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Your search keyword '"FLORIO, TM"' showing total 2 results
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2 results on '"FLORIO, TM"'

1. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin.

Author

Dhez AC, Benedetti E, Antonosante A, Panella G, Ranieri B, Florio TM, Cristiano L, Angelucci F, Giansanti F, Di Leandro L, d'Angelo M, Melone M, De Cola A, Federici L, Galzio R, Cascone I, Raineri F, Cimini A, Courty J, Giordano A, and Ippoliti R

Subjects
Animals, Cell Line, Tumor, Cell Membrane drug effects, Cell Proliferation drug effects, Glioblastoma genetics, Glioblastoma pathology, Humans, Mice, Molecular Targeted Therapy, Neovascularization, Pathologic pathology, Peptides chemistry, Phosphoproteins chemistry, RNA-Binding Proteins chemistry, Saporins chemistry, Saporins pharmacology, Xenograft Model Antitumor Assays, Nucleolin, Glioblastoma drug therapy, Neovascularization, Pathologic drug therapy, Peptides pharmacology, Phosphoproteins pharmacology, RNA-Binding Proteins pharmacology
Abstract

Targeted anticancer therapies demand discovery of new cellular targets to be exploited for the delivery of toxic molecules and drugs. In this perspective, in the last few years, nucleolin has been identified as an interesting surface marker to be used for the therapy of glioblastoma. In this study, we investigated whether a synthetic antagonist of cell-surface nucleolin known as N6L, previously reported to decrease both tumor growth and tumor angiogenesis in several cancer cell lines, including glioblastoma cells, as well as endothelial cells proliferation, could be exploited to deliver a protein toxin (saporin) to glioblastoma cells. The pseudopeptide N6L cross-linked to saporin-S6 induced internalization of the toxin inside glioblastoma cancer cells. Our results in vitro demonstrated the effectiveness of this conjugate in inducing cell death, with an ID 50 four orders of magnitude lower than that observed for free N6L. Furthermore, the preliminary in vivo study demonstrated efficiency in reducing the tumor mass in an orthotopic mouse model of glioblastoma., (© 2017 Wiley Periodicals, Inc.)

Published
2018
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2. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model.

Author

Benedetti E, Antonosante A, d'Angelo M, Cristiano L, Galzio R, Destouches D, Florio TM, Dhez AC, Astarita C, Cinque B, Fidoamore A, Rosati F, Cifone MG, Ippoliti R, Giordano A, Courty J, and Cimini A

Subjects
Adult, Aged, Animals, Antineoplastic Agents, Alkylating pharmacology, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Dacarbazine analogs & derivatives, Dacarbazine pharmacology, Drug Synergism, Female, G1 Phase Cell Cycle Checkpoints drug effects, Glioblastoma metabolism, Glioblastoma pathology, Humans, Kaplan-Meier Estimate, Mice, Inbred BALB C, Mice, Nude, Microscopy, Fluorescence, Middle Aged, Phosphoproteins metabolism, RNA-Binding Proteins metabolism, Temozolomide, Tumor Burden drug effects, Tumor Cells, Cultured, Nucleolin, Autophagy drug effects, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Peptides pharmacology, Phosphoproteins antagonists & inhibitors, RNA-Binding Proteins antagonists & inhibitors, Xenograft Model Antitumor Assays
Abstract

Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.

Published
2015
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