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Takashi Inozume, Toshiyuki Tsunoda, Takashi Morisaki, Kazutoshi Harada, Seiji Shirasawa, Tatsuyoshi Kawamura
Serine/threonine-protein kinase B-Raf (BRAF) inhibitors are very effective in treating melanoma with BRAF mutations. BRAF inhibitors suppress aberrant growth of melanoma cells caused by BRAF mutations. BRAF mutations reportedly result in melanoma cells releasing immunosuppressive factors, and BRAF inhibitors elicit anti-melanoma immune responses by reducing such factors. However, immunological characteristics of tumor cells that acquire resistance to BRAF inhibitors remain unknown. Here, we compared immunological characteristics between a melanoma cell line and its vemurafenib-resistant subline...
September 17, 2018: Journal of Dermatology
Leonardo S Lino-Silva, César Zepeda-Najar, Rosa A Salcedo-Hernández, Héctor Martínez-Said
INTRODUCTION: Acral lentiginous melanoma (ALM) is an aggressive variant of melanoma; the incidence, prevalence, and prognosis differ among populations. We analyzed clinicopathological features and survival in Hispanics, a population with high ALM prevalence. MATERIAL AND METHODS: From 1144 patients with melanoma, we analyzed 715 ALMs and 429 non-ALMs from the National Referral Cancer Centre and compared survival. RESULTS: Of the ALM group, 62...
September 15, 2018: Journal of Cutaneous Medicine and Surgery
Fei Wang, Zhaoguo Li, Lei Xu, Yongchao Li, Yi Li, Xingbo Zhang, Yue Wang, Dazhong Liu
A previous study indicated that LIM domain containing 2 (LIMD2) is an oncogene in a variety of human cancers, including breast, bladder and thyroid cancers, and melanoma; however, the role of LIMD2 in non‑small cell lung cancer (NSCLC) remains largely unknown. In the present study, by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis, it was demonstrated that LIMD2 was significantly upregulated in NSCLC tissues compared with adjacent normal tissues. Consistently, LIMD2 was also upregulated in NSCLC cell lines...
September 6, 2018: Molecular Medicine Reports
Zhen Mu, Qing Sun
Cantharidin (CTD) is an active component isolated from the blister beetle that has been demonstrated to exert antitumor effects on multiple types of cancer. The current study aimed to investigate whether the potential inhibitory effects of CTD exist in human melanoma cells and to assess the underlying antitumor mechanisms of CTD. Using the Cell Counting Kit‑8 assay, it was demonstrated that CTD treatment reduced A375 cell proliferation significantly in a dose‑dependent manner. The colony formation assay demonstrated that CTD treatment could decrease the number of A375 cell colonies...
September 3, 2018: Molecular Medicine Reports
Ane F Santos, Isabella P Ferreira, Carlos B Pinheiro, Verlane G Santos, Miriam T P Lopes, Letícia R Teixeira, Willian R Rocha, Gabriel L S Rodrigues, Heloisa Beraldo
Complexes [Ag(H2BzPh)NO3 ] ( 1 ), [Ag(H2Bz p CH3 Ph)NO3 ] ( 2 ), [Ag(H2Bz p ClPh)NO3 ] ( 3 ), and [Ag(H2Bz p NO2 Ph)NO3 ] ( 4 ) were synthesized with 2-benzoylpyridine benzoylhydrazone (H2BzPh) and its para -methyl-benzoylhydrazone (H2Bz p CH3 Ph), para -chloro-benzoylhydrazone (H2Bz p ClPh), and para -nitro-benzoylhydrazone (H2Bz p NO2 Ph) derivatives. Experimental data indicate that the nitrate ligand binds more strongly to the silver center through one of the oxygen atoms, whereas the second oxygen atom from nitrate and the hydrazone oxygen makes much weaker interactions with the metal...
June 30, 2018: ACS Omega
Zaahira Aumeeruddy-Elalfi, Ismaël Saïd Ismaël, Muzzammil Hosenally, Gokhan Zengin, Mohamad Fawzi Mahomoodally
The biofilm inhibition and eradication potential of essential oils (EOs) extracted from six tropical medicinal herbs and food plants [ Psiadia arguta (PA), Psiadia terebinthina (PT), Citrus grandis (CGp), Citrus hystrix (CH), Citrus reticulata (CR), and Cinnamomum zeylanicum (CZ)] were assessed. The mechanism of inhibition was studied via quenching of efflux pump. Cytotoxicity was evaluated using Artemia salina assay and cell lines [human cervix carcinoma (HeLa), human lung fibroblast (MRC-5), and murine melanoma (B16F10)]...
September 2018: 3 Biotech
Paola Giglio, Mara Gagliardi, Nicola Tumino, Fernanda Antunes, Soraya Smaili, Diego Cotella, Claudio Santoro, Roberta Bernardini, Maurizio Mattei, Mauro Piacentini, Marco Corazzari
The immunogenic cell death (ICD) process represents a novel therapeutic approach to treat tumours, in which cytotoxic compounds promote both cancer cell death and the emission of damage-associated molecular patterns (DAMPs) from dying cells, to activate the immune system against the malignancy. Therefore, we explored the possibility to stimulate the key molecular players with a pivotal role in the execution of the ICD program in melanoma cells. To this aim, we used the pro-ICD agents mitoxantrone and doxorubicin and found that both agents could induce cell death and stimulate the release/exposure of the strictly required DAMPs in melanoma cells: i) calreticulin (CRT) exposure on the cell membrane; ii) ATP secretion; iii) type I IFNs gene up-regulation and iv) HMGB1 secretion, highlighting no interference by oncogenic BRAF...
2018: Oncoimmunology
Natacha Bordry, Maria A S Broggi, Kaat de Jonge, Karin Schaeuble, Philippe O Gannon, Periklis G Foukas, Esther Danenberg, Emanuela Romano, Petra Baumgaertner, Manuel Fankhauser, Noémie Wald, Laurène Cagnon, Samia Abed-Maillard, Hélène Maby-El Hajjami, Timothy Murray, Kalliopi Ioannidou, Igor Letovanec, Pu Yan, Olivier Michielin, Maurice Matter, Melody A Swartz, Daniel E Speiser
Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8+ T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO)...
2018: Oncoimmunology
S Feola, C Capasso, M Fusciello, B Martins, S Tähtinen, M Medeot, S Carpi, F Frascaro, E Ylosmäki, K Peltonen, L Pastore, V Cerullo
Activation of immune checkpoint pathways and limited T- cell infiltration result in immunological escape of tumors. Although immune checkpoint inhibitors are currently approved for several types of cancers, the response rate is often limited by the lack of tumor specific T-cells within the malignant tissue. Therefore, new combinatorial strategies are needed to enhance the clinical benefit of immune checkpoint inhibitors. We have previously developed PeptiCRAd, an oncolytic vaccine platform capable of directing the immune response toward tumor epitopes...
2018: Oncoimmunology
Muhammad Zaeem Noman, Jerome Paggetti, Etienne Moussay, Guy Berchem, Bassam Janji
Natural Killer (NK) cell-based cancer immunotherapies were often disappointing in the clinic mostly due to insufficient NK cell infiltration into tumors. We found that targeting autophagy induced a massive infiltration of NK cells into melanoma tumors. These findings highlight autophagy inhibition as a cutting-edge approach to fully exploit the anti-tumor properties of NK cells in a wide variety of cancer patients.
2018: Oncoimmunology
Manja Idorn, Signe Koggersbøl Skadborg, Lauge Kellermann, Hólmfrídur Rósa Halldórsdóttir, Gitte Holmen Olofsson, Özcan Met, Per Thor Straten
Adoptive cell therapy (ACT) using in vitro expanded tumor infiltrating T lymphocytes (TILs) from biopsy material represents a highly promising treatment of disseminated cancer. A crucial prerequisite for successful ACT is sufficient recruitment of transferred lymphocytes to the tumor site; however, despite infusion of billions of lymphocytes, T cell infiltration into the tumor post ACT is limited. By PCR and Luminex analyses we found that a majority of malignant melanoma (MM) cell lines expressed chemokines CXCL1/Gro α , CXCL8/IL-8, CXCL12/SDF-1 and CCL2...
2018: Oncoimmunology
Mario M Soldevilla, Helena Villanueva, Naiara Martinez-Velez, Daniel Meraviglia-Crivelli, Marta M Alonso, Javier Cebollero, Ashwathi P Menon, Montserrat Puigdelloses, Fernando Pastor
In spite of the success of PD-1 blocking antibodies in the clinic their benefits are still restricted to a small fraction of patients. Immune-desert tumors and/or the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1 blocking therapies into a broader range of cancer patients. Although still under debate, there is a cumulative body of evidence that indicates B tumor-infiltrating lymphocytes are a good prognostic marker in most types of cancer, especially in those that form ectopic lymphoid tissue structures...
2018: Oncoimmunology
Natalia Pieper, Anne Zaremba, Sonia Leonardelli, Franziska Noelle Harbers, Marion Schwamborn, Silke Lübcke, Barbara Schrörs, Jolanthe Baingo, Alexander Schramm, Sebastian Haferkamp, Ulrike Seifert, Antje Sucker, Volker Lennerz, Thomas Wölfel, Dirk Schadendorf, Bastian Schilling, Annette Paschen, Fang Zhao
The profound but frequently transient clinical responses to BRAFV600 inhibitor (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies. Multiple clinical trials combining BRAFi and immunotherapy are under way to further enhance therapeutic responses. However, to which extent BRAFV600 inhibition may affect melanoma immunogenicity over time remains largely unknown. To support the development of an optimal treatment protocol, we studied the impact of prolonged BRAFi exposure on the recognition of melanoma cells by T cells in different patient models...
2018: Oncoimmunology
Lise Barlebo Ahlborn, Ida Viller Tuxen, Florent Mouliere, Savvas Kinalis, Ane Y Schmidt, Kristoffer Staal Rohrberg, Eric Santoni-Rugiu, Finn Cilius Nielsen, Ulrik Lassen, Christina Westmose Yde, Olga Oestrup, Morten Mau-Sorensen
Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cell-free DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi) combination therapies in non-melanoma solid tumors included in the Copenhagen Prospective Personalized Oncology (CoPPO) program. Experimental design: Patients with BRAF V600E-mutated tumors were treated with combination therapies including BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated to clinical outcomes...
August 24, 2018: Oncotarget
Li Xia Gao, Chunxiang Bian, Yan Wu, Muhammad Farrukh Nisar, Shida Chen, Chang Ming Li, Ling Yu, Ping Ji, Enyi Huang, Julia Li Zhong
Background: Generation of reactive oxygen species (ROS), triggered by ultraviolet radiation (UVR), is associated with carcinogenesis of the skin. UV irradiation induced superoxide anion (O2•- ) is the key ROS involved in the cellular damage. The cytoprotective efficacy of an unknown anti-oxidant compound can be evaluated by analyzing the production of O2•- from treated cells. Methods: In this study, a glass carbon electrode functionalized with nanotube@DNA-Mn3(PO4)2 composite was applied to quantitative determination of generation of highly unstable O2•- from the melanoma A375 cell line following UVR(UV, UVA and UVB)...
2018: Journal of Biological Engineering
Ewa Bębenek, Monika Kadela-Tomanek, Elwira Chrobak, Małgorzata Latocha, Stanisław Boryczka
The CuAAC reaction of azides and acetylenic triterpenes was used for synthesis of new triazoles of 3-acetylbetulin and betulone. The triazole derivatives were evaluated for their anticancer activity in vitro against amelanotic melanoma C-32, ductal carcinoma T47D and glioblastoma SNB-19 cell lines. 28-[1-(3'-Deoxythymidine-5'-yl)-1 H -1,2,3-triazol-4-yl]carbonylbetulone 6e exhibited a significant IC50 value (0.17 µM) against the human glioblastoma SNB-19 cell line, an almost 5-fold higher potency while compared with reference cisplatin...
2018: Medicinal Chemistry Research
G Faviez, E Bousquet, A Rabeau, I Rouquette, S Collot, C Goumarre, N Meyer, G Prevot, J Mazieres
INTRODUCTION: Immune checkpoint inhibitors are becoming a standard treatment for many different cancers. Their toxicities are variable and include organ-specific dysimmune injuries and the development of systemic diseases. CASE REPORT: We report 3 cases of sarcoid-like granulomatosis that occurred during treatment of various types of primary cancer by immune checkpoint inhibitors: lung adenocarcinoma, small cell lung cancer and melanoma. The clinical presentation, radiologic pattern and severity of this toxicity were variable...
September 13, 2018: Revue des Maladies Respiratoires
M X Chen, Y M Liu, W B Wei
Radiation treatment, including episcleral plaque radiotherapy, stereotactic radiosurgery, proton beam therapy and so on, is the primary eye-conserving choice for uveal melanoma. But the complications resulted from radiotherapy's nonselective kill to tumor cells can be visual-threatening and eventually result in the enucleation of eyeball. This review summarizes current radiation strategies for uveal melanoma and how these complications occur, develop and present, in the hope that it could provide insights for the radiation interventions and diagnosis of radiative complications...
September 11, 2018: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
Donghui Bian, Yan Wu, Guodong Song
Malignant melanoma, a tumor derived from melanocytes, shows severe drug resistance and prompt metastasis, causing a serious threat to human health. Circular RNAs (circRNAs) are widely expressed in mammals and have been indicated to play important roles in tumorigenesis. In the present study, we analyzed the variability of circRNAs in malignant melanoma by microarray and identified six differentially expressed circRNAs. In particular, we found that hsa_circ_0025039, which is formed by FOXM1 exons, is significantly upregulated in melanoma...
September 13, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Reinhard Dummer, Paolo A Ascierto, Helen J Gogas, Ana Arance, Mario Mandala, Gabriella Liszkay, Claus Garbe, Dirk Schadendorf, Ivana Krajsova, Ralf Gutzmer, Vanna Chiarion Sileni, Caroline Dutriaux, Jan Willem B de Groot, Naoya Yamazaki, Carmen Loquai, Laure A Moutouh-de Parseval, Michael D Pickard, Victor Sandor, Caroline Robert, Keith T Flaherty
BACKGROUND: Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAFV600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival. METHODS: COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAFV600E or BRAFV600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had progressed on or after first-line immunotherapy...
September 12, 2018: Lancet Oncology
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