melanoma was initiated by Y. Mishima and his associates. Following basic research of 13 years, this team started the first clinical trial of cutaneous melanoma BNCT using 10B-para-boronophenylalanine (BPA) in 1985. Since then, 32 patients have been treated. We developed the following regimen for BNCT of malignant melanoma: 1) 170 - 250 mg/kg of BPA-fructose complex is administered by drip infusion over 3-hours. 2) The minimum dose for melanoma control by single irradiation is assumed to be 25 Gy-eq. 3) The maximum tolerable dose to the skin by single irradiation is assumed to be 18 Gy-eq. 4) As the therapeutic dose, the maximum tolerable dose to the skin itself is chosen. We report the clinical results of two patients with cutaneous melanoma treated by BNCT. We believe that cutaneous melanoma are suitable for BNCT and that the excellent results will have a great impact on patients in QOL. (author)

  7. Exploiting in situ antigen generation and immune modulation to enhance chemotherapy response in advanced melanoma: A combination nanomedicine approach.

    Science.gov (United States)

    Lu, Yao; Wang, Yuhua; Miao, Lei; Haynes, Matthew; Xiang, Guangya; Huang, Leaf

    2016-08-28

    Therapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment in order to facilitate and enhance CTL activity, and induction of memory T-cells to prolong tumor rejection. While traditional as well as modern vaccines rely upon delivery of both antigen and adjuvant, a variety of clinically relevant cancers lack ideal immunogenic antigens. Building upon recent efforts, we instead chose to exploit chemotherapy-induced apoptosis to allow for in situ antigen generation in a combination, nanomedicine-based approach. Specifically, lipid-coated cisplatin nanoparticles (LPC) and CpG-encapsulated liposomes (CpG-Lipo) were prepared for the temporally-controlled and multifaceted treatment of an advanced in vivo model of melanoma. Such combination therapy established strong synergistic effects, both in apoptotic extent and subsequent abrogation of tumor growth, which were due largely to both an enhanced cytotoxic T-cell recruitment and a reduction of immune-suppressive mediators in the microenvironments of both spleens and tumor. These results underlie a prolonged host lifespan in the combination approach (45 days) as compared with control (25 days, p < 0.02), providing promise toward a personalized approach to nanomedicine by establishing effect synergy in host-specific immunotherapy following chemotherapy. PMID:27235608

  8. Three year results of stereotactic radiosurgery of large choroidal melanomas with the gamma-knife

    International Nuclear Information System (INIS)

    Eye preserving surgery in patients with large choroidal melanomas includes local resection or radiosurgery. Brachytherapy can only be applied to small tumors in adequate localisation while radiosurgery (charged particles or gamma-knife) can be applied to all other tumors. We report 3-year results of 100 patients treated with gamma-knife radiosurgery. All patients received a single fraction gamma-knife treatment with a retrobulbar block. The radiation dose was 50 Gy and all tumors were within the 50 % isodosis range. Tumors were inaccessible for Ru106 Brachy-therapy as they were either too large (max. height > 6.0 mm, basis diameter > 19 mm) or contact to optic disc exceeded 90o or infiltration into the ciliary body was present. Of the 100 patients, 73 were followed for 1 year, 33 for 2 years and 17 for 3 years. Local tumor control was 98 % (2 recurrences). Complications following radiosurgery were rubeosis iridis (12 % of patients after l year, 15 % after 2 years and 6 % after 3 years) and secondary glaucoma (14 % of patients after 1 year, 9 % after 2 years, 6 % after 3 years). Total enucleation rate was 6.3 % per year. The tumors were found at the posterior pole (61 %), middle periphery (21 %) or ciliary body (18 %). Functional results depended on tumor localisation in the eye: after a mean of 1.9 years follow-up visual acuity was stable (± 3 lines) in 71 % of patients with a tumor in the middle periphery while 19 % of tumors with infiltration into the ciliary body and 0 % of tumors at the posterior pole showed stable visual acuity. Gamma-knife-radiosurgery offers a well tolerated, eye preserving treatment for patients with large choroidal melanoma in the middle periphery. Comparing our method to other radiosurgery therapies we can offer a fast technique which only requires a single visit. (author)

  9. Proton beam radiotherapy for uveal melanoma: Results of Curie Institut-Orsay Proton Therapy Center (ICPO)

    International Nuclear Information System (INIS)

    Purpose: This study reports the results of proton beam radiotherapy based on a retrospective series of patients treated for uveal melanoma at the Orsay Center. Methods and Materials: Between September 1991 and September 2001, 1,406 patients with uveal melanoma were treated by proton beam radiotherapy. A total dose of 60 cobalt Gray equivalent (CGE) was delivered in 4 fractions on 4 days. Survival rates were determined using Kaplan-Meier estimates. Prognostic factors were determined by multivariate analysis using the Cox model. Results: The median follow-up was 73 months (range, 24-142 months). The 5-year overall survival and metastasis-free survival rates were 79% and 80.6%, respectively. The 5-year local control rate was 96%. The 5-year enucleation for complications rate was 7.7%. Independent prognostic factors for overall survival were age (p < 0.0001), gender (p < 0.0003), tumor site (p < 0.0001), tumor thickness (p = 0.02), tumor diameter (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.003). Independent prognostic factors for metastasis-free survival were age (p = 0.0042), retinal detachment (p = 0.01), tumor site (p < 0.0001), tumor volume (p < 0.0001), local recurrence (p < 0.0001), and retinal area receiving at least 30 CGE (p = 0.002). Independent prognostic factors for local control were tumor diameter (p = 0.003) and macular area receiving at least 30 CGE (p = 0.01). Independent prognostic factors for enucleation for complications were tumor thickness (p < 0.0001) and lens volume receiving at least 30 CGE (p = 0.0002). Conclusion: This retrospective study confirms that proton beam radiotherapy ensures an excellent local control rate. Further clinical studies are required to decrease the incidence of postirradiation ocular complications

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

    Science.gov (United States)

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

    2016-09-01

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

  11. Treatment of melanoma with a serotype 5/3 chimeric oncolytic adenovirus coding for GM-CSF: Results in vitro, in rodents and in humans.

    Science.gov (United States)

    Bramante, Simona; Kaufmann, Johanna K; Veckman, Ville; Liikanen, Ilkka; Nettelbeck, Dirk M; Hemminki, Otto; Vassilev, Lotta; Cerullo, Vincenzo; Oksanen, Minna; Heiskanen, Raita; Joensuu, Timo; Kanerva, Anna; Pesonen, Sari; Matikainen, Sampsa; Vähä-Koskela, Markus; Koski, Anniina; Hemminki, Akseli

    2015-10-01

    Metastatic melanoma is refractory to irradiation and chemotherapy, but amenable to immunological approaches such as immune-checkpoint-inhibiting antibodies or adoptive cell therapies. Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules. Therefore, oncolytic immuno-virotherapy of malignant melanoma is an appealing approach, which was recently validated by a positive phase 3 trial. We investigated the potency of oncolytic adenovirus Ad5/3-D24-GMCSF on a panel of melanoma cell lines and animal models, and summarized the melanoma-specific human data from the Advanced Therapy Access Program (ATAP). The virus effectively eradicated human melanoma cells in vitro and subcutaneous SK-MEL-28 melanoma xenografts in nude mice when combined with low-dose cyclophosphamide. Furthermore, virally-expressed granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated the differentiation of human monocytes into macrophages. In contrast to human cells, RPMI 1846 hamster melanoma cells exhibited no response to oncolytic viruses and the chimeric 5/3 fiber failed to increase the efficacy of transduction, suggesting limited utility of the hamster model in the context of viruses with this capsid. In ATAP, treatments appeared safe and well-tolerated. Four out of nine melanoma patients treated were evaluable for possible therapy benefit with modified RECIST criteria: one patient had minor response, two had stable disease, and one had progressive disease. Two patients were alive at 559 and 2,149 days after treatment. Ad5/3-D24-GMCSF showed promising efficacy in preclinical studies and possible antitumor activity in melanoma patients refractory to other forms of therapy. This data supports continuing the clinical development of oncolytic adenoviruses for treatment of malignant melanoma. PMID:25821063

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

    Directory of Open Access Journals (Sweden)

    John C Morris

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

  13. A Phase II Study of Fotemustine Plus Dacarbazine with Dendritic Cell Vaccines as First-Line Therapy for Chinese Patients with Advanced Acral Lentiginous Melanoma

    Institute of Scientific and Technical Information of China (English)

    Lu Si; Zhi-hong Chi; Xiang-qing Yuan; Chuan-liang Cui; Xi-nan Sheng; Jun Guo

    2009-01-01

    Objective: To investigate fotemustine plus dacarbazine (DTIC) with dendritic cell (DC) vaccines on patients with advanced acral lentiginous melanoma (ALM). Fotemustine is a cytotoxic alkylating agent with a remarkable antitumor activity as single agent but also in association with (DTIC). DC is the strongest antigen presenting cell which could induce durable clinical responses. Methods: This was a single-center study. Between July 2003 and June 2006, twenty-eight chemotherapy-naive patients of advanced ALM received fotemustine 100 mg/m2, d1, 12, DTIC 400 mg/d d2(6, DC vaccines subcutaneously d7, 9, 13 repeated every 28 days. Ten HLA-A02+24+ patients received vaccines pulsed with melanoma antigen derived peptides, melanoma antigen recognized by T-cells 1 (Mart-1) and S-100. Eighteen patients received DC loaded with allogeneic melanoma lysate. The primary end-point was progression free survival (PFS). Secondary end-points were overall survival (OS), overall response rate (ORR) and toxicity. Tumor assessment was performed every 8 weeks and evaluated according to response evaluation criteria in solid tumors (RECIST). Results: The 15 men and 13 women had a median age of 51 years. 16 patients had stage M1c disease and 11/16 had liver metastasis. Patients received an average of 3.82(1.25 cycles. Follow-up for the 18 surviving patients ranged from 7(41 months with a median of 12 months. Median PFS was 8.5 months (95% CI: 7.86(15.21) with 12 patients remaining progression free. Only 10 patients died. Median OS was 12 months (95% CI: 10.33(18.24). ORR (CR+PR) was 35.7% including 3 complete response (CR) and 7 partial response (PR). Six patients had disease stable. A total of 19 Grade III/IV toxicities were observed including thrombocytopenia (n=8), neutropenia (n=5), fatigue (n=6) and hypersensitivity reaction (n=1). One patient died of Grade IV thrombocytopenia. Conclusion: Fotemustine and dacarbazine plus DC vaccines are safe and tolerable to Chinese ALM patients. The

  14. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg; Klyver, Helle; Dahlstrøm, Karin; Oturai, Peter Sandor; Mortensen, Jann; Hesse, Birger; Schmidt, Grethe; Drzewiecki, Krzysztof

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND...

  15. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

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

  16. Melanoma risk prediction models

    Directory of Open Access Journals (Sweden)

    Nikolić Jelena

    2014-01-01

    Full Text Available Background/Aim. The lack of effective therapy for advanced stages of melanoma emphasizes the importance of preventive measures and screenings of population at risk. Identifying individuals at high risk should allow targeted screenings and follow-up involving those who would benefit most. The aim of this study was to identify most significant factors for melanoma prediction in our population and to create prognostic models for identification and differentiation of individuals at risk. Methods. This case-control study included 697 participants (341 patients and 356 controls that underwent extensive interview and skin examination in order to check risk factors for melanoma. Pairwise univariate statistical comparison was used for the coarse selection of the most significant risk factors. These factors were fed into logistic regression (LR and alternating decision trees (ADT prognostic models that were assessed for their usefulness in identification of patients at risk to develop melanoma. Validation of the LR model was done by Hosmer and Lemeshow test, whereas the ADT was validated by 10-fold cross-validation. The achieved sensitivity, specificity, accuracy and AUC for both models were calculated. The melanoma risk score (MRS based on the outcome of the LR model was presented. Results. The LR model showed that the following risk factors were associated with melanoma: sunbeds (OR = 4.018; 95% CI 1.724- 9.366 for those that sometimes used sunbeds, solar damage of the skin (OR = 8.274; 95% CI 2.661-25.730 for those with severe solar damage, hair color (OR = 3.222; 95% CI 1.984-5.231 for light brown/blond hair, the number of common naevi (over 100 naevi had OR = 3.57; 95% CI 1.427-8.931, the number of dysplastic naevi (from 1 to 10 dysplastic naevi OR was 2.672; 95% CI 1.572-4.540; for more than 10 naevi OR was 6.487; 95%; CI 1.993-21.119, Fitzpatricks phototype and the presence of congenital naevi. Red hair, phototype I and large congenital naevi were

  17. 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

  18. Fractionated stereotactic radiotherapy with linear accelerator for uveal melanoma - preliminary Vienna results

    International Nuclear Information System (INIS)

    Between June 1997 and February 1998, 21 patients suffering from uveal melanomas have been treated with a sterotactic 6 MeV LINAC (Saturne 43 trademark, General Electric, France) in conjunction with a stereotactic frame system (BrainLAB trademark, Germany). Immobilization of the eye was ensured with an optical fixation system which was proven reliable. During radiotherapy, movements of the irradiated eye were controlled on a monitor and documented by video recording. All patients co-operated very well with the optical fixation system. In 1164 measurements, the median value of horizontal deviation of the diseased eye during treatment was 0.3 mm (range: 0 to 1.3 mm). Median vertical deviation was 0.2 mm (range: 0 to 1.2 mm). For all patients, mean tumor prominence before treatment was 6.0±2.2 mm. In 20 patients, the total dose of 70 Gy (at 80%) was delivered in 5 fractions within 10 days. In one patient with a ciliary body tumor, the total dose of 70 Gy was divided into 7 fractions for better sparing of the anterior eye segment. Results: After a follow-up of at least 6 months, local tumor control was seen in all eyes. Mean tumor thickness reduction after 3, 6 and 9 months was 7%, 13% and 31%, respectively. Up to now, only mild subacute side-effects located in the anterior eye segment have been noticed. (orig.)

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  20. Subverting the B7-H1/PD-1 Pathway in Advanced Melanoma and Kidney Cancer

    Science.gov (United States)

    Harshman, Lauren C.; Choueiri, Toni K.; Drake, Charles; Hodi, F. Stephen

    2016-01-01

    Ligands for inhibitory immune receptors on T cells may be constitutively expressed on tumor cells or host cells in tumor microenvironment as a consequence of adaptive immunity. Programmed death 1 (PD-1) is 1 such receptor on T cells, which functions as a negative regulator of T cell activity. Tumors that up-regulate programmed death ligand 1 (PD-L1) (B7-H1) may abrogate the host’s effector T cell antitumor response. Higher tumoral PD-L1 expression has been linked with inferior clinical outcomes. Multiple cancers including renal cell cancers (RCCs) and melanomas have relatively high levels of PD-L1 on the cell surface. Early evaluations of antibodies that block the interaction of PD-1 and PD-L1 have shown efficacy and a favorable tolerability profile with notable inflammatory toxicities that are generally manageable. Upward of 30% of RCC patients and 50% of melanoma patients achieve objective responses. Durable responses can occur, even in some patients who have discontinued treatment. The developing investigation of PD-1/PD-L1 pathway–blocking agents in RCC and melanoma will likely alter our approaches to the treatment of these 2 deadly diseases. PMID:25098288

  1. Experimental results on advanced rotary desiccant dehumidifiers

    Energy Technology Data Exchange (ETDEWEB)

    Bharathan, D; Parsons, J; Maclaine-cross, I

    1986-08-01

    The Solar Energy Research Institute (SERI) has developed the Cyclic Test Facility (CTF) to develop and validate analytical methods for evaluating and predicting the performance of advanced rotary dehumidifiers. This paper describes the CTF, the dehumidifiers tested at the CTF, and the analytical methods used. The results reported provide an engineering data base and a design tool for evaluating rotary dehumidifiers for desiccant cooling applications.

  2. The patterns of melanoma presentation in Rijeka region.

    Science.gov (United States)

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

    2013-01-01

    There is a global rising incidence of melanoma. For different reasons, the patterns of the incidence, appearance, gender, anatomical distribution and outcome vary among different geographic areas. Screening programs have led to better early detection of melanoma in Australia and some world areas. National Cancer Registry and practice data show the incidence in Croatia to be constantly rising. Despite public education programs about early detection, at clinical departments there are still many new advanced stage melanoma patients. We analyzed data on 157 patients treated and followed up for 10 years for T1b-T4aN0 skin melanoma. There was a difference in anatomical distribution of melanoma lesions in correlation with patient age (ANOVA test, F=3.51, p=0.009). A higher prevalence of shoulder melanoma was found in young people and of head/neck melanoma in the elderly (post-hoc Sheffe test, p=0.038). T4 lesions were more commonly found in men and T1 mainly in women (Pearson χ(2)-test, χ(2)=12.08, p=0.016). There was no difference in Clark level, but a significantly higher Breslow stage was found in men (t=-2.52, p=0.013). Men were much more prone to have head and neck, body and shoulder melanoma, whereas women had more melanoma on their legs and arms. Clark and Breslow levels were strongly correlated in leg melanoma; head localization showed no correlation at all. In conclusion, more attention should be devoted to improve the results in melanoma detection in men, especially considering the prevalence of body (back) and head/neck localizations, sometimes not readily accessible for visual detection. The pattern of distribution also pointed to the need for more attention to pay to shoulder melanoma in younger people. PMID:24183221

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  4. Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma

    International Nuclear Information System (INIS)

    NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 μg with five patients included in each dose level except the 900 μg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 μg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose

  5. Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma

    Directory of Open Access Journals (Sweden)

    Osorio M

    2012-10-01

    Full Text Available Marta Osorio,1 Elias Gracia,1 Edmundo Reigosa,1 Julio Hernandez,2 Ana de la Torre,2 Giselle Saurez,3 Kirenia Perez,3 Carmen Viada,3 Meylán Cepeda,2 Adriana Carr,3 Yisel Ávila,4 Migdalia Rodríguez,4 Luis E Fernandez31National Institute of Oncology and Radiobiology, Havana, 2Dr Celestino Hernández Oncology Hospital, Villa Clara, 3Center of Molecular Immunology, Havana, 4National Center of Clinical Trials, Havana, CubaAbstract: NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 µg with five patients included in each dose level except the 900 µg dose (n = 10. Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  7. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    Science.gov (United States)

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  8. Role of radiotherapy in melanoma management

    International Nuclear Information System (INIS)

    In melanoma, radiotherapy has generally been considered as a palliative treatment option indicated only for advanced cases or disseminated disease. In the 70s of the previous century, the technological advances in radiotherapy, linked to rapid development of computer sciences, resulted in restored interest for radiotherapy in melanoma management. Although a fundamental lack of well designed prospective and/or randomized clinical trials critically influenced the integration of radiotherapy into treatment strategies in melanoma, radiotherapy was recently recognized as an indispensable part in the multidisciplinary management of patients with melanoma. Altogether, approximately 23% of melanoma patients should receive at least one course of radiotherapy during the course of the disease. In this review, radiobiological properties of melanoma that govern the decisions for the fractionation patterns used in the treatment of this disease are described. Moreover, the indications for irradiation and the results of pertinent clinical studies from the literature, creating a rationale for the use of radiotherapy in the management of this disease, are reviewed and a brief description of radiotherapy techniques is given. Basic treatment modality in melanoma is surgery. However, whenever surgery is not radical or there are adverse prognostic factors identified on histopathological examination of resected tissue specimen, it needs to be supplemented. Also, in patients with unresectable disease or in those not being suitable for major surgery or who refuse proposed surgical intervention, other effective mode(s) of therapy need to be implemented. From this perspective, supported by clinical experiences and literature results, radiotherapy is a valuable option: it is effective and safe, in curative and palliative setting

  9. Increased Frequency of Suppressive Regulatory T Cells and T-cell Mediated Antigen Loss Results in Murine Melanoma Recurrence

    Science.gov (United States)

    Jensen, Shawn M.; Twitty, Christopher G.; Maston, Levi D.; Antony, Paul A.; Lim, May; Hu, Hong-Ming; Petrausch, Ulf; Restifo, Nicholas P.; Fox, Bernard A.

    2012-01-01

    Therapeutic treatment of large established tumors using immunotherapy has yielded few promising results. We investigated if adoptive transfer of tumor-specific CD8+ T cells together with tumor-specific CD4+ T cells would mediate regression of large established B16BL6-D5 (D5) melanomas in lymphopenic Rag1−/− recipients devoid of regulatory T cells. The combined adoptive transfer of subtherapeutic doses of both TRP1-specific TCR transgenic Rag1−/− CD4+ T cells and gp100-specific TCR transgenic Rag1−/− CD8+ T cells into lymphopenic recipients, that received vaccination, led to regression of large (100–400 mm2) melanomas. The same treatment strategy was ineffective in lymphoreplete wt mice. Twenty-five percent of mice (15/59) had tumors recur (15–180 days post regression). Recurrent tumors were depigmented and had decreased expression of gp100, the epitope targeted by the CD8+ T cells. Mice with recurrent melanoma had increased CD4+Foxp3+ TRP1-specific T cells compared to mice that did not show evidence of disease. Importantly, splenocytes from mice with recurrent tumor were able to suppress the in vivo therapeutic efficacy of splenocytes from tumor-free mice. These data demonstrate that large established tumors can be treated by a combination of tumor-specific CD8+ and CD4+ T cells. Additionally, recurrent tumors exhibited decreased antigen expression and were accompanied by conversion of the therapeutic tumor-specific CD4+ T cell population to a FoxP3+ CD4+ regulatory T cell population. PMID:22723522

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

    International Nuclear Information System (INIS)

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

  11. Preliminary results from an advanced lighting controlstestbed

    Energy Technology Data Exchange (ETDEWEB)

    Avery, Douglas; Jennings, Judity; Rubinstein, Francis

    1998-03-01

    Preliminary results from a large-scale testbed of advanced lighting control technologies at the Phillip Burton Federal Building at 450 Golden Gate Ave. in San Francisco are presented. The first year objective of this project is to determine the sustainable energy savings and cost-effectiveness of different lighting control technologies compared to a portion of the building where only minimal controls are installed. The paper presents the analyzed results from six months of tests focused on accurately characterizing the energy savings potential of one type of daylight-linked lighting controls compared to the lighting in similar open-planned areas without dimming controls. After analyzing a half year;s data, we determined that the annual energy savings for this type of daylight- linked controls was 41% and 30% for the outer rows of lights on the South and North sides of the building, respectively. The annual energy savings dropped to 22% and 16% for the second row of lights for the South and North, respectively, and was negligible for the third rows of lights.

  12. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037)

    DEFF Research Database (Denmark)

    Weber, Jeffrey S; D'Angelo, Sandra P; Minor, David;

    2015-01-01

    -protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with......BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of...... permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per...

  13. 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.

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

    Science.gov (United States)

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

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. PMID:25046141

  15. Primary mucosal sinonasal melanoma - Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Aim: The place of adjuvant radiotherapy in the treatment of sinonasal melanoma. Background: Sinonasal mucosal melanoma is a rare disease with poor prognosis and requires a complex treatment. Elective neck dissection in patients with N0 and adjuvant radiotherapy has been a source of controversy. High late regional recurrence rates rise questions about elective irradiation of the neck nodes in patients with N0 stage disease. Methods: We present our two years follow up in a case of locally advanced sinonasal melanoma and literature review of the treatment options for mucosal melanoma. Results: In locally advanced sinonasal melanoma treated with surgical resection, postoperative radiotherapy and chemotherapy we had local tumor control. Two years later, a regional contralateral recurrence without distant metastasis occurred. Conclusions: Literature data for frequent neck lymph nodes recurrences justify elective neck dissection. Postoperative elective neck radiotherapy for patients with locally advanced sinonasal melanoma and clinically N0 appears to decrease the rate of late regional recurrences. (authors)

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

    Directory of Open Access Journals (Sweden)

    Alberto Julius Alves Wainstein

    2015-12-01

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

  17. Melanoma of the Foot.

    Science.gov (United States)

    Bristow, Ivan; Bower, Chris

    2016-07-01

    Melanoma is a rare form of skin cancer that is responsible for most skin cancer deaths globally. Tumors arising on the foot continue to be a particular challenge. Patients present later and lesions are frequently misdiagnosed, leading to more advanced disease with an overall poorer prognosis then melanoma elsewhere. In order to improve early recognition, this article reviews the clinical features of the disease along with published algorithms. Emerging assessment techniques such as dermoscopy are also discussed as tools to improve clinical decision making. Contemporary drug therapies in the treatment of advanced disease are also discussed. PMID:27215160

  18. Animal Models of Uveal Melanoma: Methods, Applicability, and Limitations

    Science.gov (United States)

    Stei, Marta M.; Loeffler, Karin U.; Holz, Frank G.; Herwig, Martina C.

    2016-01-01

    Animal models serve as powerful tools for investigating the pathobiology of cancer, identifying relevant pathways, and developing novel therapeutic agents. They have facilitated rapid scientific progress in many tumor entities. However, for establishing a powerful animal model of uveal melanoma fundamental challenges remain. To date, no animal model offers specific genetic attributes as well as histologic, immunologic, and metastatic features of uveal melanoma. Syngeneic models with intraocular injection of cutaneous melanoma cells may suit best for investigating immunologic/tumor biology aspects. However, differences between cutaneous and uveal melanoma regarding genetics and metastasis remain problematic. Human xenograft models are widely used for evaluating novel therapeutics but require immunosuppression to allow tumor growth. New approaches aim to establish transgenic mouse models of spontaneous uveal melanoma which recently provided preliminary promising results. Each model provides certain benefits and may render them suitable for answering a respective scientific question. However, all existing models also exhibit relevant limitations which may have led to delayed research progress. Despite refined therapeutic options for the primary ocular tumor, patients' prognosis has not improved since the 1970s. Basic research needs to further focus on a refinement of a potent animal model which mimics uveal melanoma specific mechanisms of progression and metastasis. This review will summarise and interpret existing animal models of uveal melanoma including recent advances in the field. PMID:27366747

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-01

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

  20. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung

    2012-02-01

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

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

    Science.gov (United States)

    Welte, Yvonne; Davies, Cathrin; Schäfer, Reinhold; Regenbrecht, Christian R A

    2013-01-01

    Despite improved treatments options for melanoma available today, patients with advanced malignant melanoma still have a poor prognosis for progression-free and overall survival. Therefore, translational research needs to provide further molecular evidence to improve targeted therapies for malignant melanomas. In the past, oncogenic mechanisms related to melanoma were extensively studied in established cell lines. On the way to more personalized treatment regimens based on individual genetic profiles, we propose to use patient-derived cell lines instead of generic cell lines. Together with high quality clinical data, especially on patient follow-up, these cells will be instrumental to better understand the molecular mechanisms behind melanoma progression. Here, we report the establishment of primary melanoma cultures from dissected fresh tumor tissue. This procedure includes mincing and dissociation of the tissue into single cells, removal of contaminations with erythrocytes and fibroblasts as well as primary culture and reliable verification of the cells' melanoma origin. Recent reports revealed that melanomas, like the majority of tumors, harbor a small subpopulation of cancer stem cells (CSCs), which seem to exclusively fuel tumor initiation and progression towards the metastatic state. One of the key markers for CSC identification and isolation in melanoma is CD133. To isolate CD133(+) CSCs from primary melanoma cultures, we have modified and optimized the Magnetic-Activated Cell Sorting (MACS) procedure from Miltenyi resulting in high sorting purity and viability of CD133(+) CSCs and CD133(-) bulk, which can be cultivated and functionally analyzed thereafter. PMID:23525090

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

    Science.gov (United States)

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

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID:27004972

  3. Recent advances in molecular genetics of melanoma progression: implications for diagnosis and treatment

    Science.gov (United States)

    Yeh, Iwei

    2016-01-01

    According to the multi-step carcinogenesis model of cancer, initiation results in a benign tumor and subsequent genetic alterations lead to tumor progression and the acquisition of the hallmarks of cancer. This article will review recent discoveries in our understanding of initiation and progression in melanocytic neoplasia and the impact on diagnostic dermatopathology. PMID:27408703

  4. Melanoma genetics

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Immunotherapy of Melanoma.

    Science.gov (United States)

    Snyder, Alexandra; Zamarin, Dmitriy; Wolchok, Jedd D

    2015-01-01

    The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma. PMID:26376963

  6. Upstream mitogen-activated protein kinase (MAPK) pathway inhibition: MEK inhibitor followed by a BRAF inhibitor in advanced melanoma patients.

    Science.gov (United States)

    Goldinger, Simone M; Zimmer, Lisa; Schulz, Carsten; Ugurel, Selma; Hoeller, Christoph; Kaehler, Katharina C; Schadendorf, Dirk; Hassel, Jessica C; Becker, Juergen; Hauschild, Axel; Dummer, Reinhard

    2014-01-01

    BRAF-mutant melanoma can be successfully treated by BRAF kinase inhibitors (BRAFi) and MEK kinase inhibitors (MEKi). However, the administration of BRAFi followed by MEKi did not generate promising response rate (RR). The purpose of this investigation was to evaluate the time to progression (TTP) with a mitogen-activated protein kinase (MAPK) pathway upstream inhibition strategy in BRAF mutated melanoma patients. BRAF mutation positive metastatic melanoma patients were identified within the Dermatology Cooperative Oncology Group (DeCOG) network and were treated first with a MEKi and upon progression with a selective BRAFi. A total of 23 melanoma patients (six females, 17 males, aged 47-80 years) were retrospectively analysed for TTP. The total median TTP was 8.9 months. The median TTP for MEKi was 4.8 (1.2-23.2) and subsequent for BRAFi 4.5 (1.2-15.7) months, respectively. A higher RR for MEKi (39%, nine partial responses and 0 complete responses) than previously reported was observed. Our analysis suggests that the reversed inhibition of the MAPK pathway is feasible in BRAF mutated melanoma. The median TTP (8.9 months) is close to the promising BRAF- and MEKi combination therapy (median progression-free survival (PFS) 9.4 months). The total treatment duration of the MAPK inhibition when a MEKi is administered first is similar compared to the reversed sequence, but TTP shifts in favour to the MEKi. This approach is feasible with reasonable tolerability. This clinical investigation encourages further studies in prospective clinical trials to define the optimal treatment schedule for the MAPK pathway inhibition and should be accompanied by molecular monitoring using repeated biopsies. PMID:24183461

  7. Melanoma Drug Boosting Survival for Many, Study Shows

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_158928.html Melanoma Drug Boosting Survival for Many, Study Shows Keytruda ... 2016 (HealthDay News) -- A new drug for advanced melanoma is dramatically shifting the odds in favor of ...

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

    International Nuclear Information System (INIS)

    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.'

  9. Melanoma immunotherapy dominates the field.

    Science.gov (United States)

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

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

  10. Chemovirotherapy of malignant melanoma with a targeted and armed oncolytic measles virus.

    Science.gov (United States)

    Kaufmann, Johanna K; Bossow, Sascha; Grossardt, Christian; Sawall, Stefanie; Kupsch, Jörg; Erbs, Philippe; Hassel, Jessica C; von Kalle, Christof; Enk, Alexander H; Nettelbeck, Dirk M; Ungerechts, Guy

    2013-04-01

    Effective treatment modalities for advanced melanoma are desperately needed. An innovative approach is virotherapy, in which viruses are engineered to infect cancer cells, resulting in tumor cell lysis and an amplification effect by viral replication and spread. Ideally, tumor selectivity of these oncolytic viruses is already determined during viral cell binding and entry, which has not been reported for melanoma. We engineered an oncolytic measles virus entering melanoma cells through the high molecular weight melanoma-associated antigen (HMWMAA) and proved highly specific infection and spread in melanoma cells. We further enhanced this oncolytic virus by inserting the FCU1 gene encoding the yeast-derived prodrug convertases cytosine deaminase and uracil phosphoribosyltransferase. Combination treatment with armed and retargeted MV-FCU1-αHMWMAA and the prodrug 5-fluorocytosine (5-FC) led to effective prodrug conversion to 5-fluorouracil, extensive cytotoxicity to melanoma cells, and excessive bystander killing of noninfected cells. Importantly, HMWMAA-retargeted MV showed antitumor activity in a human xenograft mouse model, which was further increased by the FCU1/5-FC prodrug activation system. Finally, we demonstrated susceptibility of melanoma skin metastasis biopsies to HMWMAA-retargeted MV. The highly selective, entry-targeted and armed oncolytic virus MV-FCU1-αHMWMAA may become a potent building block of future melanoma therapies. PMID:23223133

  11. Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-small Cell Lung Cancer, or Squamous Cell Head and Neck Cancer

    Science.gov (United States)

    2016-05-05

    Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Skin Carcinoma; Stage III Renal Cell Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Skin Melanoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Non-Small Cell Lung Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma

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

    Institute of Scientific and Technical Information of China (English)

    谢婉莹; 欧阳鑫; 江冠民; 张秋桂

    2015-01-01

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

  13. Malignant melanoma of the mandibular gingiva

    Directory of Open Access Journals (Sweden)

    Sandeep Fauzdar

    2010-04-01

    Full Text Available Oral malignant melanoma is an infrequent neoplasia making up less than 1% of all melanomas, which exhibits much more aggressive behavior than those found on the skin. We present an aggressive case of oral malignant melanoma located on the mandibular gingiva in a 24-year-old male patient, who developed metastases to not only the regional lymph nodes but also the lungs and liver. The advanced stage of the disease contraindicated any surgical intervention and palliative chemotherapy was planned.

  14. Results of Laboratory Testing of Advanced Power Strips: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Earle, L.; Sparn, B.

    2012-08-01

    This paper describes the results of a laboratory investigation to evaluate the technical performance of advanced power strip (APS) devices when subjected to a range of home entertainment center and home office usage scenarios.

  15. Novel anti-melanoma treatment:focus on immunotherapy

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  16. Novel anti-melanoma treatment: focus on immunotherapy

    Directory of Open Access Journals (Sweden)

    Meng-Ze Hao

    2014-09-01

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

  17. Chemoprevention of Melanoma

    OpenAIRE

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2012-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens h...

  18. Phase II, Open-Label, Randomized Trial of the MEK 1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

    DEFF Research Database (Denmark)

    Kirkwood, John M; Bastholt, Lars; Robert, Caroline; Sosman, Jeffrey A; Larkin, James; Hersey, Peter; Middleton, Mark R; Cantarini, Mireille V; Zazulina, Victoria; Kemsley, Karin; Dummer, Reinhard

    2011-01-01

    selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m2/day for 5 days, then 23 days off treatment). The primary endpoint was progression-free survival.RESULTS: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and......PURPOSE: To compare the efficacy and tolerability of the MEK 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naïve patients with unresectable stage III/IV melanoma.Methods: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral...

  19. Melanoma Diagnosis

    Science.gov (United States)

    Horsch, Alexander

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

  20. Update in genetic susceptibility in melanoma

    OpenAIRE

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2015-01-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identificatio...

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

    International Nuclear Information System (INIS)

    Introduction: A specific diagnosis for melanoma is strongly desired because malignant melanoma has poor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine (125I-L-PC) was found to have good substrate affinity for tyrosinase enzyme in the melanin metabolic pathway, 123/131I-L-PC had insufficient substrate affinity for tyrosinase to diagnose melanoma. In this study, we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4-hydroxyphenylcysteamine (125I-PCA) to increase affinity for the melanin biosynthesis pathway. Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis. 125I-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed biodistribution experiments using B16 melanoma-bearing mice using 125I-PCA, 125I-L-PC, 125I-α-methyl-L-tyrosine, 123I-m-iodobenzylguanidine and 67Ga-citrate. In vitro assay was performed with B16 melanoma cells, and affinity for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabine and L-tyrosine inhibitor. In addition, partition coefficients of 125I-PCA were evaluated. Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA was separated from 2-PCA at high purity. In biodistribution experiments, 125I-PCA was accumulated and retained in B16 melanoma cells when compared with 125I-L-PC. 125I-PCA showed the highest values at 60 min after radiotracer injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of 125I-PCA was significantly inhibited by phenylthiourea and thymidine. Partition coefficients of 125I-PCA were lower than those of N-isopropyl-p-[123I]iodoamphetamine and were not significantly different from

  2. Current State of Animal (Mouse) Modeling in Melanoma Research

    OpenAIRE

    Kuzu, Omer F.; Nguyen, Felix D.; Mohammad A. Noory; Arati Sharma

    2015-01-01

    Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compar...

  3. Unexpected High Response Rate to Traditional Therapy after Dendritic Cell-Based Vaccine in Advanced Melanoma: Update of Clinical Outcome and Subgroup Analysis

    Directory of Open Access Journals (Sweden)

    Laura Ridolfi

    2010-01-01

    Full Text Available We reviewed the clinical results of a dendritic cell-based phase II clinical vaccine trial in stage IV melanoma and analyzed a patient subgroup treated with standard therapies after stopping vaccination. From 2003 to 2009, 24 metastatic melanoma patients were treated with mature dendritic cells pulsed with autologous tumor lysate and keyhole limpet hemocyanin and low-dose interleukin-2. Overall response (OR to vaccination was 37.5% with a clinical benefit of 54.1%. All 14 responders showed delayed type hypersensitivity positivity. Median overall survival (OS was 15 months (95% CI, 8–33. Eleven patients underwent other treatments (3 surgery, 2 biotherapy, 2 radiotherapy, 2 chemotherapy, and 4 biochemotherapy after stopping vaccination. Of these, 2 patients had a complete response and 5 a partial response, with an OR of 63.6%. Median OS was 34 months (range 16–61. Our results suggest that therapeutic DC vaccination could favor clinical response in patients after more than one line of therapy.

  4. Genetic alterations and markers of melanoma

    Directory of Open Access Journals (Sweden)

    N. N. Mazurenko

    2014-01-01

    progress in melanoma studies allow to receive the positive results in melanoma treatment in particularly with targeted therapy. The molecular targets and future perspectives for targeted therapy of metastatic skin melanoma are discussed.

  5. Malignant Melanoma of the Foot

    Science.gov (United States)

    ... Text Size Print Bookmark Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  6. The Advanced Photon Source: Performance and results from early operation

    International Nuclear Information System (INIS)

    The Advanced Photon Source at Argonne National Laboratory is now providing researchers with extreme-brilliance undulator radiation in the hard x-ray region of the spectrum. All technical facilities and components are operational and have met design specifications. Fourteen research teams, occupying 20 sectors on the APS experiment hall floor, are currently installing beamline instrumentation or actively taking data. An overview is presented for the first operational years of the Advanced Photon Source. Emphasis is on the performance of accelerators and insertion devices, as well as early scientific results and future plans

  7. New results in atomic physics at the Advanced Light Source

    International Nuclear Information System (INIS)

    The Advanced Light Source is the world's first low-energy third-generation synchrotron radiation source. It has been running reliably and exceeding design specifications since it began operation in October 1993. It is available to a wide community of researchers in many scientific fields, including atomic and molecular science and chemistry. Here, new results in atomic physics at the Advanced Light Source demonstrate the opportunities available in atomic and molecular physics at this synchrotron light source. The unprecedented brightness allows experiments with high flux, high spectral resolution, and nearly 100% linear polarization

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

    Science.gov (United States)

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

    2014-12-01

    The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity. PMID:25016296

  9. Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

    OpenAIRE

    Schadendorf, D.; Amonkar, M. M.; Milhem, M.; Grotzinger, K.; L. V. Demidov; Rutkowski, P; Garbe, C.; Dummer, R.; Hassel, J C; Wolter, P; Mohr, P; Trefzer, U.; Lefeuvre-Plesse, C.; Rutten, A.; Steven, N.

    2014-01-01

    We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametinib.

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

    International Nuclear Information System (INIS)

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

  11. PRIMARY ENDOPROSTHETIC REPLACEMENT OF THE ANOPHTHALMIC ORBIT IN PATIENTS WITH UVEAL MELANOMA: SIX-YEAR FOLLOW-UP RESULTS

    Directory of Open Access Journals (Sweden)

    A. A. Yarovoy

    2012-01-01

    Full Text Available A locomotor stump was formed in 36 patients (28 women and 8 men, by implanting an endoprosthesis for enucleation of the eyeball with uveal melanoma (UM. The indication for endoprosthesis implantation was no signs of extrabulbar growth. A modified 17–19 mm silicone implant covered with strips from a dura mater graft and medical mesh fabric was used as an orbital implant. The follow-up was 3 to 72 months (mean 32.5 months. All the patients achieved a satisfactory cosmetic effect. None patient was found to have a recurrent orbital tumor. Out of the complications, anterior implant surface denudation was noted in 4 patients. Two patients developed metastases. The absence of recurrent orbital UM at a 6-year follow-up enables primary endoprosthetic replacement of the orbit for UM to be regarded as a safe and reasonable method for patient cosmetic rehabilitation. 

  12. Preliminary results of a phase I/II clinical trial using in situ photoimmunotherapy combined with imiquimod for metastatic melanoma patients

    Science.gov (United States)

    Li, Xiaosong; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Howard, C. Anthony; Murray, Cynthia; Chen, Wei R.

    2010-02-01

    In Situ Photoimmunotherapy (ISPI), a newly developed modality for cancer therapy, has been shown to be able to modulate the body's own immune response. This clinical trial was designed to evaluate the safety and therapeutic effect of ISPI, using imiquimod as its immunoadjuvant for metastatic melanoma patients. ISPI consisted of three main components applied directly to the cutaneous metastases: 1) local application of topical imiquimod; 2) injection of indocyanine green; and 3) an 805 nm laser for local irradiation. All patients completed at least one cycle of treatment. All the patients completed at least one cycle of treatments; one patient received 6 cycles. The most common adverse effects were rash, pruritus, pain, fatigue and anorexia. Fever, chills, vomiting and cellulitis were relative rare. No grade 4 toxicity was observed. Complete Response (CR) was observed in 6 patients. Median overall survival of the 11 evaluated patients was 12.2 months. Six of the eleven patients were still alive at the time of this report. Treatment of ISPI using imiquimod is safe and well tolerant. Our preliminary clinical results suggest that this new method can be a promising modality for metastatic melanoma.

  13. Sinclair swine melanoma

    International Nuclear Information System (INIS)

    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

  14. 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

  15. 重组人白细胞介素2治疗晚期恶性黑素瘤Ⅱ期临床研究%A phase Ⅱ clinical trial of recombinant human interleukin-2 in treatment of advanced melanoma

    Institute of Scientific and Technical Information of China (English)

    唐碧霞; 斯璐; 迟志宏; 崔传亮; 盛锡楠; 毛丽丽; 郭军

    2011-01-01

    Objective: To investigate the efficacy and safety of high-dose recombinant human interleukin-2 (rhlL-2) in treatment of patients with advanced melanoma. Methods: Twenty Chinese patients with advanced melanoma were planned to be enrolled to receive high-dose rhlL-2 treatment. The overall response rare (ORR), progression-free survival (PFS), overall survival (OS) and incidence of toxicity were evaluated. Results: Fourteen patients were enrolled, of them twelve could be evaluated. One patient achieved partial response (PR), and the maintaining duration of response was 43.0 months; three patients achieved stable disease (SD); 8 patients achieved progressive disease (PD). The median PFS was 56.0±7.6 d, and the median OS was 11.0±2.6 months. The incidence rate of grade III-IV toxicity was 40.3%, mainly manifested as gastrointestinal reaction, fever and cardiovascular reaction. Conclusion: The efficacy of high-dose rhlL-2 for Chinese patients with advanced melanoma is not as good as those previously reported in studies abroad, with high incidence rate of adverse effects. The patients can get long response duration as rhlL-2 worked. It is necessary to perform further studies on how to make choice of administration dose and select potential patients who will benefit from the treatment.%目的:评价高剂量重组人白细胞介素2(recombinant human interleukin-2,rhIL-2)治疗晚期恶性黑素瘤的疗效及其安全性.方法:拟入组20例晚期恶性黑素瘤患者,均接受高剂量rhIL-2治疗,评价总有效率、无进展生存和总生存,以及不良反应发生率.结果:共入组14例患者,其中12例可评价疗效.其中,1例部分缓解(8.3%),疗效维持时间为43.0个月;3例疾病稳定;8例疾病进展.中位无进展生存时间为(56.0±7.6)d,中位总生存期为(11.0±2.6)个月.Ⅲ~Ⅳ级不良反应发生率为40.3%,主要表现为消化系统反应、发热和心血管事件.结论:高剂量rhIL-2治疗中国晚期黑素瘤患者的有

  16. Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105 shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects

    Directory of Open Access Journals (Sweden)

    Tanja Dolinsek

    2015-12-01

    Full Text Available Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively. The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells.

  17. Choroidal melanoma

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

    Ascierto, Paolo A; Bastholt, Lars; Hersey, Peter; Cinat, Gabriela; Eggermont, Alexander M; Hauschild, Axel; Espinosa, Enrique; Robert, Caroline

    2013-01-01

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

  19. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    Science.gov (United States)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  20. Stages of Melanoma

    Science.gov (United States)

    ... melanoma cells. The disease is metastatic melanoma, not lung cancer. The method used to stage melanoma is based mainly on the thickness of the tumor and whether cancer has spread to lymph nodes or other parts of the body. The staging of melanoma depends on the following: The thickness ...

  1. Endothelin-1 in the tumor microenvironment correlates with melanoma invasion.

    Science.gov (United States)

    Chiriboga, Luis; Meehan, Shane; Osman, Iman; Glick, Michael; de la Cruz, Gelo; Howell, Brittny S; Friedman-Jiménez, George; Schneider, Robert J; Jamal, Sumayah

    2016-06-01

    Endothelin-1 (ET-1) is a vasoactive peptide that also plays a role in the tanning response of the skin. Animal and cell culture studies have also implicated ET-1 in melanoma progression, but no association studies have been performed to link ET-1 expression and melanoma in humans. Here, we present the first in-vivo study of ET-1 expression in pigmented lesions in humans: an ET-1 immunohistochemical screen of melanocytic nevi, melanoma in situ lesions, invasive melanomas, metastatic melanomas, and blue nevi was performed. Twenty-six percent of melanocytic nevi and 44% of melanoma in situ lesions demonstrate ET-1 expression in the perilesional microenvironment, whereas expression in nevus or melanoma cells was rare to absent. In striking contrast, 100% of moderately to highly pigmented invasive melanomas contained numerous ET-1-positive cells in the tumor microenvironment, with 79% containing ET-1-positive melanoma cells, confirmed by co-staining with melanoma tumor marker HMB45. Hypopigmented invasive melanomas had reduced ET-1 expression, suggesting a correlation between ET-1 expression and pigmented melanomas. ET-1-positive perilesional cells were CD68-positive, indicating macrophage origin. Sixty-two percent of highly pigmented metastatic melanomas demonstrated ET-1 expression in melanoma cells, in contrast to 28.2% of hypopigmented specimens. Eighty-nine percent of benign nevi, known as blue nevi, which have a dermal localization, were associated with numerous ET-1-positive macrophages in the perilesional microenvironment, but no ET-1 expression was detected in the melanocytes. We conclude that ET-1 expression in the microenvironment increases with advancing stages of melanocyte transformation, implicating a critical role for ET-1 in melanoma progression, and the importance of the tumor microenvironment in the melanoma phenotype. PMID:26825037

  2. Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Kavita K., E-mail: Kavita.mishra@ucsf.edu [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Quivey, Jeanne M.; Daftari, Inder K. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Weinberg, Vivian [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Cole, Tia B. [The Tumori Foundation, San Francisco, California (United States); Patel, Kishan [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California-San Francisco, San Francisco, California (United States); Lawrence Berkeley National Laboratory, Berkeley, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States); Department of Ophthalmology, University of California-San Francisco, San Francisco, California (United States); Department of Ophthalmology, Stanford University, Palo Alto, California (United States)

    2015-06-01

    Purpose: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. Methods and Materials: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Results: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). Conclusions: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

  3. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial.

    NARCIS (Netherlands)

    Eggermont, A.M.; Suciu, S.; Santinami, M.; Testori, A.; Kruit, W.H.; Marsden, J.; Punt, C.J.A.; Sales, F.; Gore, M.; Mackie, R.; Kusic, Z.; Dummer, R.; Hauschild, A.; Musat, E.; Spatz, A.; Keilholz, U.

    2008-01-01

    BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. METHODS: 1256 patients with resected stage III melanoma

  4. Melanoma biomarkers: Vox clamantis in deserto (Review).

    Science.gov (United States)

    Al-Shaer, Mays; Gollapudi, Divya; Papageorgio, Chris

    2010-05-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically. PMID:22966315

  5. Update in genetic susceptibility in melanoma.

    Science.gov (United States)

    Potrony, Miriam; Badenas, Celia; Aguilera, Paula; Puig-Butille, Joan Anton; Carrera, Cristina; Malvehy, Josep; Puig, Susana

    2015-09-01

    Melanoma is the most deadly of the common skin cancers and its incidence is rapidly increasing. Approximately 10% of cases occur in a familial context. To date, cyclin-dependent kinase inhibitor 2A (CDKN2A), which was identified as the first melanoma susceptibility gene more than 20 years ago, is the main high-risk gene for melanoma. A few years later cyclin-dependent kinase 4 (CDK4) was also identified as a melanoma susceptibility gene. The technologic advances have allowed the identification of new genes involved in melanoma susceptibility: Breast cancer 1 (BRCA1) associated protein 1 (BAP1), CXC genes, telomerase reverse transcriptase (TERT), protection of telomeres 1 (POT1), ACD and TERF2IP, the latter four being involved in telomere maintenance. Furthermore variants in melanocortin 1 receptor (MC1R) and microphthalmia-associated transcription factor (MITF) give a moderately increased risk to develop melanoma. Melanoma genetic counseling is offered to families in order to better understand the disease and the genetic susceptibility of developing it. Genetic counseling often implies genetic testing, although patients can benefit from genetic counseling even when they do not fulfill the criteria for these tests. Genetic testing for melanoma predisposition mutations can be used in clinical practice under adequate selection criteria and giving a valid test interpretation and genetic counseling to the individual. PMID:26488006

  6. Communication of Advanced Test Reactor probabilistic risk assessment results

    International Nuclear Information System (INIS)

    The Advanced Test Reactor (ATR) probabilistic risk assessment (PRA) Level 1 results were efficiently communicated in two reports following the completion of revision 1 of the ATR PRA. As the ATR PRA including external events fills four large volume, it was considered impractical to expect all of the individuals at ATR who could benefit from the information to read the entire PRA. Even though many ATR personnel received training in PRA methodology and were involved in some aspects of the PRA, another hinderance to effective communication of the PRA results is that the PRA was written and organized to meet the requirements of practitioners and reviewers who are well-versed in PRA methods. Therefore, two PRA summary reports, an ATR risk summary report and an ATR functional group summary report, were written to communicate the ATR PRA results and insights to interested ATR personnel

  7. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    Science.gov (United States)

    2016-05-17

    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

  8. Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy – Clinical results after six years of experience

    International Nuclear Information System (INIS)

    Purpose: To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. Materials and Methods: Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2–49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. Results: Initial tumor base diameters, height and volume were 11.20 mm (IQR 9.10–13.70), 9.80 mm (IQR 7.80–11.70), 4.53 mm (IQR 3.33–6.43) and 253.8 mm3 (IQR 127.5–477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p < 0.001). The most common toxicities (any grade) were radiation retinopathy (n = 39), optic neuropathy (n = 32), radiogenic cataract (n = 21), neovascular glaucoma (n = 15) and dry eye syndrome (n = 10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. Conclusion: Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile

  9. Photodynamic Treatment of Cultured Human Malignant Melanoma cells and Assessment of Resultant Cell Death and Inflicted Bio molecular Damage As Determined by Synchrotron I.R. Radiations

    International Nuclear Information System (INIS)

    Malignant melanoma is a very serious skin cancer that if not discovered early and treated by surgery can become fatal. Photodynamic treatment involves the use of a photosensitive dye that is not toxic by itself and is taken up by all cells normal and tumor cells. However it is released from normal cells in a short time while it is kept inside tumor cells for a longer time. A laser light of wave length that is maximally absorbed by the used dye is then used to illuminate tumor cells, still having the dye, and a reaction takes place resulting in the liberation of singlet oxygen, a very active form of oxygen that damages important biomolecules and results eventually in cell death. The photosensitive dye Indocyanine greenand a Ti - Sapphire laser (780 nm wave length ) and power density of 55 m Watt/ cm2 were used. The percentage of cell death increased slowly with the strength of the PDT until it reached 75% death of the exposed cells at a net dye concentration of 150 u M and laser exposure dose of 60 minute duration.Synchrotron infrared imaging was carried out on control and experimental cultures at the national synchrotron light source (BNL) using FTIR spectro microscopy to reveal the I.R. absorption characteristics of protein, lipids and nucleic acids biomolecules. It was found that increasing the strength of the PDT had an increasingly damaging effect on the concentration of cellular biomolecules, the largest effect being in the protein, lipids and nucleic acid components of the cell. More experiments are planned involving changes in the strengths of the PDT treatments for eventually reaching 100% melanoma cell death

  10. Melanoma Brain Metastasis: Mechanisms, Models, and Medicine.

    Science.gov (United States)

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

    2016-01-01

    The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases. PMID:27598148

  11. Advanced Bimanual Manipulation Results from the DEXMART Project

    CERN Document Server

    2012-01-01

    Dexterous and autonomous manipulation is a key technology for the personal and service robots of the future. Advances in Bimanual Manipulation edited by Bruno Siciliano provides the robotics community with the most noticeable results of the four-year European project DEXMART (DEXterous and autonomous dual-arm hand robotic manipulation with sMART sensory-motor skills: A bridge from natural to artificial cognition). The volume covers a host of highly important topics in the field, concerned with modelling and learning of human manipulation skills, algorithms for task planning, human-robot interaction, and grasping, as well as hardware design of dexterous anthropomorphic hands. The results described in this five-chapter collection are believed to pave the way towards the development of robotic systems endowed with dexterous and human-aware dual-arm/hand manipulation skills for objects, operating with a high degree of autonomy in unstructured real-world environments.

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

    Science.gov (United States)

    Jaworek-Korjakowska, Joanna

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Joanna Jaworek-Korjakowska

    2016-01-01

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

  14. What Is Melanoma Skin Cancer?

    Science.gov (United States)

    ... statistics for melanoma skin cancer What is melanoma skin cancer? Cancer starts when cells in the body begin ... causing the skin to tan or darken. Melanoma skin cancers Melanoma is a cancer that begins in the ...

  15. 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

  16. Some results of the advanced photon source beam lifetime studies

    International Nuclear Information System (INIS)

    Total beam lifetime consists of two components: the residual-gas-scattering lifetime and Touschek lifetime. The residual-gas lifetime is comprised of the elastic and inelastic scattering on electrons and elastic and inelastic scattering on nuclei. Touschek scattering involves scattering of particles within the bunch. One usually calculates only the elastic scattering on nuclei (single Coulomb scattering) and inelastic scattering on nuclei (bremsstrahlung) of the residual-gas-scattering lifetime component. Experience gained from computing the beam lifetime in the Advanced Photon Source (APS) storage ring shows that the electron scattering should not be neglected, particularly the inelastic contribution. Given the measured quantities from the APS storage ring, one can compare theoretical predictions with experimental results. Uncertainties in calculating the various contributions to lifetime will be discussed

  17. Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

    Science.gov (United States)

    Schadendorf, D.; Amonkar, M. M.; Milhem, M.; Grotzinger, K.; Demidov, L. V.; Rutkowski, P.; Garbe, C.; Dummer, R.; Hassel, J. C.; Wolter, P.; Mohr, P.; Trefzer, U.; Lefeuvre-Plesse, C.; Rutten, A.; Steven, N.; Ullenhag, G.; Sherman, L.; Wu, F. S.; Patel, K.; Casey, M.; Robert, C.

    2014-01-01

    Background In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Patients and methods Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. Results In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4–5 points with chemotherapy but improved by 2–3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8–11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4–8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11–12 points), insomnia (10–12 points), and appetite loss (1–5 points), whereas those for diarrhea worsened (15–16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. Conclusions This first QOL assessment for a MEK

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

    Institute of Scientific and Technical Information of China (English)

    Andrea J. McKinney; Sheri L. Holmen

    2011-01-01

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

  19. Metastatic malignant melanoma of maxillary gingiva. A case report.

    OpenAIRE

    Srinivasan S; Pal K; Dayal P; Bastian T; Patil S

    1997-01-01

    Malignant melanoma of the oral cavity can be primary or secondary due to metastasis from distant site. Incidence of oral cavity by metastasis of melanoma is 1.85%. Most common oral sites involved are tongue, buccal mucosa and parotid gland. Oral lesions occur as a part of disseminated disease during the advanced stages and has poor prognosis. An unusual case of metastatic malignant melanoma of the maxillary gingiva is reported.

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

    OpenAIRE

    Shen, Weidong; Sakamoto, Naoko; Yang, Limin

    2016-01-01

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

  1. Surgery of Primary Melanomas

    International Nuclear Information System (INIS)

    Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas

  2. 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.

  3. [Results of ligament reconstruction in advanced scapholunate dissociation].

    Science.gov (United States)

    Wieloch, P T; Martini, A-K; Daecke, W

    2005-04-01

    Scapholunate dissociation is one of the most common disorders of the wrist. Untreated it might lead to osteoarthrosis (scapholunate advanced collapse, SLAC wrist). Choosing the best surgical treatment option is still challenging, especially in cases of carpal collapse in combination with beginning osteoarthrosis of the radial styloid and the proximal pole of the scaphoid. We report the results of a homogenous group of eight patients with reducible carpal collapse and beginning arthrosis treated by reconstruction of the scapholunate ligament. The operation was performed 66 (range: 20 to 252) months after trauma. The average length of follow-up was two years. Five patients stated general improvement, while three reported a change for the worse. At follow-up, the average total range of motion of the operated wrist was decreased by 16 % compared to the unaffected side. The average grip-strength (measured with a Jamar dynamometer) was 77 % of the uninvolved wrist. The DASH score was 43 +/- 25. In three cases the Martini score showed a good or an excellent result. The average scapholunate angle was 72.3 degrees preoperatively and decreased to 61.0 degrees at follow-up. At follow-up as well as pre- and postoperatively the carpal height ratio showed pathologic mean values. Therefore, reconstruction of the carpal alignment was not achieved in most of the cases. Progression of the osteoarthrosis has to be expected. Reconstruction of the scapholunate ligament for treatment of carpal collapse with beginning osteoarthrosis therefore remains an unsolved problem. PMID:15877269

  4. Melanoma exosome induction of endothelial cell GM-CSF in pre-metastatic lymph nodes may result in different M1 and M2 macrophage mediated angiogenic processes.

    Science.gov (United States)

    Hood, Joshua L

    2016-09-01

    Angiogenesis is a key process in the preparation of lymph nodes for melanoma metastasis. Granulocyte macrophage colony stimulating factor (GM-CSF) induces hypoxia inducible factor 1 alpha (HIF-1α) in M1 or HIF-2α in M2 polarized macrophages. HIF-1α promotes neoangiogenesis while HIF-2α facilitates morphogenic normalization of neovasculature. Melanoma exosomes induce GM-CSF expression by endothelial cells in vitro and HIF-1α expression in pre-metastatic lymph nodes in vivo. This suggest a relationship between melanoma exosome induced endothelial GM-CSF and macrophage mediated angiogenesis in lymph nodes. Theoretically, induction of endothelial cell derived GM-CSF by melanoma exosomes mediates different angiogenic functions in pre-metastatic lymph nodes depending on subcapsular sinus (SCS) macrophage polarity. To explore this hypothesis, experiments utilizing melanoma exosomes in a lymph node model are outlined. Despite their opposing immune functions, indirect melanoma exosome stimulation of M1 or M2 SCS macrophages via endothelial derived GM-CSF in lymph nodes may induce different although complementary pro-tumor angiogenic processes. PMID:27515216

  5. Long-term results of PRRT in advanced bronchopulmonary carcinoid

    International Nuclear Information System (INIS)

    Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols (90Y-DOTATOC vs. 177Lu-DOTATATE vs. 90Y-DOTATOC + 177Lu-DOTATATE) were compared with regard to their efficacy and tolerability. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The 177Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The 90Y-DOTATOC + 177Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with 90Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. In a large cohort of patients with advanced BPC treated in a ''real-world'' scenario and followed up for a median of 45.1 months (range 2 - 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the

  6. Long-term results of PRRT in advanced bronchopulmonary carcinoid

    Energy Technology Data Exchange (ETDEWEB)

    Mariniello, Annapaola; Bodei, Lisa; Baio, Silvia Melania; Gilardi, Laura; Colandrea, Marzia; Papi, Stefano; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Tinelli, Carmine [IRCCS Foundation Policlinico San Matteo, Epidemiology and Biometric Unit, Pavia (Italy); Valmadre, Giuseppe [Presidio Ospedaliero E. Morelli AOVV, Sondalo (Italy); Fazio, Nicola [European Institute of Oncology, Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, Milan (Italy); Galetta, Domenico [European Institute of Oncology, Thoracic Surgery Division, Milan (Italy); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy)

    2016-03-15

    Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ({sup 90}Y-DOTATOC vs. {sup 177}Lu-DOTATATE vs. {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE) were compared with regard to their efficacy and tolerability. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The {sup 177}Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with {sup 90}Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. In a large cohort of patients with advanced BPC treated in a ''real-world'' scenario and followed up for a median of 45.1 months (range 2 - 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite

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

    Directory of Open Access Journals (Sweden)

    A. V. Ignatova

    2016-01-01

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

  8. Melanoma - neck (image)

    Science.gov (United States)

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

  9. 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.

  10. Treatment Option Overview (Melanoma)

    Science.gov (United States)

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

  11. General Information about Melanoma

    Science.gov (United States)

    ... Screening Research Melanoma Treatment (PDQ®)–Patient Version General Information About Melanoma Go to Health Professional Version Key ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  12. Advanced nuclear power options: The driving forces and their results

    International Nuclear Information System (INIS)

    Successful nuclear power plant concepts must simultaneously demonstrate satisfactory performance in terms of both safety and economics. In order to be attractive to both electric utility companies and the public, such plants must produce economical electric energy consistent with a level of safety which is acceptable to both the public and the plant owner. Programs for reactor development worldwide can be classified according to whether the reactor concept pursues improved safety or improved economic performance as the primary objective. When improved safety is the primary goal, safety enters the solution of the design problem as a constraint which restricts the set of allowed solutions. Conversely, when improved economic performance is the primary goal it is allowed to be pursued only to an extent which is compatible with stringent safety requirements. The three major reactor coolants under consideration for future advanced reactor use are water, helium and sodium. Reactor development programs focused upon safety and upon economics using each coolant are being pursued worldwide. It is seen that the safety-oriented concepts are typically of lower capacity by approximately an order of magnitude, than the economics-oriented concepts. This is the result, in the former concept, of using less efficient, but more reliable, means of accomplishing essential safety functions. (author)

  13. TMT DMs final design and advanced prototyping results at Cilas

    Science.gov (United States)

    Sinquin, Jean-Christophe; Bastard, Arnaud; Boyer, Corinne; Cornette, Sébastien; Cousty, Raphaël.; Ellerbroek, Brent; Gilbert, Xavier; Gourdet, Benoit; Grasser, Régis; Groeninck, Denis; Guillemard, Claude; Herriot, Glen; Iannacone, Albert; Jeulin, Antoine; Moreau, Aurélien; Pagès, Hubert; Wang, Lianqi

    2012-07-01

    In order to prepare for the construction phase of the two Deformable Mirrors (DMs), which will be used in the Thirty Meter Telescope (TMT) first light Adaptive Optics (AO) system, Cilas has advanced the design of these two large size piezo DMs and has manufactured and tested a scaled demonstration prototype. The work done allowed significant reduction of the risks related to the demanding specifications of the TMT DMs; the main issues were: (i) Large pupil (up to 370 mm) and high order (up to 74x74); (ii) Relatively low operational temperature (DMs working at -30°C) (iii) New piezo material. It is important to develop such a prototype to take into account these three specifications all together (dimension, low temperature and new piezo material). The new prototype is a 6x60 actuators and has the same characteristics as the future TMT DMs. In this paper, we give the conclusions of the work through the presentation of the following items: (i) Design and finite element analysis of the two DMs and prototype; (ii) Test results obtained with the prototype with validation of the finite element analysis and compliance with the TMT AO specifications; (iii) Special focus on thermal behavior, actuator reliability and shape at rest stability.

  14. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    OpenAIRE

    Odashiro, Macanori; Hans Filho, Gunter; Pereira, Patricia Rusa; Castro, Ana Rita Coimbra Motta; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHO...

  15. Cytotoxic T lymphocyte responses against melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Schwartz Erich J

    2011-07-01

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

  16. Melanoma vaccines: trials and tribulations

    Directory of Open Access Journals (Sweden)

    Dillman RO

    2013-10-01

    Full Text Available Robert O Dillman1,21Hoag Cancer Institute and Hoag Institute for Research and Education, Newport Beach, CA, USA; 2University of California Irvine, Irvine, CA, USAAbstract: Metastatic melanoma has been a target of immunotherapy for more than 4 decades. Three immunotherapeutics have received regulatory approval for treating melanoma: interferon-alpha, interleukin-2, and ipilimumab. The antitumor mechanisms of these products depend on enhancing existing immune responses, including autoimmune effects. The combination of autologous, cytotoxic T-lymphocytes plus high-dose interleukin-2 is a promising patient-specific therapy, but has limited clinical application. Other approaches include vaccines targeting melanoma-associated antigens, and patient-specific vaccines that utilize autologous tumor. Non-patient-specific vaccine approaches target melanocyte differentiation antigens (eg, tyrosinase, Melan-A, gp100, antigens identified by cytotoxic T-lymphocytes (eg, NY-Eso-1, Melan-A/Mart-1, Mage-3, and antigens originally identified by murine monoclonal antibodies (gangliosides, gp97, gp225. Self-renewing cells in tumor cell lines may represent tumor stem cells, but vaccines derived from allogeneic tumor cell lines have yielded disappointing results in randomized trials. Patient-specific vaccines can be derived from bulk autologous tumor or autologous tumor cell lines, and intratumoral injections of immunostimulatory fusion products have shown promise. While technically more complex to manufacture, patient-specific vaccines derived from autologous tumor cell lines have the potential to target tumor stem cells and overcome interpatient tumor cell heterogeneity. This article reviews sources of melanoma-associated antigens, costimulatory agents, and clinical trial results for various melanoma vaccines. Comparing Phase II trials is difficult because of the wide range of vaccine strategies and the differences in study patient populations; therefore, randomized

  17. Malignant melanoma - cutaneous metastases

    OpenAIRE

    Padmavathy L; Rao L; Ethirajan N; Swamy B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  18. 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...

  19. 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.

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

    International Nuclear Information System (INIS)

    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(188Re)-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 188Re-6D2 antibody, saline, unlabeled 6D2 antibody or 188Re-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

  1. Vaccine Therapy in Treating Patients With Stage IIC-IV Melanoma

    Science.gov (United States)

    2014-05-20

    Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Iris Melanoma; Metastatic Intraocular Melanoma; Mucosal Melanoma; Recurrent Intraocular Melanoma; Recurrent Melanoma; Stage IIC Melanoma; Stage IIIA Intraocular Melanoma; Stage IIIA Melanoma; Stage IIIB Intraocular Melanoma; Stage IIIB Melanoma; Stage IIIC Intraocular Melanoma; Stage IIIC Melanoma; Stage IV Intraocular Melanoma; Stage IV Melanoma

  2. A rare case of rynopharyngeal melanoma

    Directory of Open Access Journals (Sweden)

    Francesco Grecchi

    2012-01-01

    Full Text Available Primary mucosal melanomas (MM of the head and neck region constitute 0.5-2% of all malignant melanomas. The rynopharynx is a region that is less often involved by malignant melanomas. Because most of mucosal melanotic lesions are painless in their early stages, the diagnosis is unfortunately often delayed until symptoms resulting from ulceration, growth, and/or bleeding are noted. Here, we document the rare case of a malignant rynopharynx melanoma of a 43 year old woman. Its treatment and the pertinent literature are discussed. No complication was recorded in the post-operative period and no further surgery was performed. The follow up showed no recurrence in the same position and with the same characteristics, even after six years. Mucosal melanomas are aggressive tumours and the prognosis in these patients is poor. Clinicians must use treatment strategies that provide functional benefit, so as to maintain quality of life without excessive toxicity.

  3. TERT promoter mutations in melanoma survival.

    Science.gov (United States)

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

    2016-07-01

    Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. PMID:26875008

  4. Experimental boron neutron capture therapy for melanoma: Systemic delivery of boron to melanotic and amelanotic melanoma

    International Nuclear Information System (INIS)

    The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. The authors have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of the observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma

  5. Results of Laboratory Testing of Advanced Power Strips

    Energy Technology Data Exchange (ETDEWEB)

    Earle, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Sparn, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2012-08-01

    Presented at the ACEEE Summer Study on Energy Efficiency in Buildings on August 12-17, 2012, this presentation reports on laboratory tests of 20 currently available advanced power strip products, which reduce wasteful electricity use of miscellaneous electric loads in buildings.

  6. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J; Damsgaard, Tine E; Møller, Holger J; Bastholt, Lars; Nørgaard, Peter H; Steiniche, Torben

    2014-01-01

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

  7. Melanin content in melanoma metastases affects the outcome of radiotherapy

    Science.gov (United States)

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

    2016-01-01

    Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma. PMID:26910282

  8. Melanin content in melanoma metastases affects the outcome of radiotherapy.

    Science.gov (United States)

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

    2016-04-01

    Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma. PMID:26910282

  9. Combining immunotherapy with oncogene-targeted therapy: a new road for melanoma treatment

    Directory of Open Access Journals (Sweden)

    Mariana eAris

    2015-02-01

    Full Text Available Cutaneous melanoma arises from the malignant transformation of skin melanocytes; its incidence and mortality have been increasing steadily over the last fifty-years, now representing 3% of total tumors. Once melanoma metastasizes, prognosis is somber and therapeutic options are limited. However, the discovery of prevalent BRAF mutations in at least 50% of melanoma tumors led to development of BRAF inhibitors, and other drugs targeting the MAPK pathway including MEK inhibitors, are changing this reality. These recently approved treatments for metastatic melanoma have made a significant impact on patient survival; though the results are shadowed by the appearance of drug-resistance. Combination therapies provide a rational strategy to potentiate efficacy and potentially overcome resistance. Undoubtedly, the last decade has also born an renaissance of immunotherapy, and encouraging advances in metastatic melanoma treatment are illuminating the road. Immune checkpoint blockades, such as CTLA-4 antagonist-antibodies, and multiple cancer vaccines are now invaluable arms of anti-tumor therapy. Recent work has brought to light the delicate relationship between tumor biology and the immune system. Host immunity contributes to the antitumor activity of oncogene-targeted inhibitors within a complex network of cytokines and chemokines. Therefore, combining immunotherapy with oncogene-targeted drugs may be the key to melanoma control. Here we review ongoing clinical studies of combination therapies using both oncogene inhibitors and immunotherapeutic strategies in melanoma patients. We will revisit the preclinical evidence that tested sequential and concurrent schemes in suitable animal models and formed the basis for the current trials. Finally, we will discuss potential future directions of the field.

  10. Mentoring Faculty: Results from National Science Foundation's ADVANCE Program

    Science.gov (United States)

    Holmes, M. A.

    2015-12-01

    Faculty mentoring programs are common components of National Science Foundation ADVANCE awards. The ADVANCE program aims to increase the number of women on the faculty in science, technology, engineering and mathematics (STEM) departments through grants to individuals and to entire institutions. These grants target a change in institutional culture so that faculty from non-majority groups will succeed and thrive. Mentoring programs are generally designed to fit the particular institution(s) or target population (e.g., meteorologists at the beginning of their careers). A successful mentoring program makes the implicit knowledge necessary for faculty success explicit: policies and practices are made transparent; routes for finding answers are clarified or generated with faculty input; faculty overcome a sense of isolation and develop a community. Mentoring programs may be formal, with assigned mentors and mentees, or informal, with opportunities for beginning, middle and advanced career STEM faculty to mingle, generally over food and sometimes with a formal speaker. The programs are formally evaluated; in general, attention to mentoring generates better outcomes for all faculty. Research indicates that most successful scientists have a network of mentors rather than relying on one person to help navigate department, institution, and profession. The University of Nebraska-Lincoln's (UNL) award, ADVANCE-Nebraska, offered opportunities for faculty to informally network over luncheons with women speakers, advanced in their careers. We also offered after-hours networking receptions. In response to faculty feedback, we shifted to a series of panel discussions entitled "Conversations". Most panels were conducted by successful UNL faculty; about one-third had an outside expert on a given topic. Topics were chosen based on faculty feedback and targeted specifically to beginning faculty (How to Start Up a Lab; How to Balance Teaching and Writing), mid-career faculty (Putting

  11. Implications of age and conditional survival estimates for patients with melanoma

    Science.gov (United States)

    Banerjee, Mousumi; Lao, Christopher D.; Wancata, Lauren M.; Muenz, Daniel G.; Haymart, Megan R.; Wong, Sandra L.

    2016-01-01

    Objective Overall cancer incidence is decreasing while melanoma cases increase. Conditional survival estimates offer a more accurate prognosis for patients as they survive past diagnosis. It is unknown the effect age and stage has on a melanoma patient’s conditional survival estimate. Methods Surveillance, Epidemiology, End Results (SEER) data was utilized, identifying new diagnosis cutaneous melanoma patients (N=95,041), from 1998–2005, with up to 12 year follow up. Estimates of disease-specific survival by stage and age were determined by Cox regression and transformed to estimate conditional five-year survival. Results Localized melanoma patients have an excellent five-year survival at diagnosis and subsequent years. For patients with localized and regional disease, an age effect is present for disease-specific mortality when comparing older patients (70–79 years) to younger patients (hazard ratio (HR) for mortality 3.79 (95% confidence interval (CI) 3.01–4.84) and HR 2.36 (95% CI 1.93–2.91), respectively. No age effect difference is observed in disease-specific survival for advanced disease: HR 1.14 (95% CI 0.87–1.53). Over time conditional survival estimates improve for older patients with localized and regional disease. This improvement is not seen in distant disease nor is the age gradient. Conclusions Disease-specific mortality and conditional survival for patients with localized and regional melanoma is initially impacted by older age with effects dissipating over time. Age does not affect survival in patients with advanced disease. Understanding the conditional five-year disease-specific survival of melanoma based on age and stage can help patients and physicians, informing decision making about treatment and surveillance. PMID:26479218

  12. Advanced Rooftop Control (ARC) Retrofit: Field-Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Weimin; Katipamula, Srinivas; Ngo, Hung; Underhill, Ronald M.; Taasevigen, Danny J.; Lutes, Robert G.

    2013-07-31

    The multi-year research study was initiated to find solutions to improve packaged equipment operating efficiency in the field. Pacific Northwest National Laboratory (PNNL), with funding from the U.S. Department of Energy’s (DOE’s) Building Technologies Office (BTO) and Bonneville Power Administration (BPA) conducted this research, development and demonstration (RD&D) study. Packaged equipment with constant speed supply fans is designed to provide ventilation at the design rate at all times when the fan is operating as required by building code. Although there are a number of hours during the day when a building may not be fully occupied or the need for ventilation is lower than designed, the ventilation rate cannot be adjusted easily with a constant speed fan. Therefore, modulating the supply fan in conjunction with demand controlled ventilation (DCV) will not only reduce the coil energy but also reduce the fan energy. The objective of this multi-year research, development and demonstration project was to determine the magnitude of energy savings achievable by retrofitting existing packaged rooftop air conditioners with advanced control strategies not ordinarily used for packaged units. First, through detailed simulation analysis, it was shown that significant energy (between 24% and 35%) and cost savings (38%) from fan, cooling and heating energy consumption could be realized when packaged air conditioning units with gas furnaces are retrofitted with advanced control packages (combining multi-speed fan control, integrated economizer controls and DCV). The simulation analysis also showed significant savings for heat pumps (between 20% and 60%). The simulation analysis was followed by an extensive field test of a retrofittable advanced rooftop unit (RTU) controller.

  13. Resistance to combination BRAF and MEK inhibition in metastatic melanoma: Where to next?

    Science.gov (United States)

    Welsh, Sarah J; Rizos, Helen; Scolyer, Richard A; Long, Georgina V

    2016-07-01

    Treatment of BRAF-mutant metastatic melanoma with mitogen-activated protein kinase (MAPK) pathway targeted therapies (BRAF/MEK inhibitors) and immune checkpoint inhibitors has revolutionised management and improved outcomes for patients with advanced stage disease. However, acquired resistance to MAPK inhibitor therapy develops in the majority of patients at approximately 12 months and multiple mechanisms lead to resistance. Understanding the mechanisms of resistance is therefore critical for the development of more effective therapeutic strategies in BRAF-mutant melanoma. Recently, several distinct mechanisms of resistance to BRAF-inhibition have been proposed based on data obtained in experimental melanoma cell models and small series of human tumour samples. These include reactivation of the MAPK pathway resulting in continued extracellular signal-regulated kinase activation and activation of parallel signalling pathways including the PI3K-mTOR (phosphoinositide 3-kinase-mammalian target of rapamycin) pathway. Alterations in how the cells of the immune system respond to melanoma cells treated with targeted therapy may also influence response and progression. In this review, we discuss these mechanisms and identify potential therapeutic strategies to overcome resistance which, in turn, will lead to improved outcomes for patients with metastatic melanoma. PMID:27232329

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

    Directory of Open Access Journals (Sweden)

    Nunes, Ana Teresa

    2012-07-01

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

  15. BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.

    Science.gov (United States)

    Paoluzzi, Luca; Hanniford, Douglas; Sokolova, Elena; Osman, Iman; Darvishian, Farbod; Wang, Jinhua; Bradner, James E; Hernando, Eva

    2016-06-01

    Despite major advances in the treatment of metastatic melanoma, treatment failure is still inevitable in most cases. Manipulation of key epigenetic regulators, including inhibition of Bromodomain and extra-terminal domain (BET) family members impairs cell proliferation in vitro and tumor growth in vivo in different cancers, including melanoma. Here, we investigated the effect of combining the BET inhibitor JQ1 with the BRAF inhibitor Vemurafenib in in vitro and in vivo models of BRAF-mutant melanoma. We performed cytotoxicity and apoptosis assays, and a xenograft mouse model to determine the in vitro and in vivo efficacy of JQ1 in combination with Vemurafenib against BRAF-mutant melanoma cell lines. Further, to investigate the molecular mechanisms underlying the effects of combined treatment, we conducted antibody arrays of in vitro drug-treated cell lines and RNA sequencing of drug-treated xenograft tumors. The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with upregulation of proapoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Collectively, our data provide a rationale for combined BET and BRAF inhibition as a novel strategy for the treatment of melanoma. PMID:27169980

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

    Directory of Open Access Journals (Sweden)

    Banzi M

    2016-05-01

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

  17. Free-electron laser results from the Advanced Test Accelerator

    International Nuclear Information System (INIS)

    PALADIN is a 10.6-μm FEL amplifier experiment operating at the Lawrence Livermore National Laboratory's Advanced Test Accelerator, an induction linear accelerator designed to produce a 45-MeV, 10-kA electron beam. With a 15-m long wiggler, PALADIN demonstrated 27 dB of exponential gain from a 14-kW input signal. With a 5-MW input signal, the amplifier saturated after 10 dB of gain. The exponentially growing signal in the unsaturated amplifier was clearly seen to be gain guided by the electron beam. 7 refs., 8 figs

  18. The Impact on Morbidity and Length of Stay of Early Versus Delayed Complete Lymphadenectomy in Melanoma : Results of the Multicenter Selective Lymphadenectomy Trial (I)

    NARCIS (Netherlands)

    Faries, Mark B.; Thompson, John F.; Cochran, Alistair; Elashoff, Robert; Glass, Edwin C.; Mozzillo, Nicola; Nieweg, Omgo E.; Roses, Daniel F.; Hoekstra, Harold J.; Karakousis, Constantine P.; Reintgen, Douglas S.; Coventry, Brendon J.; Wang, He-Jing; Morton, Donald L.

    2010-01-01

    Complete lymph node dissection, the current standard treatment for nodal metastasis in melanoma, carries the risk of significant morbidity. Clinically apparent nodal tumor is likely to impact both preoperative lymphatic function and extent of soft tissue dissection required to clear the basin. We hy

  19. CDC Vital Signs: Preventing Melanoma

    Science.gov (United States)

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

  20. Implications of age and conditional survival estimates for patients with melanoma.

    Science.gov (United States)

    Banerjee, Mousumi; Lao, Christopher D; Wancata, Lauren M; Muenz, Daniel G; Haymart, Megan R; Wong, Sandra L

    2016-02-01

    Overall cancer incidence is decreasing, whereas melanoma cases are increasing. Conditional survival estimates offer a more accurate prognosis for patients the farther they are from time of diagnosis. The effect of age and stage on a melanoma patient's conditional survival estimate is unknown. Surveillance, Epidemiology, and End Results data were utilized to identify newly diagnosed cutaneous melanoma patients (N=95 041), from 1998 to 2005, with up to 12 years of follow-up. Estimates of disease-specific survival by stage and age were determined by Cox regression analysis and transformed to estimated conditional 5-year survival. Localized melanoma patients have an excellent 5-year survival at diagnosis and over subsequent years. For patients with localized and regional disease, an age effect is present for disease-specific mortality when comparing older patients (70-79 years) with younger patients (hazard ratio (HR) for mortality 3.79 [95% confidence interval (CI) 3.01-4.84] and HR 2.36 (95% CI 1.93-2.91), respectively. No age effect difference is observed in disease-specific survival for advanced disease: HR 1.14 (95% CI 0.87-1.53). Over time, conditional survival estimates improve for older patients with localized and regional disease. This improvement is not seen in distant disease, neither is the age gradient. Disease-specific mortality and conditional survival for patients with localized and regional melanomas are initially impacted by older age, with effects dissipating over time. Age does not affect survival in patients with advanced disease. Understanding the conditional 5-year disease-specific survival of melanoma based on age and stage can help patients and physicians, informing decision-making about treatment and surveillance. PMID:26479218

  1. Treatment results in case of advanced tonsillar tumors

    International Nuclear Information System (INIS)

    The authors present 99 patients irradiated for a tonsillar carcinoma. 41 patients were primarily irradiated and 52 patients postoperatively. Radiotherapy was combined with cytostatic chemotherapy in six cases. Most of the cases treated were advanced tumors: 76 patients with T3/T4 tumors. 52% out of the 23 patients with T1/T2 tumors survived five years and 45% ten years; only 26% of the patients with T3 tumors and 15% of those with T4 tumors survived five years. The prognosis was significantly influenced by the lymph node state: whereas 75% of the patients with N0 tumors survived five years, this rate is reduced to 21% in case of lymph node state N3. 22 out of the 34 recurrences were situated in the tumor region, 12 in lymph nodes. 94% of recurrences became evident during the first two years after the end of treatment. (orig.)

  2. Late results of chemotherapy of the advanced ovarian cancer

    International Nuclear Information System (INIS)

    Out of 108 patients with advanced ovarian cancer treated by postoperative combined chemotherapy with cisplatin, 13% survived 5 years, 11% with NED and 1.8% with signs of the disease. 67.6% patients responded to treatment in 33.3% of them it was CR and in 34.3% - PR. There was a close relationship between the type of response and survival, as 2 years survived 63.8% patients with CR, 31.4% with PR and only 5.4% of non-responders. Ten out of 36 patients with CR survived 5 years with NED, but out of 4 patients with PR 2 patients survived without symptoms and 2 with signs of the disease. During further follow-up in 4 out of 12 patients who survived 5 years with NED progression of cancer was diagnosed. (author)

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

    Directory of Open Access Journals (Sweden)

    Kowichi Jimbow

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Imam Ayesha

    2011-02-01

    Full Text Available Abstract Background Melanomas within the alimentary tract are usually metastatic in origin. On the other hand, primary melanomas of the gastrointestinal tract are relatively uncommon. There are several published reports of melanomas occurring in the esophagus, stomach, small bowel, and anorectum. The occurrence of primary melanoma of the colon has, however, only been rarely reported. The optimum modus operandi for the management of primary colonic melanoma remains nebulous due to the limited number of reports in literature. Methods A comprehensive search of Medline, Cochrane and Highwire was performed using the following keywords: 'melanoma', 'malignant melanoma', 'primary melanoma', 'colon', 'gastrointestinal tract', 'alimentary tract', 'digestive tract', and 'large bowel'. All patients with primary melanoma localized to the colon were included in the review. Patients with metastatic melanomas to the gastrointestinal (GI tract and primary melanomas localized to the GI tract in anatomic locations other than colon were excluded. Results There have been only 12 reported cases of primary melanoma of the colon to date. The average age of patients on presentation was 60.4 years without any significant gender predilection. Right colon (33% and cecum (33% were the most common sites for the occurrence of primary colonic melanoma while abdominal pain (58% and weight loss (50% were the most common presenting complaints. Colonoscopy is the most reliable diagnostic investigation and offers the additional advantage of obtaining tissue for diagnosis. S-100 and HMB-45 are highly sensitive and specific for the diagnosis of this malignancy. For primary colonic melanomas that have not metastasized to any distant parts of the body, surgical resection with wide margins appears to be the treatment of choice. Although the management was individualized in every case, most of the authors preferred traditional hemicolectomy as the favored surgical approach

  5. Decoding Melanoma Metastasis

    International Nuclear Information System (INIS)

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

  6. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review...... summarizes the most recent epidemiological findings regarding the incidence of cutaneous malignant melanoma, mortality, Breslow thickness and clinical stage. Studies published between 2005 and 2010 with more than 2,000 test subjects were included in this review. These studies all report an increase in...... incidence of melanoma during the last few decades, with by far the highest increase in tumours at a very early stage (T1 or IA). Little or no change was seen in mortality. However, increases in both mortality and incidence of thick melanomas were found in the oldest subgroups, especially in men. These...

  7. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-12-30

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

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

    Science.gov (United States)

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

    2016-03-01

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

  9. Pembrolizumab for Ipilimumab-Resistant Melanoma

    Science.gov (United States)

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

  10. Results of preoperative concurrent chemoradiotherapy for locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sang Gyu; Kim, Su Ssan; Bae, Hoon Sik [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2007-03-15

    We performed a retrospective non-randomized clinical study of locally advanced rectal cancer, to evaluate the anal sphincter preservation rates, down staging rates and survival rates of preoperative chemoradiotherapy. From January 2002 to December 2005, patients with pathologically confirmed rectal cancer with clinical stage T2 or higher, or patients with lymph node metastasis were enrolled in this study. A preoperative staging work-up was conducted in 36 patients. All patients were treated with preoperative chemoradiotherapy, and curative resection was performed for 26 patients at Hallym University Sacred Heart Hospital. Radiotherapy treatment planning was conducted with the use of planning CT for all patients. A total dose of 45.0 {approx} 52.2 Gy conventionally fractionated three-dimensional radiotherapy was delivered to the whole pelvis. Chemotherapy was given at the first and fifth week of radiation therapy with continuous infusion i.v. 5-FU (Fluorouracil) and LV (Leucovorine). Surgical resection was performed 2 to 4 weeks after the completion of the chemoradiotherapy regimen. The complete resection rate with negative resection margin was 100% (26/26). However, a pathologically complete response was not seen after curative resection. Surgery was done by LAR (low anterior resection) in 23 patients and APR (abdomino-perineal resection) in 3 patients. The sphincter preservation rate was 88.5% (23/26), down staging of the tumor occurred in 12 patients (46.2%) and down-sizing of the tumor occurred in 19 patients (73%). Local recurrence after surgical resection developed in 1 patient, and distant metastasis developed in 3 patients. The local recurrence free survival rate, distant metastasis free survival rate, and progression free survival rate were 96.7%, 87% and 83.1%, respectively. Treatment related toxicity was minimal except for one grade 3, one grade 4 anemia, one grade 3 leukopenia, and one grade 3 ileus. Preoperative concurrent chemoradiotherapy for locally

  11. Malignant melanoma - cutaneous metastases

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2008-01-01

    Full Text Available Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra. Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  12. Malignant melanoma - cutaneous metastases.

    Science.gov (United States)

    L, Padmavathy; L, Lakshmana Rao; N, Ethirajan; B, Krishna Swamy

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  13. Mitochondrial Respiration - An Important Therapeutic Target in Melanoma

    Science.gov (United States)

    Barbi de Moura, Michelle; Vincent, Garret; Fayewicz, Shelley L.; Bateman, Nicholas W.; Hood, Brian L.; Sun, Mai; Suhan, Joseph; Duensing, Stefan; Yin, Yan; Sander, Cindy; Kirkwood, John M.; Becker, Dorothea; Conrads, Thomas P.; Van Houten, Bennett; Moschos, Stergios J.

    2012-01-01

    The importance of mitochondria as oxygen sensors as well as producers of ATP and reactive oxygen species (ROS) has recently become a focal point of cancer research. However, in the case of melanoma, little information is available to what extent cellular bioenergetics processes contribute to the progression of the disease and related to it, whether oxidative phosphorylation (OXPHOS) has a prominent role in advanced melanoma. In this study we demonstrate that compared to melanocytes, metastatic melanoma cells have elevated levels of OXPHOS. Furthermore, treating metastatic melanoma cells with the drug, Elesclomol, which induces cancer cell apoptosis through oxidative stress, we document by way of stable isotope labeling with amino acids in cell culture (SILAC) that proteins participating in OXPHOS are downregulated. We also provide evidence that melanoma cells with high levels of glycolysis are more resistant to Elesclomol. We further show that Elesclomol upregulates hypoxia inducible factor 1-α (HIF-1α), and that prolonged exposure of melanoma cells to this drug leads to selection of melanoma cells with high levels of glycolysis. Taken together, our findings suggest that molecular targeting of OXPHOS may have efficacy for advanced melanoma. PMID:22912665

  14. Mitochondrial respiration--an important therapeutic target in melanoma.

    Directory of Open Access Journals (Sweden)

    Michelle Barbi de Moura

    Full Text Available The importance of mitochondria as oxygen sensors as well as producers of ATP and reactive oxygen species (ROS has recently become a focal point of cancer research. However, in the case of melanoma, little information is available to what extent cellular bioenergetics processes contribute to the progression of the disease and related to it, whether oxidative phosphorylation (OXPHOS has a prominent role in advanced melanoma. In this study we demonstrate that compared to melanocytes, metastatic melanoma cells have elevated levels of OXPHOS. Furthermore, treating metastatic melanoma cells with the drug, Elesclomol, which induces cancer cell apoptosis through oxidative stress, we document by way of stable isotope labeling with amino acids in cell culture (SILAC that proteins participating in OXPHOS are downregulated. We also provide evidence that melanoma cells with high levels of glycolysis are more resistant to Elesclomol. We further show that Elesclomol upregulates hypoxia inducible factor 1-α (HIF-1α, and that prolonged exposure of melanoma cells to this drug leads to selection of melanoma cells with high levels of glycolysis. Taken together, our findings suggest that molecular targeting of OXPHOS may have efficacy for advanced melanoma.

  15. [Endocrine factors influencing melanoma progression].

    Science.gov (United States)

    Dobos, Judit

    2009-03-01

    According to recent findings that beside cancers traditionally considered as hormone-dependent, several other tumor types show different behavior in the two sexes, indicating the possible role of endocrine factors in the course of these diseases. The possibility that endocrine factors may influence the clinical course of human malignant melanoma is suggested by the higher survival rate in premenopausal vs. postmenopausal women or men of any ages. However, investigations on the sex hormone receptor status of human cutaneous melanomas and experiments attempting to support the epidemiological results yielded conflicting results. In our human melanoma cell lines we failed to detect steroid receptors at protein level, while quantitative PCR demonstrated that their mRNA expression level was orders of magnitude lower compared to the positive control cell lines. Sex hormones did not influence the in vitro features of the human melanoma cells considerably. On the other hand, glucocorticoid receptor was present both at mRNA and protein level, although dexamethasone was effective in vitro only at high doses. Our previous experiments showed that intrasplenic injection of human melanoma cells resulted in a significantly higher number of liver colonies in male than in female SCID mice. We now show that this difference evolves during the first day. After injection into the tail vein we did not observe gender-dependent difference in the efficiency of pulmonary colonization. Examining the pattern of metastasis formation after intracardiac injection, we have found differences between the two sexes in the incidence or number of colonies only in the case of the liver but not in other organs. We concluded that the observed phenomenon is specific to the liver; therefore we investigated the effects of 2-methoxyestradiol, an endogenous metabolite of estradiol produced mainly in the liver, with an estrogen receptor-independent antitumor activity. 2ME2 effectively inhibited melanoma cell

  16. Advanced Meteor radar at Tirupati: System details and first results

    Science.gov (United States)

    Sunkara, Eswaraiah; Gurubaran, Subramanian; Sundararaman, Sathishkumar; Venkat Ratnam, Madineni; Karanam, Kishore Kumar; Eethamakula, Kosalendra; Vijaya Bhaskara Rao, S.

    An advanced meteor radar viz., Enhanced Meteor Detection Radar (EMDR) operating at 35.25 MHz is installed at Sri Venkateswara University (SVU), Tirupati (13.63oN, 79.4oE), India, in the month of August 2013. Present communication describes the need for the meteor radar at present location, system description, its measurement techniques, its variables and comparison of measured mean winds with contemporary radars over the Indian region. The present radar site is selected to fill the blind region of Gadanki (13.5oN, 79.2oE) MST radar, which covers mesosphere and lower thermosphere (MLT) region (70-110 km). By modifying the receiving antenna structure and elements, this radar is capable of providing accurate wind information between 70 and 110 km unlike other similar radars. Height covering region is extended by increasing the meteor counting capacity by modifying the receiving antenna structure and elements and hence its wind estimation limits extended below and above of 80 and 100 km, respectively. In the present study, we also made comparison of horizontal winds in the MLT region with those measured by similar and different (MST and MF radars) techniques over the Indian region including the model (HWM 07) data sets. The comparison showed a very good agreement between the overlapping altitudes (82-98 km) of different radars. Zonal winds compared very well as that of meridional winds. The observed discrepancies and limitations in the wind measurement are discussed. This new radar is expected to play important role in understanding the vertical and lateral coupling by forming a unique local network.

  17. Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP-targeted delivery of soluble TRAIL potently inhibits melanoma outgrowth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    van Waarde Aren

    2010-11-01

    Full Text Available Abstract Background Advanced melanoma is characterized by a pronounced resistance to therapy leading to a limited patient survival of ~6 - 9 months. Here, we report on a novel bifunctional therapeutic fusion protein, designated anti-MCSP:TRAIL, that is comprised of a melanoma-associated chondroitin sulfate proteoglycan (MCSP-specific antibody fragment (scFv fused to soluble human TRAIL. MCSP is a well-established target for melanoma immunotherapy and has recently been shown to provide important tumorigenic signals to melanoma cells. TRAIL is a highly promising tumoricidal cytokine with no or minimal toxicity towards normal cells. Anti-MCSP:TRAIL was designed to 1. selectively accrete at the cell surface of MCSP-positive melanoma cells and inhibit MCSP tumorigenic signaling and 2. activate apoptotic TRAIL-signaling. Results Treatment of a panel of MCSP-positive melanoma cell lines with anti-MCSP:TRAIL induced TRAIL-mediated apoptotic cell death within 16 h. Of note, treatment with anti-MCSP:sTRAIL was also characterized by a rapid dephosphorylation of key proteins, such as FAK, implicated in MCSP-mediated malignant behavior. Importantly, anti-MCSP:TRAIL treatment already inhibited anchorage-independent growth by 50% at low picomolar concentrations, whereas > 100 fold higher concentrations of non-targeted TRAIL failed to reduce colony formation. Daily i.v. treatment with a low dose of anti-MCSP:TRAIL (0.14 mg/kg resulted in a significant growth retardation of established A375 M xenografts. Anti-MCSP:TRAIL activity was further synergized by co-treatment with rimcazole, a σ-ligand currently in clinical trials for the treatment of various cancers. Conclusions Anti-MCSP:TRAIL has promising pre-clinical anti-melanoma activity that appears to result from combined inhibition of tumorigenic MCSP-signaling and concordant activation of TRAIL-apoptotic signaling. Anti-MCSP:TRAIL alone, or in combination with rimcazole, may be of potential value for the

  18. Mutational Heterogeneity in Melanoma: An Inconvenient Truth.

    Science.gov (United States)

    Chang, Gregory A; Polsky, David

    2015-12-01

    Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results. PMID:26569584

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

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2014-01-01

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

  20. Up scaling and test results of an advanced Fresnel greenhouse

    OpenAIRE

    Sonneveld, P.J.; Swinkels, G.L.A.M.; Tuijl, van, B.A.J.; Janssen, H.J.J.; Zwart, de, A.M.

    2012-01-01

    A greenhouse with Fresnel lenses in the south facing roof and a receiver for concentrated Photovoltaics with water cooling (CPVT system) will result in electrical and thermal energy output from the solar energy excess entering a greenhouse. The PV system converts about half of the direct radiation into heat and electricity. During periods with direct radiation this will significantly reduce the heat load on the greenhouse. For an optimal performance the roof elements must be asymmetric with a...

  1. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    incidence of melanoma during the last few decades, with by far the highest increase in tumours at a very early stage (T1 or IA). Little or no change was seen in mortality. However, increases in both mortality and incidence of thick melanomas were found in the oldest subgroups, especially in men. These...

  2. Planetary exploration and science recent results and advances

    CERN Document Server

    Jin, Shuanggen; Ip, Wing-Huen

    2014-01-01

    This contributed monograph is the first work to present the latest results and findings on the new topic and hot field of planetary exploration and sciences, e.g., lunar surface iron content and mare orientale basalts, Earth's gravity field, Martian radar exploration, crater recognition, ionosphere and astrobiology, Comet ionosphere, exoplanetary atmospheres and planet formation in binaries. By providing detailed theory and examples, this book helps readers to quickly familiarize themselves with the field. In addition, it offers a special section on next-generation planetary exploration, whic

  3. Advanced information processing system: Fault injection study and results

    Science.gov (United States)

    Burkhardt, Laura F.; Masotto, Thomas K.; Lala, Jaynarayan H.

    1992-01-01

    The objective of the AIPS program is to achieve a validated fault tolerant distributed computer system. The goals of the AIPS fault injection study were: (1) to present the fault injection study components addressing the AIPS validation objective; (2) to obtain feedback for fault removal from the design implementation; (3) to obtain statistical data regarding fault detection, isolation, and reconfiguration responses; and (4) to obtain data regarding the effects of faults on system performance. The parameters are described that must be varied to create a comprehensive set of fault injection tests, the subset of test cases selected, the test case measurements, and the test case execution. Both pin level hardware faults using a hardware fault injector and software injected memory mutations were used to test the system. An overview is provided of the hardware fault injector and the associated software used to carry out the experiments. Detailed specifications are given of fault and test results for the I/O Network and the AIPS Fault Tolerant Processor, respectively. The results are summarized and conclusions are given.

  4. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

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

  5. Comparative analysis of methods of preinvasive melanoma diagnostics

    OpenAIRE

    Kozlov S.V.; Neretin Е.У.

    2013-01-01

    The article discusses one of the problems of oncology — skin melanoma. The research objective is to study and to compare diagnostic methods of preinvasive melanoma including fluorescence diagnosis, dermatoscopy and microwave radiometry. Materials and Methods: The survey has used dermatoscope of Heine Delta 20 Company, the unit RTM-01-RES and the instrument of fluorescent diagnostics «Spectrum-Cluster.» The results suggest the possibility of early detection of melanoma with the use of dermatos...

  6. Autophagy- An emerging target for melanoma therapy.

    Science.gov (United States)

    Ndoye, Abibatou; Weeraratna, Ashani T

    2016-01-01

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

  7. New developments in the treatment of metastatic melanoma – role of dabrafenib–trametinib combination therapy

    Directory of Open Access Journals (Sweden)

    Luke JJ

    2014-06-01

    Full Text Available Jason J Luke, Patrick A Ott Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA Abstract: Development of selective inhibitors of BRAF has improved the survival of patients with BRAF-mutant melanoma. The progression-free survival after treatment with a BRAF inhibitor is modest, however, and BRAF inhibitors induce cutaneous toxicity, likely due to paradoxical activation of the mitogen-activated protein kinase pathway. Combining selective BRAF and MEK inhibition, such as the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, has been shown to improve the response rate and progression-free survival in patients with advanced melanoma while significantly alleviating the paradoxical activation of mitogen-activated protein kinase. This combination treatment results in a reduction in skin toxicity relative to that seen with a BRAF inhibitor alone; however, addition of the MEK inhibitor adds other toxicities, such as pyrexia and gastrointestinal or ocular toxicity. While combined BRAF–MEK inhibition appears primed to become a standard molecular approach for BRAF-mutant melanoma, the utility of the combination has to be considered in the rapidly changing landscape of immunotherapeutics, such as immune checkpoint blockade using anti-cytotoxic T lymphocyte antigen-4 and anti-programmed death-1/programmed death-L1 antibodies. Here we review the development of the dabrafenib plus trametinib combination, the characteristics of each drug and the combination, and the role of this combination in the management of patients with BRAF-mutant melanoma. Keywords: BRAF, dabrafenib, trametinib, melanoma

  8. Dacarbazine, a chemotherapeutic against metastatic melanoma and a reference drug for new treatment modalities

    Directory of Open Access Journals (Sweden)

    Kamila Koprowska

    2011-11-01

    Full Text Available Melanoma is a tumour derived from melanocytes, cells of neuroectodermal origin. Melanoma treatment represents a challenge to oncologists due to its aggressive course and early and multiple metastases. Surgical excision of lesions is a highly effective intervention, but only in early stages. In contrast, median survival of patients with metastatic melanoma is still below one year. In 2011 the FDA and EMA have approved new drugs, ipilimumab and vemurafenib, that might be a major breakthrough in treating patients with advanced melanoma. However, time is needed to conclude whether they replace dacarbazine, a drug used for over 30 years in the therapy of metastatic melanoma, even if the response rate was only 10–15�20The mechanism of dacarbazine action is not clear but it is probably based on methylation of purine bases in DNA. The low therapeutic efficacy of dacarbazine might be the consequence of rapid removal of DNA lesions by repair systems. A high melanoma chemoresistance is also driven by the extent and nature of alterations in signal transductions in tumour cells. None of the previously conducted trials proved superiority of any treatment modality over monotherapy with dacarbazine. Higher response rates did not correlate with survival benefit, and more intense adverse effects were frequently observed. There are some expectations for targeted therapy and immunotherapy, which have already demonstrated some efficacy in clinical studies. This review aims at providing the current knowledge on dacarbazine and its analogue, temozolomide, including the latest results of clinical studies combining these drugs with other treatment protocols.

  9. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie; Schirmacher, Peter; Mollenhauer, Jan; Kern, Michael André

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

  11. Oncogenic BRAF-Mediated Melanoma Cell Invasion

    Directory of Open Access Journals (Sweden)

    Hezhe Lu

    2016-05-01

    Full Text Available Melanoma patients with oncogenic BRAFV600E mutation have poor prognoses. While the role of BRAFV600E in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAFV600E melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM. Inhibition of BRAFV600E blocks melanoma cell invasion. In a BRAFV600E-driven murine melanoma model or in patients’ tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAFV600E inhibition. Mechanistically, BRAFV600E induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAFV600E in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.

  12. 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.

  13. Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma.

    Science.gov (United States)

    Albertini, Mark R; Ranheim, Erik A; Zuleger, Cindy L; Sondel, Paul M; Hank, Jacquelyn A; Bridges, Alan; Newton, Michael A; McFarland, Thomas; Collins, Jennifer; Clements, Erin; Henry, Mary Beth; Neuman, Heather B; Weber, Sharon; Whalen, Giles; Galili, Uri

    2016-08-01

    Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given 4 weeks apart (cohort I: 0.1 mg/injection; cohort II: 1.0 mg/injection; cohort III: 10 mg/injection). Monitoring included blood for clinical, autoimmune, and immunological analyses and core tumor biopsies. Treatment outcome was determined 8 weeks after the first α-gal glycolipid injection. Nine pts received two intratumoral injections of α-gal glycolipids (3 pts/cohort). Injection-site toxicity was mild, and no systemic toxicity or autoimmunity could be attributed to the therapy. Two pts had stable disease by RECIST lasting 8 and 7 months. Tumor nodule biopsies revealed minimal to no change in inflammatory infiltrate between pre- and post-treatment biopsies except for 1 pt (cohort III) with a post-treatment inflammatory infiltrate. Two and four weeks post-injection, treated nodules in 5 of 9 pts exhibited tumor cell necrosis without neutrophilic or lymphocytic inflammatory response. Non-treated tumor nodules in 2 of 4 evaluable pts also showed necrosis. Repeated intratumoral injections of α-gal glycolipids are well tolerated, and tumor necrosis was seen in some tumor nodule biopsies after tumor injection with α-gal glycolipids. PMID:27207605

  14. The clinical and dermoscopic features of extremity melanomas

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2015-03-01

    Full Text Available Objectives: Dermoscopy is a noninvasive tool that helps to differentiate structures which can not be seen by naked eye. Dermoscopic and clinical features of malignant melanomas on the extremities are not well described in the literature. Therefore, in this study we aim to determine dermoscopic and clinical characteristics of melanoma on the extremities. Materials and Methods: 40 patients with melanoma on the extremities were included in this study. Their dermoscopic and clinical images, histopathological and clinical data were assessed. The relations between Breslow thickness and dermoscopic characteristics were evaluated. Results: The most frequent localization for women was lower extremities, whereas it was upper extremities for men. The most common subtype of melanoma was superficial spreading melanoma on the extremities. The mean age of patients with extremity melanoma was 56,21 ± 15,20 in men, as well as the mean age of patients with extremity melanoma was 53,09 ± 13,96 in women. The most common dermoscopic feature for extremity melanoma was irregular dots (85%. There were positive correlations between Breslow thickness and diameter, 3 or more colors in lesion, blue-white veil and lineer white streaks, respectively (p< 0.005, r= +0.462 (p< 0.001, r= +0.550 (p< 0.001, r= +0.606 (p< 0.001, r= +0.662. Conclusions: To our knowledge, this is the first study investigating dermoscopic and clinical features in patients with extremity melanomas. We should suggest that melanomas on the lower extremities are more common in women than men and the patients with lower extremity melanomas were younger than the patients with upper extremity melanomas and there are associations between Breslow thickness and some dermoscopic characteristics.

  15. F-18 FDG PET in the initial evaluation of high risk melanoma

    International Nuclear Information System (INIS)

    Introduction. - Localized melanoma is a potentially aggressive tumor. Its prognosis depends mainly on pathologic factors, namely: thickness (Breslow index), presence of ulceration and microscopic nodal metastasis. FDG PET is the modality of choice for evaluation of advanced melanoma and has proven its superiority in terms of sensitivity, specificity and accuracy compared to conventional imaging. Early stages of melanoma do not seem to benefit from PET FDG. However the value of PET FDG in staging localized high risk melanoma is yet to be determined. Patients and methods. - We have evaluated 87 patients with high risk melanoma with PET FDG. 32 patients presented with a Breslow index superior or equal to 4 mm, 21 with a Breslow index inferior to 4 mm and ulceration and 34 with a positive sentinel lymphadenectomy. PET FDG was realized after at least 6 h of fasting on a hybrid PET-CT G.E. Discovery S.T. scan for 65 of them. The rest of the patients were evaluated on a Siemens Ecat H.R. + scan. Scans were interpreted by an experimented nuclear medicine physician and were classified as positive or negative. All equivocal scans or cases for which there was discordance between the scan result and follow up were reviewed by 2 experimented nuclear medicine physicians and a consensus was reached. Results. - FDG PET was positive in seven patients, four scans were true positive and identified regional metastatic disease. No distant metastatic visceral disease was found. The three false positive scans consisted of a cyst adeno-lymphoma in one case, mediastinal and axillary uptake in the other two cases and no sign of evolution more than six months after the scan. Four patients with a negative scan showed metastatic disease in the six months following the PET scan. FDG PET had an impact on therapeutic management on two patients (2%). When evaluating FDG PET for regional disease with sentinel node biopsy as a reference, we found values of sensitivity, specificity, predictive

  16. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

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

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

  17. Somatic mutations in MAP3K5 attenuate its pro-apoptotic function in melanoma through increased binding to Thioredoxin

    Science.gov (United States)

    Prickett, Todd D.; Zerlanko, Brad; Gartner, Jared J.; Parker, Stephen C. J.; Dutton-Regester, Ken; Lin, Jimmy C.; Teer, Jamie K.; Wei, Xiaomu; Jiang, Jiji; Chen, Guo; Davies, Michael A.; Gershenwald, Jeffrey E.; Robinson, William; Robinson, Steven; Hayward, Nicholas K.; Rosenberg, Steven, A.; Margulies, Elliott H.; Samuels, Yardena

    2013-01-01

    Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, upon analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples we identified several genes that harbor recurrent non-synonymous mutations. These included MAP3K5, which in a prevalence screen of 288 melanomas was found to harbor a R256C substitution in 5 cases. All MAP3K5 mutated samples were wild-type for BRAF, suggesting a mutual exclusivity for these mutations. Functional analysis of the MAP3K5 R256C mutation revealed attenuation of MKK4 activation through increased binding of the inhibitory protein thioredoxin (TXN/TRX-1/Trx); resulting in increased proliferation and anchorage-independent growth of melanoma cells. This mutation represents a potential target for the design of new therapies to treat melanoma. PMID:24008424

  18. MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes

    Directory of Open Access Journals (Sweden)

    Sabine Waigel

    2016-03-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs are potently immunosuppressive innate immune cells that accumulate in advanced cancer patients and actively inhibit anti-tumor T lymphocyte responses [1]. Increased numbers of circulating MDSCs directly correlate with melanoma patient morbidity and reduced anti-tumor immune responses [2,3]. Previous studies have revealed that monocyte-derived macrophage migration inhibitory factor (MIF is necessary for the immune suppressive function of MDSCs in mouse models of melanoma [4,5]. To investigate whether MIF participates in human melanoma-induced MDSC differentiation and/or suppressive function, we have established an in vitro MDSC induction model using primary, normal human monocytes co-cultured with human melanoma cell lines in the presence or absence of the MIF antagonist—4-IPP [4,6–9]. To identify potential mechanistic effectors, we have performed transcriptome analyses on cultured monocytes and on melanoma-induced MDSCs obtained from either untreated or 4-IPP-treated A375:monocyte co-cultures. Here, we present a detailed protocol, which can facilitate easy reproduction of the microarray results (NCBI GEO accession number GSE73333 published by Yaddanapudi et al. (2015 in Cancer Immunology Research [10].

  19. MIF inhibition reverts the gene expression profile of human melanoma cell line-induced MDSCs to normal monocytes.

    Science.gov (United States)

    Waigel, Sabine; Rendon, Beatriz E; Lamont, Gwyneth; Richie, Jamaal; Mitchell, Robert A; Yaddanapudi, Kavitha

    2016-03-01

    Myeloid-derived suppressor cells (MDSCs) are potently immunosuppressive innate immune cells that accumulate in advanced cancer patients and actively inhibit anti-tumor T lymphocyte responses [1]. Increased numbers of circulating MDSCs directly correlate with melanoma patient morbidity and reduced anti-tumor immune responses [2], [3]. Previous studies have revealed that monocyte-derived macrophage migration inhibitory factor (MIF) is necessary for the immune suppressive function of MDSCs in mouse models of melanoma [4], [5]. To investigate whether MIF participates in human melanoma-induced MDSC differentiation and/or suppressive function, we have established an in vitro MDSC induction model using primary, normal human monocytes co-cultured with human melanoma cell lines in the presence or absence of the MIF antagonist-4-IPP [4], [6], [7], [8], [9]. To identify potential mechanistic effectors, we have performed transcriptome analyses on cultured monocytes and on melanoma-induced MDSCs obtained from either untreated or 4-IPP-treated A375:monocyte co-cultures. Here, we present a detailed protocol, which can facilitate easy reproduction of the microarray results (NCBI GEO accession number GSE73333) published by Yaddanapudi et al. (2015) in Cancer Immunology Research [10]. PMID:26981417

  20. Malignant melanoma cure by selective thermal neutron capture therapy

    International Nuclear Information System (INIS)

    Thermal neutrons are easily absorbed by the nonradioactive isotope 10B, resulting in the emission of alpha particles and lithium atoms, which release an energy of 2.33 MeV for up to a 14-μm-diam melanoma cell. Thus, if 10B can be selectively accumulated in melanoma, it can be destroyed without injury to the surrounding normal tissues by concentrating high linear energy transfer particles. The authors have synthesized seven melanoma-seeking 10B compounds, two of which, 10B12-chlorpromazine(10B12-CPZ) and 10B1-p-boronophenylalanine(10B1-BPA), are found to be highly effective. The enhanced melanoma-killing effect of the 10B compounds is found by in vitro radiobiological analysis. A chemical assay and alpha-track analysis 28 h after systemic administration to melanoma-bearing hamsters reveals a 10B melanoma/blood ratio of 11.5 and a melanoma/liver ratio of 15. Establishment of a clinical therapeutic method for curing human melanoma without failure is underway by correlating biophysical, biochemical, biological, and therapeutic data analysis. Recently, the authors have also been working to develop neutron capture therapy using 10B-monoclonal antibodies for melanoma and were able to make some 10B conjugates with the specific m259-0 antibody

  1. Neutron capture therapy for melanoma

    International Nuclear Information System (INIS)

    The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs

  2. Melanoma International Foundation

    Science.gov (United States)

    ... 501(c)(3) charity, also registered as a non-profit charity in the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use ...

  3. Drugs Approved for Melanoma

    Science.gov (United States)

    ... are not listed here. Drugs Approved for Melanoma Aldesleukin Cobimetinib Cotellic (Cobimetinib) Dabrafenib Dacarbazine DTIC-Dome (Dacarbazine) IL-2 (Aldesleukin) Imlygic (Talimogene Laherparepvec) Interleukin-2 (Aldesleukin) Intron A ( ...

  4. Melanoma of the eye

    Science.gov (United States)

    ... modified July 9, 2015. www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq . Accessed October 7, 2015. Read ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. Also reviewed ...

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

    Science.gov (United States)

    2016-01-13

    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

  6. Breast-conserving surgery after neoadjuvant chemotherapy in patients with locally advanced cancer. Preliminary results

    OpenAIRE

    VERGINE, M.; SCIPIONI, P.; GARRITANO, S.; COLANGELO, M.; Di Paolo, A; LIVADOTI, G.; MATURO, A.; Monti, M

    2013-01-01

    Neoadjuvant chemotherapy (NACT) in locally advanced breast tumors may allow an adequate control of the disease impossible with surgery alone. Moreover, NACT increases the chance of breast-conserving surgery. Between 2008 and 2012, we treated with NACT 83 patients with locally advanced breast cancer. We report the preliminary results evaluating the impact of NACT on the type of surgery.

  7. Convection-enhanced delivery of sorafenib and suppression of tumor progression in a murine model of brain melanoma through the inhibition of signal transducer and activator of transcription 3.

    Science.gov (United States)

    Zou, Zhaoxia; Yin, Yufang; Lin, Jenny; Hsu, Li-Chen J; Brandon, Vanessa L; Yang, Fan; Jove, Richard; Jandial, Rahul; Li, Gang; Chen, Mike Y

    2016-05-01

    OBJECT Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma. METHODS Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival. RESULTS The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 -/- cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p sorafenib also significantly abrogated tumor growth. CONCLUSIONS The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents. PMID:26544779

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

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

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

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

    International Nuclear Information System (INIS)

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

  10. Antineoplastic effects of Rhodiola crenulata treatment on B16-F10 melanoma.

    Science.gov (United States)

    Dudek, Maxine C; Wong, Kaitlyn E; Bassa, Lotfi M; Mora, Maria Carmen; Ser-Dolansky, Jennifer; Henneberry, Jean M; Crisi, Giovanna M; Arenas, Richard B; Schneider, Sallie S

    2015-12-01

    Melanoma is an aggressive form of skin cancer with limited treatment options for advanced stage disease. Early detection and wide surgical excision remain the initial mode of treatment for primary tumors thus preventing metastases and leading to improved prognosis. Through this work, we have evaluated the antineoplastic effects of Rhodiola crenulata (R. crenulata) root extracts on the B16-F10 melanoma cell line, both in vitro and in vivo. We observed that R. crenulata treatment resulted in increased cell death as well as a reduction in tumor cell proliferation and migration in vitro. Additionally, we observed that R. crenulata decreased the expression of integrin β1 and vimentin and increased the expression of E-cadherin. Further, in mice treated with a topical R. crenulata-based cream therapy, tumors were more likely to have a radial growth pattern, a reduction in mitotic activity, and an increase in tumor necrosis. We also observed that mice drinking water supplemented with R. crenulata displayed a reduction of metastatic foci in disseminated models of melanoma. Collectively, these findings suggest that R. crenulata exhibits striking antitumorigenic and antimetastatic properties and that this extract may harbor potential novel adjuvant therapy for the treatment of melanoma. PMID:26159852

  11. Detection of Melanoma Cancer Biomarker Dimethyl Disulfide Using Cavity Ringdown Spectroscopy at 266 nm.

    Science.gov (United States)

    Wang, Zhennan; Sun, Meixiu; Wang, Chuji

    2016-06-01

    Skin cells emit volatile organic compounds (VOCs), and some of them can be used as biomarkers for screening specific diseases. Dimethyl disulfide (DMDS) has been recently reported as a biomarker of melanoma skin cancer (Kwak et al. "Volatile Biomarkers from Human Melanoma Cells". J. Chromatogr. B. 2013. 931: 90-96.). With the motivation of diagnosing melanoma using DMDS as its biomarker, we explore the potential of measuring DMDS using an advanced laser spectroscopic technique as an alternative method. We report on the first DMDS measurements using an experimental system based on cavity ringdown spectroscopy (CRDS). The test samples were mixtures of DMDS vapor and nitrogen in different concentrations. Two sampling methods were investigated to dilute the DMDS sample to low concentrations for ringdown measurements. The results showed that the ringdown system responded to various DMDS concentrations linearly and a theoretical detection limit of sub-ppb (parts per billion) could be achieved at the absorption wavelength of 266 nm. This ringdown system exhibited a high dynamic range for DMDS measurements, from ppm (parts per million) to ppt (parts per trillion) levels, given different laser wavelengths used. The feasibility of developing a portable melanoma screening sensor using the CRDS technique was also demonstrated in this study. PMID:27076515

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-01

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

  13. 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.

  14. Automatic differentiation of melanoma and clark nevus skin lesions

    Science.gov (United States)

    LeAnder, R. W.; Kasture, A.; Pandey, A.; Umbaugh, S. E.

    2007-03-01

    Skin cancer is the most common form of cancer in the United States. Although melanoma accounts for just 11% of all types of skin cancer, it is responsible for most of the deaths, claiming more than 7910 lives annually. Melanoma is visually difficult for clinicians to differentiate from Clark nevus lesions which are benign. The application of pattern recognition techniques to these lesions may be useful as an educational tool for teaching physicians to differentiate lesions, as well as for contributing information about the essential optical characteristics that identify them. Purpose: This study sought to find the most effective features to extract from melanoma, melanoma in situ and Clark nevus lesions, and to find the most effective pattern-classification criteria and algorithms for differentiating those lesions, using the Computer Vision and Image Processing Tools (CVIPtools) software package. Methods: Due to changes in ambient lighting during the photographic process, color differences between images can occur. These differences were minimized by capturing dermoscopic images instead of photographic images. Differences in skin color between patients were minimized via image color normalization, by converting original color images to relative-color images. Relative-color images also helped minimize changes in color that occur due to changes in the photographic and digitization processes. Tumors in the relative-color images were segmented and morphologically filtered. Filtered, relative-color, tumor features were then extracted and various pattern-classification schemes were applied. Results: Experimentation resulted in four useful pattern classification methods, the best of which was an overall classification rate of 100% for melanoma and melanoma in situ (grouped) and 60% for Clark nevus. Conclusion: Melanoma and melanoma in situ have feature parameters and feature values that are similar enough to be considered one class of tumor that significantly differs from

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Olga Tatti

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

  17. Vitamin D receptor polymorphisms in patients with cutaneous melanoma

    OpenAIRE

    Orlow, Irene; Roy, Pampa; Reiner, Anne S.; Yoo, Sarah; Patel, Himali; Paine, Susan; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D; Millikan, Robert C.; Thomas, Nancy E.; Gruber, Stephen B.; Anton-Culver, Hoda; Rosso, Stefano; Gallagher, Richard P.

    2011-01-01

    The vitamin D receptor (VDR) gene has been associated with cancer risk, but only a few polymorphisms have been studied in relation to melanoma risk and the results have been inconsistent. We examined 38 VDR gene SNPs in a large international multi-center population-based case-control study of melanoma.

  18. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical trials ...

  19. Alternative treatments for melanoma: targeting BCL-2 family members to de-bulk and kill cancer stem cells

    OpenAIRE

    Mukherjee, Nabanita; Schwan, Josianna V.; Fujita, Mayumi; Norris, David A.; Shellman, Yiqun G.

    2015-01-01

    For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30–90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer t...

  20. Treatment Options by Stage (Melanoma)

    Science.gov (United States)

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

  1. Melanoma screening: A plan for improving early detection.

    Science.gov (United States)

    Shellenberger, Richard; Nabhan, Mohammed; Kakaraparthi, Sweta

    2016-05-01

    US and many countries worldwide, the incidence and mortality rates have not declined despite advances seen in the detection and treatment of many cancers. Whole-body skin examination is non-invasive and has shown to be cost effective. There is evidence supporting a mortality benefit using routine, widespread skin cancer examinations. Primary care physicians have been shown to effectively use skin cancer examination for early detection and reduced melanoma mortality. The majority of US primary care residents are inadequately trained in skin cancer examination. There is a possible survival advantage and cost effectiveness for melanoma screening. PMID:26911192

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

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

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

  3. Antibody binding to membrane of cultured melanoma cells by sera of melanoma patients.

    Science.gov (United States)

    Canevari, S; Fossati, G; Vezzoni, P; Biguzzi, S; Garcia-Puche, J; Della Porta, G

    1979-02-28

    One hundred and nine sera from 75 patients with malignant melanoma and 69 sera from as many healthy donors were assayed by isotopic antiglobulin technique (IAT) on 2 melanoma cell lines. The same picture of reactivity was observed with patients' and healthy donors' sera, and in both groups 35% of the cases were high responders on 1 line and 21% on the other one. The specificity of the reactions was analyzed by absorption experiments using 12 melanoma sera selected for their high binding activity. Pools of human erythrocytes or leukocytes did not remove, except in 1 case respectively, the activity of the sera, suggesting that it was not directed against alloantigens. Quantitative absorption experiments were done with the 2 melanoma lines and with 1 colon carcinoma line. The results, evaluated on the basis of absorption capacity per cell, indicate that the 2 melanoma lines had a similar amount of shared antigens, whereas the colon line was also effective in absorbing out the serum activity, but less frequently and less efficiently. Further experiments performed to analyze the influence of culturing the target cells in presence of fetal bovine serum (FBS), showed that the activity of sera was removed, at various degrees for different sera, by absorption with free FBS, with FBS coupled to Sepharose 4B, and with normal leukocytes cultured overnight with 10% FBS. The same positive melanoma sera became negative when assayed on the same melanoma line cultured in gamma-globulin-depleted human AB serum. In conclusion, in our experimental conditions, the activity of melanoma sera seems mostly directed against components of FBS absorbed on cell membrane during culturing. PMID:87047

  4. Ipilimumab-Induced Neutropenia in Melanoma

    Science.gov (United States)

    Ban-Hoefen, Makiko; Burack, Richard; Sievert, Lynn; Sahasrabudhe, Deepak

    2016-01-01

    Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies. PMID:27570779

  5. Ipilimumab-Induced Neutropenia in Melanoma.

    Science.gov (United States)

    Ban-Hoefen, Makiko; Burack, Richard; Sievert, Lynn; Sahasrabudhe, Deepak

    2016-01-01

    Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies. PMID:27570779

  6. [Strategies for the noninvasive diagnosis of melanoma].

    Science.gov (United States)

    Fink, C; Haenssle, H A

    2016-07-01

    The diagnosis of advanced cutaneous melanoma may easily be made by the unaided eye, followed by excisional biopsy and histopathological examination. However, in the setting of melanoma screening examinations in high-risk patients with many nevi, dermatologists are challenged with the differentiation of atypical but benign nevi and early invasive or in situ melanomas. In this situation, there is a real need for additional, noninvasive examination techniques that may serve as an aide to decide for or against an excisional biopsy. Conventional dermoscopy is a well-established examination procedure and an increase in sensitivity was confirmed by two independent meta-analyses. Moreover, dynamic changes or newly developed pigmented lesions may be detected by sequential digital dermoscopy or (automated) total body photography, respectively. Over the past years, a number of medicinal products gained market access after licensing by American and European agencies for the noninvasive diagnosis of cutaneous neoplasms. These devices are based on technologies including in vivo reflectance confocal microscopy, multispectral analysis, electrical impedance spectroscopy, or Raman spectroscopy. Other technologies are still on the verge of becoming less experimental but more clinically applicable for diagnosing melanoma (in vivo multiphoton tomography, stepwise two-photon laser spectroscopy, infrared thermal image analysis, epidermal genetic information retrieval). This review provides a concise overview of general principles and sheds light on indication and added value for dermatologists. PMID:27193101

  7. Frequent MAGE mutations in human melanoma.

    Directory of Open Access Journals (Sweden)

    Otavia L Caballero

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

  8. 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.

  9. Antioxidants can increase melanoma metastasis in mice.

    Science.gov (United States)

    Le Gal, Kristell; Ibrahim, Mohamed X; Wiel, Clotilde; Sayin, Volkan I; Akula, Murali K; Karlsson, Christin; Dalin, Martin G; Akyürek, Levent M; Lindahl, Per; Nilsson, Jonas; Bergo, Martin O

    2015-10-01

    Antioxidants in the diet and supplements are widely used to protect against cancer, but clinical trials with antioxidants do not support this concept. Some trials show that antioxidants actually increase cancer risk and a study in mice showed that antioxidants accelerate the progression of primary lung tumors. However, little is known about the impact of antioxidant supplementation on the progression of other types of cancer, including malignant melanoma. We show that administration of N-acetylcysteine (NAC) increases lymph node metastases in an endogenous mouse model of malignant melanoma but has no impact on the number and size of primary tumors. Similarly, NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the glutathione system play a previously unappreciated role in malignant melanoma progression. PMID:26446958

  10. BRAF and beyond: Tailoring strategies for the individual melanoma patient

    Directory of Open Access Journals (Sweden)

    Anthony Jarkowski

    2014-01-01

    Full Text Available Until recently, options for therapy in metastatic melanoma were limited. The understanding of immune check-point blockade and the discovery of molecular pathways involving driver mutations like BRAF has transformed the therapeutic landscape in this disease. Ipilimumab was the first drug shown to improve survival while vemurafenib demonstrated rapid responses never seen before in melanoma. Drugs from these classes and others are now in advanced stages of development and primed to positively impact patient survival in an incremental fashion. In this review, we highlight some of the developments during this renaissance in melanoma therapy and discuss agents of promise. Clinical challenges we face include individualizing therapy for patients, overcoming resistance to molecularly targeted therapy and developing rationale combinations or sequences of drugs. A concerted bench and bedside effort in this direction will undoubtedly keep melanoma in the forefront in an era of personalized medicine.

  11. Outpatient Follow-up and Secondary Prevention for Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Ryan G. Gamble

    2010-06-01

    Full Text Available Health care providers and their patients jointly participate in melanoma prevention, surveillance, diagnosis, and treatment. This paper reviews screening and follow-up strategies for patients who have been diagnosed with melanoma, based on current available evidence, and focuses on methods to assess disease recurrence and second primary occurrence. Secondary prevention, including the roles of behavioral modification and chemoprevention are also reviewed. The role of follow-up dermatologist consultation, with focused physical examinations complemented by dermatoscopy, reflectance confocal microscopy, and/or full-body mapping is discussed. Furthermore, we address the inclusion of routine imaging and laboratory assessment as components of follow-up and monitoring of advanced stage melanoma. The role of physicians in addressing the psychosocial stresses associated with a diagnosis of melanoma is reviewed.

  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. 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.

  14. Tumor-infiltrating lymphocytes predict cutaneous melanoma survival.

    Science.gov (United States)

    Fortes, Cristina; Mastroeni, Simona; Mannooranparampil, Thomas J; Passarelli, Francesca; Zappalà, Alba; Annessi, Giorgio; Marino, Claudia; Caggiati, Alessio; Russo, Nicoletta; Michelozzi, Paola

    2015-08-01

    Understanding differences in survival across distinct subgroups of melanoma patients may help with the choice of types of therapy. Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the role of TILs in melanoma mortality is controversial. The aim of this study was to investigate independent prognostic factors for melanoma mortality. We carried out a 10-year cohort study on 4133 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 1998 and December 2008. The probability of survival was estimated using Kaplan-Meier methods and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). The 10-year survival rate for melanoma decreased with increasing Breslow thickness (Pfor trendhazard ratio 0.32; 95% confidence interval 0.13-0.82) after controlling for sex, age, Breslow thickness, histological type, mitotic rate, and ulceration. After including lymph node status in the multivariate analysis, the protective effect of marked TILs on melanoma mortality remained (hazard ratio 0.37; 95% confidence interval 0.15-0.94). The results of this study suggest that the immune microenvironment affects melanoma survival. PMID:25933208

  15. Update on Thin Melanoma: Outcome of an International Workshop.

    Science.gov (United States)

    Mihic-Probst, Daniela; Shea, Chris; Duncan, Lyn; de la Fouchardiere, Arnaud; Landman, Gilles; Landsberg, Jennifer; ven den Oord, Joost; Lowe, Lori; Cook, Martin G; Yun, Sook Jung; Clarke, Loren; Messina, Jane; Elder, David E; Barnhill, Raymond L

    2016-01-01

    The following communication summarizes the proceedings of a 1-day Workshop of the International Melanoma Pathology Study Group, which was devoted to thin melanoma. The definitions and histologic criteria for thin melanoma were reviewed. The principal differential diagnostic problems mentioned included the distinction of thin melanoma from nevi, especially from nevi of special site, irritated nevi, inflamed and regressing nevi, and dysplastic nevi. Histologic criteria for this analysis were discussed and the importance of clinico-pathologic correlation, especially in acral sites, was emphasized. Criteria for the minimal definition of invasion were also discussed. In addition, a new technique of m-RNA expression profiling with 14 genes was presented and facilitated the distinction of thin melanomas from nevus in histologically obvious cases. However, for particular nevi, it was not obvious why the results indicated a malignant lesion. Despite many molecular and other ancillary investigations, Breslow thickness remains the most important prognostic factor in thin melanoma. The prognostic significance of radial (horizontal) and vertical growth phases, Clark level, regression, and mitotic rate were also discussed. Because of the increasing frequency of thin melanomas, there is a great need to develop more refined predictors of thin melanomas with worse clinical outcome. PMID:26645459

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Nouritza M. Torossian

    2015-01-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Hakan Demirci

    2013-01-01

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

  20. The mitogen-activated protein kinase pathway plays a critical role in regulating immunological properties of BRAF mutant cutaneous melanoma cells.

    Science.gov (United States)

    Whipple, Chery A; Boni, Andrea; Fisher, Jan L; Hampton, Thomas H; Tsongalis, Gregory J; Mellinger, Diane L; Yan, Shaofeng; Tafe, Laura J; Brinckerhoff, Constance E; Turk, Mary J; Mullins, David W; Fadul, Camilo E; Ernstoff, Marc S

    2016-06-01

    The advent of drugs targeting the mitogen-activated protein kinase (MAPK) pathway has markedly changed the treatment of advanced-stage melanoma harboring BRAF mutations. However, drug resistance, through mechanisms not well elucidated, often occurs. A better understanding of how melanoma-derived immunologically active molecules change in response to MAPK inhibition of BRAF mutated (BRAF) and BRAF wild type (BRAF) melanomas could help identify promising treatment combinations of small molecule inhibitors and immunotherapy. To this aim, we treated 13 BRAF and 13 BRAF mutated human melanoma cell lines with either a specific BRAF inhibitor or an MEK1/2 inhibitor and analyzed changes in the secretion of 42 selected cytokines, chemokines, and growth factors. We also measured changes in the expression levels of immunologically relevant melanoma cell surface markers. The BRAF melanomas showed minimal changes in response to the inhibitors, whereas the BRAF cell lines showed, on average, a significant decrease in IFNα2, interleukin-7, Fractalkine, GCSF, GRO, TGFα2, interleukin-8, and VEGF, as well as a reduction in pERK and pMEK protein levels, upon MAPK pathway blockade. BRAF inhibition in BRAF cell lines also resulted in significant changes in the expression of several surface markers including upregulation of β2-microglobulin as well as a decrease in MIC A/B and TRAIL-R2. These results indicate that MAPK pathway inhibition leads to changes in the immunological properties of mutant BRAF melanoma cells and lends support for future studies aimed at designing effective treatment strategies that combine BRAF and MEK inhibition with immunotherapy. PMID:26974965

  1. Melanoma-associated cancer-testis antigen 16 (CT16 regulates the expression of apoptotic and antiapoptotic genes and promotes cell survival.

    Directory of Open Access Journals (Sweden)

    Camilla Nylund

    Full Text Available Cancer-testis (CT antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5 is frequently expressed in advanced melanoma but its biological function has been unknown. To examine the role of CT16 in cell survival we knocked it down in A2058 melanoma cells using specific siRNAs and exposed the cells to cancer drug cisplatin known to induce apoptosis. As a result, cell survival was markedly decreased. To study the effects of CT16 on cell survival in more detail, the cellular gene expression profiles were investigated after CT16 silencing in CT16 positive A2058 melanoma cells, as well as after CT16 overexpression in CT16 negative WM-266-4 melanoma cells. Among the 11 genes both upregulated by CT16 silencing and downregulated by CT16 overexpression or vice versa, 4 genes were potentially apoptotic or antiapoptotic genes. CT16 was recognized as a positive regulator of antiapoptotic metallothionein 2A and interleukin 8 genes, whereas it inhibited the expression of apoptosis inducing dickkopf 1 (DKK1 gene. In addition CT16 enhanced the expression of fatty acid binding protein 7, a known promoter of melanoma progression. The effect of CT16 on DKK1 expression was p53 independent. Furthermore, CT16 did not regulate apoptotic genes via DNA methylation. In twenty melanoma metastasis tissue samples average DKK1 mRNA level was shown to be significantly (p<0.05 lower in high CT16 expressing tumors (n = 3 when compared to the tumors with low CT16 expression (n = 17. Thus, our results indicate that CT16 promotes the survival of melanoma cells and is therefore a potential target for future drug development.

  2. Results of NCCTG N0275 (Alliance) - a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma.

    Science.gov (United States)

    Rule, William G; Allred, Jacob B; Pockaj, Barbara A; Markovic, Svetomir N; DiCaudo, David J; Erickson, Lori A; Deming, Richard L; Schild, Steven E

    2016-08-01

    To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan. PMID:27368067

  3. Impact of MAPK pathway activation in BRAFV600 melanoma on T cell and Dendritic Cell function

    Directory of Open Access Journals (Sweden)

    Patrick Alexander 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 CTLA-4 and PD-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 DC 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.

  4. Bioelectric Applications for Treatment of Melanoma

    International Nuclear Information System (INIS)

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma

  5. Bioelectric Applications for Treatment of Melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-09-27

    Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  6. Bioelectric Applications for Treatment of Melanoma

    Directory of Open Access Journals (Sweden)

    Richard Heller

    2010-09-01

    Full Text Available Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs. EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.

  7. Energy and cost saving results for advanced technology systems from the Cogeneration Technology Alternatives Study (CTAS)

    Science.gov (United States)

    Sagerman, G. D.; Barna, G. J.; Burns, R. K.

    1979-01-01

    An overview of the organization and methodology of the Cogeneration Technology Alternatives Study is presented. The objectives of the study were to identify the most attractive advanced energy conversion systems for industrial cogeneration applications in the future and to assess the advantages of advanced technology systems compared to those systems commercially available today. Advanced systems studied include steam turbines, open and closed cycle gas turbines, combined cycles, diesel engines, Stirling engines, phosphoric acid and molten carbonate fuel cells and thermionics. Steam turbines, open cycle gas turbines, combined cycles, and diesel engines were also analyzed in versions typical of today's commercially available technology to provide a base against which to measure the advanced systems. Cogeneration applications in the major energy consuming manufacturing industries were considered. Results of the study in terms of plant level energy savings, annual energy cost savings and economic attractiveness are presented for the various energy conversion systems considered.

  8. Angiogenesis and Melanoma

    International Nuclear Information System (INIS)

    Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described

  9. Vitamins and Melanoma

    Directory of Open Access Journals (Sweden)

    Irene Russo

    2015-07-01

    Full Text Available A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamins in chemoprevention and therapy of melanoma could be encouraged if supported by pre-clinical and clinical evidence.

  10. Investigation of FOXM1 as a Potential New Target for Melanoma

    Science.gov (United States)

    Miyashita, Azusa; Fukushima, Satoshi; Nakahara, Satoshi; Yamashita, Junji; Tokuzumi, Aki; Aoi, Jun; Ichihara, Asako; Kanemaru, Hisashi; Jinnin, Masatoshi; Ihn, Hironobu

    2015-01-01

    Recent studies have shown that immunotherapies and molecular targeted therapies are effective for advanced melanoma. Non-antigen-specific immunotherapies such as immunocheckpoint blockades have been shown to be effective in the treatment of advanced melanoma. However, the response rates remain low. To improve their efficacy, they should be combined with antigen-specific immunotherapy. Elevated expression of the transcription factor, Forkhead box M1 (FOXM1), has been reported in various human cancers, and it has been shown to have potential as a target for immunotherapy. The purpose of this study was to investigate the FOXM1 expression in human melanoma samples and cell lines, to evaluate the relationship between the FOXM1 expression and the clinical features of melanoma patients and to investigate the association between the FOXM1 and MAPK and PI3K/AKT pathways in melanoma cell lines. We conducted the quantitative reverse transcription PCR (qRT-PCR) and Western blotting analyses of melanoma cell lines, and investigated melanoma and nevus tissue samples by qRT-PCR and immunohistochemistry. We performed MEK siRNA and PI3K/AKT inhibitor studies and FOXM1 siRNA studies in melanoma cell lines. We found that FOXM1 was expressed in all of the melanoma cell lines, and was expressed in 49% of primary melanomas, 67% of metastatic melanomas and 10% of nevi by performing immunohistochemical staining. Metastatic melanoma samples exhibited significantly higher mRNA levels of FOXM1 (p = 0.004). Primary melanomas thicker than 2 mm were also more likely to express FOXM1. Patients whose primary melanoma expressed FOXM1 had a significantly poorer overall survival compared to patients without FOXM1 expression (p = 0.024). Downregulation of FOXM1 by siRNA significantly inhibited the proliferation of melanoma cells, and blockade of the MAPK and PI3K/AKT pathways decreased the FOXM1 expression in melanoma cell lines. In conclusion, FOXM1 is considered to be a new therapeutic target for

  11. Current status and perspectives of treatment of disseminated melanoma

    International Nuclear Information System (INIS)

    Melanoma is considered to be one of the most malignant human neoplasms, characterized by a steadily increasing morbidity rate, which remains a challenge for modem oncology. Despite the significant progress in prevention, diagnosis and molecular biology, the practical use of this knowledge is still limited and surgery remains the main method of treatment. A particularly unfavorable clinical course is observed in patients with metastatic melanoma. Median survival in stage IV melanoma is 6-10 months, 2-year survival is less than 10%, and 5-year survival does not exceed 5%. Despite efforts aimed at developing new strategies which would improve survival, the results have not changed for more than two decades. This is related to the limited number of cytostatic drugs available for systemic melanoma treatment and the relative resistance of melanoma cells to most therapeutic agents. In clinical practice, the most widely used drug is dacarbazine, with the highest, but still unsatisfactory, response rate reaching some 20%. The lack of effective therapies calls for the exploration of different therapeutic paths, both medical and surgical. Some hopes of new modalities are associated with the theory of melanoma immunogenicity. Currently it is believed that immuno modulation may be the solution for effective treatment of melanoma and it should be noted that new drugs, scheduled to be registered by the FDA for the treatment of metastatic melanoma, are immune system stimulating agents. Although targeted therapies are still not a standard of treatment and their use is mainly limited to clinical trials, they appear to be the future of effective treatment of metastatic melanoma. In this review we present the current methods of treatment of metastatic melanoma. (authors)

  12. Curcumin: A new candidate for melanoma therapy?

    Science.gov (United States)

    Mirzaei, Hamed; Naseri, Gholamreza; Rezaee, Ramin; Mohammadi, Mohsen; Banikazemi, Zarrin; Mirzaei, Hamid Reza; Salehi, Hossein; Peyvandi, Mostafa; Pawelek, John M; Sahebkar, Amirhossein

    2016-10-15

    Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. PMID:27280688

  13. Blade element momentum modeling of inflow with shear in comparison with advanced model results

    DEFF Research Database (Denmark)

    Aagaard Madsen, Helge; Riziotis, V.; Zahle, Frederik;

    2012-01-01

    shear is present in the inflow. This gives guidance to how the BEM modeling of shear should be implemented. Another result from the advanced vortex model computations is a clear indication of influence of the ground, and the general tendency is a speed up effect of the flow through the rotor giving a...... higher power than in uniform flow. On the basis of the consistent azimuthal induction variations seen in the advanced model results, three different BEM implementation methods are discussed and tested in the same aeroelastic code. A full local BEM implementation on an elemental stream tube in both...

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

    Directory of Open Access Journals (Sweden)

    JasonEzraHawkes

    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.

  15. Economic Costs Avoided by Diagnosing Melanoma Six Months Earlier Justify >100 Benign Biopsies.

    Science.gov (United States)

    Aires, Daniel J; Wick, Jo; Shaath, Tarek S; Rajpara, Anand N; Patel, Vikas; Badawi, Ahmed H; Li, Cicy; Fraga, Garth R; Doolittle, Gary; Liu, Deede Y

    2016-05-01

    New melanoma drugs bring enormous benefits but do so at significant costs. Because melanoma grows deeper and deadlier over time, deeper lesions are costlier due to increased sentinel lymph node biopsy, chemotherapy, and disease-associated income loss. Prior studies have justified pigmented lesion biopsies on a "value per life" basis; by contrast we sought to assess how many biopsies are justified per melanoma found on a purely economic basis. We modeled how melanomas in the United States would behave if diagnosis were delayed by 6 months, eg, not biopsied, only observed until the next surveillance visit. Economic loss from delayed biopsy is the obverse of economic benefit of performing biopsy earlier. Growth rates were based on Liu et al. The results of this study can be applied to all patients presenting to dermatologists with pigmented skin lesions suspicious for melanoma. In-situ melanomas were excluded because no studies to date have modeled growth rates analogous to those for invasive melanoma. We assume conservatively that all melanomas not biopsied initially will be biopsied and treated 6 months later. Major modeled costs are (1) increased sentinel lymph node biopsy, (2) increased chemotherapy for metastatic lesions using increased 5-yr death as metastasis marker, and (3) income loss per melanoma death at $413,370 as previously published. Costs avoided by diagnosing melanoma earlier justify 170 biopsies per melanoma found. Efforts to penalize "unnecessary" biopsies may be economically counterproductive. J Drugs Dermatol. 2016;15(5):527-532. PMID:27168261

  16. 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. PMID:24126842

  17. 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.

  18. 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…

  19. Malignant melanoma of nose

    OpenAIRE

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

    2001-01-01

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

  20. Surgical aspects of melanoma therapy

    International Nuclear Information System (INIS)

    Surgery is still the most important treatment modality to guarantee the highest survival ratio of melanoma patients. The adequacy of the surgical approach is a crucial aspect in face of the initial clinical appearances of the disease. Best results are obtained with the correct treatment of primary melanomas and lymph node metastases. To reach a general consensus on the surreal indications in terms of extension and timing, a large number of randomized trials have been conducted in the last 3 - 4 decades. The rationale behind these trials, even if proposed by different institutions on different continents, has been to find the most conservative surgical approach able to guarantee the same results as those achieved with more aggressive treatment This lay behind the design of trials designed to determine the correct excision margin around primary melanomas in the most important studies. A similar approach has been followed in the preparation of several trials dedicated to the definition of the importance of performing immediate dissection of the locoregional nodes in view of the absence of clinical evidence of metastases. Ever since the sentinel node technique has become the standard treatment in a majority of institutions, the guidelines for the treatment of locoregional nodes have undergone a kind of revolution. In fact the policy of wait and see introduced by the aforementioned trials has been overridden by a more specific and selective even if a more invasive approach to obtain precise information regarding the status of clinically non-invaded locoregional nodes. The sentinel node biopsy technique makes use of a majority of scientific surgical tools, is the most conservative (when compared to elective node dissection), extremely precise and sophisticated and provides crucial data necessary to make decisions regarding the necessity to perform radical surgery, i.e. therapeutic node dissection. Radical lymph node dissection is recommended in case of confirmed regional

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

    Directory of Open Access Journals (Sweden)

    Mashima E

    2015-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Priscilla A. Melville

    2003-01-01

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

  3. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas

    OpenAIRE

    Gong, J; Chen, N; Zhou, Q; Yang, B.; Wang, Y; Wang, X.

    2005-01-01

    Background: Malignant melanoma is highly resistant to current treatments. The inhibitor of apoptosis protein (IAP) family member, melanoma IAP (ML-IAP), is overexpressed in some melanoma cell lines, rendering them resistant to apoptotic signals. Targeting ML-IAP is a promising approach to treating melanoma. However, the status of ML-IAP expression in human melanoma tissues and the difference in expression between melanoma and melanocytic naevus are not known.

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

    Directory of Open Access Journals (Sweden)

    Ghislin Stephanie

    2012-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Z. J. Casariego

    2004-12-01

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

  6. DNA methylation characteristics of primary melanomas with distinct biological behaviour.

    Directory of Open Access Journals (Sweden)

    Szilvia Ecsedi

    Full Text Available In melanoma, the presence of promoter related hypermethylation has previously been reported, however, no methylation-based distinction has been drawn among the diverse melanoma subtypes. Here, we investigated DNA methylation changes associated with melanoma progression and links between methylation patterns and other types of somatic alterations, including the most frequent mutations and DNA copy number changes. Our results revealed that the methylome, presenting in early stage samples and associated with the BRAF(V600E mutation, gradually decreased in the medium and late stages of the disease. An inverse relationship among the other predefined groups and promoter methylation was also revealed except for histologic subtype, whereas the more aggressive, nodular subtype melanomas exhibited hypermethylation as well. The Breslow thickness, which is a continuous variable, allowed for the most precise insight into how promoter methylation decreases from stage to stage. Integrating our methylation results with a high-throughput copy number alteration dataset, local correlations were detected in the MYB and EYA4 genes. With regard to the effects of DNA hypermethylation on melanoma patients' survival, correcting for clinical cofounders, only the KIT gene was associated with a lower overall survival rate. In this study, we demonstrate the strong influence of promoter localized DNA methylation changes on melanoma initiation and show how hypermethylation decreases in melanomas associated with less favourable clinical outcomes. Furthermore, we establish the methylation pattern as part of an integrated apparatus of somatic DNA alterations.

  7. Current Status of Biological Therapies for the Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Tang, Tianyi; Eldabaje, Robert; Yang, Lixi

    2016-07-01

    Compared to early-stage melanoma when surgical excision is possible, metastatic disease continues to offer a much grimmer prognosis as traditional chemotherapy treatment regimens offer relatively little survival benefit. This has led to changes in treatment approaches over the preceding two decades as contemporary methods for the treatment of advanced or metastatic melanoma now involve a number of biological modalities, which include immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. Clinically available immunotherapeutic agents include interleukin 2 (IL-2), as well as drugs targeting the important immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v-Raf murine sarcoma viral oncogene homolog B (BRAF), receptor tyrosine kinases, MEK inhibitors and potential future therapeutic targets, such as the CDK4/CDK6, PTEN and GNAQ/GNA11 genes. Additionally, an increasing understanding of the role of epigenetic alterations in the development and progression of melanoma now offers a new potential drug target. Several of these agents have shown promising results; however, in many investigations, combinations of different therapeutic approaches, each with different mechanisms of action, have yielded improved outcomes as treatment regimens continue to be further optimized by active research and patient disease sub-group analyses. This review summarizes the novel biological agents and new treatments, directly contributing to the significant improvement of biological therapies and markedly advancing knowledge of clinical application of newly approved and developed therapies in treatment of patients with metastatic melanoma. PMID:27354579

  8. NFATc2 is an intrinsic regulator of melanoma dedifferentiation.

    Science.gov (United States)

    Perotti, V; Baldassari, P; Molla, A; Vegetti, C; Bersani, I; Maurichi, A; Santinami, M; Anichini, A; Mortarini, R

    2016-06-01

    -specific and HLA-A2-restricted CTL lines, but NFATc2 targeting significantly increased CTL-mediated tumor recognition. Taken together, these results suggest that the expression of NFATc2 promotes melanoma dedifferentiation and immune escape. PMID:26387540

  9. Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients.

    NARCIS (Netherlands)

    Franckena, M.; Lutgens, L.C.; Koper, P.C.; Kleynen, C.E.; Steen-Banasik, E.M. van der; Jobsen, J.J.; Leer, J.W.H.; Creutzberg, C.L.; Dielwart, M.F.; Norden, Y. Van; Canters, R.A.; Rhoon, G.C. van; Zee, J. van der

    2009-01-01

    PURPOSE: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. METHODS AND MATERIALS: From 1996 to

  10. 2015 Groundwater Radiological Monitoring Results Associated with the Advanced Test Reactor Complex Cold Waste Ponds

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Michael George [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This report summarizes radiological monitoring results from groundwater wells associated with the Idaho National Laboratory Site’s Advanced Test Reactor Complex Cold Waste Ponds Reuse Permit (I-161-02). All radiological monitoring is performed to fulfill Department of Energy requirements under the Atomic Energy Act.

  11. Practical experience and results with an advanced on-line gasoline blend optimization system

    Energy Technology Data Exchange (ETDEWEB)

    Serpemen, Y.; Baumeister, K.H.; Hubel, A.; Raichel, P. (Veba Oel Entwicklungs-Gessellschaft mbH, Gelsenkirchen (DE))

    1989-01-01

    Refinery profit margins increased significantly by using the on-line gasoline blend optimization system which allows considerable savings resulting from octane give-away reduction, appreciably enhanced butane utilization, optimum use of the available blend components, and increased operating flexibility by elimination of reblends. The experience with this advanced on-line blending system is described in this paper.

  12. Primary glandular melanoma of male breast with nodal metastasis

    OpenAIRE

    Jayabal Pandiaraja

    2016-01-01

    Malignant melanoma is a malignancy that develops from melanocytes. Breast is an uncommon site for malignant melanoma. Melanoma of the breast occurs in various situations such as primary melanoma of breast skin, metastatic melanoma of breast, in-transit metastasis to the breast, and primary glandular breast melanoma. Most of the melanoma breast either cutaneous melanoma or metastatic melanoma. Primary glandular melanoma of male breast with nodal involvement is rarely reported compared to prima...

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

    Directory of Open Access Journals (Sweden)

    Ascierto Paolo A

    2012-07-01

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

  14. Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

    International Nuclear Information System (INIS)

    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 10B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10B concentration in melanoma after administration of 10B-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 10B1-BPA. (author)

  15. Spontaneous regression of metastases from melanoma: review of the literature

    DEFF Research Database (Denmark)

    Kalialis, Louise Vennegaard; Drzewiecki, Krzysztof T; Klyver, Helle

    2009-01-01

    mechanisms remain unknown, some event must trigger the immune system to produce a stronger than normal response that results in regression of the melanoma metastases. Immunologic studies of patients with regression may disclose the underlying mechanisms and lead to new therapies of disseminated melanoma.......Regression of metastatic melanoma is a rare event, and review of the literature reveals a total of 76 reported cases since 1866. The proposed mechanisms include immunologic, endocrine, inflammatory and metastatic tumour nutritional factors. We conclude from this review that although the precise...

  16. Somatic Mutations in MAP3K5 Attenuate Its Proapoptotic Function in Melanoma through Increased Binding to Thioredoxin

    OpenAIRE

    Prickett, Todd D.; Zerlanko, Brad; Gartner, Jared J; Stephen C. J. Parker; Dutton-Regester, Ken; Lin, Jimmy C.; Jamie K. Teer; Wei, Xiaomu; Jiang, Jiji; ,; Chen, Guo; Davies, Michael A.; Gershenwald, Jeffrey E.; Robinson, William; Robinson, Steven

    2014-01-01

    Patients with advanced metastatic melanoma have poor prognosis and the genetics underlying its pathogenesis are poorly understood. High throughput sequencing has allowed comprehensive discovery of somatic mutations in cancer samples. Here, upon analysis of our whole-genome and whole-exome sequencing data of 29 melanoma samples we identified several genes that harbor recurrent non-synonymous mutations. These included MAP3K5, which in a prevalence screen of 288 melanomas was found to harbor a R...

  17. Microsomal PGE2 synthase-1 regulates melanoma cell survival and associates with melanoma disease progression.

    Science.gov (United States)

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

    2016-05-01

    COX-2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase-1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS-mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1-specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy. PMID:26801201

  18. MALIGNANT MELANOMA – CUTANEOUS METASTASES

    Science.gov (United States)

    Padmavathy, L; Lakshmana Rao, L; Ethirajan, N; Krishna Swamy, B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  19. Multidrug resistance in ocular melanoma.

    OpenAIRE

    McNamara, M.; Clynes, M.; Dunne, B; NicAmhlaoibh, R; Lee, W. R.; Barnes, C; Kennedy, S M

    1996-01-01

    AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap ...

  20. Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model.

    Directory of Open Access Journals (Sweden)

    Goutam Chakraborty

    Full Text Available BACKGROUND: Recent understanding on cancer therapy indicated that targeting metastatic signature or angiogenic switch could be a promising and rational approach to combat cancer. Advancement in cancer research has demonstrated the potential role of various tumor suppressor proteins in inhibition of cancer progression. Current studies have shown that axonal sprouting inhibitor, semaphorin 3A (Sema 3A acts as a potent suppressor of tumor angiogenesis in various cancer models. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be the subject of intense investigation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using multiple in vitro and in vivo approaches we have demonstrated that Sema 3A acts as a potent tumor suppressor in vitro and in vivo mice (C57BL/6 models. Mouse melanoma (B16F10 cells overexpressed with Sema 3A resulted in significant inhibition of cell motility, invasiveness and proliferation as well as suppression of in vivo tumor growth, angiogenesis and metastasis in mice models. Moreover, we have observed that Sema 3A overexpressed melanoma clone showed increased sensitivity towards curcumin and Dacarbazine, anti-cancer agents. CONCLUSIONS: Our results demonstrate, at least in part, the functional approach underlying Sema 3A mediated inhibition of tumorigenesis and angiogenesis and a clear understanding of such a process may facilitate the development of novel therapeutic strategy for the treatment of cancer.

  1. Nodular amelanotic melanoma

    Directory of Open Access Journals (Sweden)

    Nalamwar Rashmi

    2010-01-01

    Full Text Available We report a case of 65-year-old male patient who presented with multiple erythematous papules coalescing to form a nodular mass over posterior aspect of right thigh of six months duration. His general and systemic examinations were within normal range except for right inguinal lymphadenopathy. Biopsy from the lesion was done, which showed diffuse infiltrate of nests of atypical melanocytes extending upto reticular dermis. Malignant cells were positive for S100 and human melanin black 45(HMB 45. Hence, a diagnosis of amelanotic melanoma (AM - Clarke level IV and TNM stage III was reached. MRI of involved leg showed fungating soft tissue mass in the posterolateral aspect of right thigh and metastatic right inguinal adenopathy. Fine needle aspiration cytology (FNAC from the right inguinal nodes confirmed metastasis of melanoma. The patient was referred to oncosurgery department for further management.

  2. Drivers of melanoma susceptibility

    OpenAIRE

    Robles Espinoza, Carla Daniela

    2015-01-01

    Cutaneous melanoma is a cancer of melanocytes, the pigment-producing cells in our skin. It is one of the most aggressive human malignancies, constituting only about 2% of all dermatological cancers but being responsible for over 75% of all deaths from skin cancer. It has recently become a major public health problem, as it is now the fifth most common cancer in the United Kingdom after its incidence more than quadrupled in the last three decades. For these reasons, understanding the biologica...

  3. Vitamins and Melanoma

    OpenAIRE

    Irene Russo; Francesca Caroppo; Mauro Alaibac

    2015-01-01

    A tremendous amount of information was published over the past decades in relation to the role of vitamins in various neoplastic diseases. In particular, several studies showed an inverse relationship between selected vitamins intake and cancer risk. In this review we will focus on the role played by vitamins in melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin supplementation is easy, convenient, and readily accepted by patients, in the future the use of vitamin...

  4. Malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    Manohar S

    1991-01-01

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

  5. Principles of Melanoma Staging.

    Science.gov (United States)

    Boland, Genevieve M; Gershenwald, Jeffrey E

    2016-01-01

    Although now commonplace in contemporary cancer care, the systematic approach to classification of disease-specific cancers into a formalized staging system is a relatively modern concept. Overall, the goals of cancer staging are to characterize the status of cancer at a specific moment in time, risk stratify, facilitate prognostication, and inform clinical decision making. The revisions to the American Joint Committee on Cancer (AJCC) melanoma staging system over time reflect changes in our understanding of the biology of the disease. Since the 1st edition, where tumor thickness was defined anatomically by its relationship to the reticular or papillary dermis (Clark level) as well as tumor thickness (Breslow thickness), there have been significant strides in our use of clinicopathological variables to stratify low- versus high-risk patients. Management of the regional nodal basin has also changed dramatically over time, impacted by techniques such as lymphatic mapping and sentinel lymph node biopsy (SLNB) and changes in pathological evaluation of the regional lymph nodes. Additionally, stratification of distant metastases has evolved as survival outcomes have been shown to vary based upon anatomic site of metastases and serum lactate dehydrogenase levels. The variables in use in the current (7th edition) AJCC staging system are surrogate markers of biology with validated impact of survival outcomes. Going forward, it is likely that these and additional clinicopathological factors will be integrated with molecular and other correlates of melanoma tumor biology to further refine and personalize melanoma staging. PMID:26601861

  6. Experimental results on advanced inertial fusion schemes obtained within the HiPER project

    OpenAIRE

    Honrubia Checa, José Javier; Batani, D; al., et

    2012-01-01

    This paper presents de results of experiments conducted within the Work Package 10 (fusion experimental programme) of the HiPER project. The aim of these experiments was to study the physics relevant for advanced ignition schemes for inertial confinement fusion, i.e. the fast ignition and the shock ignition. Such schemes allow to achieve a higher fusion gain compared to the indirect drive approach adopted in the National Ignition Facility in United States, which is important for the fut...

  7. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    International Nuclear Information System (INIS)

    Highlights: → PAX3 retains embryonic roles in adult melanocytes and melanoma cells. → Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. → Regulates melanoma and melanocyte migration through MCAM and CSPG4. → PAX3 regulates melanoma but not melanocyte proliferation via TPD52. → Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  8. Novel Treatments in Development for Melanoma.

    Science.gov (United States)

    Bernatchez, Chantale; Cooper, Zachary A; Wargo, Jennifer A; Hwu, Patrick; Lizée, Gregory

    2016-01-01

    The past several years can be considered a renaissance era in the treatment of metastatic melanoma. Following a 30-year stretch in which oncologists barely put a dent in a very grim overall survival (OS) rate for these patients, things have rapidly changed course with the recent approval of three new melanoma drugs by the FDA. Both oncogene-targeted therapy and immune checkpoint blockade approaches have shown remarkable efficacy in a subset of melanoma patients and have clearly been game-changers in terms of clinical impact. However, most patients still succumb to their disease, and thus, there remains an urgent need to improve upon current therapies. Fortunately, innovations in molecular medicine have led to many silent gains that have greatly increased our understanding of the nature of cancer biology as well as the complex interactions between tumors and the immune system. They have also allowed for the first time a detailed understanding of an individual patient's cancer at the genomic and proteomic level. This information is now starting to be employed at all stages of cancer treatment, including diagnosis, choice of drug therapy, treatment monitoring, and analysis of resistance mechanisms upon recurrence. This new era of personalized medicine will foreseeably lead to paradigm shifts in immunotherapeutic treatment approaches such as individualized cancer vaccines and adoptive transfer of genetically modified T cells. Advances in xenograft technology will also allow for the testing of drug combinations using in vivo models, a truly necessary development as the number of new drugs needing to be tested is predicted to skyrocket in the coming years. This chapter will provide an overview of recent technological developments in cancer research, and how they are expected to impact future diagnosis, monitoring, and development of novel treatments for metastatic melanoma. PMID:26601872

  9. Interim results of the study of control room crew staffing for advanced passive reactor plants

    Energy Technology Data Exchange (ETDEWEB)

    Hallbert, B.P.; Sebok, A.; Haugset, K. [OECD Halden Reactor Project (Norway)

    1996-03-01

    Differences in the ways in which vendors expect the operations staff to interact with advanced passive plants by vendors have led to a need for reconsideration of the minimum shift staffing requirements of licensed Reactor Operators and Senior Reactor Operators contained in current federal regulations (i.e., 10 CFR 50.54(m)). A research project is being carried out to evaluate the impact(s) of advanced passive plant design and staffing of control room crews on operator and team performance. The purpose of the project is to contribute to the understanding of potential safety issues and provide data to support the development of design review guidance. Two factors are being evaluated across a range of plant operating conditions: control room crew staffing; and characteristics of the operating facility itself, whether it employs conventional or advanced, passive features. This paper presents the results of the first phase of the study conducted at the Loviisa nuclear power station earlier this year. Loviisa served as the conventional plant in this study. Data collection from four crews were collected from a series of design basis scenarios, each crew serving in either a normal or minimum staffing configuration. Results of data analyses show that crews participating in the minimum shift staffing configuration experienced significantly higher workload, had lower situation awareness, demonstrated significantly less effective team performance, and performed more poorly as a crew than the crews participating in the normal shift staffing configuration. The baseline data on crew configurations from the conventional plant setting will be compared with similar data to be collected from the advanced plant setting, and a report prepared providing the results of the entire study.

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

    Science.gov (United States)

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

    2016-07-01

    Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

  11. Meeting report: fourth international congress of the Society for Melanoma Research.

    Science.gov (United States)

    Fisher, David E; Medrano, Estela E; McMahon, Martin; Soengas, Marisol S; Schuchter, Lynn; Wolchok, Jedd D; Merlino, Glenn

    2008-02-01

    The 4th international melanoma congress of the Society for Melanoma Research (SMR), organized by Marianne Berwick (University of New Mexico), Paul Chapman (Memorial Sloan-Kettering Cancer Center), Rene Gonzalez (University of Colorado) and Ze'ev Ronai (Burnham Institute), was held at the Marriott Hotel in downtown New York on November 2007. The congress was attended by a record high number of attendees (over 500 delegates) who joined to discuss recent advances in melanoma biology and therapy. About 40% of the participants arrived from 39 countries, a testament to the high impact of this annual gathering on the international melanoma community. Over 120 of the participants were students or postdoctoral fellows, representing a most impressive fraction of young scientists engaged in melanoma research. The meeting consisted of more than 50 plenary and minisymposia presentations, stimulating the exchange of unpublished data and novel ideas, and helping to forge new collaborations that are anticipated to facilitate significant advances in basic, translational and clinical melanoma research. Another major focus of this meeting was over 160 posters, which were heavily attended and provided an effective forum for extensive informal discussions. This report will highlight the major scientific themes and advances of this most successful meeting, and provide a useful perspective on the current state of melanoma research, as well as where the field should be heading. PMID:18353140

  12. Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

    Science.gov (United States)

    Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

    2016-03-01

    Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. The raw signal detected from target cells often contains some noise caused by electronic devices, such as background noise and thermal noise. We choose the Wavelet denoising method to effectively distinguish the target signal from background noise. Processing in time domain and frequency domain would be combined to analyze the signal after denoising. This algorithm contains time domain filter and frequency transformation. The frequency spectrum image of the signal contains distinctive features that can be used to analyze the property of target cells or particles. The processing methods have a great potential for analyzing signals accurately and rapidly. By counting circulating melanoma cells termly, we obtain the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.

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

    International Nuclear Information System (INIS)

    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.

  14. 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.

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

    OpenAIRE

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

    2010-01-01

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

  16. Pronounced peptide selectivity for melanoma through tryptophan end-tagging

    Science.gov (United States)

    Duong, Dinh Thuy; Singh, Shalini; Bagheri, Mojtaba; Verma, Navin Kumar; Schmidtchen, Artur; Malmsten, Martin

    2016-01-01

    Effects of oligotryptophan end-tagging on the uptake of arginine-rich peptides into melanoma cells was investigated under various conditions and compared to that into non-malignant keratinocytes, fibroblasts, and erythrocytes, also monitoring resulting cell toxicity. In parallel, biophysical studies on peptide binding to, and destabilization of, model lipid membranes provided mechanistic insight into the origin of the selectivity between melanoma and non-malignant cells. Collectively, the results demonstrate that W-tagging represents a powerful way to increase selective peptide internalization in melanoma cells, resulting in toxicity against these, but not against the non-malignant cells. These effects were shown to be due to increased peptide adsorption to the outer membrane in melanoma cells, caused by the presence of anionic lipids such as phosphatidylserine and ganglioside GM1, and to peptide effects on mitochondria membranes and resulting apoptosis. In addition, the possibility of using W-tagged peptides for targeted uptake of nanoparticles/drug carriers in melanoma was demonstrated, as was the possibility to open up the outer membrane of melanoma cells in order to facilitate uptake of low Mw anticancer drugs, here demonstrated for doxorubicin. PMID:27117225

  17. Recent results of a seismically isolated optical table prototype designed for advanced LIGO

    International Nuclear Information System (INIS)

    The Horizontal Access Module Seismic Attenuation System (HAM-SAS) is a mechanical device expressly designed to isolate a multipurpose optical table and fit in the tight space of the LIGO HAM Ultra-High-Vacuum chamber. Seismic attenuation in the detectors' sensitivity frequency band is achieved with state of the art passive mechanical attenuators. These devices should provide an attenuation factor of about 70dB above 10Hz at the suspension point of the Advanced LIGO triple pendulum suspension. Automatic control techniques are used to position the optical table and damp rigid body modes. Here, we report the main results obtained from the full scale prototype installed at the MIT LIGO Advanced System Test Interferometer (LASTI) facility. Seismic attenuation performance, control strategies, improvements and limitations are also discussed

  18. Recent results of a seismically isolated optical table prototype designed for advanced LIGO

    Science.gov (United States)

    Sannibale, V.; Abbott, B.; Aso, Y.; Boschi, V.; Coyne, D.; DeSalvo, R.; Márka, S.; Ottaway, D.; Stochino, A.

    2008-07-01

    The Horizontal Access Module Seismic Attenuation System (HAM-SAS) is a mechanical device expressly designed to isolate a multipurpose optical table and fit in the tight space of the LIGO HAM Ultra-High-Vacuum chamber. Seismic attenuation in the detectors' sensitivity frequency band is achieved with state of the art passive mechanical attenuators. These devices should provide an attenuation factor of about 70dB above 10Hz at the suspension point of the Advanced LIGO triple pendulum suspension. Automatic control techniques are used to position the optical table and damp rigid body modes. Here, we report the main results obtained from the full scale prototype installed at the MIT LIGO Advanced System Test Interferometer (LASTI) facility. Seismic attenuation performance, control strategies, improvements and limitations are also discussed.

  19. First Results of an Experiment on Advanced Collimator Materials at CERN HiRadMat Facility

    CERN Document Server

    Bertarelli, A; Assmann, R; Berthome, E; Boccone, V; Carra, F; Cerutti, F; Charrondiere, C; Dallocchio, A; Donze, M; Francon, P; Garlasche, M; Gentini, L; Guinchard, M; Mariani, N; Masi, A; Moyret, P; Redaelli, S; Rossi, A; Calderon Cueva, M; Charitonidis, N; Peroni, L; Scapin, M

    2013-01-01

    A comprehensive, first-of-its-kind experiment (HRMT-14) has been recently carried out at CERN HiRadMat facility on six different materials of interest for Beam Intercepting Devices (collimators, targets, dumps). Both traditional materials (Mo, W and Cu alloys) as well as advanced metal/diamond and metal/graphite composites were tested under extreme conditions as to pressure, density and temperature, leading to the development of highly dynamic phenomena as shock-waves, spallation, explosions. Experimental data were acquired, mostly in real time, relying on extensive integrated instrumentation (strain gauges, temperature and vacuum sensors) and on remote acquisition devices (laser Doppler vibrometer and high-speed camera). The experiment was a success under all points of view in spite of the technological challenges and harsh environment. First measurements are in good agreement with results of complex simulations, confirming the effectiveness of the acquisition system and the reliability of advanced numerical...

  20. Growth and form of melanoma cell colonies

    OpenAIRE

    Baraldi, Massimiliano Maria; Alemi, Alexander A.; Sethna, James P.; Caracciolo, Sergio; La Porta, Caterina A. M.; Zapperi, Stefano

    2013-01-01

    We study the statistical properties of melanoma cell colonies grown in vitro by analyzing the results of crystal violet assays at different concentrations of initial plated cells and for di?erent growth times. The distribution of colony sizes is described well by a continuous time branching process. To characterize the shape fluctuations of the colonies, we compute the distribution of eccentricities. The experimental results are compared with numerical results for models of random division of...

  1. Thermal neutron capture therapy: The Japanese-Australian clinical trial for malignant melanoma

    International Nuclear Information System (INIS)

    Following the first NCT treatment for melanoma last year in Japan, it is planned to treat at least 12 patients during 1988, from Australia and Japan. Patients will be selected from those having evaluable superficial or subcutaneous local recurrence or isolated metastasis. In addition, selected Japanese patients with thick primary acral-lentiginous melanoma or superficially spreading melanoma that have poor prognosis with conventional therapy will be treated with NCT. Australian patients will be selected from those attending the Sydney Melanoma Unit at Royal Prince Alfred Hospital. They will have no detectable deep-seated distant metastases and should have an estimated life expectancy of at least 6 months. Locally recurrent or advanced melanoma are rare conditions, thanks to the increased awareness of the public and general practitioners and to the more stringent procedures adopted by surgeons

  2. Keeping a watch on melanoma.

    Science.gov (United States)

    Casparian, J Michael; Rodewald, Erin J

    2002-05-01

    When performing a total body skin examination, we discovered a melanoma in situ when a patient took off her wristwatch. This case illustrates the importance of removing jewelry when performing a complete skin examination. Furthermore, the location of this lesion highlights the association between malignant melanoma and intermittent sun exposure. PMID:12041820

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

    Directory of Open Access Journals (Sweden)

    Nicola G Ghazi

    2008-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-01

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

  5. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma

    DEFF Research Database (Denmark)

    Larkin, James; Chiarion-Sileni, Vanna; Gonzalez, Rene; Grob, Jean Jacques; Cowey, C Lance; Lao, Christopher D; Schadendorf, Dirk; Dummer, Reinhard; Smylie, Michael; Rutkowski, Piotr; Ferrucci, Pier F; Hill, Andrew; Wagstaff, John; Carlino, Matteo S; Haanen, John B; Maio, Michele; Marquez-Rodas, Ivan; McArthur, Grant A; Ascierto, Paolo A; Long, Georgina V; Callahan, Margaret K; Postow, Michael A; Grossmann, Kenneth; Sznol, Mario; Dreno, Brigitte; Bastholt, Lars; Yang, Arvin; Rollin, Linda M; Horak, Christine; Hodi, F Stephen; Wolchok, Jedd D

    2015-01-01

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

  6. Herpetic viruses and spontaneous recovery in melanoma.

    Science.gov (United States)

    Motofei, I G

    1996-08-01

    The malignant melanoma may display extremely variable forms of development, from clinical forms with a lethal course to the unforeseeable situations of spontaneous cures. The basic immunotherapeutic procedures, as well as hypotheses regarding the mechanisms involved in courses towards spontaneous regressions, are presented. Since viruses of the herpes genus are involved in the mechanisms assumed to be at the basis of spontaneous regressions, it is suggested that these viruses (selected strains) be used in the clinic, in order to check the advanced hypothesis, an opportunity which could permit to study also the very probable therapeutic alternative offered by this virus, namely the association of the well-known immunotherapeutic methods. PMID:8869920

  7. Sentinel lymph node biopsy in local recurrence of cutaneous melanoma

    International Nuclear Information System (INIS)

    Full text: Locally recurrent disease in patients with melanoma is usually defined as cutaneous or subcutaneous arising within 5 cm of the primary site after complete excision of the primary lesion. It may represent residual disease not excised with the primary tumor or the outgrowth of the satellite lesions, which are common with melanoma. Lymphatic mapping and sentinel lymph node (SLN) biopsy is highly accurate in staging nodal basins at risk of regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Our purpose was to evaluate the efficacy of sentinel lymph node mapping and biopsy in local recurrence of cutaneous melanoma when the primary lesion was less than 1.0mm thick. Three patients with local recurrence of cutaneous melanoma underwent sentinel lymph node mapping and biopsy. All patients underwent preoperative lymphoscintigraphy to identify the lymphatic basin and the site of the sentinel node. All patients subsequently underwent intra-operative lymphatic mapping and selective lymph node biopsy with vital blue dye and hand-held gamma probe. Excised SLN were analysed by conventional histological staining (H and E) and immunohistochemical staining. In all patients the lymphatic mapping and sentinel lymph node biopsy was successful. The SLN biopsy was negative in two patients and positive in one who underwent therapeutic lymph node dissection. Our results indicate that the SLN mapping and biopsy is also possible in patients having local recurrence of cutaneous melanoma. Although long-term results are not available, early results are promising. (author)

  8. Primary Desmoplastic Melanoma of the Penis

    OpenAIRE

    Chu, Julia T.; Liss, Michael A; Wu, William W.; Atreya Dash; Di Lu

    2015-01-01

    Desmoplastic melanomas are rare amelanotic melanomas that usually occur on skin with sun exposure. In this report, we present a 72-year-old man who presented with a desmoplastic melanoma of the penis. To our knowledge this represents the first reported case of primary desmoplastic melanoma of the penis. We discuss the pathologic differential and histologic evaluation.

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

    OpenAIRE

    Fisher, Paul B.; Sarkar, Devanand; LEBEDEVA, IRINA V.; Emdad, Luni; Gupta, Pankaj; Sauane, Moira; Su, Zao-Zhong; Grant, Steven; Dent, Paul; Curiel, David T.; Senzer, Neil; Nemunaitis, John

    2006-01-01

    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 e...

  10. Brain metastases from malignant melanoma.

    Science.gov (United States)

    Chiarion-Sileni, Vanna; Murr, Rita; Pigozzo, Jacopo; Sarti, Samanta; Tomassi, Ottaviano; Romanini, Antonella

    2003-01-01

    Metastatic spread of tumour cells detached from melanoma into the central nervous system (CNS) occurs haematogenously since lymphatic drainage is absent in the brain. CNS metastases occur in 10 to 40% of melanoma patients in clinical studies and up to 90% in autopsy studies. Headache is the most common presenting symptom, but brain metastases should be suspected in all melanoma patients with new neurologic findings. Magnetic resonance imaging is the best diagnostic technique for detecting CNS metastases. Median survival of melanoma patients with CNS metastases ranges between 2 and 8 months. The optimal treatment of melanoma patients with CNS metastases depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy are used in combination to obtain longer remissions and optimal symptom relieve. PMID:14732883

  11. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

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

    Directory of Open Access Journals (Sweden)

    Georgios Androutsopoulos

    2013-01-01

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

  13. Advances in derivation of Birkeland currents from iridium. Initial results from AMPERE development

    International Nuclear Information System (INIS)

    Complete text of publication follows. Because Birkeland currents are the means for conveying stress between the magnetosphere and ionosphere, the measurement of their distribution and dynamics is critical to advancing magnetosphere-ionosphere (M-I) science. Although much is known about the distributions of Birkeland currents from satellite observations we still have limited understanding of their dynamics as the M-I system changes state or of their configuration and dynamics under extreme conditions. We therefore use the magnetometer data from the Iridium constellation of more than 70 satellites in low altitude, circular, polar orbits to assess the Birkeland currents. These data, acquired for scientific use since February 1999, allow determination of the two-dimensional distribution and intensity of Birkeland currents with a few degree resolution in latitude from about one hour of observations. Here we report results obtained using advances in processing and sample higher time resolution data supported under development of NSF's Active Magnetosphere and Polar Electrodynamics Response Experiment (AMPERE) project. In particular, we have advanced the processing to allow use of the full horizontal vector for the Birkeland current inversions. This allows much more robust inversions of the currents which we use to make more detailed comparisons between different instances of M-I states, compare northern and southern hemisphere distributions and contrast different storm phases. We also present initial examples of higher sampling rate data acquired under AMPERE testing development to indicate the advances in observing capability that will be afforded by AMPERE when high-time resolution Iridium data become routinely available.

  14. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

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

  15. The spectrum of in vitro radiosensitivity in four human melanoma cell lines is not accounted for by differential induction or rejoining of DNA double strand breaks

    International Nuclear Information System (INIS)

    Purpose: Radioresistance is a significant clinical problem in advanced malignant melanoma and many melanoma cell lines show a radioresistant acute x-ray survival response in vitro. Given that the DNA double strand break is the lesion most closely correlated with x-ray induced cell lethality, differences in the induction and rejoining of these lesions may account for the radioresistance of some human melanoma cell lines. Methods and Materials: The above hypothesis was tested using pulsed field gel electrophoresis to measure x-ray induced DNA double strand break induction and rejoining in four human melanoma cell lines: MM138, MM170, MM96-L and HT 144. Results: The MM138, MM170 and MM96-L cell lines were characterized in vitro by low (α(β)) ratios and board x-ray survival curve shoulders. MM138 and MM170 were the most radioresistant and MM96-L had intermediate sensitivity. In contrast, HT144 was markedly x-ray sensitive, despite retaining a shoulder and like the other lines, having a low (α(β)) ratio. There were no significant differences in DNA double strand break induction between the cell lines, and thus no correlation existed between DNA double strand break induction and radiosensitivity. Consistent with the shoulders on the x-ray survival curves, all four cell lines showed efficient DNA double strand break rejoining. Highly efficient DNA double strand break rejoining could account for the radioresistance of one of the melanoma lines (MM138). For example, MM138 had rejoined 50% of the induced DNA double strand breaks by 5.5 min compared to 13-17 min for the other three cell lines. The development of postirradiation apoptosis was effectively excluded as the cause of the marked radiosensitivity of the HT144 cell line. Conclusion: Other factors (such as lesion repair fidelity or differential lesion tolerance) underlie the differences in the intrinsic radiosensitivity between these melanoma cell lines

  16. Primary Malignant Melanoma of Maxilla: Report of a Case with Discussion

    Directory of Open Access Journals (Sweden)

    G. Shirisha Rani

    2014-01-01

    Full Text Available Primary oral malignant melanoma, very rare neoplasm of melanocytic origin, usually presents as a bluish black to tan-brown colored lesion Which is accounting for 0.2 to 8% of all melanomas, 1.6% of all head and neck malignancies, and 0.5% of all oral neoplasia. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. Here a case of oral malignant melanoma is presented, which was undetected during the first visit to a dental clinic. When a simple oral surgical treatment was carried out in that region, it resulted in the appearance of a massive pigmented lesion which was histopathologically diagnosed as malignant melanoma. This paper is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be viewed with suspicion and proper investigation (biopsy should be carried out to rule out any untoward experiences later.

  17. Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T.

    Science.gov (United States)

    Benguedouar, Lamia; Lahouel, Mesbah; Gangloff, Sophie C; Durlach, Anne; Grange, Florent; Bernard, Philippe; Antonicelli, Frank

    2016-01-01

    Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated. PMID:26863880

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

    Directory of Open Access Journals (Sweden)

    Caglayan Geredeli

    2015-01-01

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

  19. A combination of p300 and Braf expression in the diagnosis and prognosis of melanoma

    International Nuclear Information System (INIS)

    To date only a handful of drugs are available for the treatment of melanoma. Among them vemurafenib, a BrafV600E specific inhibitor, showed promising results in terms of response rate and increase in median survival time. However, its effectiveness is limited by development of resistance and the search for additional drugs for melanoma treatment is ongoing. The present study was performed to analyze the correlation between Braf expression and the expression of p300, a known down stream target of the mitogen activated protein kinase (MAPK) pathway, which was recently shown by us to be a prognostic marker for melanoma progression and patient survival. The expression of Braf and p300 expression were correlated and analyzed by Chi-square test. A total of 327 melanoma patient cases (193 primary melanoma and 134 metastatic melanoma) were used for the study. Classification & regression tree (CRT), Kaplan-Meier, and multivariate Cox regression analysis were used to elucidate the significance of the combination of Braf and p300 expression in the diagnosis and prognosis of melanoma. Our results demonstrate that Braf expression is inversely correlated with nuclear p300 and positively correlated with cytoplasmic p300 expression. Braf and cytoplasmic p300 were found to be associated with melanoma progression, tumor size and ulceration status. CRT analysis revealed that a combination of Braf and p300 expression (nuclear and cytoplasmic), could be used to distinguish between nevi and melanoma, and primary from metastatic melanoma lesions. The combination of Braf and nuclear p300 was significantly associated with patient survival and nuclear p300 was found to be an independent predictor of patient survival. Our results indicate a cross-talk between Braf and p300 in melanoma and demonstrate the importance Braf and p300 expression in the diagnosis and prognosis of melanoma

  20. Non-melanoma skin cancer.

    Science.gov (United States)

    Griffin, Liezel L; Ali, Faisal Rehman; Lear, John T

    2016-02-01

    Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC. PMID:26833519

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

    Directory of Open Access Journals (Sweden)

    Andersen Mads

    2006-03-01

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

  2. Radiotherapy combined with cetuximab for locally advanced head and neck cancer: Results and toxicity

    International Nuclear Information System (INIS)

    Purpose. - To describe the clinical results and tolerance of the combined treatment with radiotherapy and cetuximab for locally advanced head and neck cancer. Patients and methods. - From August 2006 and October 2010, 36 patients with advanced squamous cell head and neck carcinoma were treated with radiotherapy (70 Gy/35 fractions) and cetuximab (400 mg/m2 one week before radiotherapy, following by 250 mg/m2 once weekly, until week 7 of radiotherapy). Tolerance was evaluated every week. All patients were examined every 3 months the first 3 years after therapy, and then every year. Results. - The median follow-up was 14 months. The majority of patients were male (31 out of 36). Mean age was 59 years. The tumours sites were: oral cavity (n 8); oropharynx (n = 15); hypopharynx (n = 5); larynx (n = 8). Ninety percent of tumors were T3 or T4, and 45% were N2 or N3. Complete response was seen in 74% of patients, partial response in 17% and no response in 9% of patients. The overall survival was 44.4%. Relapse occurred in six patients. Anaphylactic reaction during the first infusion of cetuximab was observed in one patient. One patient developed severe aplasia after 48 Gy and 5 weeks of cetuximab, and died of sepsis. Eighty percent of patients presented acne, 16 patients developed a mucositis grade 2-3 and 23 patients a grade 2 skin reaction. Conclusion. - The concomitant use of cetuximab and radiotherapy in locally advanced head and neck carcinoma is well tolerated in this group of patients. The results seem comparable to those in the literature. (authors)

  3. Oral amelanotic melanoma of the maxilla.

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2014-12-01

    Full Text Available Amelanotic melanoma is a variant of malignant melanoma comprising 2% to 8% of all malignant melanomas. The amelanotic presentation of melanoma in the oral cavity is extremely rare and has been reported only occasionally in the literature. Moreover, the lack of melanin makes these tumors difficult to diagnose than that of pigmented lesions and the prognosis tends to be poorer. Herein, we report an amelanotic melanoma involving the oral mucosa of the maxilla in a 27 year-old male.

  4. Advanced Test Reactor In-Canal Ultrasonic Scanner: Experiment Design and Initial Results on Irradiated Plates

    Energy Technology Data Exchange (ETDEWEB)

    D. M. Wachs; J. M. Wight; D. T. Clark; J. M. Williams; S. C. Taylor; D. J. Utterbeck; G. L. Hawkes; G. S. Chang; R. G. Ambrosek; N. C. Craft

    2008-09-01

    An irradiation test device has been developed to support testing of prototypic scale plate type fuels in the Advanced Test Reactor. The experiment hardware and operating conditions were optimized to provide the irradiation conditions necessary to conduct performance and qualification tests on research reactor type fuels for the RERTR program. The device was designed to allow disassembly and reassembly in the ATR spent fuel canal so that interim inspections could be performed on the fuel plates. An ultrasonic scanner was developed to perform dimensional and transmission inspections during these interim investigations. Example results from the AFIP-2 experiment are presented.

  5. Evaluation of how the LUCOEX results can be utilized by less-advanced programs

    OpenAIRE

    Wiberg, Ann Caroline

    2015-01-01

    The objective with this report is to study how results from the LUCOEX (Large Underground Concept Experiments) project can be utilized by less-advanced radioactive waste management programs, with respect to high-level waste and spent fuel, in member states of the European Union. Also an evaluation of how far these countries have come in their radioactive waste programs has been made. High-level long-lived waste and spent fuel requires the most comprehensive disposal of all types of radioactiv...

  6. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: First Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2011-03-01

    This report describes operations at SunLine Transit Agency for their newest prototype fuel cell bus and five compressed natural gas (CNG) buses. In May 2010, SunLine began operating its sixth-generation hydrogen fueled bus, an Advanced Technology (AT) fuel cell bus that incorporates the latest design improvements to reduce weight and increase reliability and performance. The agency is collaborating with the U.S. Department of Energy's (DOE) National Renewable Energy Laboratory (NREL) to evaluate the bus in revenue service. This report provides the early data results and implementation experience of the AT fuel cell bus since it was placed in service.

  7. 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.

  8. Spectral regions contributing to melanoma: a personal view.

    Science.gov (United States)

    Setlow, R B

    1999-09-01

    Although human cutaneous melanoma is a complicated disease, the principal etiologic agent for its incidence in fair skin individuals is exposure to sunlight. In order to understand the epidemiology of melanoma - temporal effects, latitude effects, sunscreen effects, albino susceptibility, and differences from nonmelanoma skin cancer -one must approach the problem by obtaining clues indicating which wavelengths in sunlight are effective in inducing melanomas. One way is to use an animal model. At present, the only suitable model is a backcross hybrid of small tropical fish of the genus Xiphophorus, bred to have only one tumor suppressor gene. Single UV exposures to 7-d-old fish induce melanomas readily observable by 4 mo. The initial slopes of dose-response curves for exposures at 302, 313, 365, 405, 436, and 547 nm yield sensitivity as a function of wavelength. This action spectrum does not look like the spectrum for light absorption by DNA (mostly in the UVB), but has appreciable sensitivities in the UVA and visible regions, and looks like a direct effect of light on DNA plus a large indirect effect on DNA by absorption of light by the intracellular melanin. Because the UVB is only a fraction of solar irradiance, one may calculate that 90% of melanoma induction in humans arises from UVA and visible, assuming the human spectrum is similar to the fish spectrum. The implications of this calculation are that (i) depletion of stratospheric ozone will not affect melanoma incidence, (ii) an increase in sun exposure time as a result of using UVB sunscreens could increase the risk of melanoma, and (iii) the use of high UVA sun tanning devices could increase the risk of melanoma. PMID:10537007

  9. Thermochemoradiotherapy for advanced or recurrent head and neck cancer. Analysis of clinical results and background variables

    Energy Technology Data Exchange (ETDEWEB)

    Hoshina, Hideyuki; Takagi, Ritsuo; Nagashima, Katsuhiro; Fujita, Hajime; Miyamoto, Takeshi; Sohma, Yoh; Fukuda, Jun-ichi; Imai, Nobuyuki; Nagata, Masaki [Niigata Univ. (Japan). Faculty of Dentistry

    2001-03-01

    Eighteen patients with 25 unresectable advanced or recurrent head and neck cancers (squamous cell carcinomas) received thermochemotherapy in combination with radiotherapy. The total radiation dose ranged from 50 to 82 Gy (mean, 65.6 Gy). Patients received thermochemotherapy twice a week, for a total number of 8.8 sessions, on average. The temperature in the tumor, as a result of the hyperthermia, was over 42 deg C in 185 (84.5%) of the 219 treatments. Three kinds of heating systems were used: a 13.56-MHz radiofrequency system, a 2450-MHz microwave system, and a radiofrequency interstitial system. The total amount of administered CDDP ranged from 40 to 300 mg (mean, 110 mg), combined with PEP and/or 5FU. Background factors (tumor factors and treatment factors) were investigated in detail, and the clinical results (tumor response and the 5-year cumulative focal control rate) were evaluated. The relationship between these two results was then analyzed using univariate and multivariate statistics. The clinical results of patients with a WHO histological classification of grade 3 were poor compared with patients with a classification of grade 1 or 2. The difference between these two results was significant when analyzed using univariate statistics, but not significant when analyzed using multivariate statistics. The clinical results of patients with primary lesions surrounded by bony tissues were slightly poor compared with those of patients whose lesions were surrounded by soft tissues, but the difference between these two results was not significant. Successful treatment of refractory recurrent tumors, large tumor masses, and diffuse invasive carcinomas was not affected by the treatment factors (heating systems, heating sessions, radiation dose, and CDDP dose and drug combination). These results suggest that refractory recurrence, proximity to bony tissues, tumor size, and histological malignancy might not be prognostic variables for thermochemoradiotherapy strategy

  10. Malignant cutaneous melanoma in patients from Las Tunas province

    Directory of Open Access Journals (Sweden)

    Alicia María Yabor Palomo

    2015-11-01

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

  11. Parkin Somatic Mutations Link Melanoma and Parkinson's Disease.

    Science.gov (United States)

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

    2016-06-20

    Epidemiological studies suggest a direct link between melanoma and Parkinson's disease (PD); however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in 3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson's disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases. PMID:27297116

  12. Dietary Antioxidants and Melanoma: Evidence from Cohort and Intervention Studies.

    Science.gov (United States)

    Miura, Kyoko; Green, Adèle C

    2015-01-01

    Melanoma is the most serious form of skin cancer affecting mostly people of Caucasian origin and is associated with high exposure to solar ultraviolet (UV) radiation. Antioxidants in the diet are thought to prevent UV-induced DNA damage and oxidative stress and laboratory-based studies have shown that high antioxidant intakes inhibit melanoma development. Corresponding epidemiological evidence is inconsistent, however. We therefore reviewed results from prospective observational studies and randomized controlled trials (RCTs) to clarify whether consumption of antioxidant vitamin C, E (tocopherol), and A (retinol), carotenoids and selenium, as food, supplements, or both, or high fruit and vegetable intake, reduce the incidence of cutaneous melanoma. A total of 9 studies (2 cohort, 1 nested case-control, 6 RCTs) were included. Neither antioxidant nutrients, individually or combined, nor fruit and vegetable intake showed any strong and significant associations with melanoma, though the number of relevant studies was limited and several had methodological shortcomings. In particular, melanoma was not a primary disease outcome in any of the RCTs and therefore, none adequately accounted for potential confounding by sun exposure. In conclusion, available evidence is currently inadequate to assess possible beneficial effects of antioxidant intake on melanoma risk. PMID:26147450

  13. Treatment Result in Advanced T3 and T4 Glottic Carcinoma; YUMC Experience

    International Nuclear Information System (INIS)

    Between January 1980 and September 1988, 68 patients with advanced T3 and T4 glottic carcinoma were treated with RT and surgery/RT in the Department of Radiation Oncology, Yonsei Cancer Center and ENT, Yonsei University College of Medicine. The mean age was 60 years old (range 33 to 79 year old). The 34 patients were treated with irradiation alone, and the remaining 34 patients with surgery and irradiation. Initial nodal presentation was 37% (25/68); 31% (11/34) in RT alone group and 41% (14/34) in combined treatment group. The minimum follow-up was 2 years. The local control rate after treatment was 47% in RT alone group and 65% in combined treatment group; 57% for node negative and 27% for node positive patients treated with RT alone; 65% for node negative and 64% for node positive patients treated with combined treatment. The treatment failure was observed in 30 patients; 14 patients for primary local failure, 6 patients for regional nodal failure, 6 patients for local and regional failure, 26 patients for primary failure and/or distant metastasis, and 2 patient for regional failure and/or distant metastasis. The overall 5-year survival rate was 57%; 37% in RT alone group and 76% in combined treatment group; 55% for node negative and 20% for node positive patients treated with RT alone; 73% for node negative and 77% for node positive patients treated with combined treatment. In conclusion, the combined treatment groups in the treatment of advanced T3 and T4 glottic cancer showed the better results in local control rates and 5-year actuarial survival rates than RT alone group. We suggest that total laryngectomy and postoperative RT in the most patients of advanced glottic cancer were performed. However, in cases of node negative patients, RT alone is prefer as a treatment modality over combined surgery and RT since the treatment results were comparable and furthermore functional preservation could be achieved

  14. Sentinel Node in Breast Cancer, Melanoma and Penis: Experience in Clinical Fundacion Valle del Lili

    International Nuclear Information System (INIS)

    Objectives: Describe the results of sentinel node biopsy (GC) in patients with breast cancer, melanoma, and penis, FVL. Study Design: Descriptive study. Patients: 60 patients diagnosed with breast cancer, melanoma and penis referred to nuclear medicine FVL between June 29, 2003 and June 31, 2007, for detection of sentinel node. Conclusions: The combination of dye and lymphogammagraphy with gammagraphical probe facilitate localization of sentinel nodes in breast cancer, melanoma and penis. Preoperative mapping in melanoma of the trunk is recommended for planning of surgery. There is an adequate correlation between the freezing and final histopathology

  15. Interim report on the performance test results for the Advanced Verification for Inventory sample System (AVIS)

    International Nuclear Information System (INIS)

    The AVIS (Advanced Verification for Inventory sample System) is a high accuracy nondestructive assay (NDA) system for Safeguards to measure the plutonium mass for plutonium uranium mixed oxide (MOX) powder and pellet for large scale MOX fuel fabrication plant (J-MOX). It is intended that the AVIS measurement will be substituted for a fraction of the DA samples to reduce the number of DA from J-MOX. Therefore, the AVIS has a crucial role to attain effective safeguards for J-MOX. JAEA, which has experience/knowledge to develop the NDA system and plutonium handling field, was entrusted with performance testing for the AVIS from NMCC. JAEA has conducted performance testing on the AVIS using standard radiation source (neutron and gamma). As the results of test, it was confirmed that the AVIS has the designed performance. This paper reports the performance test results and evaluation results of measurement accuracy of the AVIS. (author)

  16. Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer.

    Science.gov (United States)

    McEwan, Conor; Nesbitt, Heather; Nicholas, Dean; Kavanagh, Oisin N; McKenna, Kevin; Loan, Philip; Jack, Iain G; McHale, Anthony P; Callan, John F

    2016-07-01

    Sonodynamic therapy (SDT) involves the activation of a non-toxic sensitiser drug using low-intensity ultrasound to produce cytotoxic reactive oxygen species (ROS). Given the low tissue attenuation of ultrasound, SDT provides a significant benefit over the more established photodynamic therapy (PDT) as it enables activation of sensitisers at a greater depth within human tissue. In this manuscript, we compare the efficacy of aminolevulinic acid (ALA) mediated PDT and SDT in a squamous cell carcinoma (A431) cell line as well as the ability of these treatments to reduce the size of A431 ectopic tumours in mice. Similarly, the relative cytotoxic ability of Rose Bengal mediated PDT and SDT was investigated in a B16-melanoma cell line and also in a B16 ectopic tumour model. The results reveal no statistically significant difference in efficacy between ALA mediated PDT or SDT in the non-melanoma model while Rose Bengal mediated SDT was significantly more efficacious than PDT in the melanoma model. This difference in efficacy was, at least in part, attributed to the dark pigmentation of the melanoma cells that effectively filtered the excitation light preventing it from activating the sensitiser while the use of ultrasound circumvented this problem. These results suggest SDT may provide a better outcome than PDT when treating highly pigmented cancerous skin lesions. PMID:27234890

  17. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    International Nuclear Information System (INIS)

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m2 d1, 5FU 800 mg/m2 d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment

  18. Simultaneous chemoradiotherapy with Taxol/Carboplatin in advanced head and neck cancer. Preliminary results

    International Nuclear Information System (INIS)

    Background: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent and as well in combination drug regimens. In the present outpatient phase-II trial we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable Stage-III/IV squamous cell carcinoma of the oral cavity and oropharynx. Patients and Methods: Twelve patients were enrolled in this ongoing trial with a projected number of 30 patients and received 5 cycles of weekly Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3 to 4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. Results: So far 12 patients were evaluable for toxicity and response. Complete response was noted in 8/12 patients (Cr 66%). In 6/10 patients (60%) complete pathologic response was documented in the resection specimens. Conclusion: Our preliminary results demonstrated excellent clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as preoperative treatment modality in advanced oral and oropharyngeal cancer. (orig.)

  19. Preliminary results of proton therapy in choroidal melanoma at the centre de proton therapy d`Orsay (C.P.O.): 464 initial cases; Resultats preliminaires de la protontherapie du melanome de la choroide au centre de protontherapie d`Orsay (CPO): les 464 premiers cas

    Energy Technology Data Exchange (ETDEWEB)

    Desjardins, L.; Levy, C.; D`hermies, F.; Frau, E.; Schlienger, P.; Habrand, J.L.; Mammar, H.; Schwartz, L.; Mazal, A.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Asselain, B. [Centre de protontherapie d`Orsay, 91 - Orsay (France)

    1997-06-01

    Retrospective analysis of the treatment of choroidal melanoma with proton-therapy at the Centre de protontherapie d`Orsay, France. Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by proton-therapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. Univariate analysis showed that the actuarial local recurrence rate was 5 %, the 3-year survival rate 88 %, and the overall metastatic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. Proton-therapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor. (author) 16 refs.

  20. 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.

  1. Ocular Response of Choroidal Melanoma With Monosomy 3 Versus Disomy 3 After Iodine-125 Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To report the ocular response of choroidal melanoma with monosomy 3 vs. disomy 3 after 125I brachytherapy. Methods and Materials: We evaluated patients with ciliochoroidal melanoma managed with fine needle aspiration biopsy immediately before plaque application for 125I brachytherapy between January 1, 2005 and December 31, 2008. Patients with (1) cytopathologic diagnosis of melanoma, (2) melanoma chromosome 3 status identified by fluorescence in situ hybridization, and (3) 6 or more months of follow-up after brachytherapy were sorted by monosomy 3 vs. disomy 3 and compared by Kruskal-Wallis test. Results: Among 40 ciliochoroidal melanomas (40 patients), 15 had monosomy 3 and 25 had disomy 3. Monosomy 3 melanomas had a median greatest basal diameter of 12.00 mm and a median tumor thickness of 6.69 mm before brachytherapy; at a median of 1.75 years after brachytherapy, median thickness was 3.10 mm. Median percentage decrease in tumor thickness was 48.3%. Disomy 3 melanomas had a median greatest basal diameter of 10.00 mm and median tumor thickness of 3.19 mm before brachytherapy; at a median of 2.00 years after brachytherapy, median tumor thickness was 2.37 mm. The median percentage decrease in tumor thickness was 22.7%. Monosomy 3 melanomas were statistically greater in size than disomy 3 melanomas (p < 0.001) and showed a greater decrease in tumor thickness after brachytherapy (p = 0.006). Conclusion: In this study, ciliochoroidal melanomas with monosomy 3 were significantly greater in size than disomy 3 melanoma and showed a significantly greater decrease in thickness at a median of 1.75 years after brachytherapy. The greater decrease in monosomy 3 melanoma thickness after brachytherapy is consistent with other malignancies in which more aggressive pathology has been shown to be associated with a greater initial response to radiotherapy.

  2. Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

    Directory of Open Access Journals (Sweden)

    Kim Jung Han

    2010-04-01

    Full Text Available Abstract Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5% satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2% which was followed by nasal cavity (n = 30, 23.3%, genitourinary (n = 21, 16.3%, oral cavity (n = 14, 10.9%, upper gastrointestinal tract (n = 6, 4.7% and maxillary sinus (n = 5, 3.9% in the order of frequency. With the median 64.5 (range 4.3-213.0 months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5 for all patients, and 34.6 (95% CI 24.5-44.7 months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin, and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04. Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome.

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

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-chou; LEE Shih-tseng

    2007-01-01

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

  4. Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer: Results of feasibility study

    Institute of Scientific and Technical Information of China (English)

    Yong-Rui Bai; Guo-Hua Wu; Wei-Jian Guo; Xu-Dong Wu; Yuan Yao; Yin Chen; Ren-Hua Zhou; Dong-Qin Lu

    2003-01-01

    AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer.METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial,Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54,57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course.RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Kamofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35 %. No patient suffered more than grade Ⅲ acute toxicities induced by radiotherapy.CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.

  5. Morphogenesis of early stage melanoma

    Science.gov (United States)

    Chatelain, Clément; Amar, Martine Ben

    2015-08-01

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

  6. METASTATIC MALIGNANT MELANOMA: CASE REPORT

    Directory of Open Access Journals (Sweden)

    Satish

    2015-06-01

    Full Text Available A 32 year s old man presented with well - defined lesion on the left sole 8 months back. Biopsy and FNAC from the lesion confirmed malignant melanoma left foot & the patient was advised excision. After 4 months patient gave h/o swelling on the medial aspect of the thigh. The patient was diagnosed to have fulminant metastatic malignant melanoma of the left foot with metastasis to femoral lymph node. This case report re - emphasizes the importance of the combined approach to ascertain diagnose early KEYWORDS : Melanoma .

  7. Uveal Melanoma UK National Guidelines.

    Science.gov (United States)

    Nathan, P; Cohen, V; Coupland, S; Curtis, K; Damato, B; Evans, J; Fenwick, S; Kirkpatrick, L; Li, O; Marshall, E; McGuirk, K; Ottensmeier, C; Pearce, N; Salvi, S; Stedman, B; Szlosarek, P; Turnbull, N

    2015-11-01

    The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website. PMID:26278648

  8. SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Fourth Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Chandler, K.

    2013-01-01

    SunLine Transit Agency, which provides public transit services to the Coachella Valley area of California, has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technology (AT) fuel cell bus with a hybrid electric propulsion system, fuel cell power system, and lithium-based hybrid batteries. This report describes operations at SunLine for the AT fuel cell bus and five compressed natural gas buses. The U.S. Department of Energy's National Renewable Energy Laboratory (NREL) is working with SunLine to evaluate the bus in real-world service to document the results and help determine the progress toward technology readiness. NREL has previously published three reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from February 2012 through November 2012.

  9. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    International Nuclear Information System (INIS)

    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

  10. Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell proliferation, migration and adhesion

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  12. 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.

  13. 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.

  14. SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience

    International Nuclear Information System (INIS)

    To assess the efficacy and safety of stereotactic body radiotherapy (SBRT) in patients with either unresectable locally advanced pancreatic adenocarcinoma or by locally recurrent disease after surgery. Between January 2010 and October 2011, 30 patients with unresectable or recurrent pancreatic adenocarcinoma underwent exclusive SBRT. Twenty-one patients (70%) presented with unresectable locally advanced disease and 9 patients (30%) showed local recurrence after surgery. No patients had metastatic disease. Gemcitabine-based chemotherapy was administered to all patients before SBRT. Prescription dose was 45Gy in 6 daily fractions of 7.5Gy. SBRT was delivered using the volumetric modulated arc therapy (VMAT) by RapidArc. Primary end-point of this study was freedom from local progression (FFLP), secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Median Clinical Target Volume (CTV) was 25.6 cm3 (3.2-78.8 cm3) and median Planning Target Volume (PTV) was 70.9 cm3 (20.4- 205.2 cm3). The prescription dose was delivered in 25 patients (83%), in 5 patients (17%) it was reduced to 36Gy in 6 fractions not to exceed the dose constraints of organs at risk (OARs). Median follow-up was 11 months (2–28 months). FFLP was 91% at 6 months, 85% at median follow-up and 77% at 1 and 2 years. For the group with prescription dose of 45Gy, FFLP was 96% at 1 and 2 years. The median PFS was 8 months. The OS was 47% at 1 year and median OS was 11 months. At the end of the follow-up, 9 patients (32%) were alive and 4 (14%) were free from progression. No patients experienced G ≥ 3 acute toxicity. Our preliminary results show that SBRT can obtain a satisfactory local control rate for unresectable locally advanced and recurrent pancreatic adenocarcinoma. This fractionation schedule is feasible, and no G ≥ 3 toxicity was observed. SBRT is an effective emerging technique in the multi-modality treatment of locally advanced pancreatic tumors

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

    Directory of Open Access Journals (Sweden)

    Carlos Gustavo Leite Vieira

    2000-10-01

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

  16. 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.

  17. 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.

  18. Iodine-125 radiation of posterior uveal melanoma

    International Nuclear Information System (INIS)

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

    Directory of Open Access Journals (Sweden)

    Alvarez-Downing Melissa M

    2012-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Maio Michele

    2011-03-01

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

  1. Preliminary results with one-year minimum follow-up of the first 146 patients with a uveal melanoma treated with protons at CPO (Orsay)

    International Nuclear Information System (INIS)

    Proton therapy began at the 'centre de Protontherapy d'Orsay' (CPO) in September 1991. Our treatment protocol and the preliminary results have been presented on the first 146 irradiated patients with one-year minimal follow-up. The subsequent developments have also been mentioned. (author)

  2. 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...... 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...

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

    International Nuclear Information System (INIS)

    Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr701-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr701-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ

  4. 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.

  5. Primary cutaneous melanoma: an 18-year study

    Directory of Open Access Journals (Sweden)

    Moris Anger

    2010-01-01

    Full Text Available BACKGROUND: Primary cutaneous melanoma still constitutes the main cause of skin cancer death in developed countries, and its incidence in recent years has been increasing in a steady, worrisome manner. OBJECTIVES: This study evaluated the clinical, epidemiological and demographic aspects of this disease, and correlated them with patient prognosis. METHODS: Using epidemiologic and clinical data, we analyzed 84 patients with mild to severe primary cutaneous melanoma treated between 1990 and 2007. Slides containing surgical specimens were analyzed, and new slides were made from archived paraffin sections when necessary. RESULTS: The melanoma incidence was higher in areas of sun exposure, with lesions commonly observed in the trunk for males, and lower limbs for females. In addition to Breslow's thickness and ulceration (p = 0.043 and p 1 mm and 4 mm and the mitotic index (0 when absent or 1 when >1 per mm² allowed the establishment of a prognostic score: if the sum was equal to or over three, nearly all (91.7% patients had systemic disease. The 5-year survival was approximately seventy percent. CONCLUSION: Because American Join Committee of Cancer Staging will update the classification of malignant tumors (TNM staging in the near future, and introduce mitosis as a prognostic factor, our results show the importance of such a feature. Additional studies are necessary to confirm the importance of a prognostic score as proposed herein.

  6. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    International Nuclear Information System (INIS)

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome

  7. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Israr; Muneer, Kashiff M.; Tamimi, Iman A.; Chang, Michelle E.; Ata, Muhammad O. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Yusuf, Nabiha, E-mail: nabiha@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, AL (United States); Veteran Affairs Medical Center, Birmingham, University of Alabama at Birmingham, AL (United States); Comprehensive Cancer Center, University of Alabama at Birmingham, AL (United States)

    2013-07-01

    The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β and IL-18 secretion. The NLRP3 (NACHT, LRR, and pyrin domain-containing protein 3) inflammasome is constitutively assembled and activated in human melanoma cells. We have examined the inhibitory effect of thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone), a major ingredient of black seed obtained from the plant Nigella sativa on metastatic human (A375) and mouse (B16F10) melanoma cell lines. We have assessed whether thymoquinone inhibits metastasis of melanoma cells by targeting NLRP3 subunit of inflammasomes. Using an in vitro cell migration assay, we found that thymoquinone inhibited the migration of both human and mouse melanoma cells. The inhibitory effect of thymoquinone on metastasis was also observed in vivo in B16F10 mouse melanoma model. The inhibition of migration of melanoma cells by thymoquinone was accompanied by a decrease in expression of NLRP3 inflammasome resulting in decrease in proteolytic cleavage of caspase-1. Inactivation of caspase-1 by thymoquinone resulted in inhibition of IL-1β and IL-18. Treatment of mouse melanoma cells with thymoquinone also inhibited NF-κB activity. Furthermore, inhibition of reactive oxygen species (ROS) by thymoquinone resulted in partial inactivation of NLRP3 inflammasome. Thus, thymoquinone exerts its inhibitory effect on migration of human and mouse melanoma cells by inhibition of NLRP3 inflammasome. Thus, our results indicate that thymoquinone can be a potential immunotherapeutic agent not only as an adjuvant therapy for melanoma, but also, in the control and prevention of metastatic melanoma. - Highlights: • Thymoquinone causes inhibition of migration of melanoma cells. • Thymoquinone causes inhibition of metastasis in vivo. • Thymoquinone causes inhibition of migration by activation of NLRP3 inflammasome.

  8. Results of prototype particle-beam diagnostics tests for the Advanced Photon Source (APS)

    International Nuclear Information System (INIS)

    The Advanced Photon Source (APS) will be a third-generation synchrotron radiation source (hard x-rays) based on 7-GeV positrons circulating in a 1,104-m circumference storage ring. In the past year a number of the diagnostic prototypes for the measurement of the charged-particle beam parameters throughout the subsystems of the facility (ranging from 450-MeV to 7-GeV positrons and with different pulse formats) have been built and tested. Results are summarized for the beam position monitor (BPM), current monitor (CM), loss monitor (LM), and imaging systems (ISYS). The test facilities ranged from the 40-MeV APS linac test stand to the existing storage rings at SSRL and NSLS

  9. Results of prototype particle-beam diagnostics tests for the Advanced Photon Source (APS)

    International Nuclear Information System (INIS)

    The Advanced Photon Source (APS) will be a third-generation synchrotron radiation source (hard x-rays) based on 7-GeV positrons circulating in a 1104-m circumference storage ring. In the past year a number of the diagnostic prototypes for the measurement of the charged-particle beam parameters throughout the subsystems of the facility (ranging from 450-MeV to 7-GeV positrons and with different pulse formats) have been built and tested. Results are summarized for the beam position monitor (BPM), current monitor (CM), loss monitor (LM), and imaging systems (ISYS). The test facilities ranged from the 40-MeV APS linac test stand to the existing storage rings at SSRL and NSLS

  10. Solid Waste Management Requirements Definition for Advanced Life Support Missions: Results

    Science.gov (United States)

    Alazraki, Michael P.; Hogan, John; Levri, Julie; Fisher, John; Drysdale, Alan

    2002-01-01

    Prior to determining what Solid Waste Management (SWM) technologies should be researched and developed by the Advanced Life Support (ALS) Project for future missions, there is a need to define SWM requirements. Because future waste streams will be highly mission-dependent, missions need to be defined prior to developing SWM requirements. The SWM Working Group has used the mission architecture outlined in the System Integration, Modeling and Analysis (SIMA) Element Reference Missions Document (RMD) as a starting point in the requirement development process. The missions examined include the International Space Station (ISS), a Mars Dual Lander mission, and a Mars Base. The SWM Element has also identified common SWM functionalities needed for future missions. These functionalities include: acceptance, transport, processing, storage, monitoring and control, and disposal. Requirements in each of these six areas are currently being developed for the selected missions. This paper reviews the results of this ongoing effort and identifies mission-dependent resource recovery requirements.

  11. Protocol and result of neoadjuvant chemotherapy for locally advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    The protocol and result were described of chemotherapy and radiotherapy for locally advanced esophageal carcinoma, especially for A3 stage one with metastasis at neighboring tissues such as aorta, trachea and bronchia. Chemotherapy was done with 5-FU and CDDP and radiotherapy, with 30 Gy/15 fx/3 wk. Double contrast roentgenography, dynamic CT and MRI were performed to follow the process. The efficacy rate was 55.0% with 4 CR and 7 PR in 20 cases. Three CR patients survived at present. Major adverse effects were leukopenia and thrombocytopenia, of which grade 4 were found in 14 and 12% cases, respectively. Low-dose FP therapy might be useful for lowering the adverse effects and for elevating the efficacy rates. (K.H.)

  12. Motion-base simulator results of advanced supersonic transport handling qualities with active controls

    Science.gov (United States)

    Feather, J. B.; Joshi, D. S.

    1981-01-01

    Handling qualities of the unaugmented advanced supersonic transport (AST) are deficient in the low-speed, landing approach regime. Consequently, improvement in handling with active control augmentation systems has been achieved using implicit model-following techniques. Extensive fixed-based simulator evaluations were used to validate these systems prior to tests with full motion and visual capabilities on a six-axis motion-base simulator (MBS). These tests compared the handling qualities of the unaugmented AST with several augmented configurations to ascertain the effectiveness of these systems. Cooper-Harper ratings, tracking errors, and control activity data from the MBS tests have been analyzed statistically. The results show the fully augmented AST handling qualities have been improved to an acceptable level.

  13. Clinicopathological characteristics, diagnosis and treatment of melanoma in Serbia: The Melanoma Focus Study

    Directory of Open Access Journals (Sweden)

    Kandolf-Sekulović Lidija

    2015-01-01

    Full Text Available Background/Aim. Treatment options for metastatic melanoma in Serbia are limited due to the lack of newly approved biologic agents and the lack of clinical studies. Also, there is a paucity of data regarding the treatment approaches in different tertiary centers and efficacy of available chemotherapy protocols. The aim of this study was to obtain more detailed data about treatment protocols in Serbia based on structured survey in tertiary oncology centers. Methods. Data about the melanoma patients treated in 2011 were analyzed from hospital databases in 6 referent oncology centers in Serbia, based on the structured survey, with the focus on metastatic melanoma patients (unresectable stage IIIC and IV. Results. A total of 986 (79-315 in different centers patients were treated, with 320 (32.45% newly diagnosed patients. There were 317 patients in stage IIIC/IV, 77/317 aged 60 years. At initial diagnosis 12.5% of patients were in stage III and 4.5% in stage IV. The most common type was superficial spreading melanoma (50-66%, followed by nodular melanoma (23.5-50%. Apart from the regional and distant lymph node metastases, the most frequent organs involved in stage IV disease were distant skin and soft tissues (12-55%, lungs (19-55.5%, liver (10-60%, and bones (3-10%. The first line therapy in stage IV metastatic melanoma was dacarbazine (DTIC dimethyl-triazeno-imidozole-carboxamide in 61-93% of the patients, while the second line varied between the centers. Disease control (complete response + partial response + stable disease was achieved in 25.7% of the patients treated with the first line chemotherapy and 23.1% of the patients treated with the second line therapy, but the duration of response was short, in first-line therapy 6.66 ± 3.36 months (median 6.75 months. More than 90% of patients were treated outside the clinical trials. Conclusion. Based on this survey, there is a large unmet need for the new treatment options for metastatic melanoma

  14. Esophagectomy with gastroplasty in advanced megaesophagus: late results of omeprazole use

    Directory of Open Access Journals (Sweden)

    Celso de Castro Pochini

    2015-10-01

    Full Text Available Objective: To analyze the late results of advanced Chagasic megaesophagus treatment by esophagectomy associated with the use of proton pump inhibitor (omeprazole as for the incidence of esophagitis and Barrett's esophagus in the remaining stump. Methods : We studied patients with advanced megaesophagus undergoing esophagectomy and transmediastinal esophagogastroplasty. Patients were divided into three groups: A (20 with esophageal replacement by full stomach, without the use of omeprazole; B (20 with esophageal replacement by full stomach, with omeprazole 40 mg/day introduced after the first postoperative endoscopy and maintained for six years; and C (30 with esophageal replacement by gastric tube with use of omeprazole. Dysphagia, weight loss and BMI were clinical parameters we analyzed. Upper gastrointestinal endoscopy was performed in all patients, and determined the height of the anastomosis, the aspect of the mucosa, with special attention to possible injuries arising from gastroesophageal reflux, and the patency of the esophagogastric anastomosis. Results : We studied 50 patients, 28 males (56% and 22 (44% females. All underwent endoscopy every year. In the first endoscopy, erosive esophagitis was present in nine patients (18% and Barrett's esophagus, in four (8%; in the last endoscopy, erosive esophagitis was present in five patients (8% and Barrett's esophagus in one (2%. When comparing groups B and C, there was no evidence that the manufacturing of a gastric tube reduced esophagitis and Barrett's esophagus. However, when comparing groups A and C, omeprazole use was correlated with reduction of reflux complications such as esophagitis and Barrett's esophagus (p <0.005. Conclusion : The use of omeprazole (40 mg/day reduced the onset of erosive esophagitis and Barrett's esophagus during the late postoperative period.

  15. Malignant melanoma of the vulva

    OpenAIRE

    Ragnarsson Olding, Boel

    1999-01-01

    From a consecutive, nationwide series of 219 females with primary vulvar malignant melanomas diagnosed in Sweden during 1960 to 1984 and followed up until 1994, we analyzed epidemiological, clinical, histopathological, prognostic and molecular genetic data. The age-standardized incidence among these patients, 75 % of whom were 60 years old or more, decreased by 3.2 % annually compared to an increase of almost 6 % for contemporary cutaneous melanomas in Sweden. Relative 5-and...

  16. Perceived Intra-Family Melanoma Risk Communication

    OpenAIRE

    Loescher, Lois J.; Crist, Janice D.; Siaki, Leilani A.C.L.

    2009-01-01

    Melanoma is a skin cancer that can be deadly. Members of families with a strong history of melanoma have a high risk of melanoma occurrence or recurrence. Enhanced survival in these family members could be influenced by their knowledge of melanoma risk and by simple behaviors to decrease their risk or detect melanoma in its early, most curable, stage. Yet, there is minimal exploration on communication of risk or risk-modifying behaviors in melanoma at-risk families. In this study we described...

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

    Directory of Open Access Journals (Sweden)

    Steven N. Reuland

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Wainstein AJA

    2014-12-01

    Full Text Available Alberto JA Wainstein,1,2 Ana P Drummond-Lage,1 Milhem JM Kansaon,2 Gustavo O Bretas,2 Rodrigo F Almeida,3 Ana LF Gloria,3 Ana RP Figueiredo3 1Faculty of Medical Sciences of Minas Gerais, 2Oncad Surgical Oncology, 3Ophthalmology Department, Federal University of Minas Gerais, Belo Horizonte, Brazil Background: The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure.Methods: Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens.Results: Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility.Conclusion: Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. Keywords

  19. Symmetry Extraction in High Sensitivity Melanoma Diagnosis

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    Elyoenai Guerra-Segura

    2015-06-01

    Full Text Available Melanoma diagnosis depends on the experience of doctors. Symmetry is one of the most important factors to measure, since asymmetry shows an uncontrolled growth of cells, leading to melanoma cancer. A system for melanoma detection in diagnosing melanocytic diseases with high sensitivity is proposed here. Two different sets of features are extracted based on the importance of the ABCD rule and symmetry evaluation to develop a new architecture. Support Vector Machines are used to classify the extracted sets by using both an alternative labeling method and a structure divided into two different classifiers which prioritize sensitivity. Although feature extraction is based on former works, the novelty lies in the importance given to symmetry and the proposed architecture, which combines two different feature sets to obtain a high sensitivity, prioritizing the medical aspect of diagnosis. In particular, a database provided by Hospital Universitario de Gran Canaria Doctor Negrín was tested, obtaining a sensitivity of 100% and a specificity of 66.66% using a leave-one-out validation method. These results show that 66.66% of biopsies would be avoided if this system is applied to lesions which are difficult to classify by doctors.

  20. Staging of cutaneous malignant melanoma by CT

    International Nuclear Information System (INIS)

    Malignant melanomas are a challenge in radiological imaging diagnostics as they may metastasize into every organ and tissue. Cross-sectional imaging, in particular positron emission tomography computed tomography (PET/CT) and whole body magnetic resonance imaging (MRI), are considered the standards in the staging of melanomas. Because of its excellent availability CT, however, remains a widely employed staging modality. Familiarity with the manifold CT morphology of metastasized melanomas as it is described here is essential when interpreting dedicated CT and in addition useful when interpreting PET/CT results. In individual cases CT can assist in the detection of transient metastases. In the detection of locoregional lymph node metastases CT has a median sensitivity and specificity in meta-analyses of at best 61 % and 97 %, respectively, which is inferior to the performance of ultrasound (96 % and 99 %, respectively). According to meta-analyses, in the assessment of systemic tumor spread CT can detect the majority of metastases with a sensitivity and specificity of 51-63 % and 69-78 %, respectively, which is inferior to MRI and PET/CT. Therefore, if an exact staging is required for critical management decisions, MRI or PET/CT should be employed whenever possible. (orig.)

  1. The Role of Intralesional Therapies in Melanoma.

    Science.gov (United States)

    Agarwala, Sanjiv S

    2016-05-01

    The US Food and Drug Administration has been rapidly approving new checkpoint inhibitors and targeted therapies for melanoma and other tumors. Recently, it approved the first intralesional therapy, talimogene laherparepvec (T-VEC), for the treatment of metastatic melanoma lesions in the skin and lymph nodes. Several other intralesional therapies (PV-10, interleukin-12 electroporation, coxsackievirus A21 [CVA21]) are entering later-stage testing. Locally injected agents have clearly shown their ability to produce local responses that can be durable. The possibility that they also stimulate a regional and even systemic immune response is exciting, as this potential effect may have utility in combination regimens; such regimens are an area of active research. Favorable responses with minimal toxicities in monotherapy trials have led to the first melanoma studies of T-VEC in combination with the cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab and, separately, with the programmed death 1-blocking antibody pembrolizumab. Studies of PV-10 with pembrolizumab and of CVA21 with pembrolizumab are also being initiated. Preliminary analyses of the results of the first combination trials, which show higher response rates than with either agent alone, offer some optimism that these locoregional therapies will find application--as treatment for patients who cannot tolerate systemic immunotherapies, to alleviate locoregional morbidity, and perhaps even to "prime" the immune system. PMID:27188674

  2. Proton beam radiotherapy of iris melanoma

    International Nuclear Information System (INIS)

    Purpose: To report on outcomes after proton beam radiotherapy of iris melanoma. Methods and Materials: Between 1993 and 2004, 88 patients with iris melanoma received proton beam radiotherapy, with 53.1 Gy in 4 fractions. Results: The patients had a mean age of 52 years and a median follow-up of 2.7 years. The tumors had a median diameter of 4.3 mm, involving more than 2 clock hours of iris in 32% of patients and more than 2 hours of angle in 27%. The ciliary body was involved in 20%. Cataract was present in 13 patients before treatment and subsequently developed in another 18. Cataract had a 4-year rate of 63% and by Cox analysis was related to age (p = 0.05), initial visual loss (p < 0.0001), iris involvement (p < 0.0001), and tumor thickness (p < 0.0001). Glaucoma was present before treatment in 13 patients and developed after treatment in another 3. Three eyes were enucleated, all because of recurrence, which had an actuarial 4-year rate of 3.3% (95% CI 0-8.0%). Conclusions: Proton beam radiotherapy of iris melanoma is well tolerated, the main problems being radiation-cataract, which was treatable, and preexisting glaucoma, which in several patients was difficult to control

  3. Treatment results of different radiotherapy for 763 patients with advanced cervical cancer

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical value of different radiotherapy protocols in the treatment of advanced cervical cancer. Methods: From 1976 to 2006, 763 patients with stage III cervical cancer (722 with squamous cell carcinoma and 41 with adenocarcinoma) were treated by radiotherapy in our hospital. 113 patients were treated by two-field whole pelvic irradiation in conventional fractionation plus brachytherapy (CF group), 44 by four-field whole pelvic irradiation in accelerated hyperfractionation plus brachytherapy (AHF group), and 606 by concomitant four-field unconventional fractionation radiotherapy and brachytherapy( FRT group). Sixty-one patients were treated by radiotherapy and chemotherapy. Among 350 patients who had complete data, the shore-term efficacy and toxicities were compared. Results: For patients in CF, AHF and FRT groups, the 3-year overall survival rates (OS) were 65.7%, 66.8% and 44.3%, respectively (P=0.000), and the 5-year OS were 65.7%, 66.8% and 36.3%, respectively (P=0.000). The 10-year OS were 43.3% and 31.9% in CF and FRT groups(P=0.200). For squamous cell carcinoma,the OS was higher of patients with chemotherapy than those without. In 350 patients who had complete data, the local control rates of CF, AHF and FRT groups were 83.0%, 93.2% and 86.1%, respectively (χ2=2.70, P =0.259); AHF group had the lowest side effect rate, especially skin reaction (9.1%, χ2=20.25, P= 0.002); CF group had the lowest acute bone marrow suppression rate (χ2=25.95, P=0.000); for squamous cell carcinoma, the OS was higher in patients with chemotherapy than those without; the acute bone marrow and intestinal toxicities were more in patients with chemotherapy than those without. Conclusions: CF and AHF groups have similar 5-year OS of patients with advanced cervical cancer. AHF group has less toxicities, shorter treatment course and a trend of better local control. Concurrent chemoradiation could improve survival and local control of the patients with

  4. OVERVIEW OF RECENT EXPERIMENTAL RESULTS FROM THE DIII-D ADVANCED TOKAMAK PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    BURRELL,KH

    2002-11-01

    OAK A271 OVERVIEW OF RECENT EXPERIMENTAL RESULTS FROM THE DIII-D ADVANCED TOKAMAK PROGRAM. The DIII-D research program is developing the scientific basis for advanced tokamak (AT) modes of operation in order to enhance the attractiveness of the tokamak as an energy producing system. Since the last International Atomic Energy Agency (IAEA) meeting, the authors have made significant progress in developing the building blocks needed for AT operation: (1) the authors have doubled the magnetohydrodynamic (MHD) stable tokamak operating space through rotational stabilization of the resistive wall mode; (2) using this rotational stabilization, they have achieved {beta}{sub N}H{sub 89} {le} 10 for 4 {tau}{sub E} limited by the neoclassical tearing mode; (3) using real-time feedback of the electron cyclotron current drive (ECCD) location, they have stabilized the (m,n) = (3,2) neoclassical tearing mode and then increased {beta}{sub T} by 60%; (4) they have produced ECCD stabilization of the (2,1) neoclassical tearing mode in initial experiments; (5) they have made the first integrated AT demonstration discharges with current profile control using ECCD; (6) ECCD and electron cyclotron heating (ECH) have been used to control the pressure profile in high performance plasmas; and (7) they have demonstrated stationary tokamak operation for 6.5 s (36 {tau}{sub E}) at the same fusion gain parameter of {beta}{sub N}H{sub 89}/q{sub 95}{sup 2} {approx} 0.4 as ITER but at much higher q{sub 95} = 4.2. They have developed general improvements applicable to conventional and advanced tokamak operating modes: (1) they have an existence proof of a mode of tokamak operation, quiescent H-mode, which has no pulsed, ELM heat load to the divertor and which can run for long periods of time (3.8 s or 25 {tau}{sub E}) with constant density and constant radiation power; (2) they have demonstrated real-time disruption detection and mitigation for vertical disruption events using high pressure gas jet

  5. Carbon ion radiotherapy for uveal melanoma

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the applicability of carbon ion beams in the treatment of choroidal melanoma, with regard to normal tissue morbidity and local tumor control. Between January 2001 and August 2006, 67 patients with locally advanced or unfavorable-site choroidal melanoma were enrolled in a phase I/II clinical trial of carbon-ion radiotherapy (C-ion RT) at the National Institute of Radiological Sciences (NIRS). Primary endpoint of this study was normal tissue morbidity and secondary endpoints were local tumor control and patient survival. Fifty-nine of the patients were followed up for more than 6 months and analyzed. Twenty-three patients (39%) developed neovascular glaucoma (NVG) and 3 of them underwent enucleation because of the eye pain due to elevated intraocular pressure. The incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died by the date of analysis, 3 of distant metastasis and 2 of intercurrent diseases. All patients but one, who developed marginal recurrence, were controlled locally. Eight patients developed distant metastasis, 5 in the liver and 3 in the lung. Three-year overall survival, disease-free survival, and local control rates were 87.1%, 81.6%, and 98.0%, respectively. No apparent dose-response relationship was observed either in tumor control or in normal tissue morbidity with the dose range applied. C-ion RT can be applied to choroidal melanoma with an acceptable morbidity and sufficient anti-tumor effect, even in tumors of unfavorable size or site. (author)

  6. Melanoma: Stem cells, sun exposure and hallmarks for carcinogenesis, molecular concepts and future clinical implications

    Directory of Open Access Journals (Sweden)

    Kyrgidis Athanassios

    2010-01-01

    Full Text Available Background :The classification and prognostic assessment of melanoma is currently based on morphologic and histopathologic biomarkers. Availability of an increasing number of molecular biomarkers provides the potential for redefining diagnostic and prognostic categories and utilizing pharmacogenomics for the treatment of patients. The aim of the present review is to provide a basis that will allow the construction-or reconstruction-of future melanoma research. Methods: We critically review the common medical databases (PubMed, EMBASE, Scopus and Cochrane CENTRAL for studies reporting on molecular biomarkers for melanoma. Results are discussed along the hallmarks proposed for malignant transformation by Hanahan and Weinberg. We further discuss the genetic basis of melanoma with regard to the possible stem cell origin of melanoma cells and the role of sunlight in melanoma carcinogenesis. Results: Melanocyte precursors undergo several genome changes -UV-induced or not- which could be either mutations or epigenetic. These changes provide stem cells with abilities to self-invoke growth signals, to suppress anti-growth signals, to avoid apoptosis, to replicate without limit, to invade, proliferate and sustain angiogenesis. Melanocyte stem cells are able to progressively collect these changes in their genome. These new potential functions, drive melanocyte precursors to the epidermis were they proliferate and might cause benign nevi. In the epidermis, they are still capable of acquiring new traits via changes to their genome. With time, such changes could add up to transform a melanocyte precursor to a malignant melanoma stem cell. Conclusions : Melanoma cannot be considered a "black box" for researchers anymore. Current trends in the diagnosis and prognosis of melanoma are to individualize treatment based on molecular biomarkers. Pharmacogenomics constitute a promising field with regard to melanoma patients′ treatment. Finally, development of novel

  7. Treatment results in advanced stage Hodgkin′s lymphoma: A retrospective study

    Directory of Open Access Journals (Sweden)

    H Jain

    2015-01-01

    Full Text Available Background: Hodgkin′s lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS and progression-free survival (PFS. Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77% who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years. Stage IV disease was seen in (46 patients 37%; 75% (94 patients patients had B symptoms. International prognostic score (IPS ≤4 was seen in 95/112 (85% patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients. Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4 were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data.

  8. Aldesleukin and Pembrolizumab in Treating Patients With Stage III-IV Melanoma

    Science.gov (United States)

    2016-04-21

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

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

    Directory of Open Access Journals (Sweden)

    Spagnolo F

    2015-01-01

    Full Text Available Francesco Spagnolo,1 Paola Ghiorzo,2,3 Laura Orgiano,4 Lorenza Pastorino,2,3 Virginia Picasso,4 Elena Tornari,4 Vincenzo Ottaviano,4 Paola Queirolo4 1Department of Plastic and Reconstructive Surgery, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; 2Department of Internal Medicine and Medical Specialties (DiMI, University of Genoa, Genova, Italy; 3Genetics of Rare Cancers, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; 4Department of Medical Oncology, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy Abstract: BRAF inhibitors vemurafenib and dabrafenib achieved improved overall survival over chemotherapy and have been approved for the treatment of BRAF-mutated metastatic melanoma. More recently, the combination of BRAF inhibitor dabrafenib with MEK inhibitor trametinib has shown improved progression-free survival, compared to dabrafenib monotherapy, in a Phase II study and has received approval by the US Food and Drug Administration. However, even when treated with the combination, most patients develop mechanisms of acquired resistance, and some of them do not achieve tumor regression at all, because of intrinsic resistance to therapy. Along with the development of BRAF inhibitors, immunotherapy made an important step forward: ipilimumab, an anti-CTLA-4 monoclonal antibody, was approved for the treatment of metastatic melanoma; anti-PD-1 agents achieved promising results in Phase I/II trials, and data from Phase III studies will be ready soon. The availability of such drugs, which are effective regardless of BRAF status, has made the therapeutic approach more complex, as first-line treatment with BRAF inhibitors may not be the best choice for all BRAF-mutated patients. The aim of this paper is to review the systemic therapeutic options

  10. Melanoma Therapy via Peptide-Targeted a-Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Yubin; Hylarides, Mark; Fisher, Darrell R.; Shelton, Tiffani; Moore, Herbert A.; Wester, Dennis W.; Fritzberg, Alan R.; Winkelmann, Christopher T.; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-08-01

    Malignant melanoma is the most lethal form of skin cancer. Current chemotherapy and external beam radiation therapy regimens are ineffective agents against melanoma, as shown by a 10-year survival rate for patients with disseminated disease of approximately 5% (reference?). In this study, the unique combination of a melanoma targeting peptide and an in vivo generated a-particle emitting radioisotope was investigated for its melanoma therapy potential. Alpha-radiation is densely ionizing and energy is locally absorbed, resulting in high concentrations of destructive free radicals and irreparable DNA double strand breaks. This high linear-energy-transfer overcomes radiation resistant tumor cells and oxygen-enhancement effects. The melanoma targeting peptide DOTA-Re(Arg11)CCMSH was radiolabeled with 212Pb, the parent of 212Bi, which decays via alpha and beta decay. Biodistribution and therapy studies were performed in the B16/F1 melanoma bearing C57 mouse flank tumor model. 212Pb[DOTA]-R e(Arg11)CCMSH exhibited rapid tumor uptake and extended retention coupled with rapid whole body disappearance. Radiation dose delivered to the tumor was estimated to be 61 cGy/uCi 212Pb administered. Treatment of melanoma-bearing mice with 50, 100 and 200 uCi of 212Pb[DOTA]-Re(Arg11)CCMSH extended mean survival of mice to 22, 28, and 49.8 days, respectively, compared to the 14.6 day mean survival of the placebo control group. Forty-five percent of the mice receiving 200 uCi survived the study disease-free.

  11. Directed Dedifferentiation Using Partial Reprogramming Induces Invasive Phenotype in Melanoma Cells.

    Science.gov (United States)

    Knappe, Nathalie; Novak, Daniel; Weina, Kasia; Bernhardt, Mathias; Reith, Maike; Larribere, Lionel; Hölzel, Michael; Tüting, Thomas; Gebhardt, Christoffer; Umansky, Viktor; Utikal, Jochen

    2016-04-01

    The combination of cancer-focused studies and research related to nuclear reprogramming has gained increasing importance since both processes-reprogramming towards pluripotency and malignant transformation-share essential features. Studies have revealed that incomplete reprogramming of somatic cells leads to malignant transformation indicating that epigenetic regulation associated with iPSC generation can drive cancer development [J Mol Cell Biol 2011;341-350; Cell 2012;151:1617-1632; Cell 2014;156:663-677]. However, so far it is unclear whether incomplete reprogramming also affects cancer cells and their function. In the context of melanoma, dedifferentiation correlates to therapy resistance in mouse studies and has been documented in melanoma patients [Nature 2012;490:412-416; Clin Cancer Res 2014;20:2498-2499]. Therefore, we sought to investigate directed dedifferentiation using incomplete reprogramming of melanoma cells. Using a murine model we investigated the effects of partial reprogramming on the cellular plasticity of melanoma cells. We demonstrate for the first time that induced partial reprogramming results in a reversible phenotype switch in melanoma cells. Partially reprogrammed cells at day 12 after transgene induction display elevated invasive potential in vitro and increased lung colonization in vivo. Additionally, using global gene expression analysis of partially reprogrammed cells, we identified SNAI3 as a novel invasion-related marker in human melanoma. SNAI3 expression correlates with tumor thickness in primary melanomas and thus, may be of prognostic value. In summary, we show that investigating intermediate states during the process of reprogramming melanoma cells can reveal novel insights into the pathogenesis of melanoma progression. We propose that deeper analysis of partially reprogrammed melanoma cells may contribute to identification of yet unknown signaling pathways that can drive melanoma progression. Stem Cells 2016;34:832-846. PMID

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

    Directory of Open Access Journals (Sweden)

    Slipicevic Ana

    2012-02-01

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

  13. Recent Advances and Some Results in Plasma-Based Accelerator Modeling

    Science.gov (United States)

    Mori, W. B.

    2002-12-01

    Simulation, using particle-in-cell (PIC) methods, has played a critical role in the evolution of the field of plasma-based acceleration. Early on, simulations allowed the testing of new ideas using so-called cartoon parameters. These simulations were done in either one or two-dimensions using single processor supercomputers. Through the development of new algorithms and parallel computing, today, we can now use PIC simulations to model the full-scale of ongoing experiments in three-dimensions. These experiments are attempting to accelerate electrons to ˜1 GeV. In this article, I will present recent results in which simulation results are compared to experiment and I will discuss the future challenges in advanced accelerator modeling. Principally, these are 1.) to be able to model a 100+ on 100+ GeV collider in three-dimensions and, 2.) to develop more efficient, yet still accurate, algorithms so that simulation can be used for real-time feedback with experiment.

  14. Analysis of treatment and results in patients with advanced hypopharyngeal carcinomas

    International Nuclear Information System (INIS)

    Between 1991 and 1997, 42 patients with advanced stage III or IVA or IVB hypopharyngeal cancer received primary treatment at our clinic. Treatment and results in these cases were analyzed retrospectively. Thirty three patients with resectable hypopharyngeal carcinomas received 1-3 courses of neoadjuvant chemotherapy (NAC) involving a combination of cisplatin 60 mg/m2 and 5-fluorouracil 800 or 1,000 mg/m2 x 5 days, followed by total laryngopharyngectomy plus postoperative radiotherapy in 24 patients (group A) or followed by 70 Gy radiotherapy with radiation sensitizer in 9 patients because of self rejection of the operation (group B). Nine patients with unresectable hypopharyngeal carcinomas received neoadjuvant chemotherapy followed by radiotherapy or received radiotherapy only (group C). For the entire group, 5-year overall survival was 38% (group A 53%, group B 22%, group C 0%). The survival was statistically better (p<0.05) in group A than in group B. Better results were obtained for combined therapy including radical surgery in terms of overall survival. The response rate of NAC was 70%. In the patients who received operation, clinical and pathological CR rate was (8% in primary lesion, clinical CR rate was 5% and pathological CR rate was 23% in regional lymph nodes. Therefore sensitivity of the clinical CR evaluation was 50% in primary lesion and 20% in regional lymph nodes. Specificity of the clinical CR evaluation was 95% in primary lesion and 100% in regional lymph nodes. (author)

  15. Tool to Distinguish Moles from Melanoma

    Science.gov (United States)

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

  16. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

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

  17. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  18. Particularities of melanoma in Romania

    International Nuclear Information System (INIS)

    Full text: Malignant tumor from melanocytic origin, cutaneous melanoma is the most aggressive cutaneous cancer. The particularities of melanoma in Romania are: 1. the increasing number of cases in a geographic area dominated by the third cutaneous phototype; 2. the high level of T, represented by high levels of Breslow and Clark invasion markers; 3. the lack of a National Melanoma Register; 4. the lymph node sentinel biopsy technique introduction is the present focus; this allows an appropriate N affiliation; 5. the increasing of sanitary education in order to clinical and dermoscopical follow-up of atypical moles and the study of risk factors for melanoma; 6. the creation of a melanoma local guide. The survival prognosis could be improved by: a) the early detection in 'in situ' stage of melanoma and b) the correct TNM and/or EORTC affiliation of the case, in order to achieve an appropriate treatment. Sentinel lymph node detection and biopsy offers a new area in the evaluation of cancer spread by detecting micrometastases and performing a complete regional evaluation of the disease. The presence or absence of the metastases in the regional lymph nodes is one of the most important factors in the survival of patients with primary cutaneous melanoma. Early diagnosis of regional lymph node metastases enables the identification of those patients who are candidates for adjuvant therapy and early therapeutic lymph node dissection. At the same time, the sentinel node biopsy procedure represents a sensitive staging method. The paper presents some of gold standard diagnosis cases, dermoscopy and routine HE examination, selected from a total of 356 cases. (author)

  19. Advanced head and neck cancer: Long-term results of chemo-radiotherapy, complications and induction of second malignancies

    OpenAIRE

    Munker, Reinhold; Purmale, L.; Aydemir, Ü.; Reitmeier, M.; Pohlmann, H.; Schorer, H.; Hartenstein, R.

    2001-01-01

    Background: Chemo-radiotherapy is superior to radiotherapy alone in the treatment of advanced, inoperable head and neck cancer. The long-term treatment results, the induction of second malignant tumors, and other long-term toxicities are not well defined. Patients and Methods: 100 consecutive patients with advanced head and neck cancer who were treated at our center were studied. Treatment results, survival, the occurrence of late complications, and second malignant tumors (SMT) were investig...

  20. Melanoma chemotherapy leads to the selection of ABCB5-expressing cells.

    Directory of Open Access Journals (Sweden)

    Marine Chartrain

    Full Text Available Metastatic melanoma is the most aggressive skin cancer. Recently, phenotypically distinct subpopulations of tumor cells were identified. Among them, ABCB5-expressing cells were proposed to display an enhanced tumorigenicity with stem cell-like properties. In addition, ABCB5(+ cells are thought to participate to chemoresistance through a potential efflux function of ABCB5. Nevertheless, the fate of these cells upon drugs that are used in melanoma chemotherapy remains to be clarified. Here we explored the effect of anti-melanoma treatments on the ABCB5-expressing cells. Using a melanoma xenograft model (WM266-4, we observed in vivo that ABCB5-expressing cells are enriched after a temozolomide treatment that induces a significant tumor regression. These results were further confirmed in a preliminary study conducted on clinical samples from patients that received dacarbazine. In vitro, we showed that ABCB5-expressing cells selectively survive when exposed to dacarbazine, the reference treatment of metastatic melanoma, but also to vemurafenib, a new inhibitor of the mutated kinase V600E BRAF and other various chemotherapeutic drugs. Our results show that anti-melanoma chemotherapy might participate to the chemoresistance acquisition by selecting tumor cell subpopulations expressing ABCB5. This is of particular importance in understanding the relapses observed after anti-melanoma treatments and reinforces the interest of ABCB5 and ABCB5-expressing cells as potential therapeutic targets in melanoma.

  1. Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

    International Nuclear Information System (INIS)

    Highlights: → Elafin expression is epigenetically silenced in human melanoma cells. → Foxa2 expression in melanoma cells is silenced by promoter hypermethylation. → Foxa2 directs activation of the elafin promoter in vivo. → Foxa2 expression induces apoptosis of melanoma cells via elafin re-expression. -- Abstract: Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

  2. The role of germline alterations in the DNA damage response genes BRIP1 and BRCA2 in melanoma susceptibility.

    Science.gov (United States)

    Tuominen, Rainer; Engström, Pär G; Helgadottir, Hildur; Eriksson, Hanna; Unneberg, Per; Kjellqvist, Sanela; Yang, Muyi; Lindén, Diana; Edsgärd, Daniel; Hansson, Johan; Höiom, Veronica

    2016-07-01

    We applied a targeted sequencing approach to identify germline mutations conferring a moderately to highly increased risk of cutaneous and uveal melanoma. Ninety-two high-risk melanoma patients were screened for inherited variation in 120 melanoma candidate genes. Observed gene variants were filtered based on frequency in reference populations, cosegregation with melanoma in families and predicted functional effect. Several novel or rare genetic variants in genes involved in DNA damage response, cell-cycle regulation and transcriptional control were identified in melanoma patients. Among identified genetic alterations was an extremely rare variant (minor allele frequency of 0.00008) in the BRIP1 gene that was found to cosegregate with the melanoma phenotype. We also found a rare nonsense variant in the BRCA2 gene (rs11571833), previously associated with cancer susceptibility but not with melanoma, which showed weak association with melanoma susceptibility in the Swedish population. Our results add to the growing knowledge about genetic factors associated with melanoma susceptibility and also emphasize the role of DNA damage response as an important factor in melanoma etiology. © 2016 Wiley Periodicals, Inc. PMID:27074266

  3. Epigenetic regulation of the transcription factor Foxa2 directs differential elafin expression in melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Kyung Sook [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Jo, Ji Yoon; Kim, Su Jin [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Lee, Yangsoon [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Bae, Jong Hwan [NeoPharm Co. Ltd., Daejeon 305-510 (Korea, Republic of); Chung, Young-Hwa [Department of Cogno-Mechatronics Engineering, BK21 Nanofusion Technology Team, Pusan National University, Busan 609-736 (Korea, Republic of); Koh, Sang Seok, E-mail: sskoh@kribb.re.kr [Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of)

    2011-04-29

    Highlights: {yields} Elafin expression is epigenetically silenced in human melanoma cells. {yields} Foxa2 expression in melanoma cells is silenced by promoter hypermethylation. {yields} Foxa2 directs activation of the elafin promoter in vivo. {yields} Foxa2 expression induces apoptosis of melanoma cells via elafin re-expression. -- Abstract: Elafin, a serine protease inhibitor, induces the intrinsic apoptotic pathway in human melanoma cells, where its expression is transcriptionally silenced. However, it remains unknown how the elafin gene is repressed in melanoma cells. We here demonstrate that elafin expression is modulated via epigenetically regulated expression of the transcription factor Foxa2. Treatment of melanoma cells with a DNA methyltransferase inhibitor induced elafin expression, which was specifically responsible for reduced proliferation and increased apoptosis. Suppression of Foxa2 transcription, mediated by DNA hypermethylation in its promoter region, was released in melanoma cells upon treatment with the demethylating agent. Luciferase reporter assays indicated that the Foxa2 binding site in the elafin promoter was critical for the activation of the promoter. Chromatin immunoprecipitation assays further showed that Foxa2 bound to the elafin promoter in vivo. Analyses of melanoma cells with varied levels of Foxa2 revealed a correlated expression between Foxa2 and elafin and the ability of Foxa2 to induce apoptosis. Our results collectively suggest that, in melanoma cells, Foxa2 expression is silenced and therefore elafin is maintained unexpressed to facilitate cell proliferation in the disease melanoma.

  4. Driver Mutations in Uveal Melanoma

    Science.gov (United States)

    Decatur, Christina L.; Ong, Erin; Garg, Nisha; Anbunathan, Hima; Bowcock, Anne M.; Field, Matthew G.; Harbour, J. William

    2016-01-01

    IMPORTANCE Frequent mutations have been described in the following 5 genes in uveal melanoma (UM): BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. Understanding the prognostic significance of these mutations could facilitate their use in precision medicine. OBJECTIVE To determine the associations between driver mutations, gene expression profile (GEP) classification, clinicopathologic features, and patient outcomes in UM. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of patients with UM treated by enucleation by a single ocular oncologist between November 1, 1998, and July 31, 2014. MAIN OUTCOMES AND MEASURES Clinicopathologic features, patient outcomes, GEP classification (class 1 or class 2), and mutation status were recorded. RESULTS The study cohort comprised 81 participants. Their mean age was 61.5 years, and 37% (30 of 81) were female. The GEP classification was class 1 in 35 of 81 (43%), class 2 in 42 of 81 (52%), and unknown in 4 of 81 (5%). BAP1 mutations were identified in 29 of 64 (45%), GNAQ mutations in 36 of 81 (44%), GNA11 mutations in 36 of 81 (44%), SF3B1 mutations in 19 of 81 (24%), and EIF1AX mutations in 14 of 81 (17%). Sixteen of the mutations in BAP1 and 6 of the mutations in EIF1AX were previously unreported in UM. GNAQ and GNA11 mutations were mutually exclusive. BAP1, SF3B1, and EIF1AX mutations were almost mutually exclusive with each other. Using multiple regression analysis, BAP1 mutations were associated with class 2 GEP and older patient. EIF1AX mutations were associated with class 1 GEP and the absence of ciliary body involvement. SF3B1 mutations were associated with younger patient age. GNAQ mutations were associated with the absence of ciliary body involvement and greater largest basal diameter. GNA11 mutations were not associated with any of the analyzed features. Using Cox proportional hazards modeling, class 2 GEP was the prognostic factor most strongly associated with metastasis (relative risk, 9.4; 95% CI, 3.1–28.5) and

  5. Immunotherapy of melanoma: present options and future promises.

    Science.gov (United States)

    Rotte, Anand; Bhandaru, Madhuri; Zhou, Youwen; McElwee, Kevin J

    2015-03-01

    Metastatic melanoma is notorious for its immune evasion and resistance to conventional chemotherapy. The recent success of ipilimumab, a human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), in increasing the median survival time and stabilizing the disease progression renewed, hopes in treatment for melanoma. Currently, ipilimumab and high-dose interleukin-2 (IL-2; Aldesleukin) are approved as monotherapies for the treatment of patients with unresectable advanced melanoma, and pegylated interferon-α2b (p-IFN-α2b) is approved as an adjuvant for the treatment of patients with surgically resected high-risk melanoma. The present review describes the currently approved immune-modulators and the promising immune-based interventions that are currently in clinical trials. We present the four commonly used strategies to boost immune responses against the tumors; monoclonal antibodies, cytokines, cancer vaccines, and adoptive T cell transfer. The corresponding lists of ongoing clinical trials include details of the trial phase, target patients, intervention details, status of the study, and expected date of completion. Further, our review discusses the challenges faced by immunotherapy and the various strategies adopted to overcome them. PMID:25589384

  6. First results on disruption mitigation by massive gas injection in Korea Superconducting Tokamak Advanced Research

    International Nuclear Information System (INIS)

    Massive gas injection (MGI) system was developed on Korea Superconducting Tokamak Advanced Research (KSTAR) in 2011 campaign for disruption studies. The MGI valve has a volume of 80 ml and maximum injection pressure of 50 bar, the diameter of valve orifice to vacuum vessel is 18.4 mm, the distance between MGI valve and plasma edge is ∼3.4 m. The MGI power supply employs a large capacitor of 1 mF with the maximum voltage of 3 kV, the valve can be opened in less than 0.1 ms, and the amount of MGI can be controlled by the imposed voltage. During KSTAR 2011 campaign, MGI disruptions are carried out by triggering MGI during the flat top of circular and limiter discharges with plasma current 400 kA and magnetic field 2–3.5 T, deuterium injection pressure 39.7 bar, and imposed voltage 1.1–1.4 kV. The results show that MGI could mitigate the heat load and prevent runaway electrons with proper MGI amount, and MGI penetration is deeper under higher amount of MGI or lower magnetic field. However, plasma start-up is difficult after some of D2 MGI disruptions due to the high deuterium retention and consequently strong outgassing of deuterium in next shot, special effort should be made to get successful plasma start-up after deuterium MGI under the graphite first wall.

  7. GTOC8: Results and Methods of ESA Advanced Concepts Team and JAXA-ISAS

    CERN Document Server

    Izzo, Dario; Märtens, Marcus; Getzner, Ingmar; Nowak, Krzysztof; Heffernan, Anna; Campagnola, Stefano; Yam, Chit Hong; Ozaki, Naoya; Sugimoto, Yoshihide

    2016-01-01

    We consider the interplanetary trajectory design problem posed by the 8th edition of the Global Trajectory Optimization Competition and present the end-to-end strategy developed by the team ACT-ISAS (a collaboration between the European Space Agency's Advanced Concepts Team and JAXA's Institute of Space and Astronautical Science). The resulting interplanetary trajectory won 1st place in the competition, achieving a final mission value of $J=146.33$ [Mkm]. Several new algorithms were developed in this context but have an interest that go beyond the particular problem considered, thus, they are discussed in some detail. These include the Moon-targeting technique, allowing one to target a Moon encounter from a low Earth orbit; the 1-$k$ and 2-$k$ fly-by targeting techniques, enabling one to design resonant fly-bys while ensuring a targeted future formation plane% is acquired at some point after the manoeuvre ; the distributed low-thrust targeting technique, admitting one to control the spacecraft formation plane...

  8. DOE Advanced Controls R&D Planning Workshop, June 11, 2003, Washington DC: Workshop Results

    Energy Technology Data Exchange (ETDEWEB)

    Brambley, Michael R.; Haves, Philip; McDonald, Sean C.; Torcellini, Paul; Hansen, David G.; Holmberg, David; Roth, Kurt

    2005-04-13

    On June 11, 2003, representatives from universities, federal and state government agencies, Department of Energy national laboratories, and the private sector attended a one-day workshop in Washington, DC. The objective of the workshop was to review and provide input into DOE's assessment of the market for advanced sensors and controls technology and potential R&D pathways to enhance their success in the buildings market place. The workshop consisted of two sessions. During the morning session, participants were given an overview on the following topics: market assessment, current applications and strategies for new applications, sensors and controls, networking, security, and protocols and standards, and automated diagnostics, performance measurement, commissioning and optimal control and tools. In the sessions, workshop participants were asked to review the potential R&D pathways, identify high priority activities, and outline a five year path for each of these activities. Priorities were as follows: largest and quickest impact; best use of finite resources; greatest likelihood for market penetration; and ability to replicate results. The participants identified several promising R&D opportunities.

  9. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    Science.gov (United States)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  10. Performance test results of the advanced verification for inventory sample system (AVIS) (2)

    International Nuclear Information System (INIS)

    The Advanced Verification for Inventory sample System (AVIS) is a nondestructive assay (NDA) system to verify the plutonium mass with high accuracy in the small plutonium uranium mixed oxide (MOX) powder and pellet samples at Japan Nuclear Fuel Limited MOX fuel fabrication plant (J-MOX) under construction. The AVIS was designed by Los Alamos National Laboratory (LANL) under the auspices of the Secretariat of Nuclear Regulation Authority. The AVIS will fulfill an important role in the safeguards approach for J-MOX because the AVIS will be used as a verification tool instead of destructive analysis for a part of the samples for bias defect. Japan Atomic Energy Agency (JAEA), which has experience and knowledge to develop the NDA systems and plutonium handling fields, was entrusted with performance testing for the AVIS by the Nuclear Material Control Center of Japan. As a first phase, JAEA conducted the performance tests by using 252Cf neutron sources. In this test, neutron detection efficiency, die-away time and other detector properties were evaluated, and it was confirmed that the AVIS had the performance designed by LANL. As a second phase, JAEA conducted the performance tests by using MOX samples. In this test, the measurement accuracy of the AVIS was evaluated. From the results, it was confirmed that the AVIS could almost satisfy the performance requirements on the accuracy by IAEA. (author)

  11. Screening test results on potential alternate alloys for VHTGR applications. Advanced Gas Cooled Reactor Materials Program

    International Nuclear Information System (INIS)

    General Electric is working to define and develop the materials technology which will be required for advanced very High Temperature Gas Reactors operating at primary coolant temperatures up to 9500C. The most promising application which has been identified is providing process heat for the reforming of methane. Earlier work had identified Inconel 617 and Alloy 800H as the best of the commercially available alloys for the reformer components. Since these alloys were identified, additional alloys have been developed which may offer improved performance over the above reference reformer alloys. This report presents the results obtained to date on four possible alternate alloys, Nimonic 86, Sanicro 32X, SSS-113-MA, and X 8 NiCrMoNb 16 16, which are being evaluated by General Electric for thermal stability and compatibility with HTGR helium environments. The thermal stabilities of Nimonic 86, Sanicro 32X, and X 8 NiCrMoNb 16 16 have been shown to be good out to maximum exposure times and temperatures of 6000 hours and 9500C, respectively. The thermal stability, as measured by room temperature impact strength, and post exposure ductility of the Japanese developmental alloy SSS-113-MA have been shown to be poor. Measured impact strengths and ductilities below 15 ft-lbs and 10%, respectively, have been observed for this alloy. No conclusions regarding the helium compatibility of the alloys can be made at this time because of the limited data available

  12. A multi-antigen vaccine in combination with an immunotoxin targeting tumor-associated fibroblast for treating murine melanoma

    Science.gov (United States)

    Fang, Jinxu; Hu, Biliang; Li, Si; Zhang, Chupei; Liu, Yarong; Wang, Pin

    2016-01-01

    A therapeutically effective cancer vaccine must generate potent antitumor immune responses and be able to overcome tolerance mechanisms mediated by the progressing tumor itself. Previous studies showed that glycoprotein 100 (gp100), tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) are promising immunogens for melanoma immunotherapy. In this study, we administered these three melanoma-associated antigens via lentiviral vectors (termed LV-3Ag) and found that this multi-antigen vaccine strategy markedly increased functional T-cell infiltration into tumors and generated protective and therapeutic antitumor immunity. We also engineered a novel immunotoxin, αFAP-PE38, capable of targeting fibroblast activation protein (FAP)-expressing fibroblasts within the tumor stroma. When combined with αFAP-PE38, LV-3Ag exhibited greatly enhanced antitumor effects on tumor growth in an established B16 melanoma model. The mechanism of action underlying this combination treatment likely modulates the immune suppressive tumor microenvironment and, consequently, activates cytotoxic CD8+ T cells capable of specifically recognizing and destroying tumor cells. Taken together, these results provide a strong rationale for combining an immunotoxin with cancer vaccines for the treatment of patients with advanced cancer. PMID:27119119

  13. Advanced Modeling and Uncertainty Quantification for Flight Dynamics; Interim Results and Challenges

    Science.gov (United States)

    Hyde, David C.; Shweyk, Kamal M.; Brown, Frank; Shah, Gautam

    2014-01-01

    As part of the NASA Vehicle Systems Safety Technologies (VSST), Assuring Safe and Effective Aircraft Control Under Hazardous Conditions (Technical Challenge #3), an effort is underway within Boeing Research and Technology (BR&T) to address Advanced Modeling and Uncertainty Quantification for Flight Dynamics (VSST1-7). The scope of the effort is to develop and evaluate advanced multidisciplinary flight dynamics modeling techniques, including integrated uncertainties, to facilitate higher fidelity response characterization of current and future aircraft configurations approaching and during loss-of-control conditions. This approach is to incorporate multiple flight dynamics modeling methods for aerodynamics, structures, and propulsion, including experimental, computational, and analytical. Also to be included are techniques for data integration and uncertainty characterization and quantification. This research shall introduce new and updated multidisciplinary modeling and simulation technologies designed to improve the ability to characterize airplane response in off-nominal flight conditions. The research shall also introduce new techniques for uncertainty modeling that will provide a unified database model comprised of multiple sources, as well as an uncertainty bounds database for each data source such that a full vehicle uncertainty analysis is possible even when approaching or beyond Loss of Control boundaries. Methodologies developed as part of this research shall be instrumental in predicting and mitigating loss of control precursors and events directly linked to causal and contributing factors, such as stall, failures, damage, or icing. The tasks will include utilizing the BR&T Water Tunnel to collect static and dynamic data to be compared to the GTM extended WT database, characterizing flight dynamics in off-nominal conditions, developing tools for structural load estimation under dynamic conditions, devising methods for integrating various modeling elements

  14. ONCOLOGICAL RESULTS OF RADICAL SURGICAL TREATMENT IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

    OpenAIRE

    O. B. Loran; E. I. Veliyev; S. V. Kotov

    2014-01-01

    The authors consider and prove the efficiency of radical prostatectomy used in the treatment of patients with locally advanced prostate cancer as monotherapy and as a component of multimodality therapy.

  15. Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

    DEFF Research Database (Denmark)

    Bjerregaard, Jon K; Mortensen, Michael B; Jensen, Helle A;

    2009-01-01

    BACKGROUND: Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior...

  16. Neoadjuvant chemotherapy in advanced ovarian cancer: latest results and place in therapy

    OpenAIRE

    Sato, Seiya; Itamochi, Hiroaki

    2014-01-01

    Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is ...

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

    Directory of Open Access Journals (Sweden)

    Muhammed Beşir Öztürk

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Karagianni Evangelia

    2003-11-01

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

  19. 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.

  20. Staged Excision for Lentigo Maligna and Lentigo Maligna Melanoma

    Science.gov (United States)

    Wilson, Joshua B.; Walling, Hobart W.; Scupham, Richard K.; Bean, Andrew K.; Ceilley, Roger I.

    2016-01-01

    Introduction: Lentigo maligna is a form of in situ melanoma that occurs commonly on sun-exposed skin of middle-aged to elderly adults. Margin-control surgery offers the highest cure rate for lentigo maligna/lentigo maligna melanoma. Materials and methods: Charts from the authors’ private office from the 20-year period from January 1986 to December 2005 were reviewed to identify patients with histologically confirmed lentigo maligna or lentigo maligna melanoma treated by staged excision. Results: Sixty-eight patients (39 men, 29 women; mean age at diagnosis 67.4±10.2 years, range 48-87 years) with 68 tumors were treated in the authors’ office for lentigo maligna (58) or lentigo maligna melanoma (10) between January 1986 and December 2005. After excision, patients were followed clinically for a minimum of three years. The mean follow-up duration was 138 months (median 139 months; range 37-330 months). The overall margin for tumor clearance was 7.0±0.55mm with a recurrence rate of 5.9 percent. Limitations: The limitations of this study include the retrospective nature of the authors’ review, and data collected from a single, private practice setting. Conclusion: The authors’ findings support staged excision as an effective method of treating lentigo maligna and lentigo maligna melanoma, offering a high cure rate while maximally preserving normal tissue. PMID:27386048

  1. Nanotechnology-based strategies for combating toxicity and resistance in melanoma therapy.

    Science.gov (United States)

    Brys, Adam K; Gowda, Raghavendra; Loriaux, Daniel B; Robertson, Gavin P; Mosca, Paul J

    2016-01-01

    Drug toxicity and resistance remain formidable challenges in cancer treatment and represent an area of increasing attention in the case of melanoma. Nanotechnology represents a paradigm-shifting field with the potential to mitigate drug resistance while improving drug delivery and minimizing toxicity. Recent clinical and pre-clinical studies have demonstrated how a diverse array of nanoparticles may be harnessed to circumvent known mechanisms of drug resistance in melanoma to improve therapeutic efficacy. In this review, we discuss known mechanisms of resistance to various melanoma therapies and possible nanotechnology-based strategies that could be used to overcome these barriers and improve the pharmacologic arsenal available to combat advanced stage melanoma. PMID:26826558

  2. Angiogenesis in melanoma: an update with a focus on current targeted therapies.

    Science.gov (United States)

    Jour, George; Ivan, Doina; Aung, Phyu P

    2016-06-01

    Angiogenesis plays a crucial role in melanoma metastasis and progression. In recent years, numerous studies have investigated the prognostic and clinical significance of this phenomenon, and the development of molecular techniques has enabled us to achieve a better understanding of angiogenesis in melanoma. Herein, we review the current state of knowledge regarding angiogenesis in melanoma, including the pathophysiological, histological and immunohistochemical aspects of this phenomenon. We also review the molecular pathways involved in angiogenesis and the interplay between different components that might be manipulated in the future development of efficient targeted therapies. Recently developed targeted antiangiogenic therapies in clinical trials and included in the treatment of advanced-stage melanoma are also reviewed. PMID:26865640

  3. Skin lesion image segmentation using Delaunay Triangulation for melanoma detection.

    Science.gov (United States)

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

    2016-09-01

    Developing automatic diagnostic tools for the early detection of skin cancer lesions in dermoscopic images can help to reduce melanoma-induced mortality. Image segmentation is a key step in the automated skin lesion diagnosis pipeline. In this paper, a fast and fully-automatic algorithm for skin lesion segmentation in dermoscopic images is presented. Delaunay Triangulation is used to extract a binary mask of the lesion region, without the need of any training stage. A quantitative experimental evaluation has been conducted on a publicly available database, by taking into account six well-known state-of-the-art segmentation methods for comparison. The results of the experimental analysis demonstrate that the proposed approach is highly accurate when dealing with benign lesions, while the segmentation accuracy significantly decreases when melanoma images are processed. This behavior led us to consider geometrical and color features extracted from the binary masks generated by our algorithm for classification, achieving promising results for melanoma detection. PMID:27215953

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

    Science.gov (United States)

    Huang, Sharon K; Hoon, Dave S B

    2016-03-01

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

  5. Psychoeducational intervention for patients with cutaneous malignant melanoma

    DEFF Research Database (Denmark)

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

    2005-01-01

    modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned to......, and they used significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up. CONCLUSION: The findings of this study support the results of an earlier intervention study among patients with malignant...

  6. Update on benefit of immunotherapy and targeted therapy in melanoma: the changing landscape

    Directory of Open Access Journals (Sweden)

    Srivastava N

    2014-06-01

    Full Text Available Neeharika Srivastava, David McDermott Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Malignant melanoma is on the rise. There have been recent advances in targeted agents and immunotherapies that have improved the management and treatment of patients with advanced melanoma. This review discusses the clinical efficacy and unique side effects of targeted immunotherapy and the role of predictive biomarkers in better selection of patients who would derive most benefit from specific treatments. Additionally, this review addresses concerns about the best sequencing algorithms for the currently available targeted agents. By thoroughly and extensively researching through PubMed and the American Society of Clinical Oncology, 69 published articles and abstracts were identified as addressing topics related to malignant melanoma and immunotherapy. The research was divided into subcategories discussing cytokine-based therapy, immunotherapy, molecularly targeted agents, other novel targeted agents, and combination regimens for malignant melanoma. New immune checkpoint inhibitors and targeted agents are able to improve immune-mediated regulatory effects against tumors and, specifically in advanced melanoma, are associated with improvement in overall survival. These new agents have distinct side effects that are often controlled and reversed with dose reductions and/or use of corticosteroids. Currently, there are clinical trials underway to assess the role of combination therapy, whereas other trials are focusing on devising algorithms to delineate how best to sequentially administer these drugs. Although there has been tremendous progress in the management of advanced melanoma with immunotherapy and targeted agents, there is still much to be learned about clinically useful predictive biomarkers and combination therapies as well as how to administer these agents safely. Keywords: melanoma, immunotherapy

  7. Optic nerve invasion of uveal melanoma: clinical characteristics and metastatic pattern

    DEFF Research Database (Denmark)

    Lindegaard, Jacob; Isager, Peter; Prause, Jan Ulrik; Heegaard, Steffen

    2006-01-01

    PURPOSE: To determine the frequency of optic nerve invasion in uveal melanoma, to identify clinical factors associated with optic nerve invasion, and to analyze the metastatic pattern and the association with survival. METHODS: All iris, ciliary body, and choroidal melanomas (N = 2758) examined...... among the three patient groups. RESULTS: Optic nerve invasion was found in 157 uveal melanomas (5.7%; 95% confidence interval [CI], 4.8%-6.6%). Frequency varied during the observation period between 5% and 7%. Only choroidal and ciliary body melanomas were found to invade the optic nerve. Eighty...... perception or worse, nonvisible fundus, and large (>15 mm) tumor size were associated with postlaminar spread. In univariate analysis, patients with postlaminar invasion had significantly higher all-cause and melanoma-related mortality than the other patients. CONCLUSIONS: Optic nerve invasion in uveal...

  8. Immunoscintigraphy with anti-225.28S for ocular melanoma - a comparison with histology and immunohistochemistry

    International Nuclear Information System (INIS)

    Aim: The purpose of this prospective study was to evaluate the value of immunoscintigraphy (ISG) with anti-225.28S in clinically suspected ocular melanoma. Methods: For this purpose standardized ISG was performed in 36 patients using both planar acquisition and emission computed tomography (ECT). Ocular melanoma was present in 31 patients. In 21 patients therapy was enucleation of the eye. These specimens were evaluated by histology and immunohistochemistry in 11 of 21 patients. Results: Regarding the clinical diagnosis, ISG was positive only in 15 of 31 patients with ocular melanoma, regarding histology in 11 of 21 and regarding immunohistochemistry in 5 of 6 patients with a positive immunoreaction. 5 patients showed no immunoreactivity, their ISG was negative. Conclusion: Thus a good correlation between ISG and immunohistochemistry was observed. However ISG using the cutaneous melanoma antibody 225.28S cannot be recommended for the diagnostic work-up of an ocular melanoma considering the poor immunoreactivity. (orig.)

  9. The Effect of Exposure to Ultraviolet Radiation in Infancy on Melanoma Risk.

    Science.gov (United States)

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

    2016-01-01

    Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suffering from methodological shortcomings suggested that people born in spring carry a higher melanoma risk. Data from the Bavarian population-based cancer registry on 28374 incident melanoma cases between 2002 and 2012 were analyzed to reexamine this finding. Crude and adjusted analyses - using negative binomial regression models - were performed addressing the relationship. In the crude analysis, the birth months March - May were significantly overrepresented among melanoma cases. However, after additionally adjusting for the birth month distribution of the Bavarian population, the ostensible seasonal effect disappeared. 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. PMID:27577494

  10. Dose distribution and skin reaction of neutron capture therapy using spontaneously occurring melanoma in the pig

    International Nuclear Information System (INIS)

    The authors carried out a preclinical experiment on treatment of spontaneously occurring melanoma using B-10-para-boronophenylalanine (B-10 BPA) and also measured the actual dose distribution of neutron and γ-ray irradiation on the melanoma itself, surrounding normal tissue, and distant body surfaces. LiF sheets, and lead blocks were arranged as the collimator for shielding the pig skin except for the melanoma lesion. Owing to this collimation system, the neutron fluence to tumor surrounding normal skin was about one one-hundredth of that to melanoma, and further decreases in neutron fluence and γ-ray to distant body surface could be attained. As a result, the pig melanoma completely disappeared and the lesion was covered by normal skin without erosion and ulcerative changes

  11. Imaging of human melanoma xenografts in nude mice with a radiolabeled monoclonal antibody

    International Nuclear Information System (INIS)

    External photoscanning with display of radioactivity data as a color-scaled image detected xenografts of human melanoma in male nude inbred mice of BALB/c background 48 hours after injection of 131I-labeled monoclonal IgG 225.28S that is specific for human melanoma. A 131I-labeled polyclonal goat IgG against human melanoma-associated antigens could also image the tumor, but with this preparation there was considerable localization of radioactivity in normal tissues, resulting in less satisfactory tumor definition. Labeled normal mouse IgG did not image the melanoma grafts. Assay of radioactivity in tissues of melanoma-grafted mice confirmed tumor-specific localization of the antimelanoma antibodies. The tumor:blood ratio of radioactivity was 6.55 with the monoclonal antimelanoma IgG and 0.45 with the polyclonal IgG

  12. CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301in Treating Patients With Stage IIB-IV Melanoma

    Science.gov (United States)

    2016-06-21

    Carcinoma of Unknown Primary Origin; Iris Melanoma; Medium/Large Size Posterior Uveal Melanoma; Mucosal Melanoma; Ocular Melanoma With Extraocular Extension; Small Size Posterior Uveal Melanoma; Stage IIB Skin Melanoma; Stage IIB Uveal Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIA Uveal Melanoma; Stage IIIB Skin Melanoma; Stage IIIB Uveal Melanoma; Stage IIIC Skin Melanoma; Stage IIIC Uveal Melanoma; Stage IV Skin Melanoma; Stage IV Uveal Melanoma

  13. Lentivirus-induced 'Smart' dendritic cells: Pharmacodynamics and GMP-compliant production for immunotherapy against TRP2-positive melanoma.

    Science.gov (United States)

    Sundarasetty, B S; Chan, L; Darling, D; Giunti, G; Farzaneh, F; Schenck, F; Naundorf, S; Kuehlcke, K; Ruggiero, E; Schmidt, M; von Kalle, C; Rothe, M; Hoon, D S B; Gerasch, L; Figueiredo, C; Koehl, U; Blasczyk, R; Gutzmer, R; Stripecke, R

    2015-09-01

    Monocyte-derived conventional dendritic cells (ConvDCs) loaded with melanoma antigens showed modest responses in clinical trials. Efficacy studies were hampered by difficulties in ConvDC manufacturing and low potency. Overcoming these issues, we demonstrated higher potency of lentiviral vector (LV)-programmed DCs. Monocytes were directly induced to self-differentiate into DCs (SmartDC-TRP2) upon transduction with a tricistronic LV encoding for cytokines (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4)) and a melanoma antigen (tyrosinase-related protein 2 (TRP2)). Here, SmartDC-TRP2 generated with monocytes from five advanced melanoma patients were tested in autologous DC:T cell stimulation assays, validating the activation of functional TRP2-specific cytotoxic T lymphocytes (CTLs) for all patients. We described methods compliant to good manufacturing practices (GMP) to produce LV and SmartDC-TRP2. Feasibility of monocyte transduction in a bag system and cryopreservation following a 24-h standard operating procedure were achieved. After thawing, 50% of the initial monocyte input was recovered and SmartDC-TRP2 self-differentiated in vitro, showing uniform expression of DC markers, detectable LV copies and a polyclonal LV integration pattern not biased to oncogenic loci. GMP-grade SmartDC-TRP2 expanded TRP2-specific autologous CTLs in vitro. These results demonstrated a simpler GMP-compliant method of manufacturing an effective individualized DC vaccine. Such DC vaccine, when in combination with checkpoint inhibition therapies, might provide higher specificity against melanoma. PMID:25965393

  14. Long-term results of accelerated radiation treatment for advanced head and neck cancer

    International Nuclear Information System (INIS)

    Background and purpose: This report presents long-term follow-up data from a prospective but unrandomized trial of a continuous 3.5-week course of accelerated radiation treatment (ART) used as primary treatment for patients with loco-regionally advanced head and neck cancer. Materials and methods: Ninety-three patients in three centres in New Zealand and Australia were treated with ART (59.40 Gy in 33 fractions over 24-25 days). Their disease originated from three anatomical regions (oral cavity, 35 patients; pharynx, 31 patients; larynx, 27 patients). Seventy-nine of these patients had stage III or IV cancers. Results: Follow-up ranged from 68 to 203 months (median 139 months). Loco-regional (LR) failure occurred in 52 patients leading to a 10-year actuarial expectation of LR control of 38%. The actuarial expectation of LR control at 10 years was highly dependent on stage and for stage III, IVA and IVB patients it was 57±8.1%, 32±1.7% and 7±0.5%, respectively. Multivariate analysis could not confirm an independent impact of primary site or histological differentiation on LR failure. Two patients died of acute toxicity of treatment and six patients developed grade 3/4 late complications affecting soft tissues only, yielding an actuarial expectation of complications of this severity at 5 years of 9%. No cases of osteoradionecrosis or myelitis were observed. Conclusion: This ART, which has proved easy to use at a number of large and small centres, has produced encouraging long-term LR control at a cost of limited soft tissue morbidity. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  15. Advances in liquid metal cooled ADS systems, and useful results for the design of IFMIF

    Energy Technology Data Exchange (ETDEWEB)

    Massaut, V.; Debruyn, D. [SCK CEN, Mol (Belgium); Decreton, M. [Ghent Univ., Dept. of Applied Physics (Belgium)

    2007-07-01

    Full text of publication follows: Liquid metal cooled Accelerator Driven Systems (ADS) have a lot of design commonalities with the design of IFMIF. The use of a powerful accelerator and a liquid metal spallation source makes it similar to the main features of the IFMIF irradiator. Developments in the field of liquid metal ADS can thus be very useful for the design phase of IFMIF, and synergy between both domains should be enhanced to avoid dubbing work already done. The liquid metal ADS facilities are developed for testing materials under high fast (> 1 MeV) neutron flux, and also for studying the transmutation of actinides as foreseen in the P and T (Partitioning and Transmutation) strategy of future fission industry. The ADS are mostly constituted of a sub-critical fission fuel assembly matrix, a spallation source (situated at the centre of the fuel arrangement) and a powerful accelerator targeting the spallation source. In liquid metal ADS, the spallation source is a liquid metal (like Pb-Bi) which is actively cooled to remove the power generated by the particle beam, spallation reactions and neutrons. Based on an advanced ADS design (e.g. the MYRRHA/XT-ADS facility), the paper shows the various topics which are common for both facilities (ADS and IFMIF) and highlights their respective specificities, leading to focused R and D activities. This would certainly cover the common aspects related to high power accelerators, liquid metal targets and beam-target coupling. But problems of safety, radioprotection, source heating and cooling, neutrons shielding, etc... lead also to common features and developments. Results already obtained for the ADS development will illustrate this synergy. This paper will therefore allow to take profit of recent developments in both fission and fusion programs and enhance the collaboration among the R and D teams in both domains. (authors)

  16. Advances in liquid metal cooled ADS systems, and useful results for the design of IFMIF

    International Nuclear Information System (INIS)

    Full text of publication follows: Liquid metal cooled Accelerator Driven Systems (ADS) have a lot of design commonalities with the design of IFMIF. The use of a powerful accelerator and a liquid metal spallation source makes it similar to the main features of the IFMIF irradiator. Developments in the field of liquid metal ADS can thus be very useful for the design phase of IFMIF, and synergy between both domains should be enhanced to avoid dubbing work already done. The liquid metal ADS facilities are developed for testing materials under high fast (> 1 MeV) neutron flux, and also for studying the transmutation of actinides as foreseen in the P and T (Partitioning and Transmutation) strategy of future fission industry. The ADS are mostly constituted of a sub-critical fission fuel assembly matrix, a spallation source (situated at the centre of the fuel arrangement) and a powerful accelerator targeting the spallation source. In liquid metal ADS, the spallation source is a liquid metal (like Pb-Bi) which is actively cooled to remove the power generated by the particle beam, spallation reactions and neutrons. Based on an advanced ADS design (e.g. the MYRRHA/XT-ADS facility), the paper shows the various topics which are common for both facilities (ADS and IFMIF) and highlights their respective specificities, leading to focused R and D activities. This would certainly cover the common aspects related to high power accelerators, liquid metal targets and beam-target coupling. But problems of safety, radioprotection, source heating and cooling, neutrons shielding, etc... lead also to common features and developments. Results already obtained for the ADS development will illustrate this synergy. This paper will therefore allow to take profit of recent developments in both fission and fusion programs and enhance the collaboration among the R and D teams in both domains. (authors)

  17. ORAL MELANOMA: A FATAL ENTITY

    Directory of Open Access Journals (Sweden)

    Amit

    2014-08-01

    Full Text Available : Oral melanomas are uncommon and similar to their cutaneous counterparts, are neoplasm that developed from melanocytic cells lying in the basal layer of the mucosa, its incidence is about 1.2 cases per 10 million inhabitants per year with a variation between 0.2% to 8% of all the melanomas and 0.5% of all the malignant neoplasias of the oral cavity.1 Oral conditions with increased melanin pigmentation are common; however, melanocytic hyperplasias are rare. The relative incidence amongst mucosal neoplasms of the head and neck had been reviewed by Hormia and Vuori2, about 7253 cases of malignancies of upper respiratory and gastrointestinal tracts between 1953-1964, five cases of oral melanoma were found with an incidence of 0.07%

  18. Best estimate probabilistic safety assessment results for the Westinghouse Advanced Loop Tester (WALT)

    International Nuclear Information System (INIS)

    The nuclear industry uses the probabilistic safety assessment (PSA) technique to improve safety decision making and operation. The methodology evaluates the system reliability, which is defined as the probability of system success, and the postulated accident/problematic scenarios of systems for the nuclear power plants or other facilities. The best estimate probabilistic safety assessment (BE-PSA) method of evaluating system reliability and postulated problematic scenarios will produce more detailed results of interest, such as best estimated reliability analysis and detailed thermal hydraulic calculations using a sub-channel or Computational Fluid Dynamics (CFD) code. The methodology is typically applied to reactors, but can also be applied to any system such as a test facility. In this paper, a BE-PSA method is introduced and used for evaluating the Westinghouse Advanced Loop Tester (WALT). The WALT test loop at the George Westinghouse Science and Technology Center (STC), which was completed in October 2005, is designed to be utilized to model the top grid span of a hot rod in a fuel assembly under the Pressurizer Water Reactor (PWR) normal operating conditions. In order to safely and successfully operate the WALT test loop and correctly use the WALT experimental data, it is beneficial to perform a probabilistic safety assessment and analyze the thermal hydraulic results for the WALT loop in detail. Since October 2005, a number of test runs have been performed on the WALT test facility designed and fabricated by Westinghouse Electric Company LLC. This paper briefly describes the BE-PSA method and performs BE-PSA for the WALT loop. Event trees linked with fault trees embedding thermal hydraulic analysis models, such as sub-channel and/or CFD models, were utilized in the analyses. Consequently, some selected useful experimental data and analysis results are presented for future guidance on WALT and/or other similar test facilities. For example, finding and

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-06-15

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

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: The design of melanoma sentinel lymph node (SLN) histologic protocols is based on the premise that most metastases are found in the central parts of the nodes, but the evidence for this belief has never been thoroughly tested. METHODS: The nodal location of melanoma metastases in 149...... SLNs. In addition, the size of the metastases located exclusively outside the 2 regional protocols (ie, 3 central sections, and 3 peripheral sections) were measured and compared with each other. RESULTS: The metastasis detection rates of the central, the peripheral, and the evenly distributed protocols...... were 77%, 79%, and 78%, respectively. No difference in either the mean volume or the maximum diameter of the metastases located exclusively outside the central and the peripheral protocols was found (volume: 0.036 vs. 0.031 mm and diameter: 0.320 vs. 0.332 mm). CONCLUSIONS: In SLNs, melanoma metastases...

  1. Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.

    Directory of Open Access Journals (Sweden)

    Yuchun Luo

    Full Text Available Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a "nucleic acid-rich" and "inflammatory cell-rich" information reservoir and represents systemic processes altered by the presence of cancer cells.We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45(- and CD45(+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively.The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45(- subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients

  2. Modulation of ganglioside expression in human melanoma cell lines

    International Nuclear Information System (INIS)

    Cell surface gangliosides in human melanoma cell lines were modulated by pretreatment and adaptation to 6-thioguanine and 5-bromo-deoxyuridine. Chemo- and radiation sensitivities were compared in original cell lines and modulated cells by the human tumor colony-forming assay. Modulated cells showed decreased expression of cell surface GM2 and GD2 gangliosides. This reduction was correlated with increased resistance to bleomycin, vincristine, cisplatin and radiation treatment. These results suggest that cell surface GM2 and GD2 ganglioside expression in human melanoma cells is intimately associated with several cellular biological properties, such as drug or radiation sensitivity and cellular differentiation. (author)

  3. Clinical trial of carbon ion radiotherapy for gynecological melanoma

    International Nuclear Information System (INIS)

    Carbon ion radiotherapy (C-ion RT) is an advanced modality for treating malignant melanoma. After we treated our first case of gynecological melanoma using C-ion RT in November 2004, we decided to conduct a clinical trial to evaluate its usefulness for the treatment of gynecological melanoma. The eligibility criteria for enrollment in this study were histologically proven malignant melanoma of the gynecological regions with lymph node metastasis remaining in the inguinal and pelvic regions. The small pelvic space, including the GTV and the metastatic lymph node, was irradiated with up to a total dose of 36 GyE followed by a GTV boost of up to a total dose of 57.6 GyE or 64 GyE in 16 fractions. A series of 23 patients were treated between November 2004 and October 2012. Patient age ranged from 51-80 with a median of 71. Of the tumor sites, 14 were located in the vagina, 6 in the vulva, and 3 in the cervix uteri. Of the 23 patients, 22 were irradiated with up to a total dose of 57.6 GyE, and 1 patient was irradiated with up to a total dose of 64 GyE. Chemotherapy and interferon-β were also used to treat 11 of the patients. Acute and late toxicities of Grade 3 or higher were observed in 1 patient treated with concurrent interferon-β. The median follow-up time was 17 months (range, 6-53 months). There was recurrence in 14 patients, and the 3-year local control and overall survival rates were 49.9% and 53.0%, respectively. C-ion RT may become a non-invasive treatment option for gynecological melanoma. (author)

  4. FDG PET in early stage cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Fluorodeoxyglucose positron emission tomography (FDG PET) is not recommended in early stage melanoma; however, a significant number of cases are referred to our institution for FDG PET. We refer to early stage disease as American Joint Committee on Cancer (AJCC) stage I and II, which includes all cases without metastases. A retrospective review was undertaken to determine the clinical utility of FDG PET in this patient group. A retrospective study of FDG scans on all patients presenting to the WA PET Centre with early stage melanoma over a 5½ year period was undertaken. The positivity rate of the initial study for detection of malignant melanoma was determined. In patients with an initially negative FDG PET, the time from initial diagnosis to a positive surveillance study was determined. Both the initial positivity rate and time to a positive study were correlated with Breslow staging. Three hundred twenty-two patients were included in the study, of which 74 had initial positive FDG PET scans (23%). Adequate follow-up was available in 51 patients with the PET result confirmed as true positive in 37 (positive predictive value 73%). One hundred eight of 248 patients initially negative had follow-up scans during the follow-up period, of which 48 became positive. The 73% of recurrences were over 12 months post-diagnosis. No correlation with Breslow thickness was demonstrated. Despite FDG PET not being recommended for early cutaneous malignant melanoma, 27% of melanoma cases referred for FDG PET during the study period were AJCC stage I or II. Our results suggest FDG PET in early stage melanoma demonstrates occult disease in 17% of cases.

  5. Advances and results of the educative project: Implementation of the career of 'Technician in Radiological protection'

    International Nuclear Information System (INIS)

    In this work the obtained advances and achievements during the impartment of the technician career in radiological protection are presented. This is carried out in the 'Justo Sierra' Technological High School Center of San Mateo Atenco, Estado de Mexico, and has for objective the formation of professional-technicians. (Author)

  6. MC1R variants increase risk of melanomas harboring BRAF mutations.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Fargnoli, Maria Concetia; Pike, Kris; Pfeiffer, Ruth M; Tsang, Shirley; Rozenblum, Ester; Munroe, David J; Golubeva, Yelena; Calista, Donato; Seidenari, Stefania; Massi, Daniela; Carli, Paolo; Bauer, Juergen; Elder, David E; Bastian, Boris C; Peris, Ketty; Landi, Maria T

    2008-10-01

    Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR)=7.0, 95% confidence interval (CI)=2.1-23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (P<0.0001, test for trend), and regardless of signs of chronic solar damage. In contrast, no association with BRAF-negative melanomas was found (OR=1.0, 95% CI=0.6-1.6). No characteristics of subjects or melanomas, including age, nevus count, pigmentation, and melanoma thickness or location on chronically or intermittently sun-exposed body sites, substantially modified this association, although results could be affected by the small numbers in some categories. This study confirms that the known MC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations. PMID:18368129

  7. TLR7 Gln11Leu single nucleotide polymorphism and susceptibility to cutaneous melanoma

    Science.gov (United States)

    ELEFANTI, LISA; SACCO, GIORGIA; STAGNI, CAMILLA; RASTRELL, MARCO; MENIN, CHIARA; RUSSO, IRENE; ALAIBAC, MAURO

    2016-01-01

    Cutaneous melanoma is a life-threatening skin cancer. Its incidence is rapidly increasing, and early diagnosis is the main factor able to improve its poor prognosis. Toll-like receptors (TLRs) are transmembrane glycoproteins that recognize pathogen- and damage-associated molecular patterns, against which TLRs activate the innate immune response and initiate the adaptive immune response. Genetic variations of these receptors may alter the immune system, and are involved in evolution and susceptibility to various diseases, including cancer. The aim of the present study was to evaluate whether the presence of TLR7 glutamine (Gln) 11 leucine (Leu) polymorphism confers an increased susceptibility to cutaneous melanoma. For that purpose, a case-control study was performed with 182 melanoma cases and 89 controls. To highlight the possible association between the aforementioned polymorphism and the susceptibility to melanoma, 93 cases of single melanoma and 89 cases of multiple primary melanoma (MPM) were compared in the present study. Since the TLR7 gene is localized on the chromosome X, the allelic frequency of the Gln11Leu polymorphism was analyzed separately in males and females. The distribution of allele frequencies between melanoma cases and controls (P=0.245) and between single melanoma and MPM cases (P=0.482) was not significant. Therefore, the present results do not suggest an association between TLR7 Gln11Leu polymorphism and susceptibility to cutaneous melanoma. Further studies are required to analyze the influence of other TLR polymorphisms on the susceptibility to malignant melanoma and the involvement of innate immunity in this malignancy. PMID:27347137

  8. Endogenous PGE(2) induces MCP-1 expression via EP4/p38 MAPK signaling in melanoma.

    Science.gov (United States)

    Tang, Mingrui; Wang, Yuxin; Han, Sihuan; Guo, Shu; Xu, Nan; Guo, Jiayan

    2013-02-01

    It has been demonstrated that cyclooxygenase-2 (COX-2) is expressed in melanoma tissues and prostaglandin E(2) (PGE(2)) is produced by melanoma cells in vitro. However, the roles of COX-2/PGE(2) in melanoma are largely unknown. In the present study, we set out to analyze the correlation of endogenous PGE(2) with the expression of macrophage chemoattractant protein-1 (MCP-1) and to identify the signaling pathway involved. It was found that MCP-1 mRNA was heterogeneously expressed in 18 melanoma tissue specimens, and the levels of MCP-1 mRNA were positively correlated with those of COX-2 mRNA. Inhibition of endogenous PGE(2) production by a COX-2 inhibitor, COX-2 siRNA or an NFκB inhibitor suppressed MCP-1 expression, whereas treatment with TNF-α (to stimulate endogenous PGE(2) production) or exogenous PGE(2) enhanced MCP-1 expression in melanoma cells. Both the EP4 antagonist and the p38 MAPK inhibitor reduced MCP-1 production in melanoma cells, and abrogated the increased MCP-1 secretion induced by TNF-α or exogenous PGE(2). Conditioned medium from melanoma cells promoted macrophage migration, which was blocked by inhibitors of the PGE(2)/EP4/p38 MAPK signaling pathway. These results indicate that endogenous PGE(2) induces MCP-1 expression via EP4/p38 MAPK signaling in an autocrinal manner in melanoma, and melanoma cell-derived PGE(2) may be involved in macrophage recruitment in the melanoma microenvironment. PMID:23420676

  9. Differential PAX3 functions in normal skin melanocytes and melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Medic, Sandra [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); Rizos, Helen [Westmead Institute for Cancer Research and Melanoma Institute of Australia, University of Sydney at Westmead Millennium Institute, Westmead, NSW (Australia); Ziman, Mel, E-mail: m.ziman@ecu.edu.au [School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA (Australia); School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA (Australia)

    2011-08-12

    Highlights: {yields} PAX3 retains embryonic roles in adult melanocytes and melanoma cells. {yields} Promotes 'stem' cell-like phenotype via NES and SOX9 in both cells types. {yields} Regulates melanoma and melanocyte migration through MCAM and CSPG4. {yields} PAX3 regulates melanoma but not melanocyte proliferation via TPD52. {yields} Regulates melanoma cell (but not melanocyte) survival via BCL2L1 and PTEN. -- Abstract: The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as 'stem' cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated 'stem' cell like phenotype, PAX3 may contribute to melanoma development and progression.

  10. Malignant Melanoma in the Elderly: Different Regional Disease and Poorer Prognosis

    Directory of Open Access Journals (Sweden)

    James B. Macdonald, Amylou C. Dueck, Richard J. Gray, Nabil Wasif, David L. Swanson, Aleksandar Sekulic, Barbara A. Pockaj

    2011-01-01

    Full Text Available Purpose: Age is a poor prognostic factor in melanoma patients. Elderly melanoma patients have a different presentation and clinical course than younger patients. We evaluated the impact of age ≥70 years (yrs on the diagnosis and natural history of melanoma.Methods: Retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node (SLN database, treated from June 1997 to June 2010. Disease characteristics and clinical outcomes were compared between patients ≥70 yrs vs. <70 yrs of age.Results: 237 patients (39% were ≥70 yrs. Elderly patients had a higher proportion of head and neck melanomas (34% vs. 20%, p<0.001, and greater mean tumor thickness (2.4mm vs. 1.8mm, p<0.001. A greater proportion of T3 or T4 melanoma was seen in the elderly (p<0.001 as well as a greater mean number of mitotic figures: 3.6/mm2 vs. 2.7/mm2 (p=0.005. Despite greater mean thickness, the incidence of SLN metastases was less in the ≥70 yrs group with T3/T4 melanomas (18% vs. 33%, p=0.02. The elderly had a higher rate of local and in-transit recurrences, 14.5% vs. 3.4% at 5 yrs (p<0.001. 5 yr disease-specific mortality and overall mortality were worse for those ≥70 yrs: 16% vs. 8% (p=0.004, and 30% vs. 12% (p<0.001, respectively.Conclusions: Elderly (≥70 yrs melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer SLN metastases. Melanoma in the elderly is more common on the head and neck. Higher incidence of local/in-transit metastases is seen among the elderly. Five-year disease-specific mortality and overall mortality are both worse for these patients.

  11. The role of hyperthermia as part of a triple modality treatment in metastatic melanoma

    International Nuclear Information System (INIS)

    Full text: Response rates of cutaneous, subcutaneous, soft tissue or lymph node metastases of melanoma to systemic chemotherapy or immunotherapy are rather low. We report our clinical experience with superficial and deep regional hyperthermia in combination with chemotherapy, radiotherapy or radiochemotherapy. We treated 20 patients with metastatic malignant melanoma (8 men, 12 women; age 27 - 84 years, mean age 57.6 years) by using superficial or deep regional hyperthermia. 15 patients had cutaneous and subcutaneous metastases, 2 in the inguinal lymph nodes, 2 in the retroperitoneal lymph nodes and 1 in the cervical lymph nodes. BSD 2000 was used with either superficial applicator MA 150 or MA 120 for superficial hyperthermia or ring applicator SIGMA 60 for deep regional hyperthermia. Hyperthermia was applied one to three times a week for 2 to 10 (mean 6) sessions. In 4 patients hyperthermia was combined with chemotherapy, in 1 patient with radiotherapy and in 15 patients with both chemotherapy and radiotherapy. The clinical response was assessed with clinical evaluation and/or CT scan and/or sonography at monthly intervals. Both superficial and deep regional hyperthermia was well tolerated, only patients with deep regional hyperthermia needed additional parenteral therapy because of an increase of whole body temperature and increased necessity of analgesics. Local tumor necrosis was seen in 7 patients, 1 patient had additional bacterial infection, 3 patients developed acute radiodermatitis and 10 patients had no local side effects. We observed 5 complete local remissions (25 %), 7 partial local remissions (35 %), 5 patients with stable disease (25 %) and 3 patients with progressive disease (15 %), giving an overall local response rate of 85 %. The best results were observed in metastases located retroperitoneally or within the skin. In the absence of effective systemic therapies in advanced melanoma, local tumor control is of pivotal importance in maintaining

  12. Replacement of Lys Linker with Arg Linker Resulting in Improved Melanoma Uptake and Reduced Renal Uptake of Tc-99m-Labeled Arg-Gly-Asp-Conjugated Alpha-Melanocyte Stimulating Hormone Hybrid Peptide

    OpenAIRE

    Yang, Jianquan; Guo, Haixun; Padilla, R. Steve; Berwick, Marianne; Miao, Yubin

    2010-01-01

    The purpose of this study was to reduce the non-specific renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (α-MSH) hybrid peptide through structural modification or L-lysine co-injection. The RGD motif {cyclic(Arg-Gly-Asp-dTyr-Asp)} was coupled to [Cys3,4,10, d-Phe7, Arg11]α-MSH3-13 {(Arg11)CCMSH} through the Arg linker (substituting the Lys linker) to generate a novel RGD-Arg-(Arg11)CCMSH hybrid peptide. The melanoma targeting and pharmacokinetic properties of...

  13. Purification of melanoma growth stimulatory activity

    International Nuclear Information System (INIS)

    The Hs0294 human malignant melanoma cell line produces a monolayer mitogen that stimulates the serum free growth of low-density cultures of Hs0294 cells. This report describes the purification of that mitogen, termed MGSA for melanoma growth stimulatory activity, from serum-free conditioned medium from the Hs0294 cultures. MGSA has been purified from acetic acid extracts of lyophilized conditioned medium by gel filtration, reverse-phase high-pressure liquid chromatography (RP-HPLC), and preparative electrophoresis, resulting in a >400,000-fold purification. MGSA bioactivity resides in acid- and heat-stable polypeptides of high and low molecular weight. However, the majority of the activity is reproducibly associated with the ∼16-kd moiety eluting from RP-HPLC at ∼35% acetonitrile. Reduction with dithiothreitol or B-mercaptoethanol results in a loss of biological activity but does not convert the 24-28-kd moieties to the 125I-MGSA that has been purified by preparative electrophoresis (16 kd) specifically binds to Hs0294 melanoma cells and retains 100% of the growth-stimulatory activity. The 16-kd MGSA stimulates the proliferation of Hs0294 cells at concentrations of 0.3-30 pM. Purified MGSA does not enable anchorage-independent growth of normal rat kidney (NRK) cells and is therefore different from the previously described transforming growth factors. The amino acid composition of MGSA differs from that of other previously described growth factors. These data demonstrate that MGSA represents a separate class of growth factors with biological and biochemical properties different from other growth factors

  14. Critical Assessment of Clinical Prognostic Tools in Melanoma.

    Science.gov (United States)

    Mahar, Alyson L; Compton, Carolyn; Halabi, Susan; Hess, Kenneth R; Gershenwald, Jeffrey E; Scolyer, Richard A; Groome, Patti A

    2016-09-01

    The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources. A priori criteria were used to evaluate their quality and clinical relevance, and included intended clinical use, model development approaches, validation strategies, and performance metrics. We identified 17 clinical prognostic tools for primary cutaneous melanoma. Patients with stages I-III and T1 or thin melanoma were the most frequently considered populations. Seventy-five percent of tools were developed using data collected from patients diagnosed in 2006 or earlier, and the well-established factors of tumor thickness, ulceration, and age were included in 70 % of tools. Internal validity using cross-validation or bootstrapping techniques was performed for two tools only. Fewer than half were evaluated for external validity; however, when done, the appropriate statistical methodology was applied and results indicated good generalizability. Several clinical prognostic tools have the potential to refine survival estimates for individual melanoma patients; however, there is a great opportunity to improve these tools and to foster the development of new, validated tools by the inclusion of contemporary clinicopathological covariates and by using improved statistical and methodological approaches. PMID:27052645

  15. Improving the Data Quality of Advanced LIGO Based on Early Engineering Run Results

    CERN Document Server

    Nuttall, L K; Areeda, J; Betzwieser, J; Dwyer, S; Effler, A; Fisher, R P; Fritschel, P; Kissel, J S; Lundgren, A P; Macleod, D M; Martynov, D; McIver, J; Mullavey, A; Sigg, D; Smith, J R; Vajente, G; Williamson, A R; Wipf, C C

    2015-01-01

    The Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors have completed their initial upgrade phase and will enter the first observing run in late 2015, with detector sensitivity expected to improve in future runs. Through the combined efforts of on-site commissioners and the Detector Characterization group of the LIGO Scientific Collaboration, interferometer performance, in terms of data quality, at both LIGO observatories has vastly improved from the start of commissioning efforts to present. Advanced LIGO has already surpassed Enhanced LIGO in sensitivity, and the rate of noise transients, which would negatively impact astrophysical searches, has improved. Here we give details of some of the work which has taken place to better the quality of the LIGO data ahead of the first observing run.

  16. Recent results of a seismically isolated optical table prototype designed for advanced LIGO

    OpenAIRE

    Sannibale, V.; B. Abbott; Aso, Y.; Boschi, V.; Coyne, D.; DeSalvo, R.; Márka, S.; Ottaway, D.; Stochino, A.

    2008-01-01

    The Horizontal Access Module Seismic Attenuation System (HAM-SAS) is a mechanical device expressly designed to isolate a multipurpose optical table and fit in the tight space of the LIGO HAM Ultra-High-Vacuum chamber. Seismic attenuation in the detectors' sensitivity frequency band is achieved with state of the art passive mechanical attenuators. These devices should provide an attenuation factor of about 70dB above 10Hz at the suspension point of the Advanced LIGO triple pendulum suspension....

  17. Experimental results on advanced inertial fusion schemes obtained within the HiPER project

    Czech Academy of Sciences Publication Activity Database

    Batani, D.; Gizzi, L.A.; Koester, P.; Labate, L.; Honrubia, J.; Antonelli, L.; Morace, A.; Volpe, L.; Santos, J.J.; Schurtz, G.; Hulin, S.; Ribeyre, X.; Nicolai, P.; Vauzour, B.; Dorchies, F.; Nazarov, W.; Pasley, J.; Richetta, M.; Lancaster, K.; Spindloe, C.; Tolley, M.; Neely, D.; Kozlová, Michaela; Nejdl, Jaroslav; Rus, Bedřich; Wolowski, J.; Badziak, J.

    2012-01-01

    Roč. 57, č. 1 (2012), s. 3-10. ISSN 0029-5922. [International Workshop and Summer School on Towards Fusion Energy /10./. Kudowa Zdroj, 12.06.2011-18.06.2011] Institutional research plan: CEZ:AV0Z10100502 Keywords : advanced ignition schemes * fast ignition * shock ignition Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.507, year: 2012

  18. The results of accelerated radiotherapy and concomitant cisplatin administration in advanced oropharyngeal cancer

    International Nuclear Information System (INIS)

    The accelerated radiotherapy and concomitant infusion of cisplatin in low doses was evaluated in 15 patients with advanced squamous cell carcinoma of the oral cavity and oral part of pharynx. Clinical complete response was seen in 6 of 15 patients (40%) and 4 patients (26.6%) were alive 12 months with no evidence of disease, of all group of 15 patients 9 (60%) were alive 12 months after treatment. (author)

  19. Sequential Treatment by Ionizing Radiation and Sodium Arsenite Dramatically Accelerates TRAIL-Mediated Apoptosis of Human Melanoma Cells

    OpenAIRE

    Ivanov, Vladimir N.; Zhou, Hongning; Hei, Tom K.

    2007-01-01

    Melanoma is the most lethal form of skin cancer. There is a lack of effective treatments for individuals with advanced disease. Many melanomas exhibit high levels of radioresistance. The direct consequence of γ-irradiation for most melanoma cells is growth arrest at the G2-M phase of cell cycle. However, radiation-induced signaling pathways may affect numerous additional targets in cancer cells. We show in the present study that γ-irradiation, as well as α-particle exposure, dramatically incr...

  20. Tumor Heterogeneity in Uveal Melanomas

    NARCIS (Netherlands)

    H.W. Mensink (Hanneke)

    2010-01-01

    textabstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults with an incidence of 7-10/ million and has a predilection for hematogenous dissemination to the liver. Despite improvements in diagnosis and treatment of this intraocular tumor, there has not been a change in

  1. Biology of Human Cutaneous Melanoma

    OpenAIRE

    Sharma, Bhuvnesh K.; Hasskamp, Joanne H.; Elias, Elias G.

    2010-01-01

    A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.

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

    Directory of Open Access Journals (Sweden)

    Sanjeev Bhagat

    2010-04-01

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

  3. Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy.

    Science.gov (United States)

    Smalley, Keiran S M; Fedorenko, Inna V; Kenchappa, Rajappa S; Sahebjam, Solmaz; Forsyth, Peter A

    2016-09-15

    Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ∼30% of patients (as high as 75% at autopsy). In ∼5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a "sanctuary" sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that (1) Cancer cells migrating to the CNS may have unique molecular properties and (2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review, we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma. PMID:27084046

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

    Directory of Open Access Journals (Sweden)

    Cindy L. Lamerson

    2012-01-01

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

  5. Melanomas: radiobiology and role of radiation therapy

    International Nuclear Information System (INIS)

    diverse range of time-dose prescriptions are consistent with the wide diversity and complexity of the radiobiological data for MM. RT for Metastatic Melanoma: RT is the single most effective therapy for local palliation of metastatic disease. Complete response (CR) rates range from 24-75% and overall response (OR) rates are 59-98% with RT compared with CR rates of 3-10% and OR rates of only 15-36% with either chemotherapy or immunotherapy. Achieving a CR is important even for patients with metastatic disease. Five-year survival for patients with metastatic disease who achieve a CR is 49% compared to a 5-year survival of only 3% for patients who do not achieve a CR. RT for Primary Tumors: RT is effective therapy for selected primary sites including uveal melanoma and non-cutaneous, non-ocular mucosal MM. The RT results for ocular melanoma and non-cutaneous, non-ocular mucosal MM are superior to surgery. In addition, post-operative RT for residual microscopic/macroscopic disease following primary surgery produces long term local control rates of 75-88%. It is likely that radiation therapy is being under-utilized in current oncology practice

  6. Cutaneous melanoma in solid organ transplant patients.

    Science.gov (United States)

    Russo, I; Piaserico, S; Belloni-Fortina, A; Alaibac, M

    2014-08-01

    Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma. PMID:25068225

  7. Results from the DOE Advanced Gas Reactor Fuel Development and Qualification Program

    Energy Technology Data Exchange (ETDEWEB)

    David Petti

    2014-06-01

    Modular HTGR designs were developed to provide natural safety, which prevents core damage under all design basis accidents and presently envisioned severe accidents. The principle that guides their design concepts is to passively maintain core temperatures below fission product release thresholds under all accident scenarios. This level of fuel performance and fission product retention reduces the radioactive source term by many orders of magnitude and allows potential elimination of the need for evacuation and sheltering beyond a small exclusion area. This level, however, is predicated on exceptionally high fuel fabrication quality and performance under normal operation and accident conditions. Germany produced and demonstrated high quality fuel for their pebble bed HTGRs in the 1980s, but no U.S. manufactured fuel had exhibited equivalent performance prior to the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. The design goal of the modular HTGRs is to allow elimination of an exclusion zone and an emergency planning zone outside the plant boundary fence, typically interpreted as being about 400 meters from the reactor. To achieve this, the reactor design concepts require a level of fuel integrity that is better than that claimed for all prior US manufactured TRISO fuel, by a few orders of magnitude. The improved performance level is about a factor of three better than qualified for German TRISO fuel in the 1980’s. At the start of the AGR program, without a reactor design concept selected, the AGR fuel program selected to qualify fuel to an operating envelope that would bound both pebble bed and prismatic options. This resulted in needing a fuel form that could survive at peak fuel temperatures of 1250°C on a time-averaged basis and high burnups in the range of 150 to 200 GWd/MTHM (metric tons of heavy metal) or 16.4 to 21.8% fissions per initial metal atom (FIMA). Although Germany has demonstrated excellent performance of TRISO-coated UO

  8. Non-invasive nuclear detection of choroidal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Packer, S.; Lambrecht, R.M.; Fairchild, R.G.; Wolf, A.P.; Atkins, H.L.; Fand, I.

    1981-01-01

    The biodistribution of over 30 radiopharmaceuticals thought to be tumor-seeking agents were studied using hamsters and mice. Several radiopharmaceuticals were found to be appropriate as melanoma localizing agents. Results with modified dual pinhole collimator and a pigment affinic agent (iodine-123 labeled quinoline) and a non-specific tumor seeking agent (gallium-67 citrate) are also reported.

  9. Immune response markers in sentinel nodes may predict melanoma progression

    OpenAIRE

    Rodolfo, Monica; Castelli, Chiara; Rivoltini, Licia

    2014-01-01

    We recently reported that variable expression of immune-response genes distinguishes tumor positive sentinel nodes in melanoma patients with malignant progression from those with non-progressing disease. Our results depict sentinel nodes as sites in which immune functions are associated with metastatic disease and identify CD30 as a host immune-related cancer prognostic marker and potential therapeutic target.

  10. Nivolumab for Metastatic Melanoma without a BRAF Mutation

    Science.gov (United States)

    A summary of results from an international phase III trial show that nivolumab (Opdivo®) improves overall survival compared with the chemotherapy drug dacarbazine in patients with metastatic melanoma whose tumors do not have a mutation in the BRAF gene.

  11. Non-invasive nuclear detection of choroidal melanoma

    International Nuclear Information System (INIS)

    The biodistribution of over 30 radiopharmaceuticals thought to be tumor-seeking agents were studied using hamsters and mice. Several radiopharmaceuticals were found to be appropriate as melanoma localizing agents. Results with modified dual pinhole collimator and a pigment affinic agent (iodine-123 labeled quinoline) and a non-specific tumor seeking agent (gallium-67 citrate) are also reported

  12. Somatostatin receptor scintigraphy in advanced renal cell carcinoma. Results of a phase II-trial of somatostatine analogue therapy in patients with advanced RCC

    Energy Technology Data Exchange (ETDEWEB)

    Freudenberg, L.S.; Goerges, R.; Stergar, H.; Bockisch, A. [Dept. of Nuclear Medicine, Univ. of Duisburg-Essen (Germany); Gauler, T.; Bauer, S. [Dept. of Internal Medicine (Cancer Research), Univ. of Duisburg-Essen (Germany); Antoch, G. [Dept. of Diagnostic and Interventional Radiology and Neuroradiology, Univ. of Duisburg-Essen (Germany); Schuette, J. [Dept. of Medical Oncology/Hematology, Marien-Hospital Duesseldorf (Germany)

    2008-07-01

    Aims: objective of this prospective study was to evaluate the role of somatostatin receptor scintigraphy (SRS) in advanced renal cell carcinoma (RCC) with respect to potential therapy with somatostatin analogue (SST-A) and to assess the response rate under therapy with SST-A. Patients, methods: 16 patients with documented progression of histologically confirmed advanced RCC were included. Planar whole-body SRS was performed 4, 24 and 48h post i.v. injection of 175-200 MBq {sup 111}In-pentetreoide. 5 and 25 h p.i. SPECT of thorax and abdomen were performed. Documentation of somatostatin receptor expression via SRS in > 50% of known tumour lesions was the criteria for treatment start with SST-A (Sandostatin LAR {sup registered} -Depot 30mg i.m. every four weeks). Results: in 9/16 of the patients SRS showed at least one metastasis with moderate (n = 5) or intense (n = 4) tracer uptake. Lesion-based SRS evaluation showed only 12.1% (20/165) of all metastases. Most false-negative lesions were located in the lungs. In too patients, the majority of the known metastases was SRS positive and these patients received SST-A therapy. The first radiographic evaluation after a two-month interval showed progressive disease in both patients. Conclusions: we conclude that SRS is of limited value in staging of advanced RCC. In our patients SST-A did not result in a growth control of RCC. Consequently, the use of SST-A in advanced RCC seems to be no relevant therapeutic option. (orig.)

  13. PET/CT in malignant melanoma: contrast-enhanced CT versus plain low-dose CT

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the diagnostic value of contrast-enhanced CT (CECT) versus non-enhanced low-dose CT (NECT) in the staging of advanced malignant melanoma with 18F-fluordeoxyglucose (FDG) positron emission tomography (PET)/CT. In total, 50 18F-FDG PET/CT examinations were performed in 50 patients with metastasized melanoma. For attenuation correction, whole-body NECT was performed followed by diagnostic CECT with contrast agent. For the whole-body PET, 18F-FDG was applied. Criteria for evaluation were signs of vital tumour tissue (extent of lesions, contrast enhancement, maximum standardized uptake value >2.5). Findings suspicious for melanoma were considered lesions. NECT, CECT and 18F-FDG PET were evaluated separately, followed by combined analysis of PET/NECT and PET/CECT. Findings were verified histologically and/or by follow-up (>6 months). Overall, 232 lesions were analysed, and 151 proved to be metastases. The sensitivity of NECT, CECT, PET, PET/NECT and PET/CECT was 62, 85, 90, 97 and 100%, and specificity was 52, 63, 88, 93 and 93%, respectively. Compared to CECT, NECT obtained additional false-negative results: lymph node (n = 19) and liver/spleen metastases (n = 9). Misinterpreted physiological structures mainly caused additional false-positive findings (n = 17). In combined analysis of PET/NECT, six false-positive [other tumours (n = 2), inflammatory lymph nodes (n = 2), inflammatory lung lesion (n = 1), blood vessel (n = 1)] and five false-negative findings [liver (n = 3), spleen (n = 1), lymph node metastases (n = 1)] remained. On PET/CECT, six false-positive [inflammatory lymph nodes (n = 3), other tumours (n = 2), inflammatory lung lesion (n = 1)] and no false-negative findings occurred. However, additional false findings on PET/NECT (6 of 232) did not change staging compared to PET/CECT. Our results indicate that it is justified to perform PET/NECT instead of PET/CECT for melanoma staging. (orig.)

  14. Xmrk-induced melanoma progression is affected by Sdf1 signals through Cxcr7.

    Science.gov (United States)

    Liedtke, Daniel; Erhard, Isabell; Abe, Keiko; Furutani-Seiki, Makoto; Kondoh, Hisato; Schartl, Manfred

    2014-03-01

    Chemokine signals mediated by Sdf1/Cxcl12 through the chemokine receptor Cxcr4 are thought to play an instructive role in tumor migration and organ-specific metastasis. We have used a small aquarium fish model to contribute to a better understanding of how the course of melanoma development is influenced by Sdf1 signals in vivo. We studied oncogene-induced skin tumor appearance and progression in the transgenic medaka (Oryzias latipes) melanoma model. Similar to humans, invasive medaka melanomas show increased levels of sdf1, cxcr4, and cxcr7 gene expression. Stable transgenic fish lines overexpressing sdf1 exclusively in pigment cells showed a reduction in melanoma appearance and progression. Remarkably, diminished levels of functional Cxcr7, but not of Cxcr4b, resulted in strongly reduced melanoma invasiveness and a repression of melanoma. Our results thereby indicate that Sdf1 signals via Cxcr7 are able to constrain melanoma growth in vivo and that these signals influence tumor outcome. PMID:24279354

  15. Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

    International Nuclear Information System (INIS)

    Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. A proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated

  16. Tumor-suppressive effects of natural-type interferon-β through CXCL10 in melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Hikaru; Nobeyama, Yoshimasa, E-mail: nobederm@jikei.ac.jp; Nakagawa, Hidemi

    2015-08-21

    Introduction: Type 1 interferon is in widespread use as adjuvant therapy to inhibit melanoma progression. Considering the tumor-suppressive effects of local administration of interferon-β (IFN-β) on lymphatic metastasis, the present study was conducted to identify melanoma-suppressive molecules that are up-regulated by IFN-β treatment of lymphatic endothelial cells. Materials and methods: Lymphatic endothelial cells, fibroblasts, and melanoma cells were treated with natural-type IFN-β, and melanoma cells were treated with CXCL10. Genome-wide oligonucleotide microarray analysis was performed using lymphatic endothelial cells with or without IFN-β treatment. Quantitative real-time reverse transcription-PCR and an enzyme-linked immunosorbent assay were performed to examine CXCL10 expression. A proliferation assay was performed to examine the effects of IFN-β and CXCL10 in melanoma cells. Results: Genome-wide microarray analyses detected CXCL10 as a gene encoding a secretory protein that was up-regulated by IFN-β in lymphatic endothelial cells. IFN-β treatment significantly induced CXCL10 in dermal lymphatic endothelial cells and melanoma cells that are highly sensitive to IFN-β. CXCL10 reduced melanoma cell proliferation in IFN-β-sensitive cells as well as resistant cells. Melanoma cells in which CXCL10 was knocked down were sensitive to IFN-β. CXCR3-B, which encodes the CXCL10 receptor, was up-regulated in melanoma cells with high sensitivity to IFN-β and down-regulated in melanoma cells with medium to low sensitivity. Conclusions: Our data suggest that IFN-β suppresses proliferation and metastasis from the local lymphatic system and melanoma cells via CXCL10. Down-regulation of CXCR3-B by IFN-β may be associated with resistance to IFN-β. - Highlights: • We search melanoma-suppressive molecules induced by IFN-β. • IFN-β induces a high amount of CXCL10 from lymphatic endothelial cells. • CXCL10 induction level in melanoma cells is correlated

  17. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm3 (range, 26.89-2284.82 cm3). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

  18. Do We Know What Causes Melanoma Skin Cancer?

    Science.gov (United States)

    ... melanoma skin cancer be prevented? What causes melanoma skin cancer? Many risk factors for melanoma have been found, ... such as CDKN2A (also known as p16 ) and CDK4 that prevent them from doing their normal job ...

  19. Recombinant leukocyte A interferon in advanced breast cancer. Results of a phase II efficacy trial.

    Science.gov (United States)

    Sherwin, S A; Mayer, D; Ochs, J J; Abrams, P G; Knost, J A; Foon, K A; Fein, S; Oldham, R K

    1983-05-01

    Nineteen patients with advanced refractory metastatic breast cancer no longer responsive to chemotherapy were treated in the first phase II efficacy trial of recombinant leukocyte A interferon (IFL-rA), a highly purified single molecular species of alpha interferon prepared by recombinant DNA methods. Patients received a previously determined maximum tolerated dose for this agent (50 X 10(6) U/m2 body surface area) by intramuscular injection three times weekly for up to 3 months. The symptoms of toxicity observed in this trial resemble those previously reported for alpha interferons and include fever, chills, fatigue, anorexia, and leukopenia. All patients required dose reductions, most often for reasons of severe fatigue. Of the 17 patients evaluable for tumor response, one patient had stable disease and 16 had evidence of tumor progression. We conclude that IFL-rA is not an active agent in the treatment of advanced, refractory breast cancer when used at a maximum tolerated dose on this treatment schedule. PMID:6342490

  20. Incorporating Vibration Test Results for the Advanced Stirling Convertor into the System Dynamic Model

    Science.gov (United States)

    Meer, David W.; Lewandowski, Edward J.

    2010-01-01

    The U.S. Department of Energy (DOE), Lockheed Martin Corporation (LM), and NASA Glenn Research Center (GRC) have been developing the Advanced Stirling Radioisotope Generator (ASRG) for use as a power system for space science missions. As part of the extended operation testing of this power system, the Advanced Stirling Convertors (ASC) at NASA GRC undergo a vibration test sequence intended to simulate the vibration history that an ASC would experience when used in an ASRG for a space mission. During these tests, a data system collects several performance-related parameters from the convertor under test for health monitoring and analysis. Recently, an additional sensor recorded the slip table position during vibration testing to qualification level. The System Dynamic Model (SDM) integrates Stirling cycle thermodynamics, heat flow, mechanical mass, spring, damper systems, and electrical characteristics of the linear alternator and controller. This Paper presents a comparison of the performance of the ASC when exposed to vibration to that predicted by the SDM when exposed to the same vibration.