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Massi melanoma

Gongda Xue, Reto Kohler, Fengyuan Tang, Debby Hynx, Yuhua Wang, Francesca Orso, Vincent Prêtre, Reto Ritschard, Petra Hirschmann, Peter Cron, Tim Roloff, Reinhard Dummer, Mario Mandalà, Sandrine Bichet, Christel Genoud, Alexandra G Meyer, Manuele G Muraro, Giulio C Spagnoli, Daniela Taverna, Curzio Rüegg, Taha Merghoub, Daniela Massi, Huifang Tang, Mitchell P Levesque, Stephan Dirnhofer, Alfred Zippelius, Brian A Hemmings, Andreas Wicki
BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors (MEKi) were recently approved for therapy of metastatic melanomas harbouring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. We conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated...
May 25, 2017: Oncotarget
Mario Mandalà, Carlo Tondini, Barbara Merelli, Daniela Massi
The use of monoclonal antibodies that block immunologic checkpoints, which mediate adaptive immune resistance, has revolutionized the treatment of metastatic melanoma patients. Specifically, targeting single immune suppressive molecules such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4), or programmed cell death protein 1 (PD-1) expressed on T cells or its primary ligand, programmed cell death ligand 1 (PD-L1), resulted in pronounced clinical benefit for a subset of melanoma patients. Although single-agent immune checkpoint inhibitor therapy has demonstrated promising clinical activity in metastatic melanoma patients, there is still a significant proportion of patients who show primary resistance to these therapies...
April 21, 2017: American Journal of Clinical Dermatology
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
Vincenzo De Giorgi, Alessia Gori, Imma Savarese, Antonietta D'Errico, Federica Scarfì, Federica Papi, Vincenza Maio, Piero Covarelli, Daniela Massi, Sara Gandini
BACKGROUND: Currently, the association between body mass index (BMI) and hormone therapies and Cutaneous Melanoma (CM) development is strongly debated. This study was carried out to assess the association between BMI, hormone therapies, and CM risk. METHODS: The present study is a hospital-based case-control study with 605 consecutive CM patients and 592 controls treated for non-neoplastic conditions at the Department of Dermatology in Florence. The associations of melanoma risk with BMI and hormone therapies were assessed performing unconditional logistic regression to estimate odds ratios (OR) and their 95% confidence intervals, adjusting for potential confounders...
March 13, 2017: Journal of Cancer Research and Clinical Oncology
Vincenzo De Giorgi, Alessia Gori, Imma Savarese, Antonietta D'Errico, Federica Papi, Marta Grazzini, Federica Scarfì, Piero Covarelli, Daniela Massi
Currently, there are no specific clinical and dermoscopic features for diagnosing truly amelanotic plantar melanoma (TAPM). The present study aimed to investigate the dermoscopic features of all clinical variants of TAMPS and to evaluate their histopathological correlations. A retrospective analysis of prospectively collected data was carried out during a 10-year period (2003-2013). We analyzed the clinical data of 1321 patients, who had received a histological diagnosis of melanoma at the Melanoma Unit of the University of Florence...
June 2017: Melanoma Research
Mario Mandalà, Daniela Massi
The therapy of metastatic melanoma (MM) was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in ≈40-50% of patients. Oncogenic BRAF promotes an immune-compromised tumour microenvironment (TME). Inhibition of MAPK pathway signaling with BRAF (BRAFi) and MEK inhibitors (MEKi) attenuates immune escape and increases the melanoma immunogenicity through multiple mechanisms, including elevation of melanoma antigen expression and improved T cell infiltration and function. These changes sustain the TME for response to immunotherapy...
February 26, 2017: Handbook of Experimental Pharmacology
Valentina Audrito, Sara Serra, Aureliano Stingi, Francesca Orso, Federica Gaudino, Cinzia Bologna, Francesco Neri, Giulia Garaffo, Romina Nassini, Gianna Baroni, Eliana Rulli, Daniela Massi, Salvatore Oliviero, Roberto Piva, Daniela Taverna, Mario Mandalà, Silvia Deaglio
PD-L1 is expressed by a subset of patients with metastatic melanoma (MM) with an unfavorable outcome. Its expression is increased in cells resistant to BRAF or MEK inhibitors (BRAFi or MEKi). However, the function and regulation of expression of PD-L1 remain incompletely understood.After generating BRAFi- and MEKi-resistant cell lines, we observed marked up-regulation of PD-L1 expression. These cells were characterized by a common gene expression profile with up-regulation of genes involved in cell movement...
February 28, 2017: Oncotarget
Pietro Sollena, Giacomo Caldarola, Alessandro Di Stefani, Guido Massi, Ketty Peris
No abstract text is available yet for this article.
February 2017: Journal of the American Academy of Dermatology
Mario Mandalà, Francesco De Logu, Barbara Merelli, Romina Nassini, Daniela Massi
Treatment of metastatic melanoma was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in 40-50% of patients. Another area of advancement was the use of immunotherapy, and specifically, immune checkpoint inhibitors. There is compelling evidence that oncogenic BRAF, in addition to driving melanoma proliferation, differentiation and survival, induces T-cell suppression directly through the secretion of inhibitory cytokines or through membrane expression of co-inhibitory molecules such as the PD-1 ligands PD-L1 or PD-L2...
February 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Mario Mandalà, Francesca Galli, Laura Cattaneo, Barbara Merelli, Eliana Rulli, Simone Ribero, Pietro Quaglino, Vincenzo De Giorgi, Jacopo Pigozzo, Vanna Chiarion Sileni, Alessandra Chirco, Pier Francesco Ferrucci, Marcella Occelli, Gianlorenzo Imberti, Dario Piazzalunga, Daniela Massi, Carlo Tondini, Paola Queirolo
BACKGROUND: The 7th edition of the TNM American Joint Committee on Cancer classification incorporates mitotic rate (MR) only for primary cutaneous melanoma (PCM) with Breslow thickness (BT) ≤1 mm. OBJECTIVE: To investigate whether and to what extent MR is able to predict sentinel lymph node (SLN) status and clinical outcome of PCM patients with BT >1 mm. METHODS: The study included consecutive patients with PCM. Logistic regression and Cox regression model were used to analyze the impact of MR on SLN status, disease-free survival (DFS), and overall survival...
February 2017: Journal of the American Academy of Dermatology
Gongda Xue, Emanuela Romano, Daniela Massi, Mario Mandalà
WNT signaling regulates embryonic development and tissue homeostasis in the adult stage. Evolutionarily, activation of the WNT pathway is triggered by a large family of cytokines and activates a broad spectrum of downstream targets through two independent branches mediated by β-catenin (defined as canonical pathway) or PLC and small GTPase (defined as non-canonical pathway), respectively. Recent studies revealed the crucial role of WNT in the maintenance of cell metabolism and stemness as well as its deregulation in tumourigenesis and malignant transformation through oncogenic reprogramming, which contributes to cancer cell proliferation and differentiation, survival, stress response and resistance...
September 2016: Cancer Treatment Reviews
Anna Falanga, Marina Marchetti, Daniela Massi, Barbara Merelli, Cristina Verzeroli, Laura Russo, Eliana Rulli, Carlo Tondini, Lorenzo Legramandi, Romina Nassini, Cristian Scatena, Francesco De Logu, Laura Cattaneo, Mario Mandalà
No abstract text is available yet for this article.
June 2016: Journal of the American Academy of Dermatology
Sara Gandini, Daniela Massi, Mario Mandalà
BACKGROUND: Despite the success of immunotherapy directed at inhibiting of programmed death-1 (PD-1)/PD-ligand (L)1 signaling, it is not established whether PD-L1 expression correlates with the clinical response and outcome in different tumors. The present meta-analysis investigates whether the PD-L1 status, detected by immunohistochemistry, is associated with clinical response and mortality in patients treated with anti-PD-1/PD-L1 therapy. METHODS: A systematic literature search and quantitative analysis were planned, conducted and reported following CONSORT and QUORUM checklists, up to December 2015, to identify clinical trials with information on cancer outcome by PD-L1 immunohistochemical expression in tumor tissues...
April 2016: Critical Reviews in Oncology/hematology
Francesca M Bosisio, James S Wilmott, Nathalie Volders, Marjorie Mercier, Jasper Wouters, Marguerite Stas, Willeke Am Blokx, Daniela Massi, John F Thompson, Richard A Scolyer, Nicolas van Baren, Joost J van den Oord
Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs...
April 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Francesca Salvianti, Claudio Orlando, Daniela Massi, Vincenzo De Giorgi, Marta Grazzini, Mario Pazzagli, Pamela Pinzani
Solid tumor release into the circulation cell-free DNA (cfDNA) and circulating tumor cells (CTCs) which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma. The aim of the present study was to assess the diagnostic performance of a tumor-related methylated cfDNA marker in melanoma patients and to compare this parameter with the presence of CTCs...
2015: Frontiers in Molecular Biosciences
D Massi, D Brusa, B Merelli, C Falcone, G Xue, A Carobbio, R Nassini, G Baroni, E Tamborini, L Cattaneo, V Audrito, S Deaglio, M Mandalà
BACKGROUND: BRAF inhibitors (BRAFi) improve survival in metastatic melanoma patients (MMP) but the duration of clinical benefit is limited by development of drug resistance. Here, we investigated whether the expression of programmed death-ligand 1 (PD-L1) and the density of tumor-infiltrating mononuclear cells (TIMC) predict the occurrence of resistance, hence affecting the clinical outcome in BRAFi-treated MMP. METHODS: PD-L1 expression (cutoff 5%) was analyzed by immunohistochemistry with two different antibodies in BRAF(V600)-mutated formalin-fixed and paraffin-embedded samples from 80 consecutive MMP treated with BRAFi at a single institution...
September 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Daniela Massi, Carlo Tomasini, Rebecca Senetta, Milena Paglierani, Francesca Salvianti, Maria Elena Errico, Vittoria Donofrio, Paola Collini, Gabrina Tragni, Angela Rita Sementa, Franco Rongioletti, Renata Boldrini, Andrea Ferrari, Claudio Gambini, Maria Cristina Montesco
BACKGROUND: Diagnosis and proper management of atypical Spitz tumors in pediatric age are still controversial. OBJECTIVE: We sought to investigate the clinicopathological and molecular features of atypical Spitz tumors in patients aged 18 years or younger. METHODS: We performed a retrospective clinicopathological and fluorescence in situ hybridization study on 50 pediatric atypical Spitz tumors. RESULTS: Parameters that were significantly correlated with a diagnosis of atypical Spitz tumors over Spitz nevus included asymmetry, level IV/V, lack of maturation, solid growth, nuclear pleomorphism, high nuclear-cytoplasmic ratio, atypical and deep mitoses, and more than 6 mitoses/mm(2)...
January 2015: Journal of the American Academy of Dermatology
Raffaella Santi, Lisa Simi, Rossella Fucci, Milena Paglierani, Monica Pepi, Pamela Pinzani, Barbara Merelli, Marco Santucci, Gerardo Botti, Carmelo Urso, Daniela Massi
BACKGROUND: Mucosal melanomas (MM) represent a heterogeneous tumour population that exhibits site-specific molecular profiles. AIMS: In a multicentre retrospective study, we investigated KIT aberrations in primary anorectal (AR) melanomas compared with melanoma metastatic to the gastrointestinal (GI) tract. METHODS: Primary AR MM (n=31) and GI metastatic melanoma (n=27) were studied for KIT mutations on exons 11, 13, 17 and 18 by high-resolution melting analysis, direct sequencing and c-KIT expression by immunohistochemistry...
February 2015: Journal of Clinical Pathology
Daniela Massi, Lisa Simi, Elisa Sensi, Gianna Baroni, Gongda Xue, Cristian Scatena, Adele Caldarella, Pamela Pinzani, Gabriella Fontanini, Alessandra Carobbio, Carmelo Urso, Mario Mandalà
Testing for NRAS is now integral part in the assessment of metastatic melanoma patients because there is evidence that NRAS-mutated patients may be sensitive to MEK inhibitors, and RAS mutation is a common mechanism of acquired resistance during treatment with BRAF inhibitors. This study evaluated the sensitivity and specificity of immunohistochemical analysis using an N-Ras (Q61R) antibody to detect the presence of the NRASQ61R mutation in melanoma patients. A total of 98 primary cutaneous melanomas that have undergone examination of NRAS mutation were retrieved from a multicentric database...
April 2015: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
I Savarese, F Papi, A D'Errico, A Gori, M Grazzini, M Vannucchi, D Massi, V De Giorgi
An 85-year-old woman presented with a lesion on the sole of her right foot, which was histologically confirmed as acral lentiginous melanoma. Because of the large field involved and because the patient refused any invasive or painful treatment, topical treatment with imiquimod was commenced. At the 20-month follow-up, the patient was still continuing treatment with topical imiquimod, and no metastases to the lymph nodes or viscera were found, either clinically or in imaging studies. We believe that the success of the treatment cannot be explained only by the stimulation of the immune system induced by imiquimod...
January 2015: Clinical and Experimental Dermatology
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