Production and Evaluation of an Avian IgY Immunotoxin against CD133+for Treatment of Carcinogenic Stem Cells in Malignant Glioma: IgY Immunotoxin for the Treatment of Glioblastoma
JOURNAL OF ONCOLOGY
Authors: Chavez-Cortez, Elda-Georgina; Vargas Felix, Gustavo; Rangel Lopez, Edgar; Sotelo, Julio; Martinez-Canseco, Carlos; Perez-de la Cruz, Veronica; Pineda, Benjamin
Abstract
Background. Glioblastoma is the most common malignant tumor of Central Nervous System. Despite the research in therapeutics, the prognosis is dismal. Malignant glioma stem cells (MGSCs) are a major cause of treatment failure and increasing tumor recurrence. In general, cancer stem cells (CSCs) express prominin-1 (CD133), considered as a potential therapeutic target. In this study, we produced an avian immunotoxin directed against the subpopulation of CD133+ CSCs within a malignant glioma. We used the avian IgY because it has various advantages as increased affinity to mammal antigens and inexpensive obtention of large amounts of specific antibodies (approximately 1 mg/per egg). The design, production, purification and use of IgY anti CD133 immunotoxin constitute an original goal of this research. Methods. The immunodominant peptide of CD133 was designed to immunize hens; also, the extracellular domain of CD133 was cloned to probe the IgY antibodies. In parallel, a recombinant abrin A chain was produced in E. coli in order to join it to the Fc domain of the anti-CD133 IgY to conform the immunotoxin. This anti-CD133 IgY anti-tumor immunotoxin was tested in vitro and in vivo. Results. The cytotoxicity of the immunotoxin in vitro showed that IgY-abrin immunotoxin reduced 55% cell viability. After subcutaneous MGSCs implantation, the animals treated intraperitoneally or intratumorally with the IgY-abrin immunotoxin showed more than 50% decrease of tumor volume. Conclusion. Results showed that the IgY-abrin immunotoxin had cytotoxic activity against CD133+ MGSCs and provides a novel approach for the immunotherapy of glioblastoma.
Inospheric Weather During Five Extreme Geomagnetic Superstorms Since IGY Deduced With the Instantaneous Global Maps GIM-foF2
SPACE WEATHER-THE INTERNATIONAL JOURNAL OF RESEARCH AND APPLICATIONS
Authors: Stanislawska, Iwona; Gulyaeva, Tamara L.; Grynyshyna-Poliuga, Oksana; Pustovalova, Ljubov, V
Abstract
An assessment of the ionosphere perturbations can be made through the construction of the global instantaneous maps of the foF2 critical frequency (GIM-foF2) and the ionospheric weather index maps GIM-Wf. These maps can offer a potentially useful tool to provide users with a proper selection of the best radio wave propagation conditions over a certain area and also be used to help mitigate the effects of the disturbances on HF (High Frequency) communication and Global Navigation Satellite System positioning. This paper presents results of reconstruction of the ionospheric weather during five of the most intense superstorms observed since International Geophysical Year, IGY (1957, 1958, 1959, 1989, and 2003) with the instantaneous global maps of the F2 layer critical frequency, GIM-foF2, and the ionospheric weather index maps, GIM-Wf. The intensity of the ionospheric superstorm is characterized by the planetary Wfp index derived from GIM-Wf maps. Superposed epoch analysis of the extreme superstorms is made during 24 hr before the Wfp peak (time zero t(0) = 0 hr) and 48 hr afterwards. Model relationship is established between mean Wfp profile and geomagnetic superstorm profiles demonstrating saturation of the ionospheric storm activity toward the peak of geomagnetic storm. Time lag of Wfp(max) is found equal to 9 hr after AE(max), 6 hr after ap(max) and aa(max), and 2 hr after Dst(min), which allows model forecast of ionospheric superstorm when geomagnetic superstorm is captured with one or more of geomagnetic indices.