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metastatic melanoma

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https://www.readbyqxmd.com/read/29332716/predicting-the-incidence-and-timing-of-central-nervous-system-disease-in-metastatic-melanoma-implications-for-surveillance-and-preventative-therapy
#1
Gary B Deutsch, Richard Tyrell, Samuel Yost, Mariel B Deutsch, Garni Barkhoudarian, Daniel F Kelly, Mark B Faries
No abstract text is available yet for this article.
February 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29332608/concealed-complete-response-in-melanoma-patients-under-therapy-with-immune-checkpoint-inhibitors-two-case-reports
#2
Stefan Schliep, Abbas Agaimy, Alexander Cavallaro, Franklin Kiesewetter, Gerold Schuler, Lucie Heinzerling
BACKGROUND: The assessment of tumor size by RECIST using CT scans and MRIs is considered to be standard of care for staging cancer patients. Despite radiologic evidence of widespread disease, we document for the first time that patients were completely free of viable tumor. CASE PRESENTATION: Two patients with metastatic melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab) and progressive metastases were detected on CT-scans performed shortly before histologic examinations...
January 15, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29331888/a-longitudinal-analysis-of-ido-and-pdl1-expression-during-immune-or-targeted-therapy-in-advanced-melanoma
#3
Lukas Krähenbühl, Simone M Goldinger, Joanna Mangana, Katrin Kerl, Ines Chevolet, Liève Brochez, Christine Horak, Mitch Levesque, Reinhard Dummer, Phil F Cheng
A deepened understanding of the cellular and molecular processes in the tumor microenvironment is necessary for the development of precision immunotherapy (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry in paired biopsies from various organs of 43 metastatic melanoma patients treated with IT and targeted therapy (TT). Intraindividual biopsies taken after a period of weeks to months demonstrate discordant results in 30% of the cases. Overlap of IDO and PDL1 increased after therapy...
January 11, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29331419/the-therapeutic-potential-of-human-adipose-derived-mesenchymal-stem-cells-producing-cxcl10-in-a-mouse-melanoma-lung-metastasis-model
#4
Hamed Mirzaei, Hossein Salehi, Reza Kazemi Oskuee, Ali Mohammadpour, Hamid Reza Mirzaei, Mohammad Reza Sharifi, Reza Salarinia, Hossein Yousofi Darani, Mojgan Mokhtari, Aria Masoudifar, Amirhossein Sahebkar, Rasoul Salehi, Mahmoud Reza Jaafari
Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma...
January 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29330434/targeting-melanoma-stem-cells-with-the-vitamin-e-derivative-%C3%AE-tocotrienol
#5
Monica Marzagalli, Roberta Manuela Moretti, Elio Messi, Marina Montagnani Marelli, Fabrizio Fontana, Alessia Anastasia, Maria Rosa Bani, Giangiacomo Beretta, Patrizia Limonta
The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330296/tumor-progression-is-mediated-by-thymosin-%C3%A3-4-through-a-tgf%C3%A3-mrtf-signaling-axis
#6
Tsuyoshi Morita, Kenichiro Hayashi
Although enhanced thymosin beta-ß4 (TMSBX4/Tß4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here it is demonstrated that transforming growth factor beta (TGFß) facilitates Tß4 expression and leads to the activation of myocardin-related transcription factors (MRTFs), which are co-activators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29330295/epigenetic-reprogramming-of-pericentromeric-satellite-dna-in-premalignant-and-malignant-lesions
#7
Nadine H Brueckmann, Christina B Pedersen, Henrik J Ditzel, Morten F Gjerstorff
Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group (PcG) proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study, demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 (PRC1) deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29327717/combined-mutation-and-copy-number-variation-detection-by-targeted-next-generation-sequencing-in-uveal-melanoma
#8
Kyra N Smit, Natasha M van Poppelen, Jolanda Vaarwater, Robert Verdijk, Ronald van Marion, Helen Kalirai, Sarah E Coupland, Sophie Thornton, Neil Farquhar, Hendrikus-Jan Dubbink, Dion Paridaens, Annelies de Klein, Emine Kiliç
Uveal melanoma is a highly aggressive cancer of the eye, in which nearly 50% of the patients die from metastasis. It is the most common type of primary eye cancer in adults. Chromosome and mutation status have been shown to correlate with the disease-free survival. Loss of chromosome 3 and inactivating mutations in BAP1, which is located on chromosome 3, are strongly associated with 'high-risk' tumors that metastasize early. Other genes often involved in uveal melanoma are SF3B1 and EIF1AX, which are found to be mutated in intermediate- and low-risk tumors, respectively...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29327065/blood-predictive-biomarkers-for-nivolumab-in-advanced-melanoma
#9
Edouard Chasseuil, Mélanie Saint-Jean, Hannah Chasseuil, Lucie Peuvrel, Gaëlle Quéreux, Jean-Michel Nguyen, Aurélie Gaultier, Emilie Varey, Amir Khammari, Brigitte Dréno
Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in our department were identified. For each case, 9 potential blood biomarkers were identified. Bivariate and multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC) classification stage, Eastern Cooperative Oncology Group (ECOG) performance status, lactate dehydrogenase (LDH) level and failure to respond to first-line therapy, were used to test the association between biomarkers and overall survival (primary outcome) or progression-free survival (secondary outcome)...
December 20, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29324592/frequent-subclinical-macular-changes-in-combined-braf-mek-inhibition-with-high-dose-hydroxychloroquine-as-treatment-for-advanced-metastatic-braf-mutant-melanoma-preliminary-results-from-a-phase-i-ii-clinical-treatment-trial
#10
Akosua A Nti, Leona W Serrano, Harpal S Sandhu, Katherine E Uyhazi, Ilaina D Edelstein, Elaine J Zhou, Scott Bowman, Delu Song, Tara C Gangadhar, Lynn M Schuchter, Sheryl Mitnick, Alexander Huang, Charles W Nichols, Ravi K Amaravadi, Benjamin J Kim, Tomas S Aleman
PURPOSE: To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. METHODS: Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment...
January 10, 2018: Retina
https://www.readbyqxmd.com/read/29322243/humanistic-burden-of-disease-for-patients-with-advanced-melanoma-in-canada
#11
Winson Y Cheung, Martha S Bayliss, Michelle K White, Angela Stroupe, Andrew Lovley, Bellinda L King-Kallimanis, Kathryn Lasch
BACKGROUND: Metastatic melanoma is a highly aggressive cancer, often striking in the prime of life. This study provides new information directly from advanced melanoma (stage III and IV) patients on how their disease impacts their health-related quality of life (HRQL). METHODS: Twenty-nine in-depth, qualitative interviews were conducted with adult patients with advanced melanoma in Canada. A semi-structured interview guide was used. Interviews were transcribed verbatim and key concepts were identified using a grounded theory analytic approach...
January 10, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/29319729/effects-of-nivolumab-in-peritoneal-carcinamatosis-of-malign-melanoma-in-mouse-model
#12
Ozgul Duzgun, Inanc Samil Sarici, Serkan Gokcay, Kivilcim Eren Ates, Mehmet Bertan Yılmaz
PURPOSE: To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model. METHODS: Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS)...
December 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29317634/punctuated-evolution-of-canonical-genomic-aberrations-in-uveal-melanoma
#13
Matthew G Field, Michael A Durante, Hima Anbunathan, Louis Z Cai, Christina L Decatur, Anne M Bowcock, Stefan Kurtenbach, J William Harbour
Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29310328/the-significance-of-braf-v600e-mutation-status-discordance-between-primary-cutaneous-melanoma-and-brain-metastases-the-implications-for-braf-inhibitor-therapy
#14
Enda J Hannan, Donal P O'Leary, Stephen P MacNally, Elaine W Kay, Michael A Farrell, Patrick G Morris, Colm P Power, Arnold D K Hill
To compare BRAF V600E status of primary melanoma and brain metastases to assess for discordance by cross-sectional study, and to evaluate clinical implications on BRAF inhibitor therapy.Brain metastases are common in patients with advanced melanoma. Between 40% and 60% of melanomas demonstrate BRAF mutations, BRAF V600E being most common. Selective BRAF inhibitor therapy has shown improvement in outcome in patients with melanoma. It has been demonstrated that not all metastatic lesions carry the same BRAF mutation status as the primary, but the frequency in which discordance occurs remains unclear...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29309612/nicotinamide-phosphoribosyltransferase-nampt-as-a-therapeutic-target-in-braf-mutated-metastatic-melanoma
#15
Valentina Audrito, Antonella Managò, Sofia La Vecchia, Federica Zamporlini, Nicoletta Vitale, Gianna Baroni, Simona Cignetto, Sara Serra, Cinzia Bologna, Aureliano Stingi, Francesca Arruga, Tiziana Vaisitti, Daniela Massi, Mario Mandalà, Nadia Raffaelli, Silvia Deaglio
Background: One of the effects of oncogenic signaling is metabolic reprogramming of tumor cells to support anabolic growth, opening the way to therapeutic targeting of metabolic pathways. Methods: We studied NAD biosynthesis in BRAF inhibitor (BRAFi)-resistant (BiR) melanoma cell lines. Data in cell lines were confirmed by immunohistochemistry in biopsies from 17 patients with metastatic melanoma (MM) before and after the acquisition of resistance to BRAFi. Therapeutic potential of NAD biosynthesis inhibitors was determined by invitro monitoring cell growth and death and in mouse xenograft models...
March 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29309059/high-dimensional-single-cell-analysis-predicts-response-to-anti-pd-1-immunotherapy
#16
Carsten Krieg, Malgorzata Nowicka, Silvia Guglietta, Sabrina Schindler, Felix J Hartmann, Lukas M Weber, Reinhard Dummer, Mark D Robinson, Mitchell P Levesque, Burkhard Becher
Immune-checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable responses. Therefore, predictive biomarkers of a clinical response are urgently needed. Here we used high-dimensional single-cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of anti-PD-1 immunotherapy...
January 8, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29308322/impaired-nk-cell-recognition-of-vemurafenib-treated-melanoma-cells-is-overcome-by-simultaneous-application-of-histone-deacetylase-inhibitors
#17
Sheila López-Cobo, Natalia Pieper, Carmen Campos-Silva, Eva M García-Cuesta, Hugh T Reyburn, Annette Paschen, Mar Valés-Gómez
Therapy of metastatic melanoma advanced recently with the clinical implementation of signalling pathway inhibitors, such as vemurafenib, specifically targeting mutant BRAFV600E. In general, patients experience remarkable clinical responses under BRAF inhibitor (BRAFi) treatment but eventually progress within 6-8 months due to resistance development. Responding metastases show an increased immune cell infiltrate, including also NK cells, that, however, is no longer detectable in BRAFi-resistant lesions, suggesting NK cell activity should be exploited to prevent disease progression...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308314/serum-exosomes-as-predictors-of-clinical-response-to-ipilimumab-in-metastatic-melanoma
#18
Marco Tucci, Anna Passarelli, Francesco Mannavola, Luigia Stefania Stucci, Paolo Antonio Ascierto, Marilena Capone, Gabriele Madonna, Patrizia Lopalco, Francesco Silvestris
Immunotherapy is effective in metastatic melanoma (MM) but most studies failed in discovering a biomarker predictive of clinical response. Exosomes (Exo) from melanoma cells are detectable in sera of MM patients similarly to those produced by immune cells that control the tumor progression. Here, we investigated by flow-cytometry the levels of Exo from both T-cells and dendritic cells (DCs) in 59 patients with MM treated with IPI and the relative expression of PD-1, CD28 and ICOS as well as CD80 and CD86. We found a significant increment of PD-1 and CD28 expression in patients achieving a clinical response reflected by improvement of both PFS and OS...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308312/systemic-administration-of-%C3%AE-glucan-of-200%C3%A2-kda-modulates-melanoma-microenvironment-and-suppresses-metastatic-cancer
#19
Mei Zhang, Liane Chun, Victor Sandoval, Hallie Graor, Jay Myers, Joseph Nthale, Peter Rauhe, Zachary Senders, Kevin Choong, Alex Y Huang, Julian Kim
Converting an immunosuppressive melanoma microenvironment into one that favors the induction of antitumor immunity is indispensable for effective cancer immunotherapy. In the current study we demonstrate that oat-derived β-(1-3)-(1-4)-glucan of 200 kDa molecular size (BG34-200) previously shown to mediate direct interaction with macrophages could alter the immune signature within melanoma microenvironment. Systemic administration of BG34-200 resulted in reversion of tolerant melanoma microenvironment to an immunogenic one that allows M1-type activation of macrophages, the induction of pro-inflammatory cytokines/chemokines including IFN-γ, TNF-α, CXCL9, and CXCL10, and enhanced IRF1 and PD-L1 expression...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308310/a-novel-immunization-strategy-using-cytokine-chemokines-induces-new-effective-systemic-immune-responses-and-frequent-complete-regressions-of-human-metastatic-melanoma
#20
Fred T Valentine, Frederick M Golomb, Matthew Harris, Daniel F Roses
Immune responses have been elicited by a variety of cancer vaccines, but seldom induce regressions of established cancers in humans. As a novel therapeutic immunization strategy, we tested the hypothesis that multiple cytokines/chemokines secreted early in secondary responses ex-vivo might mimic the secretory environment guiding new immune responses. The early development of immune responses is regulated by multiple cytokines/chemokines acting together, which at physiologic concentrations act locally in concert with antigen to have non-specific effects on adjacent cells, including the maturation of dendritic cells, homing and retention of T cells at the site of antigen, and the differentiation and expansion of T cell clones with appropriate receptors...
2018: Oncoimmunology
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