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Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored.

Made available in DSpace on 2019-10-04T12:42:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Made available in DSpace on 2019-10-04T12:42:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) A fucomannogalactan (FMG-Hm), with a molecular weight of 17.1 kDa, obtained from fruiting bodies of Hypsizygus marmoreus exhibited promising in vitro antimelanoma effects. FMG-Hm was not cytotoxic, nor did it alter the cell morphology and proliferation, but was able to inhibit colony-forming ability and cell migration in B16-F10 murine melanoma cells. An analysis of the monosaccharide composition indicated that FMG-Hm was composed of fucose, mannose, and galactose in a ratio of 1.00:1.08:3.17. The FMG-Hm was structurally characterized based on methylation analysis, partial acid hydrolysis, and NMR experiments. The results indicated that FMG-Hm contained a alpha-(1 -> 6)-linked galactopyranosyl main chain, partially substituted at O-2 by non-reducing ends of alpha-L-fucopyranose and beta-D-mannopyranose. The predicted structure of the heteropolysaccharide was established as: [GRAPHICS] . Univ Fed Goias, Dept Quim, BR-75704020 Regional Catalao, Catalao, Brazil Univ Fed Parana, Dept Biol Celular, BR-81531980 Curitiba, Parana, Brazil Univ Estadual Paulista, Fac Ciencias Agron, Dept Engn Rural, BR-18610307 Botucatu, SP, Brazil Univ Fed Goias, Inst Quim, Lab Ressonancia Magnet Nucl, Campus Samambaia, BR-74001970 Goiania, Go, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Dept Quim & Bioquim, BR-19060900 Presidente Prudente, Brazil Univ Estadual Paulista, Fac Ciencias Agron, Dept Engn Rural, BR-18610307 Botucatu, SP, Brazil Univ Estadual Paulista, Fac Ciencias & Tecnol, Dept Quim & Bioquim, BR-19060900 Presidente Prudente, Brazil CAPES: 001

The ADIGE (Acceleratore Di Ioni a Grande carica Esotici) injector of the SPES (Selective Production of Exotic Species) project is now in an advanced phase of installation. Its main components have been designed following particular needs of the project: first, an Electron Cyclotron Resonance (ECR)-based Charge Breeder (SPES-CB), to boost the charge states of the radioactive ions produced at SPES and allow their post-acceleration. Then, a stable 1+ source and a complete electrostatic beam line to characterize the SPES-CB. Finally, a unique Medium Resolution Mass Spectrometer (MRMS, R=1/1000), mounted on a high voltage platform downstream the SPES-CB, to clean the radioactive beam from the contaminants induced by the breeding stage. This contribution describes the status of the injector, in particular the installation of the platform housing the MRMS, the access and safety system adopted and the first beams to be extracted from the stable 1+ source.

INFN-LNL is constructing an ISOL (Isotope Separation On Line) facility delivering neutron rich ion beams at 10 A MeV or beyond, making use of the linear accelerator ALPI as the secondary accelerator. The facility includes a direct ISOL target based on UC x and able to reach 10 13 fissions/s. In parallel, an applied physics facility will be developed, with applications in medicine and neutron production. The SPES project is a national facility, approved and funded. Commissioning with the first exotic species is expected in 2019. The primary accelerator is a commercial cyclotron, which will send a 40 MeV, 200 μA proton beam onto an UC x target, connected to SIS, PIS and LIS ion sources. The extracted beam is purified through a Low Resolution Mass Separator (LMRS, i.e. a Wien filter and a dispersive dipole), a beam cooler and a High Resolution Mass Separator (HRMS) and sent to an ECR charge breeder to boost the exotic beam charge state. The highly charged exotic beam is further separated in a MRMS (Medium Resolution Mass Separator) and injected into a 100% duty cycle RFQ and into the existing superconducting linac ALPI, which will be refurbished and upgraded to be an efficient exotic beam accelerator. The upgrade of ALPI will give ∼10 A MeV energy to 132 Sn 19+ , taken as the reference ion beam. The paper presents the status of the design and construction of the SPES facility.

Polybrominated diphenyl ethers (PBDEs) are brominated, persistent and bioaccumulative flame retardants widely used in the manufacture of plastic products. Decabromodiphenyl ether (BDE-209) is the most prevalent PBDE in the atmosphere and found in human blood, breast milk and umbilical cord. In vitro studies showed that BDE-209 interferes with murine melanoma cells (B16F10), modulating cell death rates, proliferation and migration, important events for cancer progression. In order to evaluate if BDE-209 modulates metastasis formation in murine models, C57BL/6 mice were exposed to BDE-209 (0.08, 0.8 and 8 μg⁄kg) via gavage (5-day intervals for 45 days) (9 doses in total). Then, mice were inoculated with melanoma cells (B16–F10) at caudal vein receiving 4 additional doses of BDE-209. At 20th day post-cell inoculation, blood, lung, liver, kidney and brain were sampled for hematological, biochemical and morphological analyses. The slightly higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood and pro-oxidant state in the liver of BDE-exposed mice indicated liver damage. Although the in vivo approach is for metastasis formation in the lung, they were unexpectedly observed in non-target organs (liver, brain, kidney and gonads). The similarity test showed high proximity among individuals from the control and a dissimilarity index between the control and exposed groups. The present data corroborate the known hepatotoxicity of BDE-209 to mice (C57BL/6) and demonstrate for the first time the increase of metastatic dissemination of B16F10 cells in vivo due to previous and continuous BDE-209 exposure, revealing possible implications of this organic compound with melanoma malignancy related traits.

Since fall 2017, the ADIGE (Acceleratore Di Ioni a Grande carica Esotici) injector of the SPES (Selective Production of Exotic Species) project entered the installation phase. The injector includes an ECR-based charge breeder (SPES-CB) and its complete beam line, as well as a newly designed RFQ, to allow the post-acceleration of the radioactive ions produced in the so-called Target-Ion-Source system. The injector has different peculiarities, deriving from particular needs of SPES: a complete electrostatic beam line equipped with a 1+ source for test purposes, and a unique Medium Resolution Mass Spectrometer (MRMS, R~1/1000), mounted downstream the SPES-CB, to clean the radioactive beam from the contaminants induced by the breeding stage. This contribution reports about the status of the installation of the injector, describing the various technical solution adopted, and giving a realistic planning for the commission and following operation of its main parts., Proceedings of the 23th Int. Workshop on ECR Ion Sources, ECRIS2018, Catania, Italy

International audience; The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UCx target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.