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Melanoma Research

Larisa J Geskin, James J Damiano, Christina C Patrone, Lisa H Butterfield, John M Kirkwood, Louis D Falo
In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery...
March 14, 2018: Melanoma Research
Blanca De Unamuno, Zaida García-Casado, José Bañuls, Celia Requena, José Antonio Lopez-Guerrero, Eduardo Nagore
CDKN2A germline mutations increase the risk of melanoma development and are present in 20 and 10% of familial and multiple melanoma cases, respectively. Pancreatic cancer has been associated with CDKN2A in some populations and, accordingly, its presence in first-degree or second-degree relatives of a melanoma patient is considered as a criterion for genetic testing. In this study, we show that in an area with low melanoma incidence, CDKN2A germline mutations in patients with melanoma and personal or family history of pancreatic cancer are mainly present in the setting of familial or multiple melanoma cases...
March 14, 2018: Melanoma Research
Anne M Stowman, Alexandra W Hickman, Ileana S Mauldin, Adela Mahmutovic, Alejandro A Gru, Craig L Slingluff
Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for 'pure' DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology...
March 13, 2018: Melanoma Research
Kendra C Foley, Michael I Nishimura, Tamson V Moore
Immunotherapy is a promising method of treatment for a number of cancers. Many of the curative results have been seen specifically in advanced-stage melanoma. Despite this, single-agent therapies are only successful in a small percentage of patients, and relapse is very common. As chemotherapy is becoming a thing of the past for treatment of melanoma, the combination of cellular therapies with immunotherapies appears to be on the rise in in-vivo models and in clinical trials. These forms of therapies include tumor-infiltrating lymphocytes, T-cell receptor, or chimeric antigen receptor-modified T cells, cytokines [interleukin (IL-2), IL-15, IL-12, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interferon-α, interferon-γ], antibodies (αPD-1, αPD-L1, αTIM-3, αOX40, αCTLA-4, αLAG-3), dendritic cell-based vaccines, and chemokines (CXCR2)...
March 8, 2018: Melanoma Research
Devayani Machiraju, Iris Moll, Christoffer Gebhardt, Antje Sucker, Kristina Buder-Bakhaya, Dirk Schadendorf, Jessica C Hassel
Interferons (IFN) have a direct growth-inhibiting effect on tumor cells through Janus kinase-dependent activation of the transcription factor signal transducer and activator of transcription (STAT1). In vitro, signaling through STAT5 has been demonstrated to counteract this effect and lead to IFN resistance of melanoma cell lines. In 32 patients treated with IFN-α in an adjuvant setting, we investigated paraffin-embedded tumor tissue from primary melanomas and melanoma metastases for expression of STAT3 and STAT5, by immunohistochemistry, and for expression of phosphorylated signaling transduction activating transcription factor (pSTAT)3 and pSTAT5, by immunofluorescence...
February 26, 2018: Melanoma Research
Florentia Dimitriou, Anna L Frauchiger, Mirjana Urosevic-Maiwald, Mirjam C Naegeli, Simone M Goldinger, Marjam Barysch, Daniel Franzen, Jivko Kamarachev, Ralph Braun, Reinhard Dummer, Joanna Mangana
The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today's standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features...
February 26, 2018: Melanoma Research
Maria Gonzalez-Cao, Clara Mayo de Las Casas, Nuria Jordana Ariza, Jose L Manzano, Miguel Á Molina-Vila, Virtudes Soriano, Teresa Puertolas, Ariadna Balada, Ainara Soria, Margarita Majem, Clara Montagut, Eva Muñoz, Delvys Rodriguez-Abreu, Elisabeth Perez, Almudena Garcia, Javier Cortes, Ana Drozdowskyj, Niki Karachaliou, Rafael Rosell
Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome...
February 23, 2018: Melanoma Research
Alessandro A Testori, Stefan Suciu, Alexander C J van Akkooi, Mariano Suppa, Alexander M M Eggermont, Esther de Vries, Arjen Joosse
The aim of this study was to assess the prognostic importance of lymph node ratio (LNR) in stage III melanoma after complete lymph nodal dissections. From European Organization for Research and Treatment of Cancer randomized trials 18871, 18952, and 18991, 2358 patients had full information on positive and examined lymph nodes (LNs) and were included. Cox proportional hazards models stratified by trial were used to assess the prognostic impact of LNR adjusted for confounders on melanoma-specific survival. Optimal cutoff values for LNR were calculated for each LN dissection site (axillary, inguinal, and neck)...
February 9, 2018: Melanoma Research
Giulia Ganzetti, Davide Sartini, Anna Campanati, Corrado Rubini, Elisa Molinelli, Valerio Brisigotti, Monia Cecati, Valentina Pozzi, Roberto Campagna, Annamaria Offidani, Monica Emanuelli
Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide and pyridine compounds, participating in xenobiotic and drug metabolism. Data on literature have evidenced a possible role of NNMT in many solid cancers, but no data are currently available in cutaneous melanoma. Recent important advances have been achieved in the treatment of advanced melanoma with targeted therapy and immunotherapy. However, the identification of biomarkers that can be used for the detection of early stage disease as well as for monitoring the therapeutic response during treatment is of utmost importance...
February 7, 2018: Melanoma Research
Masahiko Yanagita, Jason J Luke, Frank S Hodi, Pasi A Jänne, Cloud P Paweletz
Isolation of circulating tumor cells (CTCs) from blood of melanoma patients has been difficult owing to inconsistent expression of surface antigens. Here we report on the isolation, detection, and characterization of CTCs from blood of melanoma patients using microfiltration and fluorescent in-situ hybridization (FISH). Two tubes of blood from 15 patients with advanced melanoma were collected. These two tubes subsequently underwent filtration through a membrane with pore sizes of 7.5 μm. Isolated cells from one tube were analyzed by FISH for RREB1 (6p24), MYB (6q32), SE6 (D6Z1), and CCND1 (11q13) and the other paired specimen was analyzed by immunofluorescence for HMB45, melanoma-associated antigen recognized by T cells-1, tyrosinase and melanogenesis associated transcription factor...
February 5, 2018: Melanoma Research
Anita Kothapalli, Muhammad A Khattak
Anti-PD-1 monoclonal antibodies have shown durable long-term survival benefit in patients with metastatic melanoma. Limited evidence exists on the safety and efficacy of PD-1 inhibitors in patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections as these patients have traditionally been excluded from clinical trials because of a theoretical risk of immune reconstitution inflammatory syndrome. We aim to determine the safety and efficacy of treatment with PD-1 inhibitors in seven patients with HBV/HCV infection and concurrent metastatic melanoma or non-small-cell lung cancer (NSCLC)...
February 5, 2018: Melanoma Research
Yusuke Muto, William Ng, Kenjiro Namikawa, Akira Takahashi, Arata Tsutsumida, Makiko Nishida, Naoya Yamazaki
The mitogen-activated protein kinase pathway regulates cell growth and differentiation and is activated by BRAF mutations. BRAF mutations are present in about 40-50% of cutaneous melanomas. More than 90% of BRAF mutations are the V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant advanced melanomas. A variety of side effects have been observed with combination therapy including pyrexia, fatigue, nausea, and vomiting...
January 29, 2018: Melanoma Research
Marnix H Geukes Foppen, Willem Boogerd, Christian U Blank, Johannes V van Thienen, John B Haanen, Dieta Brandsma
Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS...
January 19, 2018: Melanoma Research
Charlee Nardin, Christine Mateus, Mathieu Texier, Emilie Lanoy, Salima Hibat-Allah, Samy Ammari, Caroline Robert, Frederic Dhermain
Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015...
January 19, 2018: Melanoma Research
Anna M Rose, Utsav K Radia, Rong Luo, Helen Kalirai, Channa N Jayasena, Philip Luthert, Sarah E Coupland, Geoffrey E Rose
No abstract text is available yet for this article.
January 17, 2018: Melanoma Research
Wenjia Zhu, Shimin Li, Bingqing Zou, Hongqin Liu, Shuyi Wang
Sinonasal mucosal malignant melanoma (SNMMM) is a rare disease. The aim of this study was to investigate the expressions of HER4 and CD44 in human SNMMM tissues and their relationship with the clinicopathological features and prognosis of patients. In total, 64 paraffin-embedded samples of SNMMM treated in our hospital from 29 December 1999 to 24 June 2011 were collected. HER4 and CD44 were detected in the tissues of SNMMM by immunohistochemistry. The differences in the HER4 and CD44 expressions in the tissues were evaluated and matched with clinicopathological parameters and the survival rate, respectively...
January 5, 2018: Melanoma Research
Luis P Del Carpio Huerta, Maria Mas Castells, Georgia Anguera Palacios, Ivana Sullivan, Alan Gonzalez Vidal, Margarita Majem Tarruella
Conjunctival melanoma is a rare disease, and little is known about its molecular background. Here, we present the case of a 48-year-old patient with conjunctival melanoma and metachronic lymph node and skin metastasis with KRAS p.K117Y mutation in exon 4 in all the lesions. The cancer genome interpreter predicted this mutation to have driver function. To our knowledge, this is the first time this mutation is found in conjunctival melanoma. An important role in the disease development is suggested.
December 20, 2017: Melanoma Research
Sara Bassoli, Cristina Pellegrini, Caterina Longo, Lucia Di Nardo, Francesca Farnetani, Anna M Cesinaro, Giovanni Pellacani, Maria Concetta Fargnoli
No abstract text is available yet for this article.
April 2018: Melanoma Research
Clara Fernández-Sartorio, Aram Boada, Marion M Chavez-Bourgeois, Gustavo J Ruiz Ares, Ana M Arance, José L Manzano, Adriana García-Herrera, Cristina Carrera
No abstract text is available yet for this article.
April 2018: Melanoma Research
Akira Takahashi, Arata Tsutsumida, Kenjiro Namikawa, Naoya Yamazaki
No abstract text is available yet for this article.
April 2018: Melanoma Research
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