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EN
Introduction: Experimental autoimmune encephalomyelitis (EAE) is a prototypic Th1-mediated autoimmune inflammatory disease of the central nervous system (CNS), and serves as a model for the human demyelinating disease, multiple sclerosis. Cisplatin is a drug widely used in the treatment of a variety of human neoplasias, such as advanced bladder carcinoma, adrenal cortex carcinoma, breast cancer, head and neck or lung carcinoma. Cisplatin binds to DNA and interferes with cellular repair and other mechanism, which eventually result into cell death. It is known that cisplatin can induce immunosuppressive effects through inhibition of T cell activity. Therefore we analyzed the anti-inflammatory effects of cisplatin in a rat EAE model. Materials and Methods: EAE was induced in male LEW rats by immunizing with a synthetic peptide of guinea pig myelin basic protein. The development of EAE and neurological signs were evaluated by a standard protocol. Immunohistochemistry was applied to show immune cell infiltration into the CNS. Results: Early treatment of EAE rats with cisplatin effectively ameliorated the development of disease and provided a significant protective effect compared to control rats. Further, histological analysis demonstrated that the formation of the typical perivascular cuffs and brain infiltration of monocytes and lymphocytes were complete absent in cisplatin treated rats, while abundant T cell infiltration was seen in the CNS of EAE rats. Conclusions: Our data show that cisplatin has protective effects in EAE, indicating that cisplatin could be a candidate in the treatment of human CNS autoimmunity.
EN
In vivo phage display has been used extensively to screen for novel targets of tumor therapy. Phage display peptide libraries can express random peptides or protein fragments and the aim of phage display is to identify peptide molecules that bind stably to a given target. Angiogenesis is essential to tumor development. Both blood and lymphatic vessels of tumors are different from those of normal tissues. Phage display has been used to analyze the structure and molecular diversity of tumor vasculature and to select tumor-specific antigens which have revealed stage- and type-specific markers of tumor blood vessels. Furthermore, peptides identified by in vivo phage display also work as vehicles to transport cargo therapeutic reagents to tumors. These peptides and their corresponding cellular proteins and ligands may provide molecular tools to selectively target the addresses of tumors and their pathological blood vessels and might increase the efficacy of therapy while decreasing side effects.
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issue 5
307-315
EN
Nucleic acid aptamers are short, single-stranded oligonucleotides or their modified analogues which avidly and specifically interact with targeted ligands through their 3-dimensional structure. Aptamers can be selected out of a large combinatorial oligonucleotide library through an in vitro evolution process termed SELEX. Since 1990, a wide variety of aptamers targeted to ligands ranging from small molecules to complex mixtures have been isolated. Most selected aptamers have shown high specificity to and affinity for their ligands and are potential detection and/or diagnostic reagents. Furthermore, some aptamers specifically inhibit biological functions of targeted proteins, resulting in potent therapeutic candidates in disease models. Some recent advances to increase the stability of aptamers, extend their in vivo circulation time and their in vivo expression have pushed aptamers closer to therapeutic applications. This review presents recent developments in the field of aptamer research and focuses on their applications to human viral diseases, particularly HIV induced diseases.
EN
Exosomes are small membrane vesicles derived from late endosome. They are about 30?100 nm in diameter. The secretion of exosomes is a process in which multivesicular bodies fuse with the cell membrane, and all cells that contain multivesicular endocytic compartments could theoretically secrete exosomes. The surprising biological functions of exosomes are only slowly being unveiled, but it is already clear that they serve to remove obsolete membrane proteins and act as messages of inter-cellular communication. Exosomes derived from tumor or antigen-presenting cells have been extensively investigated. They are released into the extracellular environment and fuse with the membranes of neighboring cells, delivering membrane and cytoplasmic proteins from one cell to another. Exosomes carry immunorelevant structures which play important roles in immune response, such as MHC molecules, costimulatory molecules, heat shock proteins, and naive tumor antigens. Therefore they have been suggested as potential vaccines. Consequently, exosomes have shown considerable anti-tumor effect in several studies and are in phase I clinical trials.
EN
Introduction: Macrophages/microglial cells are considered as immune cells in the central nervous system. Interleukin (IL)-16 is a proinflammatory cytokine produced by activated monocytic cells. Materials and Methods: Expression of IL-16 was analyzed by immunohistochemistry in human astrocytic brain tumors and the rat C6 glioblastoma tumor model. IL-16 was detected in both human astrocytic brain tumors and rat C6 glioma. Results: Compared with human control brains, a significant increase in the percentages of parenchymal IL-16+ macrophages/microglia was observed already in grade II astrocytomas, indicating that IL-16+ immunostaining could be a descriptor of a macrophage/microglia subset in astrocytic brain tumors. A further increase was observed at the transition from grade II to III astrocytomas. This increase in IL-16 immunoreactivity correlated with WHO grades of human astrocytic brain tumors. Conclusions: Therefore, IL-16 might be a so far unknown factor in the regulation of the local inflammatory milieu of human and experimental astrocytomas.
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